BIOMEDICAL IMPLICATIONS OF
MILITARY LASER EXPOSURE

The Coat of Arms

1818

Medical Department of the Army

A 1976 etching by Vassil Ekimov of an
original color print that appeared in
The Military Surgeon, Vol XLI, No 2, 1917

Textbooks of Military Medicine

Published by the

Office of The Surgeon General
Borden Institute
US Army Medical Center of Excellence
Fort Sam Houston, Texas

Edward A. Lindeke
Colonel (Retired), MS, US Army

Director, Borden Institute

The TMM Series

Published Textbooks

Medical Consequences of Nuclear W arfare (1989)

Conventional Warfare: Ballistic, Blast, and Burn Injuries (1991)

Occupational Health: The Soldier and the Industrial Base (1993)

Military Dermatology (1994)

Military Psychiatry: Preparing in Peace for War (1994)

Anesthesia and Perioperative Care of the Combat Casualty (1995)

War Psychiatry (1995)

Medical Aspects of Chemical and Biological Warfare (1997)

Rehabilitation of the Injured Soldier, Volume 1 (1998)

Rehabilitation of the Injured Soldier, Volume 2 (1999)

Medical Aspects of Harsh Environments, Volume 1 (2002)

Medical Aspects of Harsh Environments, Volume 2 (2002)

Ophthalmic Care of the Combat Casualty (2003)

Military Medical Ethics, Volume 1 (2003)

Military Medical Ethics, Volume 2 (2003)

Military Preventive Medicine, Volume 1 (2003)

Military Preventive Medicine, Volume 2 (2005)

Recruit Medicine (2006)

Medical Aspects of Biological Warfare (2007)

Medical Aspects of Chemical Warfare (2008)

Care of the Combat Amputee (2009)

Combat and Operational Behavioral Health (2011)

Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine (2012)

Medical Consequences of Radiological and Nuclear Weapons (2013)

Forensic and Ethical Issues in Military Behavioral Health (2014)

Combat Anesthesia: The First 24 Hours (2015)

Otolaryngology/Head and Neck Surgery Combat Casu alty Care in Operation Iraqi Freedom and Operation Enduring Freedom (2015)

Medical Aspects of Biological Warfare (2018)

Military Veterinary Services (2019)

Occupational Health and the Service Member (2019)

Fundamentals of Military Medicine (2019)

Biomedical Implications of Military Laser Exposure (2020)

US Army photo

This book is dedicated to Colonel Edwin S. Beatrice, MD, who is directly responsible for much of the information and many of the ideas contained herein. Through over 2 decades of pioneering work, Colonel Beatrice laid the basis for much of the research that has since been performed to advance scientific understanding of the biomedical implications and risks associated with the use of military lasers. Although many researchers and practitioners have made important contributions to the field of laser safety, no single body of work has been more essential and notable than that of Dr Beatrice, whose career was dedicated exclusively to the study and prevention of laser-induced injury. Thus, the contributors to this Textbook of Military Medicine dedicate this volume to his work and to his memory.

BIOMEDICAL IMPLICATIONS OF
MILITARY LASER EXPOSURE

Senior Editors

Bruce E. Stuck, ScD

Formerly, Detachment Director
US Army Medical Research Detachment
Walter Reed Army Institute of Research

Victoria Tepe, PhD

Senior Science Advisor

The Geneva Foundation

James W. Ness, PhD

Colonel, Medical Services Corps, US Army

Professor of Discipline and Program Director of Engineering Psychology

Department of Behavioral Sciences and Leadership, US Military Academy

Office of The Surgeon General

Borden Institute

US Army Medical Center of Excellence

Fort Sam Houston, Texas

2020

Editorial Staff:

Joan Redding

Senior Production Editor

Douglas Wise

Senior Layout Editor

Vivian Mason

Volume Editor

Robert Dredden

Illustrator

This volume was prepared for military medical educational use. The focus of the information is to foster discussion that may form the basis of doctrine and policy. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

Dosage Selection:

The authors and publisher have made every effort to ensure the accuracy of dosages cited herein. However, it is the responsibility of every practitioner to consult appropriate information sources to ascertain correct dosages for each clinical situation, especially for new or unfamiliar drugs and procedures. The authors, editors, publisher, and the Department of Defense cannot be held responsible for any errors found in this book.

Use of Trade or Brand Names:

Use of trade or brand names in this publication is for illustrative purposes only and does not imply endorsement by the Department of Defense.

Neutral Language:

Unless this publication states otherwise, masculine nouns and pronouns do not refer exclusively to men.

certain parts of this publication pertain to copyright restrictions.
all rights reserved.

no copyrighted parts of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical (including photocopy, recording, or any information storage and retrieval system), without permission in writing from the publisher or copyright owner.

Published by the Office of The Surgeon General

Borden Institute

US Army Medical Center of Excellence

Fort Sam Houston, Texas

Library of Congress Cataloging-in-Publication Data

Names: Stuck, Bruce E., editor. | Tepe, Victoria, editor. | Ness, James W., editor. | Borden Institute (U.S.), issuing body.

Title: Biomedical implications of military laser exposure / senior editors, Bruce E. Stuck, Victoria Tepe, James W. Ness.

Other titles: Textbooks of military medicine.

Description: Fort Sam Houston, Texas : Office of the Surgeon General, Borden Institute, US Army Medical Center of Excellence, 2020. | Series: Textbooks of military medicine | Includes bibliographical references and index. | Summary: “Lasers will continue to play an important and sometimes dangerous role on the modern battlefield. At present, there is no adequate comprehensive protection against accidental or intentional exposure to lasers in combat. Thus, it is critical that the field of laser safety research develop preventative protocols and prophylactic technologies to protect the warfighter and to support military operational objectives. This book details the current state-of-the-art in scientific, biomedical, and technical information concerning the effects of military lasers on the human body. An important purpose of this book is to identify current knowledge gaps in the various areas of this interdisciplinary field, and to offer specific recommendations for laser safety research and development into the future”-- Provided by publisher.

Identifiers: LCCN 2020008721 (print) | LCCN 2020008722 (ebook) | ISBN
9780160953798 (hardcover) | ISBN 9780160953712 (epub) | ISBN
9780160953774 (mobi) | ISBN 9780160953781 (pdf)

Subjects: MESH: Lasers--adverse effects | Eye Injuries | Military Personnel | Occupational Exposure Classification: LCC R857.L37 (print) | LCC R857.L37 (ebook) | NLM WW 525 | DDC 610.28--dc23

LC record available at https://lccn.loc.gov/2020008721

LC ebook record available at https://lccn.loc.gov/2020008722

PRINTED IN THE UNITED STATES OF AMERICA

27, 26, 25, 24, 23, 22, 21, 20

5 4 3 2 1

Contents

Contributors

Foreword by The Surgeon General

Preface

Introduction

Section I. History and Hazards of Military Lasers

1. The US Army Medical Department’s Role and Accomplishments in Laser Development and Use
Bruce E. Stuck and Karl E. Friedl

2. History and Development of Military Lasers
Jack B. Keller Jr

3. Relating Structural Insult to Visual Function: Selected Accident Cases
Victoria Tepe, James W. Ness, and Bruce E. Stuck

Section II. Physiological and Psychological Effects

4. Laser-Induced Changes in Visual Performance: Immediate and Long-Term Consequences in an Animal Model
David O. Robbins and Harry Zwick

5. Laser Glare Effects on Visual Performance
Peter Alan Smith

6. The Effects of Nondamaging Levels of Laser Energy on Vision and Visual Function
James W. Ness and Jonathan Ness

7. Psychological and Operational Impacts of Military Lasers
George R. Mastroianni and James W. Ness

Section III. Laser-Induced Injury Thresholds

8. Ocular Effects of Ultraviolet Laser Radiation
Joseph A. Zuclich

9. Laser-Induced Ocular Effects in the Retinal Hazard Region David J. Lund and Brian J. Lund

10. Dependence of Retinal Thermal Injury Threshold on Size and Profile of Laser Image
David J. Lund, Richard C. Hollins, and Karl Schulmeister

11. Retinal Thermal Damage and Ocular Motion
Brian J. Lund

12. Ultrashort Laser Pulses and Their Bioeffects
Benjamin A. Rockwell and William P. Roach

13. Corneal Effects of Laser Radiation
Russell L. McCally and Bruce E. Stuck

Abbreviations and Acronyms

Index

Contributors

KARL E. FRIEDL, PhD

Colonel, US Army (Retired); Senior Research Scientist for Physiology, US Army Research Institute of Environmental Medicine, 10 General Greene Avenue, Natick, Massachusetts 01760

RICHARD C. HOLLINS, DPhil

Senior Fellow, Cyber and Information Systems Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, SP4 0JQ, United Kingdom

JACK B. KELLER Jr

Lieutenant Colonel, US Army (Retired); formerly, Foreign Science Information Officer, US Army Medical Research Detachment-Walter Reed Army Institute of Research, 7965 Dave Erwin Drive, Brooks City-Base, Texas 78235

BRIAN J. LUND, PhD

Research Physicist, Ocular Trauma, US Army Institute of Surgical Research, 3698 Chambers Pass, Joint Base San Antonio, Fort Sam Houston, Texas 78234-7767

DAVID J. LUND, BA

Research Biophysicist (Retired), US Army Medical Research Detachment, 7965 Dave Erwin Drive, Brooks City-Base, Texas 78235

GEORGE R. MASTROIANNI, PhD

Professor Emeritus, US Air Force Academy, Colorado 80840

RUSSELL L. McCALLY, PhD

Principal Staff Physicist (Retired), Johns Hopkins University Ap plied Physics Laboratory, Laurel, Maryland, and Johns Hopkins University Wilmer Eye Institute, 4940 Eastern Avenue, Baltimore, Maryland 21224

JAMES W. NESS, PhD

Colonel, Medical Services Corps, US Army; Professor of Disci pline and Program Director of Engineering Psychology, De partment of Behavioral Sciences and Leadership, US Military Academy, 601 Cullum Road, West Point, New York 10996

JONATHAN M. NESS, BS

Chemical Engineer, Argos, Summerville, South Carolina 29486

WILLIAM P. ROACH, PhD

Chief, Physical and Biological Sciences Branch, Air Force Research Laboratory, Air Force Office of Scientific Research, 875 North Ran dolph Street, Arlington, Virginia 22203-1768

DAVID O. ROBBINS, PhD

Department of Psychology, Ohio Wesleyan University, 61 South Sandusky Street, Delaware, Ohio 43015

BENJAMIN A. ROCKWELL, PhD

Principal Research Physicist, Air Force Research Laboratory, 711th Human Performance Wing, Human Effectiveness Director ate, Bioeffects Division, Optical Radiation Bioeffects Branch, 4141 Petroleum Road, Joint Base San Antonio, Fort Sam Houston, Texas 78234-2644

KARL SCHULMEISTER, PhD

Consultant on Laser and Optical Radiation Safety, Seibersdorf Laboratories, Seibersdorf, Austria

PETER ALAN SMITH, PhD

Technical Fellow, Science Applications International Corporation, Tri-Service Research Laboratory, 4141 Petroleum Road, Joint Base San Antonio, Fort Sam Houston, Texas 78234

BRUCE E. STUCK, ScD

Formerly, Detachment Director, US Army Medical Research Detachment-Walter Reed Army Institute of Research, 7965 Dave Erwin Drive, Brooks City-Base, Texas 78235

VICTORIA TEPE, PhD

Senior Science Advisor, The Geneva Foundation, 917 Pacific Av enue, Tacoma, Washington 98402

JOSEPH A. ZUCLICH, PhD

Senior Scientist/Consultant, Science Applications International Corporation, 1100 Northwest Loop 410, Suite 700, San Antonio, Texas 78213

HARRY ZWICK, PhD

US Army Medical Research Detachment, Walter Reed Army Institute of Research, 3201 Sidney Brooks, Brooks Air Force Base, Texas 78235-5138; Deceased

Foreword

The number of lasers in use on the modern battlefield is rapidly growing. Worldwide, military laser systems are known to be in use by most nations. The US Department of Defense is the largest owner and user of laser systems, with applications that include range finding, communication, illumination, land mine and bomb detection and detonation, target designation, and detection of contamination. All of these laser applications are potentially hazardous to the human eye at ranges inherent to military operations. Military lasers pose other problems at much lower eye exposure energies sufficient to produce glare, dazzle, and afterimages. Depending on laser wavelength and the state of the adaptation of the eye to day or night vision, these effects may cause temporary visual decrements that can last many minutes and may interfere severely with critical tasks, such as missile guidance.

As adjuncts to other military systems, and possibly as weapons in their own right, lasers will continue to play an important and sometimes dangerous role on the modern battlefield. At present, there is no adequate comprehensive protection against accidental or intentional exposure to lasers in combat. Thus, it is critical that the field of laser safety research also advance with the development of preventative protocols and pro phylactic technologies to protect service members and to support military operational objectives. Whether or not such potentially devastating weapons ever reach the battlefield, the mere threat of their use is sufficient to cause serious concern for those who perceive themselves or their comrades as vulnerable. The depth and extent of such psychological reactions are unknown as yet, but it is reasonable to be concerned about their potential impact on operational performance.

This book details what the Army has learned about the effects of military lasers on the human body. An important purpose of this book is to identify current knowledge gaps in the various areas of this inherently interdisciplinary field and to offer specific recommendations for laser safety research and development into the future. Although the militarily relevant bioeffects of lasers predominate the contributors’ efforts, much of the material presented in this book is also relevant to laser–tissue interactions in nonmilitary environments.

RAYMOND S. DINGLE

Lieutenant General, U.S. Army

The Surgeon General and

Commanding General, USAMEDCOM

Washington, DC
June 2020

Preface

In 1977, an eloquent and dramatic first-hand account of laser-induced retinal injury was published in a laser journal; C. David Decker, PhD, provided the following accident victim’s view:

When the beam struck my eye, I heard a distinct popping sound, caused by a laser-induced explosion at the back of my eyeball. My vision was obscured almost immediately by streams of blood floating in the vitreous humor, and by what appeared to be particulate matter suspended in the vitreous humor. It was like viewing the world through a round fishbowl full of glycerol into which a quart of blood and handful of black pepper have been partially mixed. There was local pain within a few minutes of the accident, but it did not become excruciating. The most immediate response after such an accident is horror. As a Vietnam War veteran, I have seen several terrible scenes of human carnage, but none affected me more than viewing the world through my blood-filled eyeball. In the aftermath of the accident, I went into shock. 1(p1)Decker DC. Accident victim’s view. Laser Focus. August 1977;6:1. https://ehs.utoronto.ca/wp-content/uploads/2015/10/Laser-Accident-Victims-View.pdf. Accessed November 6, 2018.

The cardinal problem of laser safety is that of potential injury to the human eye, which is usually the result of retinal exposure to laser beams at visible and near-infrared wavelengths. The retina’s delicate tissue is a very effective absorber of light at these wavelengths. The refractive media of the eye focuses collimated visible or near-infrared laser radiation to a small area, increasing its effective irradiance by more than four orders of magnitude. Because the retina is part of the central nervous system, some laser-induced lesions to the retina tend to spread and cause more widespread sensory damage. If the original lesion is located near the fovea, the resulting larger lesion may ultimately involve the fovea directly, thus reducing or eliminating acute perception of shapes and colors. The prognosis of retinal injury is further adversely affected by the fact that damaged retinal tissue cannot regenerate.

The most critical laser safety issue is that of wavelength, which determines whether the laser beam will enter the eye and to what degree it will focus on the retina. Of course, the objective of laser safety research is to define nondangerous levels of irradiation. However, this objective requires that we first be able to quantify danger to the retina, which is an exceedingly complex problem. Irradiation effects on the retina and consequent potential visual deterioration depend on a multitude of factors associated with the laser instrument itself, as well as a variety of eye-related factors. Injury severity depends on laser exposure duration, laser energy, radiant exposure (dose), irradiance (dose rate), beam divergence, and pulse repetition rate.

Eye-related factors are also important, including the size of the pupil at the time of exposure; the presence or absence of ocular media opacities (eg, cataracts); the degree of accommodation; the presence and severity of uncorrected refraction errors; the degree of absorption and reflection of the beam (which depends on the degree of retinal pigmentation); the proximity of beam exposure to the fovea; and the final lesion diameter. Although the complex influences of all factors are not yet fully understood, these factors and many others have been ex- tensively studied for decades. Much of that knowledge is summarized in this book.

The field of laser–tissue interactions encompasses almost all branches of science, such as basic and applied physics, engineering, meteorology, biology, and medicine. Since the invention of lasers in the middle of the last century, lasers have become ubiquitous, and the study of laser bioeffects has utilized the talents and expertise of many scientists, engineers, and physicians around the world. The history of the invention and development of the laser and its multitude of applications is well known. It is a saga of almost unmitigated success in basic and applied research.

Less well known is the tremendous achievement of the research community whose work has been devoted to laser safety, especially eye safety. The eye is the body organ most sensitive to laser and other types of radiation. Countless millions of laser instruments are now in daily use around the world. Many are potentially hazard ous; yet, in the decades since the laser was first invented, not more than a few hundred laser-related injuries have occurred. This extraordinary record of safety is primarily the result of dedicated and coordinated efforts to design safe applications, safety standards, prophylactic procedures, and technologies.

It is hardly surprising that critical contributions to the study of lasers and laser safety have come from within the military. Members of the armed services may be exposed to laser radiation from a variety of sources in the open field. This potential hazard is made all the more dangerous by the use of magnifying optical equipment, such as binoculars. Binoculars increase the range over which laser beams may be hazardous; nearly all of the beam energy that enters the objective lens of an optical instrument is subsequently concentrated on a very small area of the retina. This concentration increases retinal tissue damage by many orders of magnitude.

In many situations, combat personnel are compelled to look directly toward the source of the laser beam itself, making it more likely that laser exposure will occur bilaterally, in or near the fovea. The fovea is a very small (0.3. μm) but critical region of the retina that is responsible for accurate daytime and color vision. Damage to the fovea itself results in partial blindness. Furthermore, because most battlefield lasers are rapidly pulsed, casualties are likely to suffer from multiple injuries to the retina.

The US military’s interest and involvement in laser bioeffects began soon after the laser was first invented in 1960. As the armed forces began to investigate and use laser instruments at wavelengths potentially injurious to the human eye, military researchers realized the need to study the extent of this new potential hazard. Many of the most notable achievements in the field of laser safety research can be traced directly to the original work of Colonel Edwin S. Beatrice, MD, and his interdisciplinary team of Army scientists, physicians, and engineers who have devoted their careers to the gathering of data necessary to formulate safety standards and procedures. Dr Beatrice’s original scientific approach to determining the safety of laser beam characteristics in the 1970s was later applied to US and international standards for the safe use of all lasers.

Most successful research programs are traceable to such a dedicated visionary who has led and inspired a team of like-minded individuals to achieve new advances that could not have been predicted.

Dr Beatrice had a remarkable ability to lead by positive inspiration:

- He motivated and challenged people to action without issuing orders.

- He was able, in a seemingly effortless way, to evaluate and appreciate the unique capabilities and strengths of each individual and to reinforce and channel them toward the attainment of research goals. He did this not by command or coercion but, rather, by selfless persuasion.

- He was always ready and willing to test and adopt compelling ideas proposed by others. He did so selflessly and always gave proper credit to those who proposed their ideas to him.

These unique characteristics and abilities played a considerable role in the consistently successful efforts of Dr Beatrice’s team both during and after his tenure.

Those who were privileged to know and work with Dr Beatrice also knew him as an optimistic, quick-witted, and resourceful man whose scientific and practical goals sometimes put him in creative conflict with the pace of bureaucracy. For example, in the late 1970s, Dr Beatrice was one of the first US Army investigators to introduce and use word-processing equipment to prepare his written works. He felt that it helped cut costs and save time. At that time, word processing was still a novelty, not yet welcome or understood by all. However, Dr Beatrice continued to use word processing as a tool to advance his profession, claiming that he was “processing data,” which was permitted on a microcomputer.

Although Dr Beatrice’s administrative persistence was essential to laboratory and program success, his greatest contributions were in science itself. Dr Beatrice was a direct participant in the work he administered, designing unprecedented experimental paradigms and solving sophisticated technical problems. His dedication to laser bioeffects research and its practical correlates was absolute and unyielding, and his lasting influence is direct in the research he performed. His ultimate impact was not only laying the groundwork for, but also establishing a model for all laser bioeffects laboratories and programs. Through the people who worked with Dr Beatrice and research that continues today, his legacy lives on. This book is a tribute to the leadership and inspiration of Colonel (Dr) Edwin S. Beatrice.

Michael Belkin, MD

Emeritus, Goldschleger Eye Institute

Tel-Aviv University, Israel

Introduction

In 2013, the US Army terminated its military investment in laser bioeffects research because laser eye injuries were no longer perceived to be a priority medical threat. It immediately became apparent that the information produced by more than 40 years of research in this area was also rapidly fading from institutional memory—in part because the content of published and unpublished reports, as well as the experimental data forming the basis for safety standards, had not been harvested, synthesized, and organized in a summary document. Drawing on decades of military medical research not previously captured in a single work, this volume presents a synthesis of the Army’s research on the biomedical effects of military laser exposure.

Initially, much of this material was drawn up under a contract from the Telemedicine and Advanced Technology Research Center at the US Army Medical Research and Materiel Command (USAMRMC) as part of an eye research program, even as access to many of the original subject matter experts who could best contribute to this knowledge base was being lost, through death or as they moved on to demanding new jobs. Several key sections stalled. After termination of the laser bioeffects research program, the need for this book became even greater, and the project was reenergized through a contract with the Military Operational Medicine Research Program (under USAMRMC), with administrative assistance from the Naval Medical Research Unit–Dayton, and with the support and assistance of the Borden Institute staff. However, some topics that should have been included for a truly comprehensive summary of the original body of work had to be abandoned, or the book might never have made it to publication.

Ultimately, the completion of this book has been through the donated time and efforts of many people, most importantly my coeditors, Colonel Jim Ness and Dr Victoria Tepe, to whom I am grateful. They have endured and persisted over a decade of effort to develop and produce this volume. Dr Tepe has been relentless in her efforts to shepherd this book to completion, including coordination of repeatedly missed deadlines with our publishers; throughout the process, Dr Tepe preserved completed work, maintained version control, and edited and reedited to get submitted manuscripts into a final format. Colonel Ness contributed steady optimistic energy, provided historical continuity, and worked tirelessly to complete new analyses, information syntheses, and updates of material in these chapters.

Dr Michael Belkin graciously provided much of the front matter for this book and originally wrote a much more detailed dedication to honor the memory of Colonel Beatrice; Belkin’s first dedication captured many examples of Colonel Beatrice’s management and leadership style and could have formed a chapter of its own on the topic of how to inspire and lead Army science initiatives. Finally, the editors acknowledge the expertise, dedication, and untiring efforts of Dr Karl E. Friedl for providing overarching guidance and resourcing for this project.

The editors organized this book into three logical sections: (1) background on the problem, (2) basis of the threat to performance, and (3) specialized biomedical injury studies. The first section (History and Hazards of Military Lasers) provides an essential overview of the history, development, and current use of military lasers and the documented laser accident cases and factors. Many accidental exposures can be prevented by proper use of eye protection. However, military and civilian operators sometimes opt not to wear protective eyewear because they find it impairs their ability to see critical displays and settings in high-risk settings (eg, an aircraft cockpit). Documented laser accident cases illustrate the need to consider accident factors, such as setting, laser type, and specific injury characteristics, to inform development of effective approaches to prevention, rapid diagnosis, early treatment, and pharmacologic and surgical interventions.

Vision, performance, and psychological effects of laser injury are explored in the second section, Physiological and Psychological Effects, which considers challenges related to the assessments of vision and performance, glare effects, aversion responses, and psychological and operational impact of exposure (or threat of exposure) to laser irradiation. Laser-induced damage to the central region of the eye is particularly important because the fovea is responsible for fine spatial resolution and color vision. Injury to the fovea can cause changes in visual acuity. Nevertheless, exposure to a visible laser that does not produce irreversible ocular damage can result in temporary but substantial visual impairment. These effects may be sufficient to compromise safety in high-risk environments such as aviation. Aversion responses to intense light (eg, blink reflex, pupillary constriction, and head and eye movement) may be protective, but they depend on contextual factors such as light source intensity, duration, and ambient luminance. Psychological response to laser exposure can be influenced in the short term by preexisting knowledge and beliefs and, in the long term, by postinjury treatment and subsequent knowledge gain.

Specific attributes of laser-induced thermal, photochemical, and mechanical injuries are addressed in the third and final section, Laser-Induced Injury Thresholds. Chapters in this section detail the dependence of injury thresholds upon specific characteristics of laser exposure such as wavelength, irradiance diameter, pulse repetition frequency, and exposure duration, including ultrashort lasers. Laser-induced damage to the retinal hazard region involves interactions among thermal, photochemical, and photomechanical mechanisms. Retinal injury thresholds and interaction mechanisms are also influenced by specific exposure conditions such as wavelength, exposure duration, and irradiation diameter.

Improved knowledge of these factors is important to inform laser safety and permissible exposure guidelines. Depending on exposure parameters, ultraviolet laser radiation can damage the cornea, lens, or retina. “Ultrashort” lasers can cause novel nonlinear optical phenomena, including unique retinal and skin damage. The cornea and skin are especially susceptible to painful and potentially disabling injuries by exposure to infrared radiation. This book summarizes the past generation of research and development in laser bioeffects with the intention of providing a strong foundation and inspiring the next generation of knowledge development in this area.

Bruce E. Stuck, former Director

US Army Medical Research Detachment

San Antonio, Texas
June 2020

Section I

HISTORY AND HAZARDS OF
MILITARY LASERS

US Army Soldiers use the MILES, or Multiple Integrated Laser Engagement System, during Exercise Iron Sword 2014, Pabrade, Lithuania, November 2–14. Laser transmitters are mounted on the barrels of their rifles, and sensors on their harnesses and headgear record either a near miss or hit. (Courtesy photo by Ieva Budzeikaite, Lithuanian Armed Forces.)

Reproduced from: https://www.dvidshub.net/image/1667870/tsae-gives-lithuania-exercises-technical-edge.

Chapter 1

THE US ARMY MEDICAL DEPARTMENT’S ROLE AND ACCOMPLISHMENTS IN LASER DEVELOPMENT AND USE

BRUCE E. STUCK, ScD,* Formerly, Detachment Director, US Army Medical Research Detachment-Walter Reed Army Institute of Research, 7965 Dave Erwin Drive, Brooks City-Base, Texas 78235 and KARL E. FRIEDL, PhD † Colonel, US Army (Retired); Senior Research Scientist for Physiology, US Army Research Institute of Environmental Medicine, 10 General Greene Avenue, Natick, Massachusetts 01760

INTRODUCTION

Human Safety and Performance Limits for Military Systems

Periodic Reinvention and Mission Reset

FRANKFORD ARSENAL, 1968–1974

Creation of the Joint Laser Safety Team

Keys to Success: Competence, Agility, and Attention to User Needs

LETTERMAN ARMY INSTITUTE OF RESEARCH, 1974–1992

Research Officer Talent and Leadership in Nonionizing Radiation

The Multiple Integrated Laser Engagement System

Laser Glare, Vision Disruption, and Military Performance

Lasers on the Modern Battlefield Conference

Protective Eyewear: Doing Science for the Soldier

Laser Radiation Safety Standards and Injury Evaluation Guidelines

Laser Accident and Incident Registry

THE USAMRD-WRAIR YEARS, 1992–2010

National and International Exposure Guidelines for Laser Radiation

Diagnosis and Treatment Research for Battlefield Laser-Induced Eye Injury

DIRECTIONS FOR FUTURE RESEARCH

INTRODUCTION

The soldier is especially vulnerable to sustaining a laser injury. Military physicians need to increase their awareness of this potential injury and to become familiar with its manifestations. More sensitive and selective clinical tests must be devised to determine the presence of low level laser injuries which may occur before ophthalmoscopically detectable lesions develop. Military ophthalmologists have a responsibility to investigate therapeutic modalities that will offer a better prognosis and a faster recovery from laser injuries. Furthermore and equally important, we must advocate and support efforts to develop better protective eyewear to prevent these injuries.

—John A. Wolfe, MD1(p184)

The US Army Medical Department (AMEDD) has been a longstanding partner of the Army’s materiel system development efforts. The AMEDD’s responsibility for system development is to ensure that hazards to soldiers who use new devices are identified and mitigated early in the development cycle. In effect, the AMEDD serves as an “independent evaluator” to assess health implications and protect the health and safety of soldiers. Shortly after the invention of the laser in 1960,[2] the Army and the AMEDD recognized the multiple potential applications of lasers to enhance the utility or performance of military systems. Typical laser emission characteristics include generation of intense beams of monochromatic optical radiation (ie, light) throughout the ultraviolet, visible, and infrared spectral regions. Laser generation facilitates the production of a highly collimated beam of light with minimal spread over distance. Nanosecond laser emissions allow accurate range and distance determinations for fire-control systems. Near-infrared “pulsed” and/or “pulse-coded” emissions allow precise, covert target designation (a missile detects the reflected pulsecoded energy from the target, which guides it to the target). Diode lasers are employed in training devices to facilitate live-fire training.

As early as 1961, the ophthalmology community recognized the potential for eye injury from lasers and began investigations.[3] Accounts of accidental eye injuries from laser radiation were published in the early to mid-1960s.4,5 Laser wavelengths are in the visible and near-infrared spectral region (ie, the retinal hazard spectral region), and the eye, specifically the retina, is particularly susceptible to laser injury because the collimated laser energy incident on the eye and transmitted through the ocular pupil and outer ocular media is focused at a small area on the sensory retina. Early systems incorporated lasers into fire-control devices including rangefinders and designators, and these devices could produce eye trauma at tactical ranges.[6] Intense, short-pulse (nanosecond) exposures generated by early laser rangefinders and designators could produce a small retinal lesion (or “burn”) at one kilometer and a retinal hemorrhage that inhibited or obscured vision at a few hundred meters.[6] Levels of laser exposure that do not cause injury (ie, laser dazzle or glare) can disrupt vision-critical performance tasks (eg, directing a TOW [tube-launched, optically tracked, wire-guided] missile during the 12 or 15 seconds of its flight; flying a helicopter at night). The potential risk increased as high-energy lasers were being developed to directly engage military materiel at tactical distances, and anti-sensor and anti-eye laser weapons with output emissions much higher than required by fire-control devices were also under development by the US military, its allies, and its adversaries.

Human Safety and Performance Limits for Military Systems

With its proactive commitment to performance and safety research concurrent with the development of new military systems, the laser biomedical research program has been the exception rather than the rule; fielding delays and retrofits have hampered many other Army technologies due to late discovery of adverse bioeffects on human operators. For example, the development of notable modern, high-powered weapons systems proceeded without consideration of blast-overpressure risks to human operators. In 1979, testing of the new M198 howitzer was stopped, and fielding could not proceed until human safety studies were conducted, because the weapon exceeded the only available biomedical standards established for noise.[7] Similarly, the most powerful shoulder-fired rocket system to date was procured with the intention that it be fired from the prone position; an after-thefact analysis demonstrated that the reflective wave would likely injure or kill its operator.[8] Other weapons systems, such as the XM95 nonlethal munition, were delayed in testing and fielding until biomedical studies determined shoulder injury thresholds from highrecoil energy (eg, 60 ft-lb of recoil energy).[9]

Military vehicles have also been designed without full consideration to human tolerances. During World War II, the Fort Knox Armored Medical Research Laboratory focused on problems associated with hot environments and produced models of human thermoregulation for designs of tanks and future vehicles.10,11 Yet in 2004, the high-mobility multipurpose wheeled vehicle (HMMWV) had to be retrofitted with individual occupant microclimate cooling systems to extend human tolerance at ambient temperatures reaching 110°F in Iraq.12,13

TABLE 1-1
SIGNIFICANT ACCOMPLISHMENTS OF THE LASER BIOEFFECTS RESEARCH TEAM

Gaps

Objectives

Solutions

Research

Characterize laser bioeffects

Determined dose-response relationships for laserinduced effects in retinal, corneal, skin, and cellular models as functions of wavelength, exposure duration, and irradiance diameter (initial focus was on lasers being incorporated into systems, including ruby, neodymium, argon, carbon dioxide, and gallium arsenide).

Determine performance consequences of glare

Characterized performance decrements from laser glare with field-relevant test outcomes directly relevant to contemporary systems such as the TOW missile (the Blaser pursuit track model).

Provide scientific exchange

Annual conference called Lasers on the Modern Battlefield instituted a unique forum to ensure continuous validation of relevant Army research priorities and, in turn, knowledge product transition to the user community.

Safety

Guidelines for design and use of lasers

Provided biomedical data to support establishment of safety guidelines or permissible limits for laser exposure for the Army, DoD, the nation, and the world (including AR 11-9, ANSI Z136, ICNIRP, ACGIH, IEC standards and guidelines).

International standards

Led/contributed to the establishment and updating of national and international safety standards (ANSI, ICNIRP, International Treaty on Blinding Lasers) based on findings from a planned and responsive laser bioeffects research program.

Protection

Protective equipment

Filled a major gap in soldier eye protection with development of the first combined ballistic and laser protective goggles.

System safety

System health hazards assessment assured deployment of modern training and “smart” weapons systems with minimal or known hazards (eg, assured that the MILES live-fire simulator was safe for soldier use; provided biomedical assessments for high-energy laser program; assisted Army Public Health Command in field laser health hazard assessment program).

Clinical tools

Field diagnostics

Developed and transitioned the Aidman Vision Screener with AMEDDC&S for inclusion in the medic kit bag.

Diagnostics

Developed metrics and imaging methods for clinical assessment of laser eye injury.

Treatment

Established treatment protocols for laser retinal injury based on pathophysiological studies and clinical experience with steroid and nonsteroid drug treatments.

ACGIH: American Conference of Governmental Industrial Hygienists

AMEDDC&S: Army Medical Department Center and School

ANSI: American National Standards Institute

AR: Army regulation

DoD: Department of Defense

ICNIRP: International Commission on Non-Ionizing Radiation Protection

IEC: International Electrotechnical Commission

MILES: Multiple Integrated Laser Engagement System

TOW: tube-launched, optically tracked, wire-guided

In contrast, the Army has continuously implemented useful laser technologies with almost seamless advances, and updates of Army, national, and international laser exposure limits have been informed by a continuous flow of biomedical research findings. This acquisition model ensures that laser systems can be implemented with confidence that they enhance soldier capability and survivability while avoiding any inadvertent impairment of soldier effectiveness or unforeseen biomedical consequences.

Periodic Reinvention and Mission Reset

The Army’s laser biomedical research team was forced to reinvent itself every 10 to 20 years. In a succession of three Base Realignment and Closure (BRAC) moves, the team pulled up stakes as a group and relocated, first from Frankford Arsenal in Philadelphia to the Letterman Army Institute of Research (LAIR) in San Francisco, in 1974, and then to the US Army Medical Research Detachment of the Walter Reed Army Institute of Research (USAMRD-WRAIR) in 1992, collocated with the Air Force Research Laboratory and Naval Health Research Center Detachment at Brooks Air Force Base, San Antonio. A proposed third BRAC move from San Antonio to Dayton in 2010 was reversed, and instead, a small remaining effort was consolidated within the trauma research assets of the US Army Institute of Surgical Research, Joint Base San Antonio, Fort Sam Houston.

Although disruptive, each move provided fresh local collaboration opportunities and updated research capabilities. Ultimately, continued success was supported by good technical leadership, group cohesion (involving a shared vision and zealous dedication), and an integrated and collective experience in solving biomedical problems. The multidisciplinary and collaborative team included staff members with expertise in medicine, vision research, physics and biophysics, and cellular biology. This chapter briefly recounts the history of the laser biomedical research group’s key research drivers and accomplishments, as well as the group’s successful “reinvention” and modernization through its successive relocations between 1968 and 2012 (Table 1-1).

FRANKFORD ARSENAL, 1968–1974

Creation of the Joint Laser Safety Team

As laser applications and their potential threats began to emerge in the 1960s, the AMEDD recognized its responsibility to ensure the development of human exposure safety standards and performance thresholds for laser technology.14–17 This required a robust database of dose-response relationships that quantified the radiation dose dependence of the biological response on wavelength, exposure duration, irradiance diameter, and pulsing characteristics.18–24

In 1968, the US Army Medical Research and Development Command (AMRDC) and US Army Materiel Command (AMC) Joint Laser Safety Team (JLST) was established at the Frankford Arsenal, where the first ruby laser rangefinder was being developed. The original team concept leveraged the optics, laser, and system development expertise already resident within the AMC and the medical expertise provided by the AMRDC. Location of the team at Frankford Arsenal also facilitated collaboration with other local biomedical expertise and assets located in the Philadelphia area, including the Wills Eye Hospital, Shea Eye Institute, and Franklin Institute of Science.

The goal of the team was to gain understanding of the nature and extent of laser energy effects on the anatomy, physiology, and function of the visual system. These findings would be used to establish permissible exposure limits, minimize long-term or chronic effects, specify and develop protective eyewear, characterize adverse overexposure events, and diagnose and treat laser-induced injury. The team evaluated dose-response relationships for both common and uncommon lasers available at the time, and measured both ocular and cutaneous injury threshold doses as functions of laser wavelengths, exposure durations, irradiance diameters, and pulse repetition frequencies.25,26 Argon lasers were already used in ophthalmology clinics, but other lasers were relatively new or rare and could not be purchased commercially. To support the necessary biomedical research, optical delivery systems were interfaced with fundus cameras, and laser systems were fabricated on site[27] at the Frankford Arsenal.[26] Biological effects of ruby, neodymium, argon, carbon dioxide, erbium, and gallium arsenide diode lasers were investigated and reported.14–17,27–30

The AMEDD component of the JLST included military and civilian physicians, pathologists, sensory psychologists, chemists, enlisted science assistants, a veterinarian, and veterinary technicians. They were complemented by AMC civilians, including physicists, a systems engineer, electronic specialists and technicians, clerical staff, and a program facilitator who coordinated operational assistance from the arsenal’s optics shop, machine shops, and fabrication facilities (Figure 1-1). The first JLST chief, Captain Maurice B. Landers, MD, was an ophthalmologist and retinal specialist; he was assisted by an AMC optical radiation physicist, deputy chief James Helfrich. The interdisciplinary military and civilian staff worked closely together in a team approach that facilitated the rapid assessment of laser health and vision bioeffects pertinent to the Army’s system development and medical needs. Without the biomedical safety data supplied by the team (eg, condition-dependent dose thresholds of eye injury), laser hazard assessments would probably be more conservative than necessary and thus inhibit the testing and fielding of new, laser-based fire-control systems. The Army’s laser biomedical research program[26] ensured that the United States remained ahead of peer countries in understanding the full implications of new laser technologies as they evolved.

Keys to Success: Competence, Agility, and Attention to User Needs

Mission success for the JLST derived from a simple formula that started with a good foundation in expert specialization in a new topic area that few outside of the field yet understood. Three key features of the program remained constant through its 45-year existence:

- expertise in a highly specialized topic area of unique importance to the Army,

- a semi-autonomous management process that increased agility, and

- recognized value to the user/developer community.

The work was achieved by a relatively small, dedicated team with the right mix of personnel and disciplines. As a semi-autonomous unit, it could function with agility to address research problems, characterize emerging laser technology effects, and test new hypotheses as quickly as they were identified. The team could do this without having to request permission and support for each new study through layers of administrative process. Accountability was achieved through an annual review conference (described below).

Figure 1-1. The Joint Laser Safety Team at Frankford Arsenal, Philadelphia, Pennsylvania, circa 1973. Front row: Major R. Bruce Bedel, Helen Stanislau, Katheryn Hersch, Lieutenant Colonel Edwin S. Beatrice. Second row: Calvin Butts, D. Jack Lund, Harry Zwick, Arnold S. Brownell, Georg D. Frisch. Third row: Bruce E. Stuck, Charles Kerensky, unidentified soldier, George Raulston, Charles T. Carver, Eugene D. Carpino. Fourth row: William Zwicker, Alvin Dallas, Kenneth Bloom, Specialist Rodgers, First Lieutenant Duane Bigler, James Helfrich, Captain Steven Dixon, Specialist Freddie A. Martin.

Additionally, the program could easily access new or unique capabilities to advance its research; 30% of the research, development, test, and evaluation budget resources were reserved for extramural research collaborations to augment internal projects. This yielded remarkably productive collaborations with other institutions, including the Virginia Commonwealth University, Ohio Wesleyan University, Johns Hopkins Applied Physics Laboratory and Johns Hopkins University, University of Western Ontario, University of Kentucky, Tel-Aviv University, Duke University, University of Illinois, and Massachusetts Eye and Ear Infirmary. Collaborative research projects included anatomical and electrophysiological studies on laserexposed animals,31–42 and addressed promising basic research themes such as electronic retinal prostheses and retinal neuroprotectant drugs.43–49

LETTERMAN ARMY INSTITUTE OF RESEARCH, 1974–1992

When the Frankford Arsenal’s closure was pending in 1974, the AMEDD members of the JLST were moved to the newly established LAIR at the Presidio of San Francisco, California. Lieutenant Colonel Edwin S. Beatrice led the core group from Frankford Arsenal to San Francisco. When the JLST members relocated to San Francisco, they joined with the Experimental Psychology Group, who had moved from Fort Knox, Kentucky, to become the Division of Non- Ionizing Radiation in LAIR’s Department of Biomedical Stress (Figure 1-2). This consolidation of Army medical research assets also brought the Army Medical Research and Nutrition Laboratory from Denver and the Armored Medical Research Laboratory from Fort Knox under one roof with other capabilities in tropical medicine, dermatology, and surgical research.

Figure 1-2. Key laser bioeffects researchers in the Division of Non-Ionizing Radiation at the Letterman Army Institute of Research, San Francisco, California, circa 1975. Pictured (left to right) are David Randolph, Bruce E. Stuck, Harry Zwick, D. Jack Lund, and Edwin S. Beatrice.

Research Officer Talent and Leadership in Nonionizing Radiation

Uniformed ophthalmologists, pathologists, psychologists, and veterinarians made important contributions to Army laser eye research. In 1972, Major Dolph O. Adams, MD, PhD, published an article in the journal Science[19] reporting observations of ultrastructural changes in photoreceptors produced at low-level laser energy exposures that suggest nonthermal biological effects on the eye; this concept is still discussed today.19,22 Many other ophthalmologists and clinical specialists contributed to the group, including Maurice B. Landers, George H. Bresnick, Edwin S. Beatrice, R. Bruce Bedell, Paul Schwaluk, Sil Biggs, Horace B. Gardner, John A. Wolfe (who introduced “Wolfe’s grades”[50]), Thomas Burk, John K. Kearny Jr, Jeffrey D. Gunzenhauser, Donald A. Gagliano, Jeremiah Brown Jr, David K. Scales (an Air Force ophthalmologist on special assignment), and Henry D. Hacker. The work of these individuals and many more team members are cited in later chapters of this volume.

During the Vietnam War, individuals with bachelor’s or higher degrees in the sciences were drafted as enlisted soldiers, and the team included enlisted personnel designated by their military occupational skills as physical, chemical, and biological science assistants. The team’s leadership recognized their talents, encouraged their involvement in the research, and provided the mentorship and leadership needed to facilitate their contributions to the team. Many of them continued with the laser team beyond their initial term of service, and several, after completing their military enlistment, were hired as Army civilian employees and devoted part or all of their professional careers to the study of laser bioeffects. These included D. Jack Lund, Georg D. Frisch, David A. Stamper, Tom Elverson, Jerome W. Molchany, Steven T. Schuschereba, and Bruce E. Stuck. Research opportunities at LAIR’s Division of Ocular Hazards, as the team was now called, were many, addressing specialties from histology to laser measurement.

The Multiple Integrated Laser Engagement System

One of the early JLST successes was its contribution to the development of a new live-fire simulator, made possible by the group’s foundational research on laser eye safety limits. The Multiple Integrated Laser Engagement System (MILES), a class of gallium arsenide (GaAs) laser-based training simulators, was fielded by the Army in 1978 to assist in live-fire training of conventional weapons. With the M-16 rifle version of the MILES device, soldiers directed laser radiation at other soldiers in training for the first time. The Army leadership wanted to ensure the system was safe before its widespread use with soldiers being purposely exposed. The relocated LAIR team conducted a series of biological effect studies investigating the retinal effects of near-infrared GaAs laser radiation, the dependence of the retinal injury threshold on the retinal irradiance diameter (ie, “spot” size) from the GaAs diode, and extensive investigation and analysis of additive effects of repetitive pulses inherent to the MILES devices.23,24,26,51–53 These studies expanded the understanding of laser bioeffects. Over the years, over 100,000 MILES devices were used in Army force-onforce training without any adverse effects.

Laser Glare, Visual Disruption, and Military Performance

In October 1980, a Los Angeles Police Department (LAPD) helicopter in flight was illuminated by an aircooled argon ion laser in a Halloween prank. The aircrew, a pilot and copilot, were startled but maintained control; subsequently the LAPD obtained the laser used and asked LAIR to investigate the incident. The LAIR team evaluated the aircrew’s eyes and vision and assessed the laser itself and the likely exposure conditions. When the laser was obtained for inspection, it was set to operate at a wavelength of 448 nm. However, there was no retinal injury as would be expected by an overexposure to that wavelength. One of the crew had a corneal abrasion, apparently due to rubbing the eye secondary to the startle experience from the laser exposure. Evaluation of the laser’s emission characteristics and its distance from the helicopter indicated that the exposure was well below levels that could produce retinal injury, but even at levels below the permissible exposure limit, the laser glare appeared extremely bright and compromised the crew’s ability to fly the aircraft. It became clear that laser glare, particularly under low-luminance conditions (dawn, dusk, or night), could interfere with military operations by presenting a secondary hazard. This may have been the first investigated incident of cockpit laser illumination, with risks to aviation safety that had not been previously identified.

At the time, Colonel Beatrice had repeatedly emphasized the need for a military performance metric instead of the usual laboratory tests with uncertain translation to field performance. The LAPD incident indicated a need to develop such a metric and use it to describe laser glare effects for a wide range of exposure conditions (wavelength, exposure duration, ambient luminance, etc) so that laser accident cases could be evaluated.54–56 JLST members D. Jack Lund and David Stamper, led by Major Peter O’Mara, a research psychologist and an early Heathkit computer enthusiast, responded with the design and construction of the “Blaser,” a field-relevant tracking simulator and visual performance test system.57–60 The system consisted of a terrain board with track-mounted scale-model tanks, with angular movements adjusted to move as if the target were at 1.5 km. (The Blaser is further described in Chapter 6, and shown in Figure 6-6.)

Major Rick Levine, a pioneer in glare research work, was assigned by Colonel Beatrice to convince the members of LAIR’s very cautious and conservative human use committee and the institute’s commander that it would be safe to purposely expose the human eye to laser radiation. Their ultimate approval opened the door to many important laser glare-pursuit tracking studies, all conducted with no adverse effects.58,59 The Blaser simulator provided a large body of literature on the performance impact of laser glare.55,56 Data including time-resolved horizontal and vertical tracking error were collected and analyzed on an early Heathkit H8 computer. The LAIR investigators included Major Dave Penetar, who characterized performance effects of glare and studied the effects of chemical defense antidotes on visual function and performance metrics61,62; Major Elmar Schmeisser, who contributed important electrophysiology studies[37]; and Major George Mastroianni, who explored the psychological aspects of laser exposure with and without clear indication of injury and accompanying visual disfunction.63,64

These laser glare data were also relevant to the operation of the wire-guided TOW missile because a small disruption in tracking performance during the missile flight would result in errant missile direction and a target miss. Laboratory test results were validated in a field-based TOW missile simulator when the Army provided a modified TOW missile training system to the researchers to assess pursuit tracking deficits produced by laser glare in the field (Figures 1-3 and 1-4; see also Chapter 6, Figure 6-3). This field system was used at Camp Roberts in California to confirm or validate the laboratory terrain board results. Many studies were conducted in the Blaser laboratory simulator with soldier volunteers from the nearby 3rd Infantry Division.

Lasers on the Modern Battlefield Conference

In 1979, Lieutenant Colonel Beatrice initiated an annual research findings and critical review meeting called the Lasers on the Modern Battlefield (LMB) conference (Table 1-2). The vision for LMB was to focus on issues surrounding the development, deployment, and use of lasers by the military and provide a forum for interaction across programs and services. The LMB conference was classified, and thus limited to Department of Defense (DoD) and allied government employees covered by an official exchange agreement. The conference quickly became the DoD’s annual forum to discuss laser threat intelligence and foreign science developments associated with laser technologies; development of US laser systems; military laser users’ issues and concerns; laser bioeffects supporting laser safety in the laboratory and in the field; laser protection technologies for soldiers’ eyes and electro-optic sensors, including protective technology developments and human factors issues (ability to perform military duties through laser protective eyewear) associated with fielding protective eyewear; and triage and treatment of laser-induced eye injuries.

Figure 1-3. Major George Mastroianni observes laser glare from a moving Bradley fighting vehicle, at a range of 1,600 m, through the TOW (tube-launched, optically tracked, wire-guided) missile tracking device modified to measure tracking error. Although the laser glare was below the exposure limit, the exposure obscured the target during bright ambient daylight, which resulted in an off-target response.

Protective Eyewear: Doing Science for the Soldier

The LMB provided an important forum to advance solutions to Army problems. In 1980, the second annual LMB conference focused on combat ocular problems; this watershed meeting led to the development of the AMEDD’s first protective eyewear. The focus of the conference was broader than the laser threat issue and included eye trauma from fragments, which had become common traumatic injuries in recent conflicts. Colonel Francis G. LaPiano, a prominent ophthalmic plastic and orbital surgeon, postulated that over 90% of the injuries from fragments in and around the eye that he had managed in the Vietnam War could have been prevented by a 3- to 4-mm thickness of polycarbonate (Lexan, General Electric Company).65,66 Dr Michael Belkin made a similar argument, based on his experience as an ophthalmologist in the Israeli Defense Forces Medical Corps during the Six-Day War in 1967 and the Yom Kippur War in 1973.[67] The Army surgeon general’s ophthalmology consultant, Colonel Floyd L. Wergeland Jr, agreed that fragment-protective eyewear was needed.

a
b

Figure 1-4. (a) Image of the Bradley fighting vehicle at 1,600 m through the TOW missile launcher sight. (b) Image through the TOW sight with a 514.5-nm laser glare from the argon laser mounted on the Bradley turret. The level of laser glare was a factor of 10 below the 10-second exposure limit of the eye; however, the target was still obscured and the user’s ability to track the target was dramatically reduced.

TABLE 1-2
LASERS ON THE MODERN BATTLEFIELD CONFERENCE

Description

An annual, classified, 4- to 5-day meeting, held from 1979 to 2010, focused on the development, deployment, and use of military lasers

Purpose and scope

To enhance communications within the Army and the DoD on military laser issues

Participation

US DoD and allied governments with exchange agreements (eg, United Kingdom, Canada, Australia)

Typical topical agenda

- Plenary Briefings on Military Laser Issues

- Foreign Intelligence and Threat

- Foreign laser technology

- Foreign military systems

- Foreign laser threat

- US Military Laser Developments

- Laser technology

- Military system applications

- User concerns in military laser use

- Biological Effects and Laser Hazard Assessment

- New biological effects data pertinent to military systems

- Exposure limits, maximum permissible exposures

- Range safety issues

- Medical Implication of Military Laser Use

- Triage and treatment of laser-induced eye injury

- Military and other laser exposure incidents from laser glare effects to acute injury

- Visual function metrics and new imaging methodologies in assessment of laser-induced retinal injury

- Laser Eye Protection (LEP)

- Threat and deployed laser system-based requirements for LEP

- Protection technologies for eyes and sensors, near term and future

- Human factors issues associated with military LEP

Impact

- Near-term military laser issues identified in a multidiscipline environment

- Early involvement of technologists, developers, and users working military laser issues

- Communication of medical issues to understand the scope of hazards and threats

- Reshape and/or prioritize research efforts pertinent to near-term operational issues

- Facilitated safe and effective employment of military lasers

DoD: Department of Defense

The human factors issues and limitations of protective solutions (absorptive dyes in glass or plastic) for laser protection were also discussed. The dyes used to provide protection against even a few selected visible wavelengths limited the overall visible light (luminous) transmission, which limited vision and distorted perception of the color space. For example, users wearing eye protection designed for ruby laser emissions at 694.3 nm were unable to readily detect red warning lights.

Furthermore, although polycarbonate provided protection against fragments, no specific Army requirement for fragment protection existed; the requirements process lagged behind the identified military medical problem and the emerging technological solutions. Although current technology programs were developing laser protection, no program addressed fragment protection as well. Absorbing dyes introduced into the polycarbonate or surface preparations to protect against lasers unfortunately degraded fragment protection properties. Polycarbonate had other drawbacks: it was “soft” and difficult to edge when formed into corrective lenses; it was very susceptible to scratches; and the lifetime of a spectacle or an aviator visor was estimated to be very short in a dusty or dirty combat environment. Another obstacle, reported by representatives from the DoD optical fabrication laboratories at Fitzsimmons, Colorado, and Yorktown, Virginia, was a lack of proper tooling to work with polycarbonate corrective lenses.

Colonel Beatrice, supported by Major General Garrison Rapmund, commanding the US Army Medical Research and Development Command, identified a clear Army need to protect soldier vision: soldiers needed functional eye protection they could use, day or night, protective against a few selected laser wavelengths and ballistic fragments. Beatrice initiated a program to develop laser radiation and fragment-protective eyewear at LAIR, and over the next 4 to 6 years, the Ballistic and Laser Protective Spectacles (BLPS) were developed.[68] The BLPS kit consisted of six elements: two toroidal polycarbonate eye wraps—one clear for use at night or under low-luminance conditions and one brown with sun protection; a laser-protective clip-on filter; side shields; silicon nose bridge pads; a corrective lens carrier for users with ametropia; and a carrying case.

The BLPS had some weaknesses. It was a “one size fits all” system, requiring an adjustable nose bridge feature. The laser protective clip-on filter was less than ideal, providing protection against just two common wavelengths used by the military, and had difficulties meeting the solarization specification. Saturation of absorbing dyes limited the protection against intense nanosecond pulses of laser radiation. To improve the system, D. Jack Lund led an effort to describe saturation measurement methods[69]; this method of testing the properties of the spectacles was written into the specification for laser protective concepts, and more recently, has been adopted by the American National Standards Institute (ANSI) in guidance for commercial laser-protective eyewear.[70] The BLPS program also produced visors for the US Army Aviation Systems Command as part of the HGU 56/P (Gentex Corporation, Zeeland, MI) helmet program. Subsequently, the BLPS system was type classified (specification for the acquisition management process that precedes procurement of an item, following provisions of Army Regulation 700-142), and some units in the Persian Gulf War were equipped with it. Some soldiers liked the BLPS system, but others did not.[71]

In 1991, a statement of work and request for proposals were issued for a follow-on program, called the “Emerging Laser Threat Eye Protection (ELTEP).” However, Major General Thomas Travis, commander of the US Army Medical Research and Development Command, canceled the ELTEP program and AMEDD’s soldier eye protection programs due to mission conflict with the Program Executive Office (PEO) (Soldier). Henceforth, development of personal protective equipment (“skin out” research) would be the responsibility of PEO-Soldier, while investigation of human biomedical limits (“skin in” research) was AMEDD’s mission; however, the AMEDD remained responsible for corrective lenses.

Although the BLPS system was the first fielded fragment- and laser-protective eyewear for soldiers, it never achieved overwhelming acceptance. However, the development and fielding process formed the basis for subsequent protective eye armor. Technical specifications developed for the BLPS program still guide advancements in military protective eyewear development today. These issues include level of fragment protection, solarization, saturation, scratch resistance, and numerous human factors such as operations in low-luminance environments, compatibility with other military display and lighting systems, and systems such as vehicle lighting, helmets, and optical sites.

Laser threat and hazard updates provided at the annual LMB conferences impacted military eye protection decisions in the near term and the far term. These conferences served as a forum for information exchange for all DoD eye protection development programs and identified significant human factors issues with the use of spectrally specific laser eye protection. The US Air Force and Navy managed and supported successful advanced programs that resulted in demonstrations and fabrication of advanced protective concepts, such as laser protective holograms, “dyes and dielectrics” hybrid combinations to maximize protection while preserving luminance transmittance, particle cell switches for optical sites, and graded index approaches. There is more work to be done on advanced eye protective devices, especially with new concepts to minimize or mitigate the adverse medical effects of blast, and potentially development of more effective light absorbers and diffusers.

Laser Radiation Safety Standards and Injury Evaluation Guidelines

As new cases of laser eye injury emerged, bringing demands for better protection strategies, diagnostic methods, and medical treatments, the team’s research emphasis shifted from performance impairment to a more clinical focus. New technologies provided better assessment of laser injury through enhanced ophthalmic imaging diagnostics such as confocal scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT), novel visual function assessments, and emerging molecular biological assays to complement light and electron microscopy characterizations of laser-induced eye injury.

In the late 1980s, the laser threat increased as new systems began to proliferate worldwide. The DoD developed high-energy laser systems to engage targets at long ranges. Low-energy lasers were employed in many fire-control and mission-assist applications. Predictions of laser-induced eye injuries to military personnel emerged, and laser weapons became prominent in DoD threat statements. These developments were reviewed at each LMB conference. The new threat estimates stimulated early triage and treatment investigations for laser-induced retinal injury. Pharmacological approaches were investigated.50,72–74 The time course of injury was characterized by the assessment of stress protein release.75–80 Emerging genomics and regenerative technologies were explored for laserinduced eye injuries.47,81–83

The LAIR Ocular Hazards Division assisted the AMEDD Center and School in drafting US Army Field Manual (FM) 8-50, Prevention and Medical Management of Laser Injuries .[84] Published in 1990, just prior to the Persian Gulf War, FM 8-50 included a unique field evaluation system to assist the combat medic in assessing acute laser eye injury: the Aidman Vision Screener (AVS),[85] a two-sided 5 × 7-inch plastic card with LogMAR and Landolt C vision acuity charts on one side and an Amsler grid on the back (Figure 1-5). The AVS was a stand-alone screening tool with instructions and a triage decision box. Although test users did not all respond favorably, AVS was eventually accepted as a vision screening tool, type classified, and furnished as required.

New potential risks also arose from the proliferation of lasers in medicine; by the early 1990s, laser use in hospitals had become common in most medical specialties. To address the new threats, including the proliferation of lasers in medicine (especially ophthalmology), industrial hygiene and occupational health guidance were established and continually updated to facilitate the safe use of lasers in the workplace. This guidance was based on exposure limits (eg, the maximum permissible exposure) for optical radiation that were based on biomedical research predominately supported by tri-service DoD research.

a b

Figure 1-5. The Aidman Vision Screener (front and back of the field diagnostic card) assists the combat medic in rapidly assessing laser-induced injury in an operational environment. It provides an Amsler grid (a), a visual acuity chart, and evacuation criteria (b). The screener is required to triage laser-induced eye injury in accordance with the guidance given in US Army Field Manual 8-50, Prevention and Medical Management of Laser Injuries (Washington, DC: Headquarters, Department of the Army; August 8, 1990).
Photographs: Courtesy of the US Army Medical Research Detachment.

Over the years, the Army laser effects group maintained a close relationship with directed-energy experts at the US Army Center for Health Promotion and Preventive Medicine (USACHPPM, now the US Army Public Health Center), led by Dr David H. Sliney, who worked untiringly to draft exposure limits for laser radiation worldwide and articulate the biological effects of laser exposure and their mechanisms.[86] USACHPPM’s Health Hazard Assessment Program identified urgent biomedical research requirements in support of Army laser systems and communicated these priorities to the US Army Medical Research and Materiel Command (USAMRMC) for support at the LAIR laser laboratory. Likewise, the LAIR group informed the USACHPPM of new research and research trends that impacted laser exposure limits and health hazard assessment; these interactions worked synergistically to promote the safe use of laser systems by soldiers. LAIR communications and research reports were synthesized and published in guidance on exposure limits and operational medical advice published in an Army medical technical bulletin, Control of Hazards to Health From Laser Radiation, in 2006.[87]

Laser Accident and Incident Registry

For the duration of their existence, the LAIR Ocular Hazards group, in cooperation with Ophthalmology Services at the Letterman Army Medical Center (LAMC), assisted in the evaluation of laser exposure incidents in the military. Emerging ocular imaging diagnostics such as SLO and OCT arrived early at the LAIR due to the pioneering work of Dr Harry Zwick in establishing the Visual Function Laboratory to assist LAMC ophthalmologists in assessment of suspected laser-induced eye injury.54,88 In addition to advanced ocular imaging systems, nonstandard measures of visual function were used to assist diagnosis and assessment. Chromatic and achromatic threshold contrast sensitivity, color vision assessments (eg, Ishihara color plates and the Farnsworth-Munsel 100 hue test), the Amsler grid, and dynamic visual acuity metrics were used in these assessments.

In 2006, collections of data from these investigations were combined with data from the literature into a database called the “Laser Accident and Incident Registry”[89] and published as a CD ROM. The registry included clinical data and a detailed description of the operational exposure situation in each reported incident. The registry was sustained for only a few years until it was deemed not appropriate for a research, development, test, and evaluation (RDT&E) funded activity, yet no health surveillance activity was interested in continuing the effort. Nevertheless, the DoD Instruction for the DoD Laser Protection Program (DoDI 6055.15, May 4, 2007) specified the Army’s responsibility for maintaining a “Laser Accident and Incident Registry” and analyzing data for use in laser safety, protection, and treatment programs for the DoD, and this directive has not been further updated. This action remains unrealized, although the Tri-Service Vision Conservation Program has retained the database in a different format.

THE USAMRD-WRAIR YEARS, 1992–2010

In September 1992, the Ocular Hazards Division moved to Brooks Air Force Base (renamed Brooks City-Base in 2002), San Antonio, to be collocated with the Air Force Research Laboratory’s directed-energy bioeffects research; the Navy’s nonionizing radiation programs, relocated from Pensacola, Florida, became the Naval Health Research Detachment (primarily focused on electromagnetic radiation issues). Fifty rhesus monkeys were also moved from the Presidio of San Francisco to Brooks Air Force Base. The USAMRDWRAIR executed its mission at Brooks from 1992 through 2010. WRAIR’s Department of Microwave Research was also consolidated with the USAMRD in San Antonio in 1994. Active collaborations between the two Army groups and the Air Force and Navy assets resulted in productive research initiatives addressing radiofrequency radiation hazard issues. A tri-service effort with assistance from the Johns Hopkins University produced a clear result for L-band exposure of the primate retina near the exposure limit.[90] A visiting scientist program under the National Research Council contributed work on the effects of high peak power microwaves on synaptic transmission.[91]

The USAMRMC laser bioeffects research program continued to focus on acute laser bioeffects to address gaps in the biological database required to define optical radiation exposure limits pertinent to emerging military exposure conditions. These gaps were driven by military system developments such as the use of the oxygen-iodine laser with emissions at 1.315 μm, the use of “particle cell switches” against pulsed lasers operating in the retinal hazard spectral region, and reexamination of laser glare issues surrounding the use of green laser illuminators to deter unknown encroachers on valued assets. In addition, accidental laser eye injuries continued to occur within the military, albeit at a low rate. The unit continued to help assess these exposures using advanced imaging (SLO and OCT) and measurements of visual function.88,92 Although laser-induced eye injuries were infrequent and predominately involved the misuse of lasers in military settings, the information obtained from these and laser-induced eye injuries occurring in the private sector was important in enhancing the understanding and collection of cases from industry, medicine, and research laboratories.[93]

The emergence of the carbon suspension cell optical switch for pulse-visible and near-infrared laser exposures reopened the issue of retinal injury threshold dependence on retinal irradiance diameter. Determining the protection quality of these switches required assessment of very non-uniform retinal irradiance patterns (irradiation patterns with “hot spots”). These assessments led to biological research using the intact nonhuman primate eye to verify injury prevention efficacy and to establish measurement procedures to evaluate future suspension cell switches.[94]

Evaluation of corneal, lens, iris, and retinal injury thresholds for laser wavelengths in the 1.1 to 1.4 μm region was driven by DoD efforts to build high-energy lasers operating at the chemical oxygen-iodine laser (COIL) wavelength of 1.315 μm. Collocation of the directed-energy bioeffects research program at Brooks allowed collaboration and design of complementary research on these issues. Assisted by others in the USAMRD and the Air Force Research Laboratory’s Optical Radiation Program, D. Jack Lund and Dr Joseph A. Zuclich designed and conducted a complex series of experiments addressing both the wavelength dependence and locus of ocular injury for exposures in the near-infrared spectral region, and dependence of the retinal injury threshold on retinal irradiance diameter.95–98

National and International Exposure Guidelines for Laser Radiation

The Brooks tri-service team published a series of papers that formed the basis for major adjustments to exposure limits that are just now being incorporated into exposure limit guidelines.96–98 Other international collaborators made significant contributions to practical interpretations of the data for incorporating them into best practices for optical radiation hazard analysis and establishing condition-dependent maximum permissible exposures.[99] During the Brooks years, the USAMRD-WRAIR supported the DoD Joint Staff, the Army’s judge advocate general, and the Department of State by providing technical advice and expertise in discussions of the “Blinding Laser Weapon Protocol” (Protocol IV of the Convention on Certain Conventional Weapons) negotiated in Vienna in 1995.

The emergence of high-powered laser diodes resulted in the proliferation of laser pointers, first red and later green. The availability of high-power laser illuminators drew attention to laser glare and purposeful exposure issues. David Stamper and Jerome Molchany continued laboratory and field studies of laser glare to assess the operational impact of non-injuring exposures.100,101 They investigated natural protective mechanisms and described the kinetics of the pupillary response, the aversion response (consisting of head or eye movement, squint, and blink), and laser-induced afterimages from visible lasers below the exposure limits.100,101 Major James W. Ness measured eye movements during deliberate fixations to more accurately assess the hazards of purposeful exposures.[102] Utilizing Major Ness’s data, Dr Brian J. Lund developed the first retinal thermal injury model in which the source moved on the retina commensurate with the measured eye movements during deliberate fixation. With the emergence of wavefront corrected retinal imaging systems, Dr Brian J. Lund and D. Jack Lund conducted a series of experiments measuring the retinal injury threshold with wavefront correction for optical aberrations in the eye being exposed[103] (Figure 1-6). This research over a period of several years was critical to the refinement of exposure limits for optical radiation.

Figure 1-6. D. Jack Lund adjusts an optical element in one of the many optical delivery systems he developed to expose the eyes of animal models so that injury thresholds for a wide range of exposure conditions and response criteria could be measured. These data were the basis for setting safe exposure limits for humans. D. Jack Lund, in collaboration with his son, Dr Brian J. Lund (not pictured), were the first to measure retinal response thresholds with and without wave-front correction in support of the safety analysis of advanced, high-resolution retinal imaging systems.

National and international laser safety standards are important products of the Army laser safety research program. Bruce E. Stuck has been the longstanding chair, with David H. Sliney as the co-chair, of the technical subcommittee for biological effects and medical surveillance within the ANSI Accredited Standards Committee for the Safe Use of Lasers (responsible for ANSI Z136 standards). Bruce Stuck also served on the International Commission on Non-Ionizing Radiation Protection (the international standards-setting body) subcommittee on optical radiation from 1999 to 2016. Sliney and Stuck have continued to synchronize the standards for industrial hygienists and occupational health specialists through the American Conference of Governmental Industrial Hygienists Physical Standards Committee, which develops threshold limit values for optical radiation.

Diagnosis and Treatment Research for Battlefield Laser-Induced Eye Injury

Treatment of laser-induced retinal injury was addressed particularly during the Brooks years (Figure 1-7). New approaches to understanding fundamental mechanisms of photoreceptor injury and repair were developed, including refinement of animal models and a novel snake eye model.[76] Major Jeremiah Brown Jr, assisted by Lieutenant Colonel Mastroianni, led a comprehensive study of the efficacy of steroids and nonsteroidal antiinflammatory agents on thermal lesions and pulsed lesions.[48]

These built on more than a decade of basic research studies led by Dr Steven T. Schuschereba. Initial trials with corticosteroids and nonsteroidal antiinflammatory drugs were inconclusive in a rabbit model,49,80 but further work demonstrated potent effects of corticosteroid treatment in retinal injury and highlighted the critical timing of treatments. During the early acute inflammatory phase of retinal injury, methylprednisolone worsened the inflammatory response and increased long-term scarring.[49] Neuroprotectant drugs and factors that moderated initial inflammatory responses, such as an iron scavenger (deferoxamine) and a neurotrophic factor (bFGF), protected or rescued photoreceptors from laser injury.[72]

Specific inquiries into the thresholds and timing of thermal energy damage distinguished apoptotic changes due to cell death from heat fixation, and characterized the genetic expression of heat shock proteins.78,104 These studies suggested therapeutic targets such as heat shock protein induction by prior heat exposure and herbimycin A administration.104,105 Novel attempts to transplant retinal cells indicated future treatment options.[47] Subsequent studies by Dr Heuy-Ching Hetty Wang investigated applications of stem cells in the treatment of retinal trauma, including novel strategies to track the fate of quantum dotlabeled stem cells transplanted into the vitreous.81,82 Lieutenant Colonel Deborah Whitmer conducted a study investigating treatment regimens that could be initiated by first responders, followed by therapies administered later at higher medical care echelons.[83] Lieutenant Colonel Cheryl DiCarlo investigated the use of optical radiation in the treatment of laserinduced retinal injury and advanced the state of the art for using multifocal electroretinography to assess focal, laser-induced retinal injury.[77]

Figure 1-7. The US Army Medical Research Detachment in front of building 176 at Brooks City-Base, San Antonio, Texas, circa 2004. Front row: Lieutenant Colonel David Scales, D. Jack Lund, Harry Zwick, Bruce E. Stuck, Steven T. Schuschereba, David A. Stamper, Jack B. Keller Jr, Captain James W. Ness. Second row: Thomas Nemeth, Fremont E. Wood, Peter R. Edsall, Ruthanne Jensen, Charles W. Van Sice, Joseph A. Zuclich, Reynaldo Broas, Sergeant First Class Stephen Hoxie, Specialist Jensen. Third row: unknown soldier, Guo Li, Michael Cross, Staff Sergeant Dan Fuller, Roosevelt Cunningham. Fourth row: Sergeant Veronica Ujimora, Sergeant First Class Sally Ruiz, Staff Sergeant Janis Loveday, Sergeant Maqsood Nawim, Claudia Wood, Jerome W. Molchany, André Akers, Roe Elliott. Fifth row: Sergeant Connie Henrichs, Specialist John Dembrowski.

Contemporary treatment approaches will ultimately be based on the taxonomy of the lesion or injury. This work, along with diagnostic imaging and novel assessments of visual function, stands as the basis for future ocular trauma management. Optical radiation exposure guidelines based on DoD research findings also facilitate the development and safety of advanced ocular imaging devices.

DIRECTIONS FOR FUTURE RESEARCH

Treatment of laser-induced retinal injury remains a key gap research area, with the goal of minimizing the potential loss of vision induced by laser radiation for a wide range of exposure conditions inherent to military uses of directed energy.[83] While previous work has demonstrated the relative efficacy of some drugs based on the taxonomy of laser-induced injury, combined therapies and stem-cell applications will offer better treatment efficacy. Eye injuries from blasts and fragments remain a problem in current operations,106,107 and pharmacological and surgical interventions under investigation for laser-induced retinal trauma also have applicability to eye trauma from blasts. Local administration of drugs to the eye (vs systemic administration) requires testing innovative approaches. Ocular pharmacokinetics and techniques to make both qualitative and quantitative assessments are required as enablers for treatment of ocular trauma.

The medical aspects of the full range of laser exposures, from glare to laser-induced hemorrhage, must be more fully understood. Evaluation of laser accident cases has demonstrated changes in the retina occurring over a year postinjury. Long-term follow-up of these cases should be continued. Definition of the degree and time course of visual impairment inherent to battlefield laser exposure requires additional research. With the emergence of visible laser dazzlers, the issue of long-term effects is not well understood; there is a need to characterize effects of repeated exposure in a single engagement (eg, several focal “full bleach” exposures with no ophthalmoscopically observable changes) and cumulative effects (over days or months). Advanced, rapid visual function assessment capabilities are needed to assure visual health in operational scenarios and to provide early assessment of potential functional changes from repeated or chronic exposures. Advanced diagnostic imaging of the retina (eg, OCT, SLO, and wavefront corrected retinal imaging) have great potential in assisting far-forward ocular evaluations, particularly when coupled with telemedicine. Medical research programs must be focused and sustained to provide better triage and treatment solutions for the future. Interim triage and treatment protocols must be established now. Research is needed to explore the efficacy of new drugs and drug combinations based on mechanism of injury at the molecular level, and subsequent time course and manifestation of the injury pathway.

The biological database supporting development of laser exposure guidelines must be expanded to meet the challenges posed by new military systems. With the emergence of nonlethal directed-energy systems, soldier protection must be assured by the availability of results-based directed-energy exposure guidelines. The database must also be expanded for use in specifying levels of protection required for laser eye protection systems.

Closer cooperation between medical researchers and military laser developers is needed to ensure system technology does not exceed current understanding of its biomedical implications for soldiers who may be exposed.83 The emergence of nonlethal directed energy will require updates to testing and training policies for soldier exposure to nonionizing radiation. New technology must be employed to assess radiation bioeffects, to understand injury mechanisms, and to determine the efficacy of treatment regimes. As research in the use of these technologies matures, the results must be integrated in military medical doctrine and practice.

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99. Schulmeister K, Stuck BE, Lund DJ, Sliney DH. Review of thresholds and recommendations for revised exposure limits for laser and optical radiation for thermally induced retinal injury. Health Phys. 2011;100(2):210–220.

100. Stamper DA, Lund DJ, Molchany JW, Stuck BE. Transient disruption of pursuit tracking performance for laser exposures below the permissible exposure limits. In: Belkin M, Stuck BE, eds. Laser-Inflicted Eye Injuries: Epidemiology, Prevention and Treatment . SPIE Proceedings Vol 2674. Birmingham, WA: SPIE; 1997: 7–20.

101. Stamper DA, Lund DJ, Molchany JW, Stuck BE. Human pupil and eyelid response to intense laser light: Implications for protection. Percept Motor Skills. 2002;95(3):775–782.

102. Ness JW, Zwick H, Stuck BE, et al. Retinal image motion during deliberate fixation: Implications to laser safety for long duration viewing. Health Phys. 2000;78(2):131–142.

103. Lund BJ, Lund DJ, Edsall PR. Laser-induced retinal damage threshold measurements with wavefront correction. J Biomed Opt . 2008;13(5):064011-1-10.

104. Dinh HK, Zhao B, Schuschereba ST, Merrill G, Bowman PD. Gene expression profiling of the response to thermal injury in human cells. Physiol Genomics. 2001;7(1):3–13.

105. Din HK, Stavchansky S, Schuschereba ST, Stuck. BE, Bowman PD. Cytoprotection against thermal injury: Evaluation of herbimycin A by cell viability and cDNA arrays. Pharmacogenomics J. 2002;2(5):318–326.

106. Hacker HD, Lund DJ, Charamie R, Stuck BE. Ocular laser bioeffects in Operation Iraqi Freedom. In: Belkin M, Stuck BE, Manna F, Soderberg PG, Ho A, eds. Ophthalmic Technologies XVIII. SPIE Proceedings Vol 6844. Bellingham, WA: SPIE; 2008: 1–8. doi: 10.111/12.764311.

107. Thach AB, Johnson AJ, Carroll RB, Huchin A. et al. Severe eye injuries in the war in Iraq, 2003-2005. Ophthalmol. 2008;115(2):377–382.

Chapter 2

HISTORY AND DEVELOPMENT OF MILITARY LASERS

JACK B. KELLER, JR * Lieutenant Colonel, US Army (Retired); formerly, Foreign Science Information Officer, US Army Medical Research Detachment-Walter Reed Army Institute of Research, 7965 Dave Erwin Drive, Brooks City-Base, Texas 78235

INTRODUCTION

INVENTING THE LASER

MILITARIZING THE LASER

SEARCHING FOR HIGH-ENERGY LASER WEAPONS

SEARCHING FOR LOW-ENERGY LASER WEAPONS

RETURNING TO HIGHER ENERGIES

INTRODUCTION

This chapter will examine the history of the laser, from theory to demonstration, for its impact upon the US military. In the field of military science, there was early recognition that lasers can be visually and cutaneously hazardous to military personnel—hazards documented in detail elsewhere in this volume—and that such hazards must be mitigated to ensure military personnel safety and mission success. At odds with this recognition was the desire to harness the laser’s potential application to a wide spectrum of military tasks. This chapter focuses on the history and development of laser systems that, when used, necessitate highly specialized biomedical research as described throughout this volume. This presentation is neither exhaustive nor definitive, but describes numerous developmental and fielded laser systems that cover a range of militarily important applications.

Military advantage is greatest when details are concealed from real or potential adversaries (eg, through classification). Classification can remain in place long after a program is aborted, if warranted to conceal technological details or pathways not obvious or easily deduced but that may be relevant to future developments. Thus, many details regarding developmental military laser systems cannot be made public; their descriptions here are necessarily vague.

Once fielded, system details usually, but not always, become public. Laser systems identified here represent various evolutionary states of the art in laser technology, design, and application during their development. Emitted beam characteristics vary widely and are important to the specific application and assessment of potential hazards.

INVENTING THE LASER

“A splendid light has dawned on me about the absorption and emission of radiation.”

—Albert Einstein, letter to Michele Angelo Besso, September 6, 1916(p82)

Light amplification by stimulated emission of radiation (“laser”) is the optical demonstration of Einstein’s theorized “splendid light.” Einstein realized that an atom in an excited state can be induced to make a downward transition while emitting a photon, if the atom is irradiated at a frequency that matches the atomic transition energy of the host material. Even so, in science, realization without proof is mere theory. Einstein’s “splendid light” remained theory for several years.

Civilian Efforts

In 1928, at Kaiser Wilhelm Institute, Rudolf Ladenburg proved negative absorption (stimulated emission) near resonant wavelengths in neon gas.[2] However, Ladenburg’s demonstration was of an uncontrolled emission, and nothing practical flowed from his proof. Another 26 years would pass before demonstration of a controlled stimulated emission. In 1954, at Columbia University, Charles Townes, Herbert Zeiger, and James Gordon stimulated ammonia gas with microwave radiation and created the first “maser” (microwave amplification by stimulated emission of radiation).

Three years later, Gordon Gould, a Columbia graduate student, coined the acronym “laser.” In a notarized but unpublished paper, Gould described how a laser could be built, and was later awarded a patent just for his design. Historical credit for the invention of the laser went instead to Bell Labs researchers Charles H. Townes and Arthur L. Schawlow, whose detailed and published proposal for building what they called an “optical maser” created an instant stir when it appeared in Physical Review on December 15, 1958. [3]

The race to build the first laser began immediately, but there was no agreement about which of several candidate materials might be an acceptable host.[4] Townes led a team at Columbia to build a potassium-vapor laser. Similarly, Gould, at Technical Research Group, worked on alkali metal vapors. In the Soviet Union, Nicolay G. Basov concentrated on semiconductors. Ali Javan, at Bell Labs, worked to build a helium-neon gas laser. Schawlow, also at Bell Labs, considered ruby, but then dismissed it as unsuitable. Theodore Maiman, at Hughes Research Laboratory, became convinced that Schawlow was wrong to dismiss ruby as a host material. On May 16, 1960, Maiman used a cylindrical ruby crystal and a xenon flash lamp to generate a monochromatic beam of coherent radiation.[5] The ruby laser emitted a 0.5-millisecond pulse that approximated the pump lamp’s emission duration with a primary emission wavelength of 694.3 nm. The pulse on higher-energy ruby lasers could linger from 1 to 5 milliseconds. These are relatively long pulses compared to what is possible through Q-switching. (Q-switched lasers emit short pulses. “Q” refers to the “quality” factor describing the state of a laser cavity.)

Military Interest

Researchers at the Defense Department’s Advanced Research Projects Agency (ARPA) and military services’ research and development (R&D) laboratories, including the Army’s R&D labs at Picatinny Arsenal, New Jersey, and Ft Monmouth, New Jersey, quickly recognized that laser energy possessed a number of special properties, not least of which are spatial and temporal coherence. Coherent and almost parallel beams of light can achieve extremely high radiation densities when tightly pulsed and highly focused, creating transitory temperatures exceeding those on the sun’s surface.

Even the low-powered, Q-switched ruby laser inspired excitement among those who understood its potential. Q-switching produces a more intense pulse. While output energy is somewhat decreased, the pulse duration is markedly shortened, resulting in a tremendous increase in emitted power density; a 10 ns pulse of 1 J represents a pulse of about 100 million W. The effect of such a pulse on target materials, whether rigid or elastic, is more “explosive” or ablative than long pulses. Thus, the transition from ruby to neodymiumdoped yttrium aluminum garnet (Nd:YAG) as the preferred solid-state laser changed the potential not only for laser application, but also for resulting medical hazards.

ARPA and the military services’ R&D laboratories naturally hoped that laser technology could be manageably scaled, powered, and packaged as deployable combat tools. The ultimate goal was development of a “ray gun.” In 1968, Frederick Schollhammer obtained US Patent Number 3,392,261 for the “Portable Beam Generator,” also known as the handheld laser ray gun. [6] Of course, owning a patent and making a product are two different things.

Impressive though they are, even today’s most modern laser applications still pale in comparison to the power and efficiency of those depicted in science fiction. Early military applications were all the more benign by contrast. ARPA awarded seed money for research to develop and test new laser action materials (“lasants”). The original ruby lasant was applied to a number of applications with military potential. Within a year of Maiman’s original achievement, the first prototype military laser device—an artillery laser rangefinder— had been designed and built. In much the same way that radar modernized air operations, some visionaries believed the laser could fundamentally change future battlefields across a wide spectrum of military functions.

MILITARIZING THE LASER

Although many nations have harnessed the potential of military lasers, none have done so as extensively as the United States. Prior to the development of the first laser, American military scientists had envisioned light-sourced applications to support distance measurement, target designation, and wireless guidance. Unfortunately, none of these applications could be achieved with noncoherent light sources. The laser provided a tight, collimated, and discrete wavelength beam that was immediately applied to support these and other applications:

Rangefinders

The first successful American military application of laser technology was for the purpose of distance measurement, or “rangefinding.” The idea in this case was to employ the energy density of the laser beam, the strength of which guaranteed reflection back from almost any irregular surface of military interest. Using ruby, the first artillery laser rangefinder was built at the US Army’s Pitman-Dunn Laboratory at Frankfort Arsenal, Pennsylvania. Dubbed the XM23, this device was the first of a larger family of rangefinders. The well-engineered ruby laser rangefinder was deployed within every main battle tank the US Army fielded until the introduction of the M1 Abrams tank series in 1978.

Although the ruby laser system was useful in early work, faster and cooler lasers were subsequently made possible through the use of Nd:YAG as a lasant. The switch to Nd:YAG was concurrent with the introduction of the M1 Abrams in 1978 and continued in the M1A1 (1985). A laser rangefinder known as the eyesafe laser rangefinder (ELRF) used erbium-doped glass as a lasant that did not exceed the radiation protection exposure limits. It was introduced with the M1A2 in 19867 (Table 2-1).

The mainstay for US ground as well as nontank vehicle laser rangefinders has been the neodymium-based AN/GVS-5. Since 1977, more than 8,000 such units have been fielded to Army and Marine Corps forward observers. The AN/GVS-5 delivers one ranging measurement per second and can be operated by battery or vehicular electrical power. This system’s 7 × 50 mm sighting optics, multiple target indicator, and minimum range adjustment provide wide versatility and adaptability.

The LAV-AD (Light Armored Vehicle–Air Defense) and LAV-105 are both eight-wheeled armored cars. Each is augmented with a different laser rangefinder.

TABLE 2-1
US TANK RANGEFINDER SYSTEMS GROUPED BY THEIR LASER MEDIUMS AND TANK MODELS

Laser Medium

Ruby

Nd:YAG

Er:Glass

Tank Rangefinder System
(Tank Model)

AN/VVS-1
(M60A2 Tank)

AN/VVG-1
(M551A1 Sheridan)

AN/VVG-2
(M60A3 Tank)

AN/VVG-3
(M1 and M1A1 Tank)

ELRF
(M1A2 Tank)

Er:Glass: erbium-doped glass

ELRF: eyesafe laser rangefinder

Nd:YAG: neodymium-doped yttrium aluminum garnet

The LAV-105 uses the AN/GVS-5, and the LAV-AD uses a transversely excited atmospheric carbon dioxide (CO_2) laser. The Avenger air defense system also uses a CO_2 laser. [8] Other rangefinders also exist (Table 2-2).

As military rangefinders transitioned from use of ruby to Nd:YAG lasant, an additional military application became possible. Because neodymium was cooler than ruby, neodymium permitted faster repetition rates. Although largely unnecessary for rangefinders, these faster rates were essential for target designation.

Target Designators and Markers

Target designation relies on beam reflection and fast repetition rates. A laser target designator emits a coded train of pulses to a designated point of reflectivity on the target. A seeker on the weapon identifies and locks onto the reflected, coded train of pulses. Guidance surfaces or steering jets then maneuver the delivery system (bomb, missile, or warhead) to strike the target at the designated point.

The US Army first began research into laser target designation in 1962. Simultaneously, the Army began research into laser guidance of smoothbore cannon projectiles. The US Air Force joined this effort and developed the first laser-guided bomb (BOmb, Laser, Target-117) (BOLT-117) in 1967. The BOLT-117 was essentially a gravity bomb equipped with a laser seeker, guidance logic, and attached control system. The system’s signals steered the bomb by controlling its fins. Target designation for the bomb was achieved by laser designator (AN/ALQ-10) operated from a separate observation aircraft. 9,10

In 1968, the BOLT-117 was field-tested in Vietnam. [9] Because the BOLT-117 was a “dumb bomb” adapted to a “smart task,” this bomb was limited in terms of its seeker sensitivity, glide agility, and range. Although it needed an improved and integrated system in a more maneuverable body, its concept was compelling.

The limitations of the BOLT-117 were overcome by the GBU (Guided Bomb Unit)-10 Paveway, which was designed and built to be a laser-guided bomb.A prototype of the GBU-10 was successfully employed over North Vietnam in 1972.9 Near Hanoi, four GBU- 10s released during a single sortie scored four direct hits and dropped the Than Hoa Bridge, which had previously survived more than 800 attack sorties by dumb bombs over a 5-year period. As a proof-of-concept mission, the Than Hoa raid was a resounding success. The accomplishment was quickly followed by dropping Hanoi’s equally vexing Paul Doumier bridge. [11]

TABLE 2-2
A COMPARISON OF US HANDHELD AND VEHICLE-MOUNTED LASER RANGEFINDERS

System

Known As

Platform Use

Medium

AN/GVS-5

GVS-5

Handheld

Nd:YAG

AN/PVS-X

MLRF

Handheld

Nd:YAG

AN/TWQ-1

Avenger

HMMWV Air Defense

TEA CO_2

LAV-105

LAV

Armored Car

Nd:YAG

LAV-AD

LAV-AD

Armored Car - AD

CO_2

AN/PVS-6

MELIOS

Handheld

Erbium

AD: air defense

CO_2: carbon dioxide

HMMWV: high-mobility multipurpose wheeled vehicle

LAV: light-armored vehicle

MELIOS: mini-eyesafe laser infrared observation set

MLRF: miniature laser rangefinder

Nd:YAG: neodymium-doped yttrium aluminum garnetr

TEA CO_2: transversely excited atmospheric carbon dioxide

The GBU-12, GBU-15, GBU-16, GBU-24, GBU-27, and GBU-28 succeeded the GBU-10.[10] These follow-on systems had maneuverable bodies and could be self-designated. This meant that the delivery aircraft could designate its own target, eliminating the need for an additional aircraft on station. Some of the aircraft and helicopter laser designators in the US inventory are listed in Table 2-3.

TABLE 2-3
LASER DESIGNATORS AND THEIR ASSOCIATED US AIRCRAFT PLATFORMS

System

Known As

Platform Association

AN/AVQ-9

Pave Light

OV-10 and F-4

AN/ALQ-10

Pave Knife

F-16

AN/AVQ-11

Pave Sword

O-2A and F-4

AN/AVQ-11

Pave Sword

O-2A and F-4

AN/AVQ-12

Pave Spike

OV-10

AN/AVQ-13

Pave Nail

OV-10

AN/AAQ-14

LANTIRN

F-14, F-15E, and F-16C/D

AN/AVQ-14

Pave Arrow

O-2A and C-123

AN/AVQ-19

Pave Spectre

AC-130

AN/AAQ-22

Safire NTIS

UH-1N and P-3

AN/AVQ-25

Pave Tack

A-7D, A-10A, F-4, and F-111

AN/AVQ-26

Pave Tack

F-4, RF-4, and F-111F

AN/AAS-32

ATL

AH-1F

AN/AAS-33A

TRAM

A-6E

AN/AAS-35

Pave Penny

F-16, A-7D, A-10A, F-4, F-111, and OV-10A

AN/AAS-37

LRFD

OV-10

AN/AAS-38A

Nite Hawk

AH-1W

TADS LTD

TADS

AH-64

M65

LAAT

AH-1F and AH-1S

MMS LRF/D

Mast Mount

OH-58D

ATL: advanced tactical laser

LAAT: laser augmented airborne tube-launched, optically tracked, wire-guided missile

LANTIRN: low-altitude navigation and targeting infrared for night

LRFD and LRF/D: laser rangefinder designator

LTD: laser target designator

MMS: mast-mounted sight

NTIS: navigational thermal imaging system

NTS: night targeting system

Safire: shipboard airborne forward-lookingF infrared equipment

TADS: target acquisition and designation sights

TRAM: target recognition attack multisensor

Smart bombs can also be designated from the ground. The AN/PAQ-1 laser target designator, which can be fitted with a night sight, was issued to Special Forces, Army artillery observers, and Air Force forward air controllers as early as 1972. In 1977, the modular universal laser equipment (MULE) was introduced. The MULE was an extremely adaptable piece of equipment used by artillery forward observers, naval gunfire spotters, and forward air controllers. Two years later, the ground/vehicular laser locator designator (G/VLLD, often referred to simply as the GLD, pronounced “glid”) was fielded. This system could be man-packed, but its primary mount was the fire support team vehicle (FIST-V). Both the MULE and G/ VLLD performed target location and laser designation for all fielded laser-guided munitions (LGM) in the US and North Atlantic Treaty Organization inventories.[10]

As the US Army worked to solve problems associated with cannon-launched guided projectiles (CLGPs), the Marine Corps adapted the air-to-ground missile AGM-65 Maverick to laser guidance as the AGM-65E, [12] dubbed the LMav (laser-guided Maverick) to differentiate it from other Maverick models guided by electro-optics, television, or infrared imaging. The Army would later field a helicopter-launched, antitank LGM known as the Hellfire, and later the Hellfire II, with 20 variants between them. The LGM can be fired from eleven different helicopters, six fixed-wing aircraft, four unmanned aircraft, and at least two naval craft.[13]

During this time, the Army also finally fielded its Copperhead antitank round. The M712 Copperhead laser-guided, 155-mm CLGP is fired from any model 155-mm Howitzer to within the general vicinity of the target. When the round reaches apex and begins its downward flight, a forward observer illuminates its target by laser. The Copperhead’s seeker locks onto the reflected laser energy and steers itself to the target. The Copperhead is effective in locating both stationary and moving targets. However, its price tag limited its use to very high-value targets. Its last reported use was in 2003 during Operation Iraqi Freedom, after which a new family of smart projectiles incorporated global positioning system/inertial navigation system-guided bombs and precision artillery.[14]

In 1986, the compact laser designator was fielded for Army Special Forces and Navy Seals. At about the same time, military scientists began to analyze the concept of portable and handheld laser markers that could be used to illuminate or mark targets (Table 2-4). The Special Operation Forces laser marker was then developed to illuminate a target for hand-off to a laser designator. Officially known as the AN/PEQ-1, the Special Operations Forces laser marker was further developed to a whole family of target pointers, illuminators, and aiming lights. Members of this family are handheld, pistol-mounted, or rifle-mounted, and are monocular or binocular. Some can be used with night vision devices—the most recent being the AN/ PEQ-16A/B. The laser target marker was used by ground-based forward controllers. The handheld systems LPL-30 (International Technologies Ltd, Rishon LeZion, Israel) and TD-100 (Target Designator-100) were developed to mark targets for identification using low-light viewing devices such as night vision goggles or low-light television. [6]

The purpose of laser designation, laser spot detection, and laser target marking systems is to support laser homing by illuminating targets to enable munitions to lock on and guide toward the point of beam reflectivity. The primary disadvantage of laser homing is that rain, fog, dust, and smoke can interfere with the laser beam or even completely obscure it, causing the munition’s seeker to lose its lock and miss its target. This problem can be avoided through the use of another type of laser guidance known as laser beam “riding.”

Beam Riders

Beam rider sensors are located in the aft of the munition. Rather than looking forward at the target, beam rider sensors look back at the launching platform’s laser and attempt to “ride” the laser beam itself. In this case, the laser need not actually illuminate the target at which it is aimed during the entire engagement. A gunner can “lead” a moving target, anticipating where the target will be when the missile closes on it. In theory, as long as the system operator (gunner) can see the target and can hold the beam on it in the final seconds before impact, the munition will continue to ride the beam until it strikes the target or loses sight of the beam.

Because the guidance beam is flat, without trajectory, the munition must likewise be capable of achieving and maintaining a flat flight path without trajectory. Only a missile (tube- or gun-launched) can do this. There are several examples of laser-beam rider autonomous missile 15-18 and gun-launched antitank guided missile19–23 systems in foreign military arsenals. For example, Russia has at least six beam-riding, gunlaunched antitank guided missiles and at least ten variants delivered by their family of 100-mm, 115-mm, and 125-mm guns, as well as three adjunct antitank guided missiles mountable on vehicles, watercraft, helicopters, and high-performance aircraft.[24]

The US military explored only initial development of adding such a system—the line-of-sight antitank (LOSAT)—to its own arsenal (Table 2-5). The LOSAT was a four-missile launcher mounted on a stretched high-mobility multipurpose wheeled vehicle (HMMWV), with a trailer carrying eight additional missiles. The LOSAT’s guidance incorporated a CO_2 laser,[25] and the LOSAT’s missiles rode the laser beam at hypervelocity (5,000 fps) to deliver long penetrator rod warheads. Only 12 delivery systems and 435 missiles were delivered before the LOSAT program was canceled in favor of a lighter-weight missile system. 26,27

TABLE 2-4
US HANDHELD AND VEHICLE-MOUNTED LASER DESIGNATORS AND MARKERS BY MOUNT

System

Known As

Platform Association

AN/PAQ-1

LTD

Handheld

AN/TVQ-2

G/VLLD

FIST-V

AN/PAQ-3

MULE

Man-packed

LTM86 CLD

Clid

Handheld

AN/PEQ-1

SOFLAM

Handheld or mounted

AN/PEQ-2

ATPIAL

Mounted

LTM

LTM

Man-packed

LPL-30 [*]

Commander’s Marker

Handheld

TD-100

Marking Laser

Handheld

*This system name was originally trademarked by International Technologies, Ltd, Rishon, LeZion. Israel.

ATPIAL: advanced target pointer illuminator aiming laser

CLD: compact laser designator

FIST-V: fire support team vehicle

G/VLLD: ground/vehicular laser locator designator

LTD: laser target designator

LTM: laser target marker

MULE: modular universal laser equipment

SOFLAM: special operation forces laser marker

Multiuse Lasers

When it became obvious that a coupling of laser rangefinder and target designator tasks was a good idea, the first Army contract was awarded in 2002. The result was the human-portable AN/PED-1 lightweight laser designator rangefinder (LLDR 1), followed by the AN/PED-1A (LLDR 2) and AN/PED-1B (LLDR 2H). The variants include or are being upgraded to include the following capabilities: thermal imaging, day camera, laser designation, ELRF, electronic display, data export, and transmission; in the LLDR 2H, variants include digital magnetic compass and selective availability and antispoofing module GPS. With this system, US Army and Marine Corps forward observers and US Air Force terminal or forward air controllers can identify and target enemy assets in day, night, haze, smoke, fog, or rain at ranges up to 7 km. 28-30

TABLE 2-5
SELECTED LASER BEAM RIDER MISSILE SYSTEMS BY COUNTRY, TYPE, AND MAXIMUM RANGE

Country

System

Type

Maximum Range

Sweden

RBS 70, RSB 70 NG, and RSB 90

SAM

7,000 m

Russia

AT-10 [*] (9M117 Bastion – fired through rifled guns of T-55 tank)

ATGM and GLATGM

4,000 m

Russia

AT-11 [*] (9M119/9M119M/9M119M1 Svir/Refleks/Invar – fired through smoothbore guns of T-64, T-72/T-80, T-84, and T-90 tanks and through Sprut-SD self-propelled AT gun)

ATGM and GLATGM

ATGM and GLATGM or 5,000 m (GLATGM)

Russia

AT-12 [*] (9M118 Sheksna – fired through smoothbore gun of T-62 tank series)

ATGM and GLATGM

4,000 m

Russia

AT-14 [*] (9M133 Kornet with variants – adjunct to BMP-3, other APCs and IFVs, and boats)

ATGM

5,500 m (day) or 3,500 m (night)

Russia

AT-15 [*] (9M123 Khrizantema with variants – autonomous tank destroyer- or helicopterlaunched)

ATGM

6,000 m (claimed)

Russia

AT-16 [*] (9K121 Vikhr – launched from ships,helicopters, and Su-25T aircraft; can also belaunched against aircraft on frontal axis)

ATGM

8,000–10,000 m (day) or 5,000 m (night)

South Africa

ZT3 and ZT3A2 Ingwe – vehicle- and helicopter-mounted

ATGM

5,000 m

United States

LOSAT

ATGM

Classified

*NATO reporting name for military equipment of Russia and the former Soviet Union (https://en.wikipedia.org/wiki/List_of_NATO_reporting_names_for_anti-tank_missiles).

APC: armored personnel carrier

AT: antitank

ATGM: antitank guided missile

BMP: Boyevaya Mashina Pekhoty, Russian for “infantry fighting vehicle”

GLATGM: gun-launched antitank guided missile

IFV: infantry fighting vehicle

LOSAT: line-of-sight antitank

RBS: Robotsystem

SAM: surface-to-air missile

The US Marine Corps, with different coordination requirements, fielded the target location, designation, and hand-off system for use by Marine tactical air control parties, fire support teams, firepower control teams, and reconnaissance teams. The target location, designation, and hand-off system possesses additional capabilities for mission hand-off, but otherwise performs on par with the LLDR. Two configurations are fielded as military ruggedized tablets (MRTs): the MRT-A and MRT-B.[31]

Aiming Lasers

Although the handheld TD-100 laser marker (see Table 2-4) is often described as an “aiming laser,” this term is now more commonly used to describe systems that are fitted onto weapons. These include the families of the AN/PAQ-4 and the AIM-1 systems (International Technologies Ltd), which fit many individual and crew-served weapons used by the US Army and Marine Corps. In a similar category are the handheld, clip-on, or finger-mounted ground commander’s pointer and air commander’s pointer. These pointers are small infrared aiming lasers that can be used with night vision devices to identify and illuminate targets at night. They are used by all US military services.[6] Other aiming lasers also exist (Table 2-6).

Laser Training Devices

Laser training devices have been in use since the late 1970s. The multiple-integrated laser engagement system (MILES) is a training system that provides a realistic battlefield environment for soldiers involved in direct fire, force-on-force training exercises that utilize tactical engagement simulation and eyesafe lasers.

TABLE 2-6
OTHER US LASER AIMING DEVICES BY SYSTEM MODELS

System Series

AN/PAQ-4

AIM-1 [*]

GCP-1

ACP-2

Aiming devices

AN/PAQ-4, AN/PAQ-4A, AN/PAQ-4B, and AN/PAQ-4C

AIM-1, AIM-1/D, AIM-1/MLR,AIM-1/EXL, and AIM/MLR

GCP-1 and GCP-1A

ACP-2 and ACP-2A

*AIM-1 is trademarked by International Technologies, Ltd., Rishon, LeZion, Israel.

ACP: air commander’s pointer

GCP: ground commander’s pointer

As described in the US Army’s Technical Bulletin 524, Control of Hazards to Health From Laser Radiation (2006), on occupational and environmental health, “[t] hese lasers are designed to be pointed at personnel during combat training. Although there is relatively little risk of eye injury from these lasers, the beams sometimes exceed the maximum permissible exposure (MPE) within a few meters (less than 10 m for the unaided eye).” 32(p48) The subsequent system version, the MILES II, increased usability and training effectiveness by sensing hits, performing casualty assessment, and recording all “hit” events for after-action analysis. MILES 2000 is the latest in this family of devices.[8]8

The technical bulletin also notes that “[h]azards from MILES devices are based on a 10-second exposure duration. A shorter exposure duration lessens the hazard but does not eliminate it.” 32(p176) However, repetitive or repeated exposures can create a cumulative exposure that exceeds the safe exposure limits. [32] The scope and environment of MILES-based training has been extended considerably by the air-to-ground engagement system/air defense, laser air-to-air gunnery system, and precision gunnery training system. [8] A list of laser training devices and their hazardous envelopes is available in Technical Bulletin 524. [32]

A different approach is followed for the indoor simulated marksmanship trainer (ISMT) series, which includes the infantry squad trainer. Training in this series involves the projection of images on a screen. The trainee fires a laser at the projected target to record a hit or miss. The ISMT-E (enhanced) employs 3-dimensional technologies and programmable training scenarios to expand every aspect of training, including the addition of new weapons or capabilities at any time.[33] Table 2-7 lists US laser training systems and their associated weapons.

In addition to all of the applications described above, lasers have many other uses on, behind, and above the modern battlefield. These include remote explosive ordnance detonation, chemical and biological dispersion detection, secure communications, and laser radar (known both as LADAR and LIDAR).

SEARCHING FOR HIGH-ENERGY LASER WEAPONS

When lasers were still very new, ARPA arbitrarily defined a high-energy laser (HEL) as one that could produce an output energy of 10 kW. That criterion was quickly raised to 100 kW, and then to 400 kW. Within the Department of Energy, the megawatt-class laser was considered a HEL. As a practical matter, the term “HEL” is one whose output causes the destruction or mission-neutralization of a target, whether it is an electro-optical missile seeker, a helicopter in attack mode, an intercontinental ballistic missile in flight, or a satellite in orbit. For example, mounted on a tracked vehicle, a single-kW (but more likely 10-kW) laser might be considered a HEL. However, for the purposes of this section, “HEL” will refer to any laser that satisfied or exceeded ARPA’s original definition (10 kW).

Rumors in the press and intelligence channels have suggested that Soviet laser weapons were used in remote skirmishes from China to Afghanistan.34-36 In 1975, American early-warning satellites were reportedly temporarily blinded by Soviet HELs. US defense officials denied that lasers were involved but not that US satellites were temporarily blinded.[37] For those who understood the military’s increasing dependence on satellites, the potential ramifications of an antisatellite capability were horrific to contemplate and would constitute a tremendous vulnerability in US strategic deterrence. [38]

Not surprisingly, the United States has investigated the possible development of US HEL weapons. As early as 1962, scientists at the Air Force Special Weapons Center, Kirtland Air Force Base, New Mexico, were tasked with calculating the laser energy that would be required to destroy an intercontinental ballistic missile. At the time, there were no lasers in existence that could possibly deliver the energy necessary to meet this objective.39 However, the CO_2 laser was invented in 1964, and by 1967, a CO_2 gas dynamic laser (GDL) could produce more than enough energy (10 kW) to cause severe damage to the human body. Other countries may have pursued development of such a lethal weapon, but the United States, instead, remained focused on its goal to develop a laser system that could only be used to destroy missiles. Several types of these laser systems are described below.

TABLE 2-7
US LASER TRAINING SYSTEMS AND PLATFORM ASSOCIATIONS

System

Platform Association

MILES, MILES II, and MILES 2000

Individual and crew-served weapons

AGES/AD family

Chapparal, Vulcan, Stinger, and TADS

AN/ASQ-193 LATAGS

Various

PGTS

TOW and Dragon

TWGSS/PGS (AGES II)

Kiowa (.50 cal); Apache Hellfire (20 mm)

M55 Trainer

All tanks, M2/M3 BFV, and M551

Javelin FTT

Javelin AT system

ISMT/IST

11 individual and crew-served weapons

ISMT-E

15+ individual and crew-served weapons

AD: air defense

AGES: air-to-ground engagement system

AT: antitank

BFV: Bradley fighting vehicle

FTT: field tactical trainer

ISMT: indoor simulated marksmanship trainer

IST: infantry squad trainer

LATAGS: laser tactical air gunnery system

MILES: multiple integrated laser engagement system

PGS: precision gunnery system

PGTS: precision gunnery training system

TADS: target acquisition and designation sights

TOW: tube-launched, optically tracked, wire-guided

TWGSS: tank weapons gunnery simulation system

Tri-Service Laser

By early 1968, Pratt & Whitney’s XLD-1 and AVCO Corporation’s MK-5 (both were CO_2 GDLs) achieved output beams of 77 kW and 138 kW, respectively. These systems created expectations of grossly higher output energies as a matter of course. Indeed, the XLD-1 would achieve 455 kW output in May 1969 and exceeded 500 kW in 1970. However, in December 1968, AVCO’s MK-5 appeared to be the more power powerful device. The armed services purchased the MK-5 scaled up to 150 kW and named it the Tri-Service laser (TSL). [39]

The TSL program became a 4-year odyssey that culminated in December 1972 at Sandia Optical Range, Kirtland Air Force Base. There, researchers at the Air Force Weapons Laboratory mated the 100- to 150-kW beam of the TSL-1 CO_2 GDL with the Hughes Aircraft field test telescope and held it on a moving target that was approximately 3-in. square for several seconds at a distance of 1,760 m. This feat was followed 11 months later with the successful use of the same system to shoot down a 12-ft drone flying 200 mph over Sandia Range. [39]

Airborne Laser Laboratory

With these objectives met, the next logical step was to install a HEL in an airframe as a weapon testbed. In March 1972, the Air Force Weapons Laboratory took possession of a Boeing NKC-135A aircraft and instrumented it with a 400-kW CO_2 GDL. The system was integrated with a Hughes optical pointing and tracking system and a Perkin Elmer dynamic alignment system to become the Airborne Laser Laboratory, a program platform that lasted 11 years and was successfully used to shoot down five AIM-9B Sidewinder air-to-air missiles in 1983. [39]

Mobile Test Unit

The US Air Force was not alone in its efforts to develop HEL capability (Table 2-8). The US Army mounted an AVCO 30-kW CO_2 electric discharge laser in a modified Marine Corps LVTP-7 (landing vehicle, tracked, personnel-7) amphibious assault vehicle. Christened the “mobile test unit” (MTU), this system successfully disabled a 300-mph fixed-wing drone and a tethered helicopter drone at Redstone Arsenal, Alabama, in 1976. Technically, this system was a medium-powered laser, not a HEL, but the MTU demonstrated what could be done with less. Unfortunately, it nearly filled the interior of the vehicle in which it was mounted and, at that time, was neither scalable nor robust enough for Army standards. Despite its successful “hard kill” engagements to structurally destroy drones and helicopters, the Army’s MTU program ended inconclusively in 1978. [39]

Mobile Army Demonstrator and Multipurpose Chemical Laser

In 1981, the mobile Army demonstrator (MAD), a 100-kW deuterium-fluoride laser, was built as a prototype for an air defense weapon against missiles under the Strategic Defense Initiative umbrella. The MAD was scheduled to be scaled up to 1.4 MW, but deuterium-fluoride technology then proved unsuitable for a mobility mission, so the effort was omitted from the Strategic Defense Initiative budget in late 1983. With Army funding to Bell Aerospace Textron, the MAD laser survived under a new name: the multipurpose chemical laser. [40]

TABLE 2-8
COMPARISON OF US HIGH-ENERGY LASER TESTBEDS

Program

Platform

Type Laser

Output

Successful Engagements

TSL-1

Fixed

CO_2 GDL0

150 kW

Drones

ALL

KC-135A

CO_2 GDL

400 kW

Sidewinder AA missiles

MTU

LVTP-7

CO_2 EDL

30 kW

Drones and helicopter

MAD

[*]

DF

100 kW

[*]

UNFT

Fixed

DF

400 kW

TOW missiles, helicopter

MIRACL

Fixed

DF

2.2 MW

Drones, missiles, and satellite

*In 1981, the MAD was built as a 100-kW deuterium-fluoride laser prototype for an air defense weapon against missiles under the Strategic Defense Initiative (SDI) umbrella. The MAD was scheduled to be scaled up to 1.4 MW, but deuterium-fluoride technology then proved unsuitable for a mobility mission. The effort was omitted from the SDI budget in late 1983. It was later continued under its new name, the Multipurpose Chemical Laser.

AA: air-to-air

ALL: airborne laser laboratory

CO_2: carbon dioxide

DF: deuterium-fluoride

EDL: electrical discharge laser

GDL: gas dynamic laser

LVTP: landing vehicle, tracked, personnel

MAD: mobile Army demonstrator

MIRACL: midinfrared advanced chemical laser

MTU: mobile test unit

TOW: tube-launched, optically tracked, wire-guided

TSL: tri-service laser

UNFT: unified Navy field test

Unified Navy Field Test Program

While the US Army tested the MTU, the US Navy entered the HEL arena. In 1978, the Navy mated a 400-kW TRW Inc (Cleveland, OH), deuterium-fluoride HEL with a Hughes pointer-tracker. Dubbed the Unified Navy Field Test Program, this system destroyed four out of five tube-launched, optically tracked, wire-guided antitank missiles in flight. Later, a UH-1 Iroquois helicopter was targeted and destroyed. 38,39

Midinfrared Advanced Chemical Laser

The midinfrared advanced chemical laser (MIRACL) [41] was built in the mid-1970s by TRW for the Navy at White Sands Missile Range, New Mexico. Located at the High- Energy Laser Systems Test Facility, MIRACL was the first megawatt-class, continuous wave, chemical laser built in the United States. The MIRACL system is a closed-loop, 2.2-MW, deuterium-fluoride HEL. In the late 1970s, the Navy tested and proved the pointing and tracking technology then under development for MIRACL’s partner, the Sea Lite beam director (Hughes Aircraft Company, Westchester, CA). Sea Lite has a 28,000-lb, 1.8-m aperture gimbaled telescope and optics that can focus from 400 m to infinity while tracking a small crosssection missile flying directly at it. MIRACL and Sea Lite have a long record of successful tests against highly dynamic targets, including 500-mph drones, supersonic Vandal missiles, and satellites in orbit 37,41 (see Table 2-8).

Although some of the US HEL systems could have been adapted as weapon systems, none were developed as such. Rather, these systems were testbeds built to demonstrate and delimit specific types of technology and packaging. Testing revealed that the HELs were too large, heavy, expensive, and hazardous. Deuterium-fluoride systems discharge deadly waste gases, which was a primary fault of the MAD system originally intended for deployment; gases from the MAD were found dangerous to unprotected personnel in the immediate vicinity of its discharges. All HEL systems also created extreme heat and were technologically difficult to operate.

SEARCHING FOR LOW-ENERGY LASER WEAPONS

As noted above, the US Army’s medium-energy MTU laser program ended inconclusively in 1978, despite successful hard-kill engagements against drones and helicopters. Although discontinued, the MTU program demonstrated what could be achieved by lasers with energy less than that produced by very high-energy laser systems.

Certain foreign developments and activities prompted the United States to conclude that although low-energy lasers (LELs) were incapable of producing hard kills, the LELs could certainly be applied to achieve “soft kills.” Soft kills are successful attacks against a variety of essential enemy systems and components (eg, sensors; computer functions; software and memory; electrical integrity; command, control, and communications nodes; or biological functions) sufficient to cause system failure or degradation to the point of unreliability. For example, a LEL system might be used to inflict serious damage to the gunner’s aiming sights on an enemy tank, which, in turn, could effectively degrade the ability of the gunner to engage any distant target. An enemy tank that cannot attack or defend its tactical effective range is effectively “dead.”

The most desirable soft targets susceptible to degradation by LELs consist of all types of optics, including low-light and night vision equipment, electro-optic sensors, aircraft canopies and windscreens, and, quite incidentally, human eyes. It takes more energy to degrade all but the latter, so although low energy by definition, the safest LEL weapons require a “onetwo punch” involving different energy levels. Table 2-9 compares US LEL weapons and countermeasure systems described below.

Close-Combat Laser Assault Weapon

In the early 1980s, the US Army commenced development of a laser system known as the close-combat laser assault weapon (C-CLAW), nicknamed “Roadrunner.” The C-CLAW used modestly low-powered lasers to attack and neutralize electro-optic sights, night vision equipment, and helicopter canopies. The system employed the primary frequency of pulsed CO2 at 1 kW and both the primary and doubled frequencies of Nd:YAG. As a consequence of the latter, the system was quite capable of inflicting severe damage to enemy eyes, although these were not its intended targets. The goal was to build a 900-lb system to be mounted adjunct on an armored vehicle, but by 1983, the system had grown too heavy (3,000 lb) and was too expensive to meet specifications. As a result, the C-CLAW program was canceled.[36]

Stingray

Around the same time, the US Army contracted with Martin Marietta for a new system, the AN/VLQ- 7, or “Stingray,” an adjunct, bolt-on system designed for the M2 Bradley infantry fighting vehicle and other assault platforms. 8,36,42 The Stingray uses advanced technology and risk-assessment assumptions to locate, acquire, and target enemy optical systems in focal alignment with the system. In a target-rich environment where a single target must be selected among several, the assumption is made that the greatest threat to a given vehicle or platform is the one that has its gunnery or guidance optics trained on the vehicle or platform.

TABLE 2-9
US LOW-ENERGY LASER WEAPONS AND COUNTERMEASURE SYSTEMS, PLATFORMS, AND TARGETS

System

Known As

Platform

Targets

C-CLAW

Roadrunner

Armored vehicle

Optics

AN/VLQ-7

Stingray

Bradley

Optics

AN/ALQ-191

Cameo Bluejay

AH-64

Optics

AN/ALQ-179

Coronet Prince

Various airframes

Optics

Jaguar

Jaguar

M1A2 Abrams

Optics

Outrider

Outrider

HMMWV and LAV

Optics

C-CLAW: close-combat laser assault weapon

HMMWV: high-mobility multipurpose wheeled vehicle

LAV: light-armored vehicle

The Stingray employs a very low-power laser to scan the battlefield with energy pulses. When a focal plane is determined to be in alignment with the Stingray, indicating that it is acquiring or tracking the system, some of the Stingray’s emitted laser energy will be reflected back to and detected by the system at an intensity well above the background scatter. The principle is much the same as that responsible for the retroreflection of a flashlight or headlight beam in an animal’s eyes at night. The light reflected back is only visible when the animal (or optical system) is looking directly at the emitter.

When the Stingray detects optical reflection, the system centers its crosshairs on the point of intense reflectivity and fires a more powerful laser at the targeted optic. This more powerful laser degrades, damages, or destroys the enemy optical system. The Stingray then returns to its previous search mode to identify additional targets. The Stingray’s search laser is not hazardous to enemy eyes at tactical ranges, but its weapon laser is. 36,42,43 As a safety precaution, the Stingray is programmed with a library of common animal optical cross-sections of reflectivity and thus will not react to retroreflection from these animal eyes.

The Stingray has been extensively tested and produced in limited numbers. It was deployed during the Persian Gulf War but was not used because the receiving unit had neither trained with it nor integrated its tactical employment into its battle drills. The Stingray has since been mothballed and production canceled, but its effectiveness did not go unnoticed.

Cameo Bluejay

In 1987, a similar program was initiated to develop an airborne optical countermeasure system for AH-64 attack helicopters. Officially the AN/VLQ-191, more commonly known as Cameo Bluejay, this system applied some of the same assumptions and technologies as the Stingray 36,43 but incorporated growth requirements that could not yet be met. The Cameo Bluejay program was suspended in 1989 to await technology evolution.

Coronet Prince

Other, similar systems also exist (see Table 2-9). The Coronet Prince (AN/ALQ-179) is a US Air Force pod-mounted adjunct system similar to the Stingray in concept. The Coronet Prince is a LEL countermeasure system designed to locate, target, and neutralize enemy air defense systems dependent upon optical and electro-optical acquisition, tracking, or guidance. 36,43

Outrider

The Outrider is another Stingray derivative, this one developed by the Marine Corps. The Outrider can be mounted on a HMMWV, light-armored vehicle, or other high-mobility wheeled vehicle and can be used to augment reconnaissance forces. The Outrider could also be deployed with an armored spearhead force to protect the advancing armor by locating and degrading immediate optically guided or adjusted threats. 42,43

Jaguar

The Jaguar system began development in 1985 and passed validation testing in 1988. This system was designed for use as an adjunct antioptics system with the M1A2 Abrams tank. The Jaguar was known to use a laser, but that is all that can reliably be said of it. [36]

Other Attempts to Produce Weapons-Mounted Lasers for the Battlefield

Despite the many aforementioned examples of laser countermeasure and weapon systems, no one has yet managed to build the handheld laser ray gun envisioned by Frederick Schollhammer. Attempts have been made, however. When the US Army first expressed interest in acquiring a rifle-mounted laser weapon for the purpose of attacking sensors and vision, at least two companies answered the call, followed by a military response.

Dazer

Allied Corporation produced the Dazer, [43] a potentially tunable LEL, based on an Alexandrite analogue, with a frequency spread of 700 to 815 nm. The Dazer system was powered by a battery backpack and designed to attack sensitive sensors such as low-light television, night vision equipment, and human eyes. As its name implied, Dazer was designed to temporarily “dazzle” vision but not to produce permanent blindness.

Cobra

McDonnell Douglas produced a similar riflemounted system dubbed Cobra, based on a different frequency range and using different output energy. Cobra weapons were developed and tested in the 1980s but were never integrated into the US armed forces. 43-45

TABLE 2-10
US LOW-ENERGY RIFLE-MOUNTED LASER WEAPONS, DEVELOPMENT STATUS, AND TARGETS

System

Known As

Status

Targets

Dazer

Dazer

Prototype

Electro-optics and eyes

Cobra

Cobra

Prototype

Electro-optics and eyes

AN/PLQ-5

LCMS

Canceled

Electro-optics and eyes

LCMS: laser countermeasures system

Laser Countermeasures System

The Army initiated a new program to develop a human-portable laser countermeasures system (LCMS) from the ground up. Initially classified as the AN/PLQ-5, the LCMS was a rifle-mounted laser system that resembled the Cobra and employed three wavelengths. 43-45 In 1995, the LCMS program was restructured. Its weapon was removed in response to the Department of Defense prohibition on blinding lasers (1995).[46] US efforts to field a rifle-like “ray gun” are summarized in Table 2-10.

Nonweapon Low-Energy Lasers on the Modern Battlefield

Target Location and Observation System

Although the LCMS itself was canceled, a good deal of its technology investment was salvaged by transition to the man-packed target location and observation system (TLOS), designated AN/PLQ-8. TLOS used a gallium-aluminum-arsenide (GaAlAs) diode array that allowed individual soldiers to find threat optical and electro-optical surveillance devices and provide covert illumination for fire direction, improved night vision sighting, and landing zone marking. However, since TLOS emissions exceeded radiation protection exposure limits, the TLOS was not widely fielded. 43-47

Saber 203 Laser Illuminator

The US Air Force also developed a “dazzle” device, known as the Saber 203 Laser Illuminator.[43] This device uses a semiconductor laser fitted into an unmodified M-203 40-mm grenade launcher attached to a standard M-16 rifle. Saber 203 illuminates an opponent with harmless, low-power laser light to an effective range of 300 m, which impairs an adversary’s ability to fire a weapon or otherwise threaten friendly forces. Saber 203 can also be used as a laser designator and can counter night vision devices. In 1995, it was used successfully by US Marines in Somalia.[48]

LX-5 Laser Diode Illuminator

The US Air Force also developed the LX-5 Laser Diode Illuminator, which is a compact, lightweight system for illuminating the battlefield at night. The LX-5 operates in the near-infrared range and is used with night vision goggles. The system uses 230 W of power at 28 V and provides up to 9.5 W of illumination, adjustable from spot to floodlight size. Completely self-contained, the LX-5 can be operated by battery pack or platform electrical system. [49]

Pocket Laser Communicator

Among the most novel and innovative applications of laser technology is the US Air Force’s pocket laser communicator (PLC). This prototype is meant for secure communications between aircraft in formation but could be adapted for ground maneuver units when radio jamming is encountered. In 1978, laser line-of-sight transmissions of data up to 1 gigabit per second were demonstrated at White Sands Missile Range over a 12-mile distance. The PLC is a lightweight, compact laser device capable of transmitting and receiving secure voice line-of-sight communications without radio transmission. Its effective range is 0.6 miles, but this can be increased to as much as 1.2 miles by using a narrow beam.50,51

The PLC system consists of a transmitter, receiver, and headset. The transmitter contains a diode laser that operates at near-infrared wavelengths and does not interfere with night vision equipment. Additional wavelengths are also being investigated. The PLC’s transmitter is about the size of a miniature flashlight and can function as an infrared illuminator. A lens is used to vary beam size from a pinpoint to a floodlight. The receiver contains the electronics, battery, and infrared detector and is powered by a 9-V, rechargeable battery that allows 4 hours of operation. The receiver weighs about 8 oz and is roughly the size of a cassette tape. Two different headsets are available. One is a lightweight, adjustable model that covers one ear and has a small, adjustable microphone. The second is a combined earphone and microphone that is inserted into the ear and operates on the principle of bone conduction. 50,51

Rapid Optical Beam Steering

The rapid optical beam steering (ROBS) system is a one-of-a-kind laser radar system operating at White Sands Missile Range. ROBS utilizes a 0.5-m aperture optical system, two tunable 3- to 5-μm imaging cameras, and a CO^2 laser radar for range and Doppler measurements. The optical system is based on a roving fovea design, enabling signal target tracking over large angles at a high-track update rate and rapid retargeting among multiple targets. Although this is currently a singular system, it hints at what is possible. [52] A transportable ROBS system was under development in 2003.

TABLE 2-11
OTHER US LOW-ENERGY LASER DEVICES AND THEIR FUNCTIONAL OBJECTIVES

System

Function

Objectives

TLOS

Illuminator

Illumination, sighting, and marking

Saber 203

Illuminator

Riot and security police crowd control

LX-5

Illuminator

Surface illumination from air

PLC

Communicator

Secure line-of-sight voice

ROBS

Laser Radar

High-resolution target tracking

LNS/LINS

Navigation

Laser ring gyro and global positioning

CAINS

Navigation

Carrier aircraft LINS

LST

Target Tracker

Relates target location to self

CAINS: carrier aircraft inertial navigational system

LINS: laser inertial navigational system

LNS: laser navigation system

LST: laser spot tracker

PLC: pocket laser communicator

ROBS: rapid optical beam steering

TLOS: target location and observation system

Laser Navigation Systems

A host of laser navigation systems, laser inertial navigation systems, and laser inertial navigation attack systems have also been in use by the military for many years. These systems employ a three-axis ring laser gyroscope and laser inertial navigation system. Carrier aircraft use one of several generations of carrier aircraft inertial navigation systems.

Laser Spot Tracker

Numerous laser spot trackers are also in service. Normally aircraft associated, these devices lock onto the reflected energy from a laser-marked or designated target and define the direction of the target relative to itself. The pilot can then self-designate the target for an LGM, relay target coordinates, or select another type of precision or conventional munition for delivery to the target. Once the laser spot tracker achieves target lock, the operator who designated the target can cease designation activity and exit the area or designate another target. Table 2-11 presents a few of the many other uses to which low-energy lasers can be applied on the modern battlefield.

RETURNING TO HIGHER ENERGIES

Early efforts in the 1970s to develop HEL systems were quite successful in demonstrating that HELs could be used to destroy dynamic aerial targets. Although the technology demonstrator systems were large and heavy, their effectiveness was not lost on the military. By the mid-1990s, a multitude of technologies had matured to inspire yet another round of HEL development projects in the United States.

Nautilus

A US Army program known as Nautilus was launched as the first step toward fulfilling an April 1995 mission needs statement for the development of a tactical air defense system.[53] Nautilus was a demonstration program, which evolved into two concepts: (1) a static (immobile) system, the tactical high-energy laser (THEL) and (2) a mobile system, the mobile tactical high-energy laser (MTHEL).

Tactical High-Energy Laser

Nautilus used a fraction of the available energy from the MIRACL to test acquisition, pointing, and tracking equipment that would be mated to a scaleddown MIRACL and called the THEL. In February 1996, only 9 months after the program had begun, Nautilus successfully destroyed a short-range rocket in flight. Later that same year, the United States agreed to make THEL available to Israel and thus began a joint effort. 53,54

THEL underwent a series of successful tests, but packaging the THEL was no easy task. It had a large footprint and essentially was a permanent installation. The logical next step was to package the system components so they could be moved and set up whenever and wherever the situation demanded.

Mobile Tactical High-Energy Laser

Much has been written about the MTHEL. Concept renderings have been produced and widely publicized in a multivehicle configuration. In whatever breadboard or prototype configuration MTHEL was eventually tested, it performed 28 in-flight kills of Katyusha rockets and engaged and destroyed multiple artillery projectiles in flight.[55]

Technical details of the THEL and MTHEL have been kept as closely guarded secrets, despite much speculation. The fact that MIRACL was used in early tests suggests involvement of a deuterium-fluoride laser. It is probable that THEL and MTHEL are beneficiaries of the US Army’s investment in the multipurpose chemical laser program of the mid-1980s. These technologies were shared with Israel. However, THEL’s large footprint and MTHEL’s reported lack of ruggedness, coupled with a toxic and corrosive fuel and extreme heat evacuation, brought the programs to a close.

Airborne Laser

About the same time Nautilus was hailed a technical success, the US Air Force received $1.1 billion in funding to begin building the military airborne laser (ABL), designated officially as the YAL-1A (Boeing, Seattle, WA). ABL’s predecessor, the Airborne Laser Laboratory, had used a 400-kW CO_2 GDL in a militarized Boeing 707. ABL used a megawatt-class chemical oxygen-iodine laser in a militarized Boeing 747-400F. The ABL was designed to detect and destroy theater ballistic missiles in the powered boost phase of flight immediately after missile launch. Infrared, wide-field telescopes installed along the length of the aircraft’s fuselage would detect the missile plume from a loiter altitude of 40,000 feet at ranges up to several hundred kilometers. 56,57

The ABL’s pointing and tracking system would track the target missile, compute its launch location, and predict impact location. The turret at the nose of the aircraft would then swivel toward the target missile and a 1.5-m beam director inside the aircraft nose would focus the ABL beam onto the target missile. By heating a spot on the missile’s fuel tank or an arc around the missile’s circumference, the beam could then lock onto and destroy the missile near its launch area within seconds. However, unsolved technical problems, failure to meet range requirements, and budgetary reality finally caught up with the ABL, which was canceled in December 2011.[58]

Advanced Tactical Laser

In 2002, the Special Operations Command entered into a contract with Boeing to install an underbelly turret on a Lockheed C-130 Hercules to direct a 100 kW air-to-ground laser, which became officially known as the advanced tactical laser. A scaled-down chemical oxygen-iodine laser was produced, tested, and fitted into the aircraft. The turret was developed by L-3 Communications (New York, NY) and Brashear (Pittsburgh, PA); prototype testing began in 2007 and continued into 2009. Although the tests were favorable against 3 x 3-foot stationary targets and moving vehicles, the program has disappeared. Its disappearance is generally credited to a 2008 Air Force Scientific Advisory Board’s conclusion that the advanced tactical laser testbed was not operationally useful. By 2010, development and testing presumably ceased (no further advancements were cited in the open literature). 57,59,60

Aero-Optic Beam Controller

The airborne laser concept is not entirely dead. The Defense Advanced Research Projects Agency (DARPA, successor to ARPA) and the Air Force Research Laboratory are now pursuing another airborne laser project. Capitalizing on a breakthrough in aero-adaptive optics dubbed the aero-optic beam controller turret, the unusual approach is to perfect a protruding, 360° turret that can deliver a focused beam to enemy aircraft and missiles above, below, and behind the aircraft using high-energy lasers. Two major components (and a lot of minor ones) are still needed: (1) an airframe and (2) a laser. However, these component issues have not hampered aerooptic beam controller development. The decision to terminate the ABL has divorced the concept from the chemical oxygen-iodine laser, while concurrently freeing an aircraft defensive laser from the size and expense of a militarized and heavily modified Boeing 747-400 host. DARPA’s thinking is that there are plenty of other lighter, scalable, and cooler lasers to select from, and if the right laser does not exist today, it might exist tomorrow. [61]

High-Mobility Multipurpose Wheeled Vehicle Laser Ordnance Neutralization System

Technologically reliable and using considerably less energy than required for air defense is the HMMWV laser ordnance neutralization system, often called Zeus. Zeus’s initial development was by the Air Force as the mobile ordnance disrupter system, using a 0.3 kW Nd:YAG and 0.8 kW CO^2 laser fitted into an M113A2 armored personnel carrier. The program then transitioned to the Army, and a 0.5 kW laser was packaged on a HMMWV. In March 2003, the 0.5 kW Zeus was deployed to Afghanistan at the request of the vice chief of staff of the Army. During a 6-month period, it destroyed 200 ordnance items.

In early 2004, Zeus was upgraded to 1 kW, and later that year, the laser was replaced with a 2 kW Yb:glass, diode-pumped fiber laser weighing 2,000 lb less than its predecessor. In 2006, Zeus was deployed to Iraq, where it had mixed success because it often could not burn through materials hiding improvised explosive devices. The latest generation of Zeus uses a 10 kW solid-state heat capacity neodymium-doped glass disc laser. Zeus applies remote viewing of the doubled frequency of neodymium, which is visibly green, to point its otherwise invisible primary wavelength onto unexploded ordnance. The 10 kW laser then burns through the metal body of the munition and causes detonation from a distance of 200 or more meters. The Zeus program is now managed by the US Army Space and Missile Defense Command.62-64

High-Energy Laser Technology Demonstrator and Mobile Demonstrator

In 2007, Boeing was awarded a contract to begin development of a truck-mounted laser weapon system to counter rockets, artillery, and mortar rounds (C-RAM); unmanned aerial vehicles (UAVs); and cruise missiles. A prototype of the HEL technology demonstrator (TD), or HEL TD, was delivered exactly 4 years later at Redstone Arsenal, Alabama, and then underwent rigorous component testing and tweaking at the Army’s solid-state laser testbed experiment site at White Sands Missile Range. In the next phase of its development, the system was renamed the HEL mobile demonstrator (MD), or HEL MD. Currently using a 10 kW solid-state laser, HEL MD was initially envisioned to be boosted to 50 kW and eventually to 100 kW; these goals have been increased to 60 kW and 120 kW.

The Army intends to upgrade the system with Lockheed Martin’s 60 kW fiber laser. The HEL MD is completely self-sustaining on an eight-wheeled, heavy, expanded mobility tactical truck and is designed to be parked for stationary site defense; however, the HEL MD needs a target cue from a local or networked radar system to acquire a target. The 2015 demonstrator requires a driver and a system operator (gunner) to operate the system with a laptop computer and an X-Box (Microsoft, Redmond, WA) console. 65,66

The 100 kW milestone target has been achieved by Textron Defense Systems (Providence, RI) and Northrop-Grumman Corp (Falls Church, VA). In early 2010, under the Joint Technology Office’s Joint High-Power Solid-State Laser Program, each team demonstrated average power levels in excess of 100 kW under laboratory conditions. Textron announced its achievement on the same day the Army awarded Northrop Grumman a contract to install its laser at the solid-state laser testbed experiment site at the Army’s High-Energy Laser System Test Facility at White Sands, where the laser will be aligned with the THEL beam control system for performance demonstrations.

Northrop Grumman’s solid-state laser (SSL) also achieved a turn-on time of less than 1 second and attained 5 minutes of continuous operation with very good beam quality and efficiency. SSLs are important because they are pumped by electric diodes, not noxious or toxic chemical reactions fueled by tons of precursors, and create far less heat than chemical lasers. If a platform can generate the required electricity, it can fire its SSL laser. Therefore, it is assumed that the new requirement of 120 kW can be achieved. 67,68

Excalibur

DARPA is funding a 21-element optical phased array (OPA) that combines three identical 10-cm diameter clusters of seven tightly packed fiber lasers. The array allows each individual fiber to correct for atmospheric turbulence at levels comparable to larger, conventional optical solutions. Power efficiencies of 35% have been achieved in near-perfect beam quality with precise targeting at 6.4 km at kW levels thus far. Tests were conducted at several tens of meters (100–200 m) above ground level, where the density of Earth’s atmosphere can degrade laser beam quality and propagation. The goal is a 100 kW package 10 times lighter and more compact than previously tested, comparable laser systems. Cooling at the 100 kW level is still an obstacle, but DARPA assesses the OPA technology as extremely promising and will pursue it.[69]

High-Energy Liquid Laser Area Defense System

Meanwhile, General Atomics (GA) (San Diego, CA) has developed a third generation (Gen 3) tactical laser weapon module with a single laser oscillator producing a single beam with 75 kW output. The module was built under DARPA’s high-energy liquid laser area defense system (HELLADS) architecture, which requires a 150 kW laser that can be installed in a tactical aircraft for air-to-ground engagements, weighs less than 5 kg/kW, and has a volume of 3 cm^3. To meet HELLADS requirements, two Gen 3 laser oscillators can be coupled together to produce a single 150 kW beam and still beat all HELLADS size and weight requirements, or combine four to produce a 300 kW beam. The Gen 3 is powered by a compact lithium-ion battery that can be recharged by any mobile platform. The current module is sized for installation in GA’s Avenger unmanned aerial vehicle, but GA intends to place the Gen 3 in competition for multiple programs and program upgrades, including the HEL MD when it progresses to the 120 kW requirement. 70,71

Potential Shipboard Lasers

A shift in attention from chemical lasers to SSLs has reduced the size, weight, and complexity of systems, with rewards similar to those projected by DARPA in the airborne domain. For example, there is no longer any need for enormous stores of hazardous chemical fuels. SSLs require one fuel—electricity—which surface vessels can generate in abundance. Also, the problem of heat evacuation has potentially been reduced by orders of magnitude.

Three types of lasers are currently being developed for potential shipboard use: (1) fiber SSLs, (2) slab SSLs, and (3) free electron lasers. Fiber and slab SSLs are mature technologies that appear very promising. 57,72,73 Using these, the US Navy has been pursuing development of three systems: (1) the tactical laser system, (2) the laser weapon system, and (3) the maritime laser demonstration. All three systems have been tested against over-water surface and aerial threat-representative targets at various times since 2009.57,73

Tactical Laser System

The tactical laser system is a 10 kW laser developed under contract to be integrated into the MK 38 Mod 2 close-in antiaircraft or small surface vessel shipdefense machine gun system. The system is referred to as the MK 38 tactical laser system with an output power of 10 kW supplied by a Boeing SSL fiber laser. System integration is by BAE Systems, Farnborough, United Kingdom.73–75

Laser Weapon System

The AN/SEQ-3 (XN-1) Laser Weapon System (LaWS) is a 30 to 33 kW fiber optic SSL that integrates six 5.4 kW lasers into a converged beam-on-target at tactical ranges regarded as close (maximum range is classified). The system can use a stand-alone or Phalanx-integrated close-in weapon system (General Dynamics, West Falls Church, VA); is currently installed on the USS Ponce; and is serving in the Persian Gulf at the time of this writing. The captain of the USS Ponce received permission to use LaWS operationally if the situation warrants such engagement. The system is operated using a standard monitor and gaming control system. The LaWS is potentially scalable upward to about 100 kW, but this has not been demonstrated. Navy leadership has said the follow-on system, rated at 100 to 150 kW, will go to sea for demonstration trials by FY 2018. 57,69,73,76–79

Maritime Laser Demonstration

The Maritime Laser Demonstration (Northrop Grumman, Falls Church, VA) utilizes seven 15 kW slab SSLs that coherently create a single beam of about 105 kW. The Maritime Laser Demonstration is presumed scalable to 300 kW using current technologies.

Solid-State Laser Technology Maturation Program

The deployment, demonstration, and operational status of the Navy’s LaWS has resulted in its extended deployment in the Persian Gulf, where it drew the attention of Iran. In early July 2015, the USS Forrest Sherman (DDG-98) and its attached helicopter came under repeated laser targeting by an Iranian flagged merchant vessel. As a result of this and other laser incidents, Navy Secretary Ray Mabus concluded that the Navy should have a single group in charge of all directed energy to understand how each project met the Navy’s overall needs. The Navy’s SSL Technology Maturation (SSL TM) program was initiated to produce a 100 to 150 kW laser for at-sea testing in 2018, to provide increased effectiveness against small boats and UAVs. This is another program in which the GA Gen 3 laser module may be considered. 69,70,72,73

Ground-Based Air Defense Directed Energy Onthe- Move

Included in the programs the Navy secretary alluded to is the Navy’s pursuit of a C-RAM (now called C-RAMD to include drones) capability, secondary to anti-UAV and anticruise missile capability, on a land vehicle for the Marine Corps, but one quite unlike the Army’s HEL technology demonstrator or HEL MD. Whereas the Army’s HEL HD and HEL MD are stationary site defense systems when deployed, the Marines require a system that performs its mission while moving. The requirement is named groundbased air defense directed energy on-the-move (the unwieldy G-BAD DE OTM acronym is usually shortened to G-BAD).

The initial testbed will be installed on a HMMWV, but the final expeditionary HEL system is to be installed on the four-wheeled joint light tactical vehicle (JLTV) being built for the Army, Marine Corps, and Special Operations Command as a new vehicle and, where applicable, the eventual replacement for the HMMWV. Raytheon (Waltham, MA) has been contracted to deliver a fully integrated, short-range laser weapon system with a minimum power output of 25 kW. The laser weapon itself must not exceed 2,500 lb and must be able to fire at full power, cumulatively or continuously, for 2 minutes, followed by a 20-minute cool-down and recharge to 80% total capacity. The envisioned weapon system (completion expected in 2020) is not a one-vehicle system but will consist of the laser weapon vehicle, a volume-surveillance radar vehicle, and a fully integrated command, control, and communications element with target acquisition, tracking, and firecontrol capabilities. The latter two elements may be able to network to more than one laser weapon system, although this has not been publicly stated as a requirement. 63,77,80

TABLE 2-12
RECENT HIGHER-ENERGY LASER SYSTEM TYPES AND PURPOSES

System

Laser Type

Energy

Purpose

THEL

DF

HEL

Antimissile and antiartillery

MTHEL

DF

HEL

Antimissile and antiartillery

ABL

COIL

HEL

Antitheater ballistic missile

ATL

COIL

100-kW

Air-to-ground tactical support

ABC

To be determined [*]

To be determined [*]

Antimissile and antiaircraft

Zeus HLONS

Nd:Glass SSHC

10-kW

Unexploded ordnance

HEL TD/MD

Fiber SSL

10-kW

Counter rocket, artillery, and mortar

Excalibur

Fiber SSL

Classified

Aerial and surface

HELLADS

Classified

75-kW

Air-to-ground engagements

TLS

Fiber SSL

10-kW

Close-in ship defense

LaWS

Fiber SSL

33-kW

Close-in ship defense

MLD

Slab SSL

105-kW

Close-in ship defense

SSL TM

Fiber/Slab SSL

150-kW

Close-in ship defense

GBAD DE OTM

Fiber SSL

25-kW

C-RAM, UAV, and cruise missile

*The ABC is a 360° turret that can deliver a focused beam to enemy aircraft and missiles above, below, and behind the aircraft using highenergy lasers. Laser system type has not been determined.

ABC: aero-optic beam controller

ABL: airborne laser

ATL: advanced tactical laser

COIL: chemical oxygen-iodine laser

C-RAM: counter-rocket, artillery, mortar

DF: deuterium-fluoride

GBAD DE OTM: ground-based air defense directed-energy on-the-move

HEL MD: high-energy laser mobile demonstrator

HEL TD: high-energy laser technical demonstrator

HELLADS: high-energy liquid laser area defense system

HLONS: high-mobility multipurpose wheeled vehicle laser ordnance neutralization system

LaWS: laser weapon system

MLD: maritime laser demonstration

MTHEL: mobile tactical high-energy laser

Nd:Glass: neodymium glass

SSHC: solid-state heat capacity

SSL TM: solid-state laser technology maturation

THEL: tactical high-energy laser

TLS: tactical laser system

UAV: unmanned aerial vehicle

Raytheon’s contract award grew out of an earlier demonstration program, the laser area defense system (LADS), which used an Air Force Research Laboratory 20 kW IPG Photonics (Oxford, MA) fiber laser and a beam director mated to a Phalanx mount. The Naval Surface Warfare Center selected Kratos Defense & Security Solutions (San Diego, CA) to develop the LaWS. Raytheon’s 20 kW fiber SSL has grown to 25 kW for the G-BAD.[57]

Table 2-12 provides a succinct summary of recent higher energy laser programs. Serious HEL programs also exist for shipboard defense against surfaceskimming antiship missiles and ground-based antisatellite weapons. At present, these efforts exist only as research programs, but history has shown that such programs can lead to successful application. Indeed, the successes of early research are still obvious today in midenergy laser projects and systems.

SUMMARY

The invention of the laser was very quickly and successfully applied to military tasks involving line of sight from laser to target, including rangefinding, target illumination, marking, and designation. The latter evolved concurrently with the ability to place laser seekers on maneuverable munitions. These applications involved low-energy lasers. Weapons required higher energies.

America’s initial search for high-energy laser weapons embodied a willingness to try anything. Early quests were exploratory programs that solved important engineering problems concerning coupling, pointing, tracking, beam quality, and dynamic focusing, to name but a few. But the lasers themselves were large and somewhat fragile and posed problems associated with their excessive heat, dangerous gases, recovery time, and complex logistical requirements. Much was learned in the process.

Low-energy weapons can be described as blinders and dazzlers, both of which were designed to serve as countermeasures to optical systems. Blinders used a scanning laser to acquire on-axis optical or electro-optical targets and a more energetic laser to damage the optics. Dazzlers used a rifle-mounted low-energy laser to temporally disrupt sensors, optics, and eyes at tactical ranges; at close range, these lasers could cause perma-nent eye damage. These weapons were mothballed or discontinued due to a policy decision stemming from the United Nations Vienna Protocol IV of 1995.

As technologies matured, higher-energy lasers were again investigated, this time with an expectation of fielding a system. The first efforts were again too large, too complex, too dangerous, too expensive, or a combination thereof. Only at the lower end of high energy were successful systems deployed, due entirely to breakthrough advances in solid-state laser technologies.

The United States has not been alone in its efforts to develop lasers for use on the battlefield. The former Soviet Union (now Russia), France, Germany, the United Kingdom, and China are five of the nine or ten nations that have tried or succeeded in developing laser weapons. As far as is known, all have abandoned the search for a megawatt class of weaponry and, instead, have found promise in the revolution in SSLs, especially fiber SSLs.

Acknowledgment

Distribution A: Approved for public release; distribution unlimited. PA Case No.: TSRL-PA-2015-0119.

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80. Self-propelled laser systems. Surviving in the City website. Encyclopedia of Safety. http://survincity.com/2011/12/selfpropelled-laser-systems/. Published December 7, 2011. Accessed August 17, 2018.

Chapter 3

RELATING STRUCTURAL INSULT TO VISUAL FUNCTION: SELECTED ACCIDENT CASES

Victoria Tepe, PhD * Senior Science Advisor, The Geneva Foundation, 917 Pacific Avenue, Tacoma, Washington 98402 ; James Ness, PhD † Colonel, Medical Services Corps, US Army; Professor of Discipline and Program Director of Engineering Psychology, Department of Behavioral Sciences and Leadership, US Military Academy, 601 Cullum Road, West Point, New York 10996 ; and Bruce Stuck, ScD ‡ Formerly, Detachment Director; US Army Medical Research Detachment-Walter Reed Army Institute of Research, 7965 Dave Erwin Drive, Brooks City-Base, Texas 78235

INTRODUCTION

ASSESSING IN-VIVO RETINAL MORPHOLOGY

Confocal Scanning Laser Ophthalmoscopy

Optical Coherence Tomography

FUNCTIONAL METRICS AND STRUCTURAL CORRELATES

Assessing Visual Function along the Visual Pathway

Integrating Imaging With Visual Function

LASER ACCIDENT CASES

Case 1

Case 2

Case 3

Case 4

Case 5

REVIEW

SUMMARY

Adapted from: Zwick H, Ness JW, Belkin M, Stuck BE. In vivo diagnostics and metrics in the assessment of laser-induced retinal injury. In: Friedl KE, Santee WR, eds. Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine. In: Lenhart MK, ed. Textbooks of Military Medicine. Fort Detrick, MD: Borden Institute; 2012: 129–155.

INTRODUCTION

Laser-induced retinal injury is a function of both the nature of the laser exposure and the retina’s acute and long-term response to the exposure. Conventional classifications of laser-induced retinal damage are based on acute laser-induced central retinal injury[1] with little attention given to secondary functional abnormalities that manifest as the effects of acute damage diminish. However, laser eye injuries associated with military laser fire-control (including rangefinding, designation, and illumination) systems have made evident the importance of suprathreshold laser-induced injury, revealing significant consequences for visual function even when laser-induced retinal damage is not restricted to the central retina.[2] Specific consequences involve the development of intraretinal scar formation (IRSF), associated retinal traction, and retinal nerve fiber layer (RNFL) damage. These secondary sequelae extend concern well beyond the macular region and, therefore, require new ophthalmic and functional techniques to assess their development, progression, and long-term consequences for visual function to distinguish normal functioning retina from dysfunctional retina.

The US Army Medical Research and Development Command and US Army Materiel Command established the Joint Laser Safety Team in 1968. Its mission was to study the nature and extent of potentially hazardous laser radiation emitted by military systems. A founding member of the team was Dr Harry Zwick, who dedicated his life’s work to studying the relationship between laser exposure effects on the retina and the etiology of sequelae linked to changes in visual function. Together with the application of well-targeted functional assessment, advanced imaging techniques have enhanced the understanding of laser-induced retinal sequelae.[3] This chapter presents clinical evaluation of five military laser accident cases, representing a range of laser-induced retinal damage. These cases and evaluation techniques, first described by Zwick and his colleagues, were also featured in historical context to exemplify unique accomplishments and advances in the field of military quantitative physiology.[4] Each case underscores the complex relationship between structure and function and illustrates the importance of combining imaging techniques to precisely identify structural damage with well-targeted assessments to identify functional changes. These cases demonstrate that functional diagnostic tools should not be limited to examination of neural mechanisms that can be observed at the retina. As structural damage resolves, the processing of visual neural code along the visual pathway can lead to changes in visual function outcomes that are not immediately evident by observing the structural damage at the retina.

The next section of this chapter is an examination of imaging and visual techniques to assess retinal structure and visual function. Subsequent sections briefly explain how these techniques can be integrated to determine structural and functional relationships, as illustrated by each of the five presented accidental exposure cases included at the end of the chapter.

ASSESSING IN-VIVO RETINAL MORPHOLOGY

Confocal Scanning Laser Ophthalmoscopy

Confocal scanning laser ophthalmoscopy (CSLO) provides the capability for imaging the retina along its axial dimension, yielding image “slices” in eyes with relatively large focal lengths, from the anterior RNFL-dominated retinal surface posterior to the retinal vasculature.5-8 Figure 3-1 shows CSLO images for a nonhuman primate (NHP) (Figure 3-1 ,a and b) a garter snake (Figure 3-1 , c and d). The graph reflects the current state of the art in axial domain resolution (18 μm) for eyes with relatively large focal lengths (eg, NHPs). The art of the possible in axial resolution is demonstrated in the garter snake eye, whose focal length is relatively short. For the NHP, however, the range of confocal slices is greater than for the snake eye. The optical properties of the NHP eye permit an axial range from the RNFL (see Figure 3-1a) to the retinal vasculature (see Figure 3-1b). The optical properties of the garter snake eye permit, by comparison, a narrower range of axial separation, which is from the RNFL (see Figure 3-1c) to the photoreceptor layer (see Figure 3-1d). However, the optical properties of the snake eye yield finer resolution of retinal structures than those of the NHP eye.

This comparative CSLO work, imaging eyes of species with differing optical properties, reveals the definitive advantage of imaging retinal elements and blood flow in the small eye. The small eye model allows for assessing damage to relatively fine retinal structure and for observing the repair cascade over time. New wave front correction techniques utilize adaptive optics algorithms to correct for optical aberrations of the imaged eye, allowing for diffraction limited imaging in the “large” human eye. Confocal applications now allow observation of the photoreceptors and retinal pigmented epithelium in a human eye. These advances promise the detailing of morphological sequelae in the retina, from the RNFL to the retinal vasculature, to better understand and predict functional loss.

Figure 3-1. Comparison of range of confocal slice between rhesus monkey (a,b) and garter snake (c,d). Photographs: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Optical Coherence Tomography

Optical coherence tomography (OCT) images provide an in vivo cross-section of the retina. Images are rendered in false color to indicate retinal layers and respective structures. Figure 3-2a shows the path of the OCT scan that rendered the image shown in Figure 3-2b. Figure 3-2, a and b, shows the OCT-rendered image taken through the macular region from superior parafoveal retina into foveal retina and ending in inferior parafoveal retina. The thickness of the parafoveal retina is 250 microns; the foveal retina, 150 microns. These thicknesses correspond with histological retinal measurements and thus can be used to characterize the condition of the retina.

Figure 3-2. (a) Vertical scan through the fovea. (b) Optical coherence tomography image yields a full retinal thickness cross-section of scanned retina. Photographs: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

FUNCTIONAL METRICS AND STRUCTURAL CORRELATES

Assessing Visual Function Along the Visual Pathway

High spatial resolution vision (ie, visual acuity) (VA) is mediated by the central foveal region.[9] VA demands a higher-order neural integration and augmentation, resulting in a relatively robust visual function. It is, therefore, not surprising that foveal retinal damage must be extensive, with a significant degree of secondary damage, to result in significant loss in VA. Maximal visual spatial resolution, measured as VA, is mediated at the center of the fovea. It was originally thought that center foveal ganglion cells innervated the most central region of foveal photoreceptors in a ratio of 1 ganglion cell to 1 photoreceptor,[10] resulting in an off-axis acuity function with a characteristic peak at the fovea and sharp declines in acuity with distance from the foveal axis.[11]

However, work by Curcio has shown that the central foveal cones have a 2:1 ratio with retinal ganglion cells.12,13 When the 2:1 ratio is accounted for in the off-axis acuity function, it reveals a resulting small plateau of maximal acuity over the central foveal retinal space.[11] This structure-function relationship suggests that neural plasticity associated with central foveal cones may actually begin in the inner retina. At the inner retina, central foveal cone innervation with ganglion cells via Henle’s fibers proceed to striate cortical visual space where the foveola (≈150 μm) is represented in a magnification of 7:1. In healthy visual systems, acuity provides a general measure of visual function. In laser accident cases where damage is confined to local areas of the retina, VA is often insensitive to associated visual function changes because there is significant neural plasticity and redundancy associated with VA.

Figure 3-3. Farnsworth-Munsell (FM) 100 Hue test metrics for a human subject with normal color discrimination function (a), a human congenital color deficient subject showing a bipolar deutan axis with a significant second-order Fourier frequency component (b), and a human laser accident case (c) at 3 months postexposure showing a significant tritan monopolar error score and a highly significant first-order Fourier harmonic component. The axes of the FM 100 Hue test indicated in the center of the radial plots are B, blue; G, green; P, purple; R, red; and Y, yellow.
Illustrations: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Contrast sensitivity, on the other hand, measures the reciprocal of the minimal contrast required (sensitivity) for detection of visual stimuli across spatial (size) or temporal (target flickered on/off) frequencies. Stimuli are modulated sinusoidally across light and dark bands subtending a specific visual angle in the spatial domain and across on/off cycles in the temporal domain. The spatial contrast function yields a relatively lower-order assessment of retinal integrity (magno/parvocellular ganglion cell systems) because higher-order processing of spatial information tends not to compensate for anomalies at the retina.[14] Further, evaluation of temporal sensitivity is important to characterize visual function changes or loss after laser-induced eye injury. Contrast sensitivity of the macular retina (targeting the more transiently responding magnocellular system involved in directing gaze) should be compared to the more sustained responding, centrally dominated parvocellular system.[15] In sum, the forms of the spatial and temporal contrast sensitivity functions provide a complete picture of threshold sensitivity across target size to register detection and movement predominately at the level of the retina.

As with VA, traditional clinical color vision metrics such as the Farnsworth Munsell 100 Hue (FM 100 Hue) are of limited utility because of their inability to accurately measure individual cone system damage. They involve measurements along the color (hue) discrimination dimension, which is not a direct measure of individual cone viability but, rather, is a measure of the neural reorganization of cone input that takes place in the inner layers of the retina.

The FM 100 Hue presents hues along the entire cycle of the color wheel. Given that the colors and their discrimination scores represent a position in the cycle of hues, one can pattern the data using frequency domain time series models.[16] Figure 3-3 shows the FM 100 Hue polar plots and their corresponding frequency density plots for a person whose vision is within normal limits (Figure 3-3a), a person with a congenital color deficiency (Figure 3-3b), and a laser accident case (see Figure 3-3c ). The resultant frequency density plots from a Fourier transform reveal the content of the color vision error function along the color circle and quantify the relative contributions of the primary color deficit F1 and the primary deficit axis F2. F0 gives the average magnitude of error along the color circle. The remaining components are analogous to harmonics, suggestive of the magnitude of sequelae. Relatively symmetrical axis deficits are typical of congenital defects (see Figure 3-3b) with weak F1 contributions suggestive of a primary color deficit. In laser cases (see Figure 3-3c), significant F1 and F2 contributions exist. The F1 contribution suggests the extent of retinal alteration to cone types, and F2 suggests disruption of higher opponent processes.

Figure 3-4. Confocal scanning laser ophthalmoscopy (CSLO) imaging of visual function test target placement on a patient’s retina during measurement of contrast sensitivity. The schematic shows customized CSLO design, where Amp is amplifier, AOM is acousto-optic modulation, and Det is detector. PC is personal computer, and C is a Landolt C projected directly on the retina. Photographs and illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Figure 3-5. A normal eye movement map (c) acquired using a Stanford Research Institute (SRI) dual Purkinje eye-tracker (formerly, SRI International, Washington, DC; currently, Ward Technical Consulting, Jameson, Missouri) from a patient (a) who had reacquired normal fixation. The panel (b) shows the first and fourth Purkinje images, which are used to determine fixation to within 1 minute of arc and to differentiate eye rotation from head translation.
Photographs and illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

The FM 100 Hue presents a focal target of color and, as such, may be less sensitive to outer retinal photoreceptor assessment of exposure effects that present with minimal ophthalmoscopic evidence of structural damage, but with subjective awareness of visual dysfunction. Under these conditions, several metrics involving outer retinal assessment have demonstrated the effectiveness of spectral sensitivity measures for VA criteria. These permit measurements of spectral sensitivity functions that are made sensitive to parafoveal and foveal retina by manipulation of spatial resolution (acuity) criteria ,17,18 the development of color contrast grating techniques,[19] and the application of equal luminance color acuity charts.[20] The Rabin charts are especially notable in that they provide the capability to assess specific cone system functionality in the clinical environment. This capability could be applied to the current Aidman Vision Screener[21] with additional development and testing. The Screener was revised and now uses spectral Logmar acuity targets. Charts added to the Screener with and without neural opponent chromatic backgrounds may provide the capability of diagnosing laser exposure effects that present with minimal ophthalmoscopic evidence.

Integrating Imaging With Visual Function

Two separate techniques have been developed by US military medical researchers to assess the functionality of laser-damaged retinal sites. In the first technique, the CSLO raster pattern is modulated to provide a sufficient range of Landolt ring gap sizes (Figure 3-4). The technique is used to determine a contrast sensitivity function for local retinal areas. The operator can place the visual stimulus, via the CSLO raster, on areas of the retina that are of clinical interest and generate contrast sensitivity functions for those areas. In this way, the operator can interrogate morphologically anomalous regions suspected of laser-induced damage. This technique is particularly effective when the ophthalmoscopic evidence is equivocal, despite a visual complaint and suspected exposure.

A second technique utilizes normal fixation eye movement pattern technology[22] to evaluate individuals with laser-induced retinal damage. Such patterns have been shown to produce minimal visitation in retinal regions that are dysfunctional, thereby providing a “map” of functional and nonfunctional retina based on frequency of ocular motor visitation (Figure 3-5). Figure 3-5c shows the typical normal foveal fixation pattern. This pattern takes the general form of an ellipse, with the larger axis along the temporal/nasal extent, and typically spans an elliptical area of 150 x 100 microns. Deviations from this pattern are strongly associated with disruptions in the sensory system, which, in turn, disrupt the governing of the motor system directing eye movements.

LASER ACCIDENT CASES

The five laser retinal accident cases presented in this chapter all occurred in military settings and were all associated with laser-induced macular retinal hemorrhage. All cases were evaluated using techniques previously described. Four of the accidental exposures were induced by military laser rangefinders, and one was induced by a laser designator. Despite similarities in dose for the first four cases, lesion location was critical to outcome, but in ways not predicted by central versus peripheral convention. Case 5 was comparable to Case 4 in terms of lesion placement; this similarity highlights the importance of sensory-motor relationships, as well as the plasticity of the ocular sensory/motor system in reestablishing the visual system’s ability to resolve fine-resolution targets.

Case 1

Case 1 received multiple accidental exposures to the right eye (OD) from an AN/GVS-5 laser rangefinder with an operating wavelength of 1064 nm at an energy output at the aperture of 15 mJ/pulse. The rangefinder was held at arm’s length from the eye and delivered several pulses with an estimated total intraocular energy (TIE) of 2.0 mJ/pulse, which resulted in four retinal lesions, two of which produced vitreous hemorrhages. The TIE is the total energy incident on the cornea that can be transmitted through the pupil and can be focused on the retina. The TIE is not corrected for absorption and scatter through the outer ocular media. These two hemorrhagic exposures occurred nasal and temporal to the macula and a bridging scar though the foveal region was evident by 5 days postexposure. 23,24 Figure 3-6 shows the resulting intraretinal scar at 18 months postexposure.

Figure 3-6. Case 1: Multiple exposures about the fovea and intraretinal scar formation (IRSF) between two of these lesion sites. Retinal traction extending from the IRSF is evident well beyond the macula.
Photograph: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Measurement of VA in the OD at 24 hours postexposure was 20/400, improving to 20/200 at 3 months postexposure. Measurements of VA for this case, made over a subsequent 2-year postexposure period, remained unchanged at 20/200 (OD) and in the unexposed eye at 20/20 ocular sinister (OS). Spatial and temporal contrast sensitivity measured at 6 months postexposure, using the CSLO technique already described, showed both high and low spatial frequency deficits. Figure 3-7 shows the maximum difference in spatial (stationary) and temporal (dynamic) contrast sensitivity between the OS and the OD. The spatial contrast sensitivity function shows the largest difference at approximately 4 cycles/degree, with the peak of the normal function at 6 cycles/degree. Furthermore, suppression for targets > 4 cycles/degree is greater than for targets < 4 cycles/ degree. This indicates that there is significant disruption to both magnocellular and parvocellular systems, with the magnocellular system disruption making a larger contribution to the overall visual function deficit.

Figure 3-7. Measurements of stationary and dynamic contrast sensitivity (1-Hz luminance modulation) reveal maximum deficits in contrast sensitivity at 4 cycles/degree “Stationary” and 1 cycle/degree “Dynamic.”
OD: right eye
OS: left eye
Illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

The temporal contrast sensitivity function confirms the larger contribution of the magnocellular system disruption to the overall visual function deficit. The temporal contrast sensitivity function (see Figure 3-7, Dynamic) shows that for sinusoidal targets luminance modulated at 1 Hz, maximal deficit is at 1 cycle/degree. Under these measurement conditions, the typical temporal contrast sensitivity function peaks at 4 cycles/ degree.[25] The fact that the largest deficit for spatial contrast was in the low- to mid-spatial frequency (4 cycles/ degree) and that the temporal contrast sensitivity peak is shifted to the higher spatial frequencies (deficit is smallest at 11 cycles/degree) further confirms magnocellular system disruption. Note in the fundus photograph (see Figure 3-6) the extensive parafoveal traction, a secondary sequela from the tension caused by the contracting intraretinal scar. The traction may be contributing to the magnocellular system deficit since the magnocellular pathway arises principally from the parafovea.

Color deficits were assessed in the exposed eye (OD) with the FM 100 Hue test. Tests were performed 6 months subsequent to exposure and were given with and without fixation restrictions. Figure 3-8 shows the resolving of the color deficit from a large, average, relatively undifferentiated deficit weighted toward the blue to an average deficit that is within normal limits but, nonetheless, shows anomalies in the blue, green, and purple. Of note are the distinct clusters of frequency components for the restricted fixation conditions measure. The frequency component distribution shows a very large overall deficit (f0) and a strong unipolar component (f1), which is a strong blue weighting. The cluster of frequency components beyond f6 are indicative of the lack of a well-formed system to govern color discrimination, most likely the result of an inability to reliably fixate areas of the retina structurally intact enough to make a discrimination due to test-imposed fixation restrictions. When fixation restrictions were relaxed, the deficit resolved to a more well-formed frequency component distribution showing an overall deficit at f0, a weighting to the blue (f1) with differentiated green and purple contributing anomalies, and a nominal red pole (f4).

The persistence of the blue (S cone) anomaly across conditions is consistent with paramacular injury and magnocellular system disruption.[26] That is because medium and long wavelength-sensitive cones are concentrated almost exclusively in the fovea whereas short wavelength-sensitive cones are principally distributed parafoveally, and signals from these cones are carried by the magnocellular pathway. Thus, parafoveal damage impacts the chromatic system principally by disrupting the perception of blue and related hues. The color discrimination results are confirmatory of the contrast sensitivity results, indicating a strong magnocellular system disruption. Further, the fundus showed only paramacular lesions with the insult to the fovea due to the intrusion of an intraretinal scar. Visual field analysis did show functional central retina in the vicinity of the scar. Thus, when fixation restrictions for the FM 100 were relaxed, color discrimination improved to within normal limits, albeit with anomalies evident in the blue and related hues.

Figure 3-8. Farnsworth-Munsell (FM) 100 Hue scores for affected right eye (OD) show a shift from (a) a large fundamental indicating a large average error, with a strong first harmonic that is indicated in the graph as a strong blue deficit. This di-minishes (b), when fixation restrictions are relaxed, to an average error within normal limits although with significant first and fourth harmonic components. The axes of the FM 100 Hue test indicated in the center of the radial plots are B, blue; G, green; P, purple; R, red; and Y, yellow.
Illustrations: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Case 2

Case 2 received bilateral accidental exposures from an AN/GVS-5 laser rangefinder with an operating Q-switched wavelength of 1064 nm with an energy output at the aperture of 15 mJ/pulse. The rangefinder was held about 0.6 m from the eyes and delivered at least two pulses with an estimated TIE of 1.0 mJ/pulse, which resulted in bilateral retinal lesions that produced macular holes. The focus of this case is the sequela observed in the OD over a 2-year period.

The OD received a paramacular exposure temporal to the optic disk and nasal to the macula in the papillomacular bundle (PMB). The lesion produced a vitreous hemorrhage in this region that took about 3 weeks postexposure to resolve. The lesion itself eventually developed into a full-thickness paramacular hole. Immediately following exposure, VA was 20/50 (OD); at 3 weeks postexposure, VA was 20/70 (OD); and by 13 months postexposure, VA deteriorated to 20/800 (OD) postsurgery. At 13 months, contrast sensitivity was not measurable beyond 6 cycles/degree.

Figure 3-9 shows the CSLO image of the paramacular hole and the CSLO image of the PMB–RNFL defect (Figure 3-9a) and an OCT scan through the center of the paramacular hole revealing complete loss of sensory retina (Figure 3-9b). The dotted outline shows the extent of retinal nerve fiber layer pruning in the region of the PMB showing a wedge defect. This particular defect was first described by Frische et al.[27] Zwick and colleagues later modeled the phenomenon in NHP to investigate the functional implications of the laser-induced retinal neural pruning that was shown to progress with Wallerian degeneration.[28]

Figure 3-9c shows the fixation eye movement patterns at 18 months after surgery to remove epiretinal scar tissue that was producing traction and inducing retinal detachment. The map of functional retina rendered by this technique allows for the assessment of functional retina from which to interpret the images of structural damage. Normal fixation eye movements map in an elliptical pattern, with the majority of visitation times within the fovea. The average extent of the nasal/temporal axis of the elliptical pattern is ≈150 μm and that of the superior/inferior axis ≈100 μm.[29] Comparatively, the fixation eye movement pattern shown in Figure 3-9c suggests a lack of strong sensory input to govern the eye movements. Although there appears some visitation in the area of the fovea, there is also a significant amount of searching around the functional boundary of the macular hole. Together, this suggests that the remaining sensory retina produces insufficient signal quality to govern target fixation. Note that the irregular shape of the boundary of functional retina and that the rendered map does not mirror exactly the size and shape of the hole. The functional map is dependent not only on the integrity of the neural elements, but also on communication between the sensory and motor systems. Thus, disruption in pathways will affect the functional map such that areas not visited in the eye movement map may appear relatively well formed in the structural imagery. The Wallerian degeneration of nerve fiber in the PMB can account for the differences between structural and functional imagery. Nonetheless, without the structural image showing nerve fiber track pruning, the functional map cannot be differentially interpreted

Figure 3-9. (a) Confocal scanning laser ophthalmoscopy image of a right eye (OD) paramacular hole taken after stabilization surgery at 18 months postexposure. The dashed outline shows the retinal nerve fiber layer defect. (b) Optical coherence tomography scan through this hole (left white arrow) shows loss of sensory retina, leaving retinal pigmented epithelium and choroidal vasculature. (c) Fixation eye movement map obtained for the OD postsurgery. Map shows a dysfunctional fixation pattern with fixation at any one location minimal. The grid is ≈400 × 400 μm; one grid square is ≈9 μm.
Photographs and illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Figure 3-10. (a) Farnsworth-Munsell (FM) 100 Hue scores show no trends in total error scores. The frequency composition shows a transition in the distribution from (b) first harmonic contribution suggestive of a monopolar blue weighted deficit at 4 weeks postexposure to (c) a large f0 undifferentiated error at 192 weeks, suggesting an inability to discriminate color. The axes of the FM 100 Hue test indicated in the center of the radial plots are B, blue; G, green; P, purple; R, red; and Y, yellow.
BY: blue-yellow
RG: red-green
SQRT: square root
wks: weeks
Illustrations: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Figure 3-10 shows FM 100 Hue color discrimination error scores over 192 days postexposure. There appears to be no trend in total and partial error scores, with all scores well beyond normal limits. The long-term absence of any significant harmonic frequency component indicates that the trichromatic receptor components have been equally affected (Figure 3-10c). This is most likely caused by the Wallerian neuronal degeneration observed in the PMB. These fibers transmit trichromatic cone output from the third-order neuron to higher brain regions that require this input for color discrimination.

Case 3

Case 3 received unilateral (OD) accidental exposure to a 1064 nm beam emitted by a battery-operated Nd:YAG laser rangefinder. The exit port of the rangefinder was held approximately 0.6 m from the eye. The eye received an estimated TIE of 2.5 to 3.0 mJ/pulse, which produced vitreal hemorrhage.[30] By 3 weeks postexposure, the vitreous hemorrhage had cleared. A fullthickness 100-μm diameter macular hole with evidence of traction was diagnosed at the 3-month postexposure fundus examination (Figure 3-11, a and b). An OCT image taken through the center of the lesion site (Figure 3-11c) revealed total loss of sensory retina in the macula hole and a significant choroidal extension beneath the fovea. Reflectance in the CSLO indocyanine green (ICG) image indicated vascular blockage (Figure 3-11d). ICG is a clinical imaging technique using dye to evaluate blood flow in the retina. At 12 months, CSLO images revealed a reduction in hole size and the disappearance of traction bands; changes in the choroidal entity appeared weaker in reflectance, but broader in extent (Figure 3-12a). The OCT showed evidence of tissue bridging the gap of the macular hole consistent with spontaneous reduction of the macular hole size (Figure 3-12b).

Figure 3-11. A full-thickness fundus photograph of the macular hole at 3 months postexposure (a), a corresponding confocal scanning laser ophthalmoscopy (CSLO) image showing evidence of traction (b), an optical coherence tomography vertical scan through the center of the macular hole (c), and a CSLO indocyanine green image with reflections indicating macula choroidal vasculature blockage (d).
Photographs: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Figure 3-12. Macula hole diameter is reduced in size at about 12 months postexposure compared to 3 months postexposure (see Figure 3-11). (a) Confocal scanning laser ophthalmoscopy reveals an absence of retinal traction about the macular hole. Changes in choroidal entity appear weaker in reflectance at 12 months, but broader in extent. (b) Optical coherence tomography shows tissue bridging the gap of the macular hole.
Photographs: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

VA changed concomitantly with evidence of improvement in macular integrity. Upon presentation, VA was 20/150 (OD) and 20/20 (OS). At 3 weeks, VA improved to 20/60 (OD), then declined to 20/70 at 3 months, and improved to 20/40 by 12 months postexposure. Color discrimination FM 100 Hue functions were within normal limits at 12 months with no further change observed at 24 months postexposure. Contrast sensitivity measured using the CSLO technique showed a long-term deficit (OD) in sensitivity for high spatial frequency targets (Figure 3-13).

Fixation eye-movement patterns at 3 months were dominated by a vertical search pattern (Figure 3-14a). The vertical pattern spans an area greater than that of the foveal region. This pattern indicates a search for sensory retina to attract fixation eye movements. At 3 months postexposure, focal areas of the functional sensory retina were unable to produce a strong enough signal to govern eye movements. At 12 months postexposure, the fixation eye movements showed an attraction focus and the development of a significant horizontal component. This component spans the typical ≈150 μm extent. However, the persistence of the vertical component suggests the signal attracting eye movement visitations is weak (Figure 3-14b).

Figure 3-13. Contrast sensitivity, measured using the confocal scanning laser ophthalmoscopy technique, showed long-term right eye (OD) deficit in sensitivity for high spatial frequency visual stimuli. Note the significant suppression in OD sensitivity from 6–30 cycles/degree.
OS: left eye
Illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Case 4

Case 4 received bilateral accidental exposures from an AN/GVS-5 laser rangefinder with an operating Qswitched wavelength of 1064 nm, producing an energy output at the aperture of 15 mJ/pulse. The rangefinder was held about 0.6m from the eyes and delivered at least two pulses with an estimated TIE of 1.0 mJ/pulse, which resulted in bilateral retinal lesions that produced macular holes. The focus of this case is on the sequelae observed in the OS over a 2-year period.[31]

The OS suffered an acute macular vitreous hemorrhage with long-term damage restricted to the fovea. Figure 3-15 shows a fundus (Figure 3-15a) and CSLO image (Figure 3-15b), demonstrating a discontinuity through the center of the fovea. Figure 3-15c shows an OCT image revealing the extent of a small, flat macular hole through the center of the fovea.

Figure 3-14. Fixation eye movements changed significantly from 3 (a) to 12 (b) months postexposure. At 3 months, an atypical vertical movement was observed that spanned over a 300-μm vertical range with little horizontal movement. At 12 months, fixation eye movements show a definite focus and a more typical horizontal extent (b).
(Scale a: 1 box = 6 μm; Scale b: 1 box = 10 μm)
Illustrations: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Figure 3-15. The fundus photograph (a) shows a central anomaly in the macular area (note light spot in the center of the typical darker central macular area). The confocal scanning laser ophthalmoscopy image shows a small foveal break in the retina and the track of the optical coherence tomography (OCT) scan across the break (b). The OCT image shows a small, flat central hole (c).
Photographs: Courtesy of the Laser Laboratory, with the technical assistance of Andre’ Akers.

VA at 48 hours postexposure was 20/200; by 8 days postexposure, VA improved to 20/25; and by 3 years postexposure, VA improved to 20/15. Color discrimination measured with the FM100 Hue test at 3 years postexposure demonstrated error scores within normal limits, with no significant axis or harmonic components.

Landolt ring contrast sensitivity measured under CSLO retinal observation confirmed that foveal placement was not used in discriminating small Landolt ring targets normally requiring foveal utilization. Instead, such targets were consistently placed superior and slightly temporal to the fovea. The contrast sensitivity function peaked at the typical 6 cycles/degree, and sensitivity across spatial frequency was within normal limits although at the lower limit (Figure 3-16).

At 4 years postinjury, VA was recorded at 20/15. Figure 3-17 shows the fixation eye-movement patterns at this time, the focus of which is consistent with that of the earlier CSLO observation (Figure 3-16a). The focus of the fixation eye movements tracks along the superior boundary of the foveal hole. The map of the eye movements about a focus superior and slightly temporal to the anatomical fovea shows a pattern typical of healthy eyes, indicating the formation of a psuedofovea.[32] The eye movement map also shows visitations outlining the extent of nonfunctional fovea, which corresponds to the size and shape of the hole identified in the fundus examination. This case provides functional support to Curcio’s structural findings12,13 and suggests that the VA function peak corresponding to the foveola (≈150 μm) is most likely a result of its visual cortex representation, which is magnified at a ratio of 7:1.[11]

Figure 3-16. confocal scanning laser ophthalmoscopy image shows contrast sensitivity test for the preferred retinal location (PRL) for resolving fine-resolution targets (a). The placement of fine-resolution targets is superior and temporal to the fovea. Contrast sensitivity at 912 days postexposure shows a contrast sensitivity function within—although at the lower limit of normal (b).
OS: left eye
Photograph and illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Case 5

Case 5 received bilateral accidental exposures from a Q-switched Nd:YAG laser designator, which emitted 10 laser pulses/second at a wavelength of 1064 nm. The exit beam diameter (10 cm) was large enough to permit a simultaneous bilateral exposure. Eye position at exposure was a few centimeters from the exit aperture with a received TIE estimated at 315 μJ/pulse. The exposure induced confined bilateral macular hemorrhages. The hemorrhage was slightly larger in the OD and centered on the fovea. The patient was treated within 6 hours postexposure with a moderate steroid dose, and a taper continued for a postexposure period of 2 weeks.[33] This case describes sequelae in the OD.

Figure 3-18 shows the laser designator and a reconstruction of the bilateral exposure scenario. At 4 days postexposure, OCT imaging showed a fovea with a break in retinal pigment epithelium (RPE) integrity beneath the fovea. At 1 month, the RPE break resolved to minimal foveal thickness. Foveal thickness at 4 months showed significant thickening close to the normal foveal thickness and was accompanied by a return of normal color discrimination, VA, and contrast sensitivity within this same 4-month time frame. In the third column of images, corresponding CSLO images are shown, revealing a reduction in the lesion size from 2 days to 1 month and the disappearance of an ophthalmoscopically visible lesion by 12 months postexposure.[34]

Figure 3-17. Fixation eye movements recorded at 4 years postexposure for fine-resolution targets. The pattern confirms the earlier finding with confocal scanning laser ophthalmoscopy showing, in relation to the fovea, a superior/ temporal fixation locus. Other than the shift in locus and visitation along the boundary of the hole, the fixation pattern is typical of those seen in healthy eyes.
Illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Figure 3-18. The large exit port of the designator makes it possible for bilateral exposure at ocular distances of a few centimeters (a). Optical coherence tomography (b) images show the progression of right eye wound healing from 4 days through 4 months and confocal scanning laser ophthalmoscopy (c) images from 2 days through 12 months postexposure.
Photographs: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

VA at 3 hours postexposure was 20/50 (OD) and diminished to 20/200 (OD) by 2 days postexposure. VA recovered to normal levels within 3 months postexposure. Color discrimination was nominally beyond normal limits at 2 days postexposure. At 1 month postexposure, color discrimination functions were within normal limits, as measured with the FM 100 Hue examination.[34] Landolt ring contrast sensitivity functions measured under CSLO visualization at 4 days postexposure showed uniform suppression, with peak sensitivity shifted from the typical 6 cycles/degree mid-spatial frequency peak to a peak at 1 cycle/degree. The peak shift to lower spatial frequencies indicates a disruption in foveal function. At 9 months, contrast sensitivity functions were within normal limits and corresponded to a shift in preferred retinal location (PRL) from fixation superior and slightly temporal to the fovea to within the fovea (Figure 3-19a). Figure 3-19b shows that fixation eye movements at 9 months are consistent with typical, human-fixation eye-movement patterns.[22] The map shows no functional disruption within the foveal region.

REVIEW

Five laser injury cases involving retinal hemorrhage were evaluated with ophthalmic techniques that related structural insult to visual function. The cases’ results indicate the complexity of the structure-function relationship and the scope of visual system resilience (Table 3-1). Despite similarities in dose, placement of the lesion on the retina contributed significantly to visual function outcome, but not in a classically expected manner. For example, Cases 4 and 5 demonstrate that foveal damage does not equate to diminished VA in that foveal-like function can be recovered through a shift in PRL from the fovea to a position superior and slightly temporal to the fovea.[35]

Figure 3-19. The confocal scanning laser ophthalmoscopy image shows the shift in preferred retinal location (PRL) for placing fine-resolution targets (<10 cycles/degree) from a focus superior/temporal to the fovea to a focus within the fovea (a). With the PRL return to the fovea, the fixation eye movement map (b) shows a typical pattern, with no indication of residual functional damage.
Photograph and illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

TABLE 3-1
SUMMARY OF CASE FINDINGS

Dose TIE mJ

Injury Initial

Hemorrhage

Visual Acuity Initial

Visual Acuity Resultant

Contrast Sensitivity Resultant

Color Discrimination Resultant

Ocular Motor

Resultant Secondary Sequelae

Case 1

2.8

4 Paramacular retinal lesions; 2 producing macular holes

2 Paramacular holes produced vitreous hemorrhage

20/400

20/400

Significant overall suppression peak shift to 10 c/d

Overall disruption, blue axis most prominent

Some functional central retina in vicinity of scar

Retinal scar between paramacular holes bridging macular and associated traction

Case 2

1.0

Full-thickness paramacular hole; temporal to optic disc, nasal to macular in PMB

Vitreous hemorrhage

20/50

20/800

Not measurable beyond 6 c/d

Uniform suppression with no dominant axis

Atypical vertical scan pattern with no dominate retinal site attracting eye movement

Considerable nerve fiber degeneration in PMB, with evidence of Wallerian degeneration to the optic nerve

Case 3

2.5–3.0

Full-thickness 100 μm diameter center macular hole

Vitreous hemorrhage

20/150

20/40

Significant suppression in sensitivity OD from 6 to 30 c/d

WNL

Significant typical horizontal scan with persistence of atypical vertical component

Reduction in hole size and disappearance of traction bands

Case 4

1.0

Small, flat macular hole through the center of the fovea

Vitreous hemorrhage

20/200

20/15

Contrast sensitivity function within, although at the limit of normal

WNL

Superior/Temporal to fovea fixation with typical movement pattern

No change in initial injury

Case 5

0.315

Break in RPE integrity beneath the fovea

Confined macular hemorrhage centered in fovea

20/50 OD at 3 hours and 20/200 at 2 days post

20/15 OU at 10 months and 20/25 OU at 14 months, OD not recorded

Recovered from uniform suppression with peak sensitivity; shifted to 1 c/d to a function within normal limits

WNL

PRL shift from superior/temporal back to fovea

Treated with steroid; significant thickening close to the normal fovea thickness

c/d = cycles per degree

mJ – millijoule

OD = right eye

OU = both eyes

PMB = papillomacular bundle

PRL = preferred retinal location

RPE = retinal pigmented epithelial layer

TIE = total intraocular energy

μm = micrometers

WNL = within normal limits

Adapted from Zwick H, Ness JW, Belkin M, Stuck BE. In vivo diagnostics and metrics in the assessment of laser-induced retinal injury. In: Friedl KE, Santee WR, eds. Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine. In: Lenhart, MK, ed. Textbooks of Military Medicine. Falls Church, VA: Department of the Army, Office of The Surgeon General, Borden Institute; 2012: 129–155.

Structural damage was detailed through the utilization of CSLO and OCT imaging techniques that demonstrated the depth of IRSF and RNFL-PMB damage in vivo, confirming previous NHP histological studies of these secondary damage processes.[30] CSLO imaging demonstrated that retinal traction exists above the RNFL and often may extend into the vitreous, possibly altering normal photoreceptor orientation, which has been demonstrated to cause reduction in visual sensitivity.[36]

Spatial visual function metrics of VA and contrast sensitivity are seriously affected by retinal traction and IRSF. These damage mechanisms alter receptor orientation of large retinal areas, reduce retinal thickness, and induce neural disorganization in the process of their formation. Case 1 showed the most serious example of traction and IRSF effects on spatial vision metrics, affecting both stationary and dynamic measures of contrast sensitivity associated with the global effects of IRSF and traction. Failure of acuity to recover over the 2-year period is also significant, as acuity is highly “protected” by cortical magnification of the fovea (relative to the parafoveal region) and by findings that indicate neural receptor field plasticity or expansion that provides added neural redundancy for reduced foveal retinal neural output.[37]

The mechanism that prevents neural plasticity in Case 2 is associated with the interruption in the PMB region of the RNFL caused by induction of the paramacular hole that formed following resolution of vitreous hemorrhage. Evidence that the fovea was still functional, but could not transmit its spatial and chromatic neural output to higher-order visual brain systems was supported by fixation eye movement maps demonstrating foveal visitation capability. While this lesion was parafoveal, and ordinarily such lesions are given less importance than more central retinal lesions, this particular lesion interrupted the major neural pathway carrying foveal neural retinal code to higher-order brain mechanisms.

In the absence of secondary damage mechanisms previously described, spatial and chromatic vision may recover over a time span of about 3 to 6 months, as seen in Cases 4 and 5. The surprising release of traction in Case 3 and the ensuing full recovery of color discrimination and near complete recovery of VA was unexpected, but documented by the capability of CSLO imaging to capture anterior retinal pathology. Nevertheless, while acuity continued to recover, presumably via cortical neural compensation for reduced foveal receptor output, contrast sensitivity remained constant, showing a consistent deficit in the high spatial frequencies. This is indicative of the strong association between contrast sensitivity and lower-order retinal ganglion cell systems.[38] On the other hand, the rapid recovery of color discrimination to normal levels at 12 months may relate to the fact that color vision photoreceptor systems are distributed over broader regions within the fovea, where photoreceptor to ganglion cell ratios are larger than those in the central fovea.[39]

A critical factor in understanding the mechanism of neural plasticity in Case 4 is the observation made with the OCT that showed a “break” in the central foveal region. This break may have caused some degree of failure in normal foveal function, resulting in a degree of dysfunction in spatial vision and PRL replacement neural mechanisms. Evidence for this hypothesis was observed in both the development of a new PRL superior and slightly temporal to the fovea and in the fixation eye movements for fine-resolution targets as mapped with the dual Purkinje eye tracker. The latter confirmed the establishment of a new PRL and further showed optical accommodation with this shift of about 0.25 diopters, sufficient to produce a baseline acceptable point spread function.[29]

Case 5 initially showed a PRL superior and slightly temporal to the fovea, identical to that of Case 4. However, during this 3- to 6-month postexposure period, other visual functions—including VA and sine wave contrast sensitivity—were still recovering. During this recovery period, CSLO Landolt ring contrast sensitivity showed frequent, but not sustained, placement of Landolt ring contrast sensitivity targets within the fovea, prognostic of the recovery of foveal function. This function did recover between 6 and 9 months postexposure. Color discrimination, measured with the FM 100 Hue examination, had recovered in both eyes within the first month postexposure, indicating that cone mechanisms had recovered or were sufficiently active to minimize possible residual selective cone dysfunction. This is most likely due to a greater inherent redundancy of the cone-to-ganglion cell ratio in the foveal regions and further magnification of this relationship to the visual cortex.

At nonhemorrhagic levels, metrics that evaluate outer retinal cone system functionality appear to be more sensitive than those that rely on achromatic metrics of VA and not on contrast sensitivity.[17] When accidental exposure is repeated by malfunction[19] or by intentional exposure,[40] functional loss in spatial retinal-based metrics may become permanent, although high-contrast achromatic VA may still be compensated by static or dynamic visual cortex plasticity. Of special note is the color contrast examination developed by Arden et al that uses both color opponency and color contrast.[19] These metrics interrogate both retinal ganglion cells as well as higher-order visual processing that render contrast, color opponency, and color contrast information. While this test represents a major advance in utilizing various levels of neural code arising from the retina, this test could also be improved to track the neural code arising from the fovea by utilizing a broader range of spatial frequencies in evaluation of retinal systems associated with central fovea visual function.[18]

Finally, the animal behavioral and morphological evaluations of outer retinal cone function require some discussion. Sperling et al demonstrated the photic toxicity of short-wavelength light to S cone photoreceptors and that such exposures occurred in the range of 5 log_10 Td.[41] This brightness level is slightly higher than comfortable brightness, but not considered a thermal threat. However, prolonged exposure to such levels of highly monochromatic blue light did produce permanent deficits in S cone incremental spectral sensitivity, indicating vulnerability of either the S cone or some other component in the retina sensitive to such visible radiation.[42]

Reidenbach et al reported a persistent afterimage lasting 108 hours after exposure to a 405-nm source at a cumulative TIE of 3.813 mJ.[43] In total, there were nine exposures, each 1 second in duration, at increasing power from 1 nW to 560 μW in a trial series with a cumulative TIE of 1.27 mJ per series. Three trial series of exposures were delivered over a 2-hour period to allow time for visual recovery before each subsequent exposure. Retinal illuminance for the 560- μW exposure was about 6.88 log_10 Td. As reported by Ness et al (see Chapter 6, The Effects of Nondamaging Levels of Laser Energy on Vision and Visual Function), the 405-nm exposure is more than two orders of magnitude less than that of Stamper et al,[44] who exposed volunteers to a 514.5-nm source at 9.23 log10 Td retinal illuminance, producing an afterimage that lasted no more than a minute. These exposures are well below the maximum permissible exposure level, yet the 405-nm exposure had a profound effect on vision. Zuclich reported damage threshold for near-ultraviolet (UV) at 0.28 J.[45] The cumulative TIE reported by Reidenbach et al was 0.0038 J.[43] Given the multiple exposures, the possibility of a phototoxic conditioning effect may have occurred.[46] Taken together, the research supports the phototoxic effect of near-UV on S cones as reported by Sperling et al.[41] This issue has taken on greater relevance with the discovery of third harmonic effects from pulsed 1.3-micron laser systems.[47]

The experiments of Zwick[3] and Schmeisser[48] bring another aspect to this review, which is the possibility that the unique interference patterns (speckle) induced by visible laser light when irradiating a surface may have peak powers high enough to produce significant retinal dysfunction or photoreceptor loss. While this hypothesis remains to be validated, it should be pointed out that higher-order brain mechanisms continue to form complex methods of producing images from unique neural signals and that prolonged viewing of speckle with moderate peak powers above average power may induce neural reorganization in ways that may degrade visual function. Parallel exposures made on NHPs revealed unique histopathological findings of increases in basal bodies and striated rootlets within the RPE that indicate significant physiological changes can be induced by such exposure.[49] These changes may have been responsible for detuning receptor systems associated with high acuity criteria and sensitizing receptor systems at lower acuity criteria; however, over about a 2-year period, receptor systems appear to have been reorganized with peaks and levels of sensitivity consistent with those of higher-acuity spectral sensitivity functions. These observations are consistent with similar long-wavelength cone system emergence following acute foveal injury to small spot Q-switched 690 nm dye laser exposure,[3] suggesting that such effects may be triggered by a wide range of laser energy exposure levels.

The ability to address the diagnostic issues reviewed in this chapter with an animal model capable of providing an in vivo view of such processes in “action” is unique. In vivo imaging of laser-induced retinal injury and repair processes has shown changes in the internal reflection of photoreceptors, indicative of changes in mode structure.[50] Changes in mode structure suggest a change in photoreceptor orientation and, thus, in sensitivity to particular spectral frequencies.[51] Such reflectivity is not the same as a lesion observed in a large eye (eg, NHP) because of the full thickness and low resolution with respect to cellular structure in the large eye. The in vivo small eye model is also different from histological preparations because it exists in its natural state within the retina. The behavior of the in vivo small eye model can be documented to include changes in orientation, reflectivity, and migration into the center of a laser retinal injury site. The latter has been suggested as a retinal plasticity mechanism and documented by retinal photoreceptor histology, suggesting that, over time, peripheral photoreceptors may migrate into lesion sites clear of damage photoreceptors.[52] The importance of this observation relates to the fact that, in the NHP and human retina, damaged photoreceptors in the fovea are dominated by cones. If migration is a relevant explanation of visual functional recovery, replacement receptors from the peripheral retina must have characteristics that provide trichromatic cone characteristics. Such characteristics may simply be greater redundancy, as in Case 5 for return of color discrimination. However, long-wavelength cone emergence was also demonstrated over very different spectral and energy levels. This suggests that the reemergence of long-wavelength cone systems may involve unique photoreceptor spectral tuning, requiring an active rootlet system within the photoreceptor and the RPE, to provide a range of movement parameters that might be necessary for such spectral tuning of the waveguide.[53]

SUMMARY

In this chapter, metrics that combine structural and functional diagnostic techniques revealed a wide variety of damage and recovery processes. These techniques are needed for reliable, rapid, and valid measures of visual function deficits associated with laser retinal injury. Further development will be needed as lasers become smaller, more spectrally agile, and more widespread. Techniques are needed to interrogate the full spectrum of visual function, including the contrast required to resolve features that subtend a range of visual angles, the ability to detect fine differences in hue, and the sensory-motor coordination of fixation eye movements. Until deficits in these functions are diagnosed, researchers are limited in their ability to evaluate the functional consequences of laser retinal injuries and differentiate changes that are primarily retinal in origin from higher-order sequelae. In the military situation, rapid differential diagnostic procedures are required to identify laser-induced retinal injury. These procedures will require compact ophthalmoscopes with axial, as well as transverse, retinal imaging capability with integrated visual function tests that interrogate the span of visual processing from the retina into higherorder visual centers. This investigative functionality will allow for the identification of vision loss that may be due to retinal or brain physiological dysfunction.

As adjunct to other military systems, and possibly as weapons in their own right, lasers will continue to play an important and sometimes dangerous role on the modern battlefield. At present, there is no adequate comprehensive protection against accidental or intentional exposure to lasers in combat. Thus, it is critical that the field of laser safety research move forward toward the development of preventative protocols and prophylactic technologies to protect military personnel and to support military operational objectives.

Acknowledgments

The authors acknowledge the memory of Harry Zwick, with gratitude to him and his colleagues for their previous work in this area. Special thanks also to the US Army Medical Research Detachment-Walter Reed Army Institute of Research Laser Laboratory and, in particular, André Akers for images, illustrations, and technical assistance.

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Section II

PHYSIOLOGICAL AND
PSYCHOLOGICAL EFFECTS

The Embarked Security Team (EST) on Board USNS Rainier (T-AOE 7), along with Sailors from Coastal Riverine Squadron THREE (CRS-3) boarded on Riverine Command Boats (RCBs), defend the vessel using a dazzler nonlethal weapon and blank rounds during a simulated attack as it departs to support ships during Rim of the Pacific (RIMPAC) 2016. Twenty-six nations, comprising over 40 ships and submarines and over 200 aircraft and 25,000 personnel, are participating in RIMPAC from June 30 to August 4, in and around the Hawaiian Islands and southern California. RIMPAC provides a unique training opportunity that helps participants foster and sustain the cooperative relation-ships that are critical to ensuring the safety of sea lanes and security on the world’s oceans. RIMPAC 2016 is the 25th iteration in the series that began in 1971 and is the world’s largest international maritime exercise. (Navy photograph by Mass Communication Specialist First Class Martin Wright/Released.)

Reproduced from: https://www.dvidshub.net/image/2770749/afloat-training-group-simulates-defending-attack-usns-rainer.

Chapter 4

LASER-INDUCED CHANGES IN VISUAL PERFORMANCE: IMMEDIATE AND LONG-TERM CONSEQUENCES IN AN ANIMAL MODEL

DAVID O. ROBBINS, PhD,* Department of Psychology, Ohio Wesleyan University, 61 South Sandusky Street, Delaware, Ohio 43015 and HARRY ZWICK, PhD † US Army Medical Research Detachment, Walter Reed Army Institute of Research, 3201 Sidney Brooks, Brooks Air Force Base, Texas 78235-5138; Deceased

INTRODUCTION

METHODS

Subjects and Apparatus

Discrimination Task

Laser Exposures

Data Analysis

RESULTS

DISCUSSION

SUMMARY

INTRODUCTION

The nature of the eye’s highly absorptive pigments, as well as its optical and mechanical properties, makes this organ a prime candidate for light-induced damage. Damage to the central region of the eye, the fovea, is particularly important in any clinical or applied analysis because this retinal region is responsible for fine spatial resolution and color vision. The retinal layers in this region are thin and form the foveal “pit,” where the density of cone photoreceptors is the highest. The distribution of cone photoreceptors containing visual pigments with different absorption spectra is not uniform within this area. 1,2 Hence, predicting the amount of loss in visual functioning resulting from tissue damage in this area is a complex fusion of many considerations. The specific characteristics of laser exposure are important as are considerations of the exposure site, including its absorption characteristics and plasticity. The nature of the exposure site can also be influenced by the age and general health of the patient, as well as the patient’s prior exposure to light.

As reported elsewhere in this book, retinal damage thresholds from laser irradiation traditionally have relied on fundoscopic and/or histological evidence from single or multiple exposures presented to anesthetized animals over a very limited time period. These studies have provided clear evidence for the presence and location of morphological insult that result from relatively intense retinal exposures, and the additional impact that multiple pulses presented in the same general retinal region have on the shape and degree of retinal insult. 3,4 Using different exposure conditions, various damage mechanisms have been proposed to explain variations in the susceptibility and severity of the elicited damage. Generally, on the one hand, a thermal model has been attributed to those changes resulting from relatively long-duration, low-energy exposures to long-wavelength coherent light. On the other hand, mechanical damage mechanisms have typically been associated with extremely high-energy, short-duration (Q-switched) pulses. Less frequently cited are the more subtle changes associated with repeated low-energy exposures at power levels well below those where either thermal or mechanical disruptions would be predicted. In these cases, it has been proposed that laser irradiation might produce photoreceptor and/or photopigment damage that ultimately could affect the receptor transduction process and even the viability of the receptor cell itself. 5–7 It might be expected that functional changes associated with these more subtle retinal alterations would be a more sensitive measure of the adverse effects of low-level laser irradiation because these types of subtle physical changes in retinal morphology and/or photochemistry would be extremely difficult to detect in an intact retina.

As morphological techniques for detecting minimal retinal alterations have been refined, the energy densities necessary to produce observable retinal lesions have themselves decreased. Associated with these refined techniques and combined with minimal exposure conditions have been a shift in the site of primary anatomical alteration from the corneal and pigment epithelial layers to the outer segments of the photoreceptors.8–10 Although the site of morphological disruption observed is the location where the initial transduction of light energy to electrochemical energy occurs, it is also important to consider the behavioral (functional) consequences of any induced physical change. Changes in the functional capacities of the retina have specific legal, medical, and, ultimately, practical consequences, especially considering how much human behavior is based on accurate visual assessments of the physical world.

Developing a model for predicting the amount of loss in visual performance that results from laser-induced damage to the retina is a complex, but obviously important, part of any laser safety program. Clearly, the type and degree of visual deficits depend not only on the specific characteristics of the laser exposure, but also on the amount, location, and severity of retinal dysfunction, as well as on the functional integrity of surrounding retinal regions. Accurately predicting behavioral outcomes may also depend on two other considerations. Exposed individuals often develop other viewing strategies that consciously or unconsciously depend on the use of surrounding unexposed areas within the affected eye and/or shift to the unexposed eye that previously may not have been the individual’s dominate eye. It is also possible that regenerative retinal mechanisms and/or brain mechanisms may be activated to override transformation alterations in the eye’s opacity to light. Changes in subtle photochemical transduction mechanisms could also influence the electrochemical cascades that initiate neural signals within the retina and beyond.

Obviously, direct human experimentation in this area is impossible, and the study of human laser accident cases lacks precision because dosimetry estimates are necessarily post hoc, and sustained participation from the patients is often difficult to procure. Regardless, human studies have again demonstrated the morphological and functional uniqueness of the fovea.11,12 Damage to the fovea has been shown to cause rather dramatic deficits in visual acuity consistent with the morphological and resolution capacities of the surrounding retinal regions. Some recovery in visual acuity is typically seen in patients receiving low-level exposures, suggesting possible retinal and/or brain regeneration mechanisms that might override any initial morphological damage.13–15 Early explanations of this recovery implied that normal photoreceptors adjacent to the damaged site might passively repopulate the damaged fovea and restore some of the original foveal receptor matrix density.[8]

In patients who have experienced more intense exposures, no recovery is evident.[9] In such cases, secondary damage mechanisms, such as retinal scar formation and nerve fiber layer (NFL) damage, have been induced. This type of damage may physically alter photoreceptor density in the fovea by traction induced by scar tissue. Damage to the NFL in the papillomacular bundle could also impact neural communication to the brain.[16] The nature and limiting factors regulating the regeneration of damaged neurons were first described by Ramon and Cajal[17] and suggested that damaged neurons are capable of only abortive sprouting and little functional recovery. One of the major barriers to regeneration is the formation of glial scarring. More recent research has shown that the previously considered sterile dystrophic end bulbs can return to active growth states[18] and remain active for days after injury.[19] Interestingly, the ability of axons to regenerate depends not only on the maturity of astrocytes and the astroglial reaction to injury, but also on the type of neuron. Sensory neurons, especially retinal ganglion cells, appear capable of eliciting the most growth, although all evidence to date suggests that these cells eventually succumb to the reactive glial response that inhibits such growth.20,21

Experimental studies using animals to determine the minimal visible lesion threshold energy provide excellent dosimetry, because exposure levels can be measured during the experimental operations. However, these investigations typically employed small spot exposures involving large areas outside of the fovea to minimize variability in threshold determinations. Foveal photoreceptor architecture and photopigment and pigment epithelium layer absorption properties within the fovea differ dramatically from one spot to another.[22] The majority of these studies also excluded any direct assessment of the actual visual loss and assumed instead that these losses could be predicted based on traditional psychophysical investigations of the sensitivity of various retinal regions in the intact eye.

A number of lines of evidence might lead one to conclude that the loss of foveal function would be catastrophic. One would expect the greatest loss of photoreceptors, as well as the greatest loss in acuity and color vision. Recent laser accident studies and animal behavioral studies assessing the impact that acute foveal injury has on visual acuity support this notion, but also suggest some degree of neural plasticity.[23] Under certain exposure conditions, foveal exposures that seriously damage photoreceptors produce only minimal scar, traction, and retinal NFL damage. In these cases, animals may fully recover their initial loss in visual acuity.[24] Proposed mechanisms for this recovery have been based in part on the repopulation of lost foveal photoreceptors that has been observed histologically.[8] It has also been based in part on more active mechanisms that might involve efferent cortical retinal modulation16,24 and neural plasticity in higher centers within the visual pathway.[25]

In the earlier days of what was then called the Laser Safety Program—in collaboration with researchers at Frankford Arsenal in Philadelphia and the Armed Forces Institute of Pathology in Washington, DC—we developed a reliable behavioral task to measure visual acuity losses in animals that, under anesthesia, had been previously exposed to multiple spots of continuous wave (CW) laser light. These animals demonstrated variable degrees of loss in visual acuity and wavelength sensitivity, depending on the location and severity of the retinal damage. Unfortunately, the training technique that we used to measure visual acuity in these animals took a considerable amount of time to complete and did not begin until after the animals were exposed. As a consequence, the initial measures of visual loss did not begin until months after the exposures had been made. Pathological identification of the lesion sites in these animals was further delayed by behavior analysis and, in some cases, was not completed until years later. During this time, one could expect considerable changes in both retinal pathology and function.

Given our success in identifying acuity losses to even minor retinal changes, we changed our approach and developed a method to expose awake, task-oriented animals without the use of anesthesia.[26] This method required the animal to look through a pinhole and fixate on a specific location on a small viewing screen that allowed us to accurately place exposures in and around the fovea. Because the animal was awake during these exposures, we were able to complete behavioral analysis of visual acuity changes during and immediately after each exposure. The initial CW laser exposures that we made were relatively long (>100 ms) and large in diameter (>100 µm). To evaluate the effectiveness of our procedure, we conducted a number of experiments examining the relationship between spot size and exposure duration on the magnitude and duration of the induced visual loss. For foveal exposures, the laser was positioned so that it became coaxial with the critical feature in the visual image that the animal was required to discern. Once validity and reliability of methodology were established for cases of flash blindness, our basic empirical question shifted first to define the transitional zone between transient and permanent changes in visual acuity for various types of CW and Q-switched exposures, then to contrast the impact of foveal versus parafoveal exposures. It was followed by the impact of cumulative exposures over a period of days or weeks at or below the median effective dose (ED_50) level, and it finally examined the plasticity of retinal functioning due to any regenerative processes occurring within the fovea. This chapter outlines the results of these experiments.

METHODS

A reliable behavioral technique was developed for the accurate placement of single, small spot exposures onto predetermined retinal areas in an awake, task-oriented animal. This method did not require the use of anesthesia or undue physical restraint.[27] Instead, the animal was trained to maintain fixation on a small target that was placed in the middle of a rear projection screen.26,27 The animal received a positive cue as long as it maintained its fixation on the targets and was negatively reinforced for failure to do so. The impact of random, involuntary, and voluntary eye movements was further reduced by using relatively short-duration exposures that were presented while the animal was actively engaged in a threshold visual discrimination task that required central fixation on a single known critical feature of briefly presented visual targets.

Subjects and Apparatus

Adult male rhesus monkeys with normal vision were used as participants. The animals were tested in a portable restraint device that was also used to transport the animal to and from the housing colony.[28] A custom-fitted helmet molded from high-impact plastic and equipped with an inner, high-density foam liner with an inflatable air bladder stabilized the monkey’s head without undue force or discomfort. An opaque facemask with adjustable iris diaphragms was aligned with the animal’s line of sight. This required the monkey to voluntarily align its pupil with an artificial pupil to view the test screen. With positive reinforcement, the animals were quickly trained to voluntarily leave their home cages and enter the restraint apparatus.

Discrimination Task

Animals were trained to press a lever whenever they detected the presence of a Landolt ring (“C”). These incomplete rings were randomly positioned within a series of equally sized gapless rings (“O”). Individual rings were successively projected onto a rear projection screen placed 1 m in front of an artificial pupil that was mounted onto the animal’s head restraint. The animal’s failure to press the lever to the Landolt ring when presented (miss), or if the lever was pressed during presentation of a gapless ring (false alarm), resulted in presentation of a brief discriminative tone and, on a variable reinforcement schedule, the administration of a brief electrical shock.

Threshold acuity was derived using a tracking technique. In this technique, if the subject correctly detected the Landolt ring (hit) by pressing a lever, the next series of Landolt rings and gapless rings were 10% smaller, whereas an incorrect detection (miss) produced presentation of rings 10% larger. The critical feature of each Landolt ring that distinguished it from corresponding gapless rings varied from a 0.25- to 30-min visual angle in 10% steps. The position of the gap was always in the same location on the viewing screen. By varying the payoff matrix used during training, the number of false alarms was remarkably low (<10%), and animals maintained stable acuity for periods in excess of 45 min of testing. In well-trained animals, baseline visual acuity varied from a Snellen acuity of 20/25 to 20/12, depending on the parameters of the viewing conditions (Figure 4-1). Darkened rings of various diameters were projected onto different wavelength and intensity backgrounds to determine any selective spectral, contrast, or brightness acuity effects.[5]

Figure 4-1. Preexposure baseline acuity. The animal’s threshold acuity was averaged in consecutive 2-min intervals using maximum photopic viewing conditions. Established acuity level of 1.1 (min of arc)-1 or a Snellen acuity of 20/18 was typical for our animals under these viewing conditions. Ongoing acuity was tracked for 30 min without a break; during this period, average threshold acuity for any running 2 min never dropped below 1.0 (min of arc)-1 once maximum threshold level was established. Similar to other animals, this subject’s false-positive response rate was <10%. No negative reinforcement was applied during the test period. A criterion of two successive misses to threshold Landolt rings was typically used before shock was applied to the third consecutive miss. Normally, a well-trained animal avoided negative reinforcement altogether once motivated to perform.

Laser Exposures

Several different laser systems were used at various times during the course of this research. Initially, He-Ne (helium-neon), krypton, and argon CW lasers were used to generate relatively long-duration exposures (50–500 ms) of different wavelengths; later, in our research, a Nd:YAG (neodymium-doped yttrium aluminum garnet) pulsed laser was used to produce Q-switched pulses for shorter-duration, higher-energy exposures. Each of these laser systems also varied in output wavelength. The lasers were positioned on an optical bench outside the test chamber. The beam was first directed through several neutral density filters and a manual safety shutter before passing through an electronic shutter and beam splitter. A portion of the attenuated beam was incident upon an absorbing disc calorimeter for monitoring exposure energy. The transmitted portion of the beam was diverted by a front surface mirror and passed through a variable beam expander and a convex lens placed in front of the animal’s pupil. A coated pellicle beam splitter placed 5 cm in front of the lens was positioned at the intersection of the diverging laser beam and the light beam from the viewing screen. The laser beam was positioned such that it was presented to the animal coaxial with a line between the artificial pupil and the gap in a specified, threshold Landolt ring; or, in the case of off-axis exposures, it was positioned 1° above the gap in the specified Landolt ring. Beam diameter could be varied from <50 to >800 µm on the retina. The number of pulses presented was controlled by a remote electronic shutter placed in the beam pathway. Varying the duration of the shutter from <50 to >250 ms resulted in the presentation of one to six pulses within the brief exposure session. Longer-duration exposures were avoided to eliminate the impact that voluntary eye movements could have on the position of the exposure on the retina.

Figure 4-2. Sample raw data demonstrating immediate drop in visual acuity following laser exposure. The ordinate indicates sizes of the gaps in presented Landolt rings measured in reciprocal minutes of arc. The abscissa represents time (in minutes) of presentation of threshold Landolt rings relative to exposure (marked as 0) based on our tracking technique. Two, 0.1-μJ Q-switched pulses, 300 μm diameter, were presented on-axis to produce the transient acuity deficit shown here. Only 4 min of preexposure acuity is shown. Normally, preexposure was measured until the animal established a stable baseline (typically within approximately 10 min) before laser exposure; baseline testing continued for another 30 min or until the animal established a stable postexposure acuity, whichever came first.

Figure 4-3. Average recovery functions in visual acuity fol-lowing low-level (0.1-µJ), multiple-pulse exposures (small spot size). This animal was exposed to two Q-switched pulses presented on-axis within a 100-ms window. Retinal spot size was 150 µm; postexposure acuity was measured immediately after exposure (marked as 1 min on the abscissa) and computed continuously in 2-min intervals for the next 31 min. Only two 532-nm pulses (exposure) were presented per session (day); the recovery function shown represents the average postexposure deficit of four separate exposure sessions over as many days. The animal’s postexposure acuity was plotted relative to its preexposure baseline as percent deficit. The vertical bars through each data point (diamonds) represent the range of acuity variability (minimal and maximal) observed for the four separate exposure sessions.

All exposures were presented while the animal was tracking its threshold visual acuity and immediately after the animal had correctly detected the minimal gap in the Landolt ring. Observations of animals working under these conditions have shown that they typically maintain their fixation on the screen for several seconds after lever pressing. Normally, animals were exposed only once per day and only after their preexposure baselines were reliably established. The animal’s postexposure acuity was followed until it regained its preexposure level or the elicited deficit had stabilized (Figure 4-2). All acuity measurements were made under monocular viewing conditions using both high-luminance (photopic) and low-luminance (scotopic) chromatic and achromatic targets. Figure 4-3 demonstrates the reliability of derived recovery functions using this technique. In this example, the same animal was exposed on separate sessions to low-level, repetitive Q-switched pulses that each sustained 150 µm on the central fovea. The total exposure duration for each session was 100 ms. The average time for full recovery was approximately 30 min, and the average initial deficit ranged from 20% to 25% within the first 5 min after exposure.

Data Analysis

Each animal’s preexposure average acuity was derived over a 15- to 20-min period at the beginning of each exposure session. To determine any motivational or lingering exposure effects, the average preexposure acuity, as well as degree of variability (number of different-sized gaps represented), was compared to previous session baselines and to those from the animal’s control eye. Postexposure acuity was analyzed in 2-min-long intervals beginning immediately after the exposure. For each interval, the percent deficit was derived by comparing the average acuity during this 2-min period to the overall preexposure acuity derived for the animal immediately prior to exposure. In those cases where prolonged acuity changes were noted, no additional exposures were made, and postexposure acuity was measured using different spectral and contrast conditions.

RESULTS

When either large (200–500 µm) diameter foveal exposures were presented for a brief period (single Q-switched pulse) or when small (50–150 µm) diameter foveal exposures were presented for relatively prolonged exposure periods using multiple Q-switched pulses (up to 250 ms), the immediate impact on visual acuity was relatively dramatic. These types of Nd:YAG exposures produced deficits reminiscent of those produced by short-duration (50–100 ms) CW argon and HeNe flashes as previously reported elsewhere.[29] In these millisecond time-domain exposures, where full recovery was possible, immediately after exposure the animal’s acuity typically decreased significantly (20%–80% of preexposure acuity) and remained depressed for some time (4–20 min) before gradually recovering to its preexposure baseline. Both the size of the initial deficit and the total time for recovery were dependent on the parameters of the exposure that included its energy density, spot diameter, duration, and position on the retina. For some exposure conditions defined as being within the transition zone between temporary and permanent effects, the initial deficits were as high as 80%, and full recovery took as long as several days. Typically below the transitional zone, the magnitude of the initial deficit was largely dependent on the size and location of the exposure site, whereas the duration of the deficit was dependent on exposure energy. For energy densities near or within the transitional zone, the overall impact (size of initial deficit and time for recovery) of individual exposures gradually increased with repeated exposures even though these exposures were separated from each other by as much as several days. Often, these cumulative effects produced permanent shifts in postexposure acuity that were only noted after the fourth or fifth exposure at a specific energy density.

When single Q-switched pulses of small diameters (< 50 µm) were presented, however, there was little obvious decrement in visual acuity at or below the ED_50 level. Under these nanosecond time-domain exposures, the animal was able to maintain a stable acuity after the exposure and throughout the postexposure session. With larger-diameter (>150-µm) exposures, the adverse impact of single pulses on visual acuity was more evident and generally the same as the transient deficits produced by smaller-diameter exposures presented either with CW irradiation (100-ms flashes) or with multiple Q-switched pulses in rapid succession of each other. With either type of condition, immediately after exposure, the animal’s baseline acuity dropped and remained depressed for some time before postexposure acuity gradually began to return to its preexposure baseline. Both the magnitude and duration of the observed visual deficits were related to the amount of retinal area involved (exposure spot size) and to the number of Q-switched pulses presented. Increasing the power density of single Q-switched pulses for small-diameter exposures produced little additional impact on the animal’s derived acuity, even for energy levels significantly above (10×–100×) the ED_50.

With larger-diameter exposure sites, however, the energy of the pulses clearly influenced the duration of the deficit, as well as the likelihood of full recovery within the remaining time of the test session. The impact of multiple exposures under this condition often became prolonged and sometimes permanent for Q-switched pulses above the ED_50. But, unlike the millisecond time-domain exposures, no transitional zone was found where cumulative effects could be noted for repeated exposures when single pulses of very small spot sizes (<150 µm) were used. Control trials in which low-energy exposures were positioned as little as 1° off of the animal’s point of central fixation dramatically reduced the overall adverse impact of laser irradiation. Measuring immediate postexposure acuity under different viewing conditions (high- vs low-contrast or achromatic vs chromatic) produced little relative difference in either the percent deficit or the duration of transient deficits, and contributed little to a fuller understanding of the nature of these changes. In those exposures where permanent changes were noted, however, postexposure acuity was often significantly different for different contrast, luminance, and chromatic targets; these types of long-term changes did provide some discernment of the location and nature of the damage produced.

a

b

c

d

Figure 4-4. (a) On- and off-axis exposures to single Q-switched pulses at energy levels below the transition zone for permanent deficits (large spot size). One 532-nm Q-switched pulse was presented per session (day) within a 50-ms exposure window either coaxial with (on-axis) or temporal (off-axis) to the gap in a threshold Landolt ring. The energy of the pulse was 0.1 µJ, and the beam diameter on the retina was approximately 500 µm. Acuity is plotted as percentage of preexposure acuity for each running 2 min following exposure. Triangles represent acuity following an on-axis exposure; diamonds represent acuity following an off-axis exposure. (b) On- and off-axis exposures to multiple (3) Q-switched pulses at energy levels below the transition zone for permanent deficits (large spot size). Three 532-nm Q-switched pulses were presented within a 150-ms exposure window either coaxial with (on-axis) or temporal (off-axis) to the gap in a threshold Landolt ring. The energy of the pulse was 0.1 µJ, and the beam diameter on the retina was approximately 500 µm. Acuity is plotted as a percentage of preexposure acuity for each running 2 min following exposure using our tracking technique. Triangles represent the acuity following an on-axis exposure; diamonds represent acuity following an off-axis exposure. (c) On- and off-axis exposures to low-level, multiple (4, 5) Q-switched pulses at energy levels below the transition zone for permanent deficits (large spot size). Repetitive, 532-nm Q-switched pulses were presented within a 200-ms (c) or 250-ms (d) exposure window either coaxial with (on-axis) or temporal to (off-axis) the gap in a threshold Landolt ring. The energy of each exposure was 0.1 µJ, and the beam diameter on the retina was approximately 500 µm. Acuity is plotted as a percentage of preexposure acuity for each running 2 min following exposure using our tracking technique. Triangles represent the acuity following an on-axis exposure; diamonds represent acuity following an off-axis exposure.

The transient impact of retinal exposure position on visual acuity is shown in Figure 4-4. Even with relatively large-diameter (500 µm), low-energy, Q-switched exposures, the magnitude and duration of transient deficits were small for single-pulse exposures compared to those deficits produced by multiple pulses or CW exposures. In Figure 4-4, the beam was positioned either coaxial with the gap in a threshold Landolt ring (on-axis) or 1° temporal to the gap (off-axis). Off-axis exposures should have little impact on foveal function because they should expose areas outside of the central fovea. In Figure 4-4a, a single, low-level, Q-switched pulse was presented either on-axis or 1° off of the animal’s fixation point. For the on-axis exposure, the animal’s visual acuity decreased by approximately 15% during the first 3 min following irradiation before quickly returning to its preexposure baseline within 7 min of exposure. This visual deficit was rather minor and transient compared to those elicited by millisecond time-domain flashes or multiple Q-switched pulses.

Consistent with other examples of low-level exposures (see Figure 4-4, b–d), immediately after the animal’s postexposure acuity deficit recovered, the animal’s acuity became temporarily enhanced for several minutes before gradually returning to its normal preexposure baseline. In this example, the animal’s transient enhancement was approximately 20% better than its baseline, an increase in visual acuity to 1.44 (min of arc)-1 or a Snellen acuity of 20/14. This enhancement effect gradually began within 11 min of the exposure and lasted approximately 8 min before the animal’s acuity again stabilized at its preexpo-sure level, some 17 min after exposure. The off-axis exposure produced no immediate deficit or delayed enhancement in visual acuity. This animal was able to maintain its preexposure acuity level after exposure and, if anything, slightly improved during the course of the 20-min test session. For the most part, postexposure acuity was elevated by approximately 5% during the first 13 min after exposure. Although minor, this shift occurred consistently and was outside this animal’s normal within-session variability. In Figure 4-4b, the same comparison of on- and off-axis exposures was made except in this example the number of Q-switched pulses presented was increased from one pulse to three pulses within a 150 ms exposure window. Again, for the off-axis exposure, little if any deficit was noted during the 20-min postexposure session; but, for the on-axis exposure, an immediate and significant drop in visual acuity was noted. For the on-axis condition, the initial postexposure deficit was >25%, and the animal’s acuity remained depressed for approximately 7 min before returning to its preexposure acuity in 9 min. Similar to the previous example (see Figure 4-4a), the elicited visual deficit was followed by a brief, but significant, enhancement in acuity that lasted several minutes before the animal’s acuity stabilized at its preexposure level. Overall acuity effects were the same for single and repetitive Q-switched pulse conditions.

The presentation of more on-axis pulses within a restricted time frame produced even larger initial deficits without significantly affecting the overall du-ration of the recovery function. With four Q-switched pulses (see Figure 4-4c), for example, the initial deficit increased to > 40% (with a Snellen acuity of 20/28), and the animal’s acuity remained depressed for approximately 10 min before gradually returning to its preexposure acuity level. Similar to the previous examples, the elicited visual deficit was again followed by a brief, but significant, enhancement in acuity before it stabilized at its preexposure level. With five pulses (see Figure 4-4d), the initial deficit was closer to 45% of its preexposure level and reached its maximum within the first 7 min following exposure before gradually returning to its baseline within 13 min. The animal again demonstrated hyperacuity for the last 4 min of postexposure testing. The off-axis exposures for one to five pulses were virtually identical to each other and showed no consistent or significant drop in acuity either during or immediately following laser exposures.

The impact of retinal exposure position on postexposure acuity appears independent of the exposure time domain. Using millisecond time-domain exposures, we have demonstrated a similar decrease in effect because the exposure site is positioned farther away from an animal’s point of central fixation. For example, in Figure 4-5, a series of recovery functions from four different 100-ms exposures is shown where the exposure position relative to the animal’s fixation point varied from on-axis to as much as 6° off-axis. Somewhat independent of their actual position on the retina, these longer duration CW exposures also involved a larger retinal region than the previous Q-switched pulses. Continuous and random eye movements during the exposure, even when the animal was fixating on the visual target, resulted in a larger area of involvement when millisecond as opposed to nanosecond time-domain exposures were made. When multiple Q-switched pulses were presented over the same 100 ms period, only two 15 ns pulses would normally be delivered. Hence, only two discrete areas were exposed in the nanosecond time domain. In Figure 4-5, an animal was exposed to a series of different exposures positioned varying distances away from the point of central fixation. Again, only one exposure was presented per session. The sham exposure represents the control where no exposure was made, but where the discriminanda size was shifted to the approximate level that an on-axis exposure could first be visible. This curve thus represents the time it takes for a subject using our tracking technique to return to baseline without making any discrimination errors. The recovery functions for exposures of 5° and 6° off-axis were virtually identical to that observed in the sham condition. With a 3° off-axis exposure, recovery was delayed by approximately 6 min; for an on-axis exposure, recovery in visual acuity was not complete within the 14-min postexposure session. Follow-up postexposure testing in this animal revealed no lasting deficit or lingering effects from these or other exposures at this power density.

Figure 4-5. Recovery functions following different continuous wave exposures at various eccentricities. This animal was exposed to single, 100-ms, 150-µm, 647-nm flashes from a krypton continuous wave laser. The spot was positioned on-axis (0° [diamonds]) and off-axis (3° [squares], 5° [triangles], and 6° [crosses]) to the gap in a threshold Landolt ring. Immediately after exposure, the size of the target (discriminanda) was manually adjusted to the size normally able to be just detected after an on-axis exposure. Postexposure acuity was then tracked for each running 2 min until the animal achieved its preexposure baseline acuity. Acuity was measured using high-contrast targets on an achromatic background. The energy of the exposure was below the transitional zone between temporary and permanent effects. The sham exposures (circles) represent the time it took using our tracking technique for the animal to reestablish its baseline acuity when no laser irradiation was presented.

Using millisecond time-domain exposures, we have demonstrated the effects that variations in exposure duration can have on the duration of the recovery function when minimal diameter spots (<50 µm) are used. In Figure 4-6, the individual recovery functions are shown for four different duration exposures ranging from 19 to 103 ms. As the figure shows, recovery to flashes of 19 and 50 ms are almost immediate (within 4–8 min) and represent the recovery times not significantly different from the sham condition shown in Figure 4-5. For longer or repeated exposures using either CW lasers or multiple pulses from a Q-switched energy source, however, the duration of the recovery function for minimal diameters spots was similar to those observed when larger diameter exposures were administered. From these data, it would appear that the consequence of one longer, 103 ms flash was slightly greater than that of two 50 ms flashes presented 2 min apart. Such might be the case if eye movements alone were the prevailing catalyst for this type of effect.

Figure 4-6. Effects of different continuous wave laser exposure durations (millisecond time domain) on postexposure visual acuity. The individual recovery functions were derived for one animal exposed repeatedly over different days to 1.0-mW flashes from an argon (514.5 nm) laser. Each exposure was presented coaxial with a gap in a threshold Landolt ring and produced an approximate 50-µm spot on the retina. Each data point represents the average running 2-min postexposure intervals of several separate exposure sessions. The duration of the exposures was produced by a programmable electronic shutter whose pulse duration was measured on a standard oscilloscope. Durations of 19 ms (squares), 50 ms (circles), 90 ms (triangles), and 103 ms (diamonds) are shown. Similar to Figure 4-5, the size of Landolt rings was manually increased immediately following exposure to the level expected for this type of exposure. Using our tracking technique, the animal then adjusted its threshold acuity until it returned to its preexposure baseline.

The influence of the acuity task on delineating the magnitude and duration of the transient visual deficit is shown in Figure 4-7 for low-level laser irradiation. In Figure 4-7, the animal’s pre- and postexposure acuities were measured using either a high-luminance background (high acuity) or a low-luminance background (low acuity) against darkened visual targets. Typically, an animal’s preexposure acuity in the high-acuity (high-luminance) condition was approximately 1.2 (min of arc)-1 or had a Snellen acuity of 20/17, whereas preexposure acuity derived under the low-acuity (low-luminance) condition was approximately 0.65 (min of arc)-1 or had a Snellen acuity of 20/31. Our animals’ preexposure acuity varied little from session to session and was extremely consistent within a testing session when no exposure was made.

Generally, the recovery functions for repeated exposures using the same conditions (either exposure or performance) were remarkably similar, especially when large-diameter spots and multiple Q-switched pulses were presented. When single Q-switched exposures were used and/or when the diameter of the exposure on the retina was minimal (< 50 µm), the elicited deficit was smaller, and more variability existed across exposure sessions and between animals. The observed increased within-subject variability likely represents the degree to which the exposure was centered on the fovea and the extent to which surrounding foveal regions were still functional. The between-animal variability also likely represents the degree to which different animals use various strategies to detect threshold targets after exposure, especially when off-axis fixations are required. As expected, deriving postexposure acuity functions using percent change from preexposure acuity (vs absolute acuity) considerably reduced the between-subject variability. In spite of generally higher energy densities for Q-switched pulses, more variable recovery functions were noted in this study using nanosecond time-domain exposures than in previous studies with lower-energy CW laser exposures in the millisecond time domain. The majority of exposures in this study, however, involved smaller-diameter spots and briefer duration exposures that could easily explain the observed increased variability.

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Figure 4-7. (a) Effects of measuring postexposure acuity using high- and low-luminance targets following Q-switched Nd:YAG (neodymium-doped yttrium aluminum garnet) laser exposures. In each figure, the animal was exposed to a single Q-switched pulse (a) or to five Q-switched pulses within a 250-ms window (b). The energy per pulse was 0.1 µJ presented coaxial with the gap in a specified Landolt ring (on-axis). Each pulse produced an exposure diameter of approximately 500 µm on the retina. Postexposure acuity was measured in 2-min intervals for 20 min after each exposure, using different-sized Landolt rings projected onto white light backgrounds of two different luminance levels. The differences in luminance density between the high and low backgrounds was 3.0 log units. Squares represent postexposure acuity for high-luminance targets; triangles represent postexposure acuity for low-luminance targets.

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b

Figure 4-8. (a) Average recovery functions derived for different luminance backgrounds after low-level, multiple (5) Q-switched Nd:YAG (neodymium-doped yttrium aluminum garnet) laser exposures (small spot size = 150 µm). A comparison of the recovery functions of one animal is shown for both high- (a) and low-luminance (b) backgrounds for the darkened Landolt rings. This animal was exposed to five Q-switched pulses from a Nd:YAG laser presented within a 250-ms window. Only one series of 532-nm pulses (exposure) was presented per session (day); each recovery function represents the average of four separate exposure sessions. The vertical bars through each data point (diamond) represent the range (minimal and maximal) of acuity variability observed for the separate exposure sessions presented. Retinal spot size was 150 µm and energy per pulse was 0.1 µJ.

In Figure 4-8, an average recovery function derived for one animal from four separate exposure sessions is shown for both high- and low-acuity criterion. No sta-tistically significant difference was found between the two recovery functions. For each criterion, the animal’s visual acuity decreased rather significantly within 7 to 10 min after exposure and remained depressed for the next 20 min before gradually returning to its preexpo-sure level within 35 min of exposure. In the recovery functions shown in Figure 4-8, the initial visual deficit appeared to occur earlier during the postexposure period when high-acuity criteria, as opposed to low-acuity criteria, were used. However, in Figure 4-9, no significant differences were found between the time course of the initial deficit and acuity criterion used.

a

b

Figure 4-9. (a) Average recovery functions derived for different luminance backgrounds after low-level, multiple (4) pulse exposures (large spot size = 200 µm). A comparison of the recovery functions of one animal is shown for both high- (a) and low-luminance (b) backgrounds for the darkened Landolt rings. This animal was exposed to four Q-switched pulses from a Nd:YAG (neodymium-doped yttrium aluminum garnet) laser presented within a 200-ms window. Each recovery function represents the average of four separate exposure sessions; vertical bars through each data point represent the range of variability (minimal and maximal) observed for the separate exposure sessions presented. Retinal spot size was 200 µm, and energy per pulse was 0.1 µJ.

In Figure 4-9, the diameter of the exposure on the retina was increased from 150 to 200 µm, whereas the number of pulses was decreased from five Q-switched pulses presented within a 250-ms exposure window to four pulses presented within a 200 ms window. In spite of these changes in exposure parameters, both the magnitude of the initial deficit and time for full recovery for each derived recovery function did not change significantly from those recovery functions as previously shown. For the high-acuity criterion (see Figure 4-9a), postexposure acuity dropped to 25% of its preexposure level approximately 7 min after exposure. During the next 14 min, the animal’s acuity gradually improved, and eventually returned and stabilized at its preexposure baseline. For the low-acuity criteria (see Figure 4-9b), neither the initial deficit nor the size of the maximum deficit was as large as that shown for the high-acuity criterion; but, here again, the immediate deficit in visual acuity stabilized in approximately 7 min before finally returning to its preexposure baseline within 17 min of exposure. The variability in results across different exposure sessions was actually quite small, as represented by the error bars in Figure 4-9a and Figure 4-9b. Each of these curves represents the average of four separate exposure sessions. Similar results were also observed with other spot sizes and number of Q-switched pulses at this energy level.

Figure 4-10. Comparison of two different spot sizes (100 vs 400 µm) on the initial magnitude and total duration of the visual deficit. Two low-energy, Q-switched pulses from a Nd:YAG (neodymium-doped yttrium aluminum garnet) laser were presented coaxial with the gap in a threshold Landolt ring under maximum photopic conditions. Each pulse produced either a 100- or 400-µm diameter spot on the retina. Only one exposure (two consecutive pulses) was presented per day; acuity was measured as a percentage of preexposure acuity for successive 2-min postexposure intervals. Triangles represent high acuity: 100 µm, 2 pulses; squares represent high acuity: 400 µm, 2 pulses.

Differences in the diameter of the retinal laser exposure did have an impact on the likelihood of observing a deficit and on the magnitude of any observable acuity shift. As previously reported, for very small-diameter Q-switched pulses, deficits observed were often very small and transient in spite of the fact that they were presented on-axis and were relatively high in energy. This minimal consequence was most evident when only 1 or 2 ns pulses were presented. When larger spot sizes were used, larger and more sustainable visual deficits were elicited. The comparison of deficits produced by two different spot sizes is shown in Figure 4-10.

In this figure, the animal was exposed on two separate occasions to two Q-switched pulses of low-energy light that generated either a 100- or 400-µm diameter spot on the retina. These exposures were presented coaxial with the gaps in threshold Landolt rings, and postexposure visual acuity was measured using high-luminance targets. There was a significant decrease in the animal’s visual acuity immediately after either diameter spot. For the 100 µm diameter spot, the initial visual deficit leveled off after 4 min and remained at this depressed level for approximately 12 min before gradually returning to its preexposure level in 16 min. The average deficit that was sustained during the initial phase of the recovery was 15%. For the 400 µm diameter spot, the animal’s visual acuity also immediately dropped and within 6 min had reached a maximum deficit of 45%. The animal’s deficit remained at this acuity level for approximately 12 min before the visual deficit gradually returned to its preexposure baseline in 18 min. The time course of the recovery curves for these two different exposures was remarkably similar, differing only in the degree of the initial deficit.

A direct comparison of the size of the initial acuity deficit, with eight different retinal spot sizes, is shown in Figure 4-11. For a relatively small (50 µm) diameter spot, little or no deficit was observable using our behav-ioral paradigm; but, as the spot diameter increased, an almost monotonic relationship developed between the magnitude of the maximum deficit and retinal spot size. In this example, the animal was exposed to only a single, 15 ns pulse for each exposure diameter. This virtually eliminated any impact that voluntary or involuntary eye movements might have on the actual size of the retinal irradiation. When the exposure duration was longer (millisecond domain) or multiple pulses (nanosecond domain) were presented sequentially, we have always assumed that ongoing eye movements actually created larger retinal exposure areas. In Figure 4-11, the calculated diameter of the exposure site on the fovea varied from approximately 50 to 825 µm. The largest-diameter spots likely irradiated the animal’s entire fovea and produced a significant loss in photopic acuity that peaked at about 45% of the animal’s preexposure acuity level. For smaller areas of retinal involvement, the deficit was proportionally smaller. Overall, little variability was observed between exposures of the same diameters. A random design of different spot sizes was presented over different test sessions. A somewhat heightened deficit was observed for spot diameters of 100 µm in comparison to spot diameters of 50 and 200 µm.

Figure 4-11. Effects of retinal spot size on the magnitude of the initial maximum postexposure acuity deficit. This subject was exposed daily to a single 3-µJ, Q-switched pulse from a Nd:YAG (neodymium-doped yttrium aluminum garnet) laser. All exposures were presented on-axis. Acuity was measured using high-contrast, achromatic targets. Each data point represents the mean of five different exposures over as many days; vertical bars represent range of deficits observed for each of the eight different spot sizes. The abscissa represents different retinal spot sizes varying from 50 to 825 µm; the ordinate represents maximum deficit relative to the animal’s preexposure acuity produced by the laser exposure.

Doubling the number of Q-switched pulses presented within a 100 ms exposure window produced a less dramatic overall impact than retinal spot size had on determining the magnitude of the initial deficit. In Figure 4-12, a similar comparison of retinal spot size is shown for a double rather than a single Q-switched pulse, although in this example the different graphs represented different exposure energies. The maximum deficit occurred after only tripling the retinal spot size in most cases, especially for those energy densities above 0.5 µJ. The magnitude of the maximum deficit varied from <10% to >50% of its preexposure level. In this example, the energy per pulse varied from 0.1 µJ to 5.0 µJ for the six different spot diameters used. Under these exposure conditions, the energy per pulse appeared to have little consistent impact on the magnitude of the initial deficit. For example, when 50 µm spot sizes were used, the initial deficit was quite small (<10%) and differed little regardless of the energy of the pulses. Increasing spot diameters to 100 µm or more changed the magnitude of the maximum deficit from 10% to >50% of its preexposure level. However, little systematic change in the magnitude of the initial deficit was observed for spot sizes that varied as much as 600 µm from each other. Typically, the maximum deficit was observed within the first 5 to 8 min after exposure, and full recovery was complete within 30 to 40 min of exposure. No long-term shift in acuity was observed for any of the exposures used to produce the data in Figure 4-12.

As might be expected, the area of involvement was related not only to the magnitude of the initial deficit, but also to the total time for recovery. Figure 4-13 demonstrates the length of time required for full recovery following single, double, and triple Q-switched pulses of different retinal spot diameters. All exposures were below the ED_50 level and were presented on-axis. This figure shows that the length of recovery following a single Q-switched pulse was considerably shorter than that following either a double or triple exposure. For this subject, a single, minimal diameter (<50 µm) Q-switched pulse produced no significant shift in postexposure acuity, and only a minor shift was noted for multiple pulses. As the size of the retinal exposure area increased from 100 µm to >800 µm, not only did the size of the maximum deficit increase, as previously shown in other figures, but also the duration of the visual deficit increased from 5 min to almost 40 min. For all pulse conditions, larger-diameter exposures produced more consistent and sustained deficits than those for small-diameter exposures. The relationship between the two- and three-pulse conditions was complex, with the two-pulse condition often producing a longer-lasting deficit than the three-pulse condition.

Figure 4-12. Effects of different (5) energy pulses and spot diameters (6) on the magnitude of maximum postexposure acuity deficit. This subject was exposed daily to two Q-switched pulses within a 100-ms window from a Nd:YAG (neodymium-doped yttrium aluminum garnet) laser. All exposures were presented on-axis; acuity was measured using high-contrast, achromatic targets. For each of the six diameter exposures, the pair of 532-nm pulses varied in energy density from 0.1 to 5.0 µJ (diamonds: 0.1 µJ, squares: 0.5 µJ, triangles: 1.0 µJ, crosses: 3.0, and circles: 5.0 µJ).

Figure 4-13. Duration of visual deficit for single, double, and triple Q-switched Nd:YAG (neodymium-doped yttrium aluminum garnet) pulses. This animal received only one exposure per day; that exposure varied in either the number of Q-switched pulses presented (1–3) or in the size of the spot on the retinal surface. The diameter of the on-axis exposure shown on the abscissa varied from <50 to 825 µm, and the duration (minutes) of the postexposure deficit as a percentage of preexposure acuity is plotted on the ordinate. The energy of these pulses was several log units below the ED_50 (effective dose for 50% of the population) and averaged 0.01 µJ per pulse. Postexposure acuity was measured using high-luminance backgrounds, and the duration of the visual deficit was defined as the total time from exposure to the animal’s return to its preexposure baseline. Diamonds represent a single Q-switched pulse, circles represent two pulses, and triangles represent three pulses.

Variations in the energy per pulse had some impact on the nature of the visual deficit, but these differences were only evident for relatively large spot sizes. As previously shown, single Q-switched pulses of minimal spot size (<50 µm) produced little observable change in postexposure acuity even for high-energy exposures at or slightly above the ED_50. Increasing the area of retinal involvement by increasing the spot size and/or by increasing the number of presented Q-switched pulses, however, did produce immediate, but still transient, changes in the animal’s postexposure acuity.

In Figures 4-14 and 4-15, the recovery functions for relatively large-diameter exposures (500 µm) are shown for two different energy levels, 1.0 µJ (ED_50 for small spot exposures) and 0.1 µJ (1 log unit below the ED_50), and pulse rates (single and triple pulses). In Figure 4-14, the animal was exposed on two separate sessions to a single Q-switched pulse at both of these energy levels. In Figure 4-15, the same animal under the same exposure conditions was exposed to three, rather than two, Q-switched pulses within a 150-ms time interval at these same two energy levels. All exposures were presented on-axis, and the animal’s postexposure acuity was measured using high-luminance targets. When exposed to a single, low-level, Q-switched pulse, the animal’s postexposure acuity dropped only slightly for a brief period before quickly returning to its preexposure level within approximately 8 min. This curve (see Figure 4-14) demonstrates little initial impact of this exposure on the ability of the animal to maintain a consistent postexposure threshold comparable to its preexposure level. However, during the later portions of the test session, the animal demonstrated the same type of enhancement in visual performance that had been noted previously for those exposures where an immediate deficit was observed. The initial deficit was <15% (with a Snellen acuity of 20/20) and was very transient in nature.

Figure 4-14. Single Q-switched pulse exposure at two different exposing energy levels. A single pulse was presented at either 1.0 µJ (triangles) or 0.1 µJ (squares). Both exposures were made on-axis, and each exposure produced a retinal spot size of 500 µm. Postexposure acuity was measured using high-luminance backgrounds against darkened Landolt rings. Our tracking technique was used to plot postexposure acuity. The abscissa represents the minutes following exposure; the ordinate represents the animal’s average acuity relative to its preexposure acuity.

Figure 4-15. Three Q-switched pulses at two different energy levels. Three pulses at 1.0 µJ (triangles) and 0.1 µJ (squares) were presented within a 150-ms window. Both the high- and low-energy exposures were made on-axis; each pulse produced a retinal spot size of 500 µm. Postexposure acuity was measured using high-luminance backgrounds against darkened Landolt rings. Our tracking technique was used to plot postexposure acuity. The abscissa represents the minutes following exposure; the ordinate represents the animal’s aver-age acuity relative to its preexposure acuity.

The enhancement in postexposure acuity was somewhat more pronounced and less transient in nature, although by the end of the 20-min postexposure test session, the animal’s acuity had returned to its preexposure baseline. At the higher energy level (1.0 µJ), the initial deficit was not remarkable during its early stages, especially compared to previously reported initial deficits; but, with time, the animal demonstrated a gradual, but significant, drop in visual acuity that lasted for the duration of the test session. Within the 20-min postexposure session, visual acuity had dropped by approximately 25%, and no recovery or enhancement effect was noted. By the next day, the animal’s acuity had returned to its preexposure baseline level; and, in the days that followed, no permanent deficit was noted. No additional exposures were presented to this animal for several weeks, and no similar decline in acuity during the later portions of the exposure sessions were noted in this animal when a triple, rather than a single, Q-switched pulse was presented (see Figure 4-15).

Larger, more consistent and prolonged visual deficits were observed for minimal spot diameters of higher energy density when the number of successive pulses presented within an exposure session was increased. Shown in Figure 4-16 are the recovery curves following two different energy exposures presented to the same animal over the course of several different sessions. In Figure 4-16a, four Q-switched pulses were presented within a 200 ms exposure window. Each pulse had an energy density of 0.5 µJ and produced a retinal spot diameter of approximately 50 µm. However, given the number of individual pulses presented, the actual size of the exposure site was likely significantly larger due to the animal’s involuntary and ongoing voluntary eye movements. The total area of exposure could have varied from 50 µm, assuming total overlap to greater than several hundred microns, and assuming little retinal overlap in individual pulses. The total energy presented was slightly below the ED_50 for this exposure condition. In Figure 4-16a, immediately after exposure, this animal’s visual acuity dropped to 35% of its preexposure acuity and remained depressed at this level for approximately 15 min before gradually returning to its preexposure level within 21 min. Increasing the energy density per pulse to 1.0 µJ produced a similar recovery function (Figure 4-16b). In this case, however, the animal’s preexposure acuity decreased by as much as 25% during the first 15 min after the exposure; within 17 min, the animal’s acuity had returned to its preexposure level. In both of these exposures, the animal’s long-term acuity remained unaffected even though exposure energy densities were at or near the ED_50. This animal’s baseline acuity was followed for several days after exposure with no additional laser irradiation. Postexposure acuity remained at baseline and was consistent with acuity in the animal’s control (unexposed) eye. With higher-energy pulses or with pulses that exposed a greater overall area of the fovea (larger spot diameters), some increased variability in acuity was noted in subsequent test sessions even though the animal’s average acuity approximated its preexposure level. Within days, however, these slight variability differences disappeared, and the animal appeared fully recovered from the exposure.

a

b

Figure 4-16. Multiple (4) Q-switched pulses at two different energy levels. On separate exposure sessions, this animal was exposed to four Q-switched pulses from a Nd:YAG (neodymium-doped yttrium aluminum garnet) laser. All four pulses were presented within a 200-ms exposure window and were presented coaxial with the gap in a threshold Landolt ring (on-axis) producing a 50-µm diameter spot on the retina. The energy density of each pulse was the same, but was (a) 0.5 µJ per pulse and (b) 1.0 µJ per pulse. Postexposure acuity was measured using high-luminance backgrounds against darkened Landolt rings. The abscissa represents the minutes following exposure; the ordinate represents the animal’s average acuity relative to its preexposure acuity.

As previously shown, variations in the number of pulses, the energy per pulse, or the area of involvement (spot diameter) produced no significant lingering effects beyond the actual exposure session for those exposures at or below the maximum permissible exposure (MPE). The impact of each exposure appeared independent of previous exposures, and there were considerable similarities in recovery for each exposure in terms of the magnitude of the initial deficit and the time required for full recovery. At the transitional zone between temporary and permanent visual loss, however, the impact that any one exposure had on the recovery from another exposure was dependent on the energy of the exposure, as well as the number and sequence of previous high-energy exposures. As the energy per pulse increased and individual exposures approached the transition zone between temporary and permanent visual loss, there were predictable increases in the time course of recovery functions for successive exposures presented over days or weeks. This cumulative effect on the nature of recovery occurred in spite of the fact that individual exposures were separated from each other by at least 24 h, and recovery from previous exposures often appeared complete within their immediate 30-min postexposure sessions. Typically, in the transition zone, successive exposures produced only slight variations in the size of the initial deficit, but there were significant differences in the time to full recovery for each exposure. In some cases, recovery first appeared complete within 30 to 45 min. However, 24 h later, the animal had more difficulty maintaining a stable baseline and often showed slight decreases in acuity.

In Figures 4-17 and 4-19, the differential effects of successive exposures are shown for two animals exposed to 50 and 100 µJ pulses. Each animal was exposed to only one 15 ns pulse per day. Following the first several exposures at these energy levels, recovery was complete within a matter of minutes. In the case of the 50 µJ exposures (see Figure 4-17), for the first three exposures at this energy level, the animal’s postexposure acuity returned to its baseline preexposure level within the test session; no prolonged effect beyond the initial transient deficit was noted in subsequent baseline testing over the next several days. The maximum initial deficit elicited by these high-energy, large spot exposures was approximately 70%, and acuity began to improve almost immediately after this unusually large initial acuity shift. Total recovery time for the first exposure was approximately 10 min, for the second exposure 14 min, and for the third exposure 18 min. For the fourth exposure, the size of the initial deficit was similar to the previous three exposures, and the animal’s acuity again returned to its baseline within 18 min.

However, unlike the first three exposures, for this fourth exposure the animal was unable to maintain this baseline level, and its acuity again dropped and leveled off at approximately 35% of its preexposure level. Full recovery did not occur within the next 30 min, and this animal’s postexposure acuity on subsequent days appeared unusually inconsistent both within- and between-test sessions. This animal received no additional exposures, and its postexposure acuity baseline remained somewhat depressed over the next 6 months. During this period, the animal failed to consistently maintain a stable baseline in its exposed eye, varying by as much as 50% from the preexposure baseline. The acuity in its unexposed eye was normal and consistent over the course of the next 6 months.

Figure 4-18 shows the actual daily average postexposure acuity for this animal following a fourth single 50 µJ pulse, with considerable uncharacteristic day-to-day variability. This animal’s postexposure acuity to various background targets was also followed over the next several weeks. Overall, the animal’s acuity during this 16-day period averaged nearly 25% below its previous consistent baseline, varying some days by as much as 50% from its preexposure level. Several other animals exposed in a similar manner did not show as great a day-to-day variation as seen in this example; instead, their acuity remained more consistently depressed for several days after exposure before any significant recovery occurred. All animals exposed to single 50 µJ pulses ultimately regained their acuity to a level consistent with both their control eye and their preexposure baseline. Often, however, it took several months before this recovery occurred.

Figure 4-17. Changes in visual acuity following four separate 50-µJ exposures. This animal was exposed over several weeks to single, high-energy, 532-nm, Q-switched pulses from a Nd:YAG (neodymium-doped yttrium aluminum garnet) laser. Each exposure was presented on-axis and created a 250-µm diameter spot on the retina. Only one exposure was made per session (day); postexposure acuity was measured using high-luminance backgrounds against darkened Landolt rings. The abscissa represents the minutes following exposure; the ordinate represents the animal’s average acuity relative to its preexposure acuity. Blue diamonds represent the animal’s postexposure acuity to the first of four laser pulses, red diamonds represent the second pulse, circles represent the third pulse, and triangles represent the fourth pulse.

Figure 4-18. Mean daily postexposure acuity following multiple 50-µJ exposures. This animal was exposed to four separate 50-µJ, 532-nm, Q-switched pulses (see Figure 4-17). Each laser pulse was separated from the other by at least several days. Following each exposure, postexposure testing continued until a stable baseline was again established consistent with this animal’s preexposure acuity level. Once a stable baseline was established, the animal was reexposed to another 50-µJ pulse, and postexposure testing continued until the animal had apparently recovered from that exposure. This figure demonstrates the day-to-day changes in baseline acuity over a 16-day period following the fourth and final 50-µJ pulse. Each data point represents the average deficit derived from a minimum of 30 to 45 min of testing. No laser exposures were made during this time period. The abscissa presents the days after the last exposure; the ordinate represents the animal’s average postexposure acuity relative to its preexposure acuity.

Similar to the exposure paradigm shown in Figure 4-17, Figure 4-19 demonstrates changes in an animal’s immediate postexposure acuity following four separate 100 µJ pulses. Again, each exposure consisted of a single Q-switched pulse that was positioned coaxial with the gap in a threshold Landolt ring and produced a 250 µm spot on the retina. Only one Q-switched pulse was presented per day and only after the animal had established a stable preexposure baseline. In contrast to the exposure paradigm for the 50 µJ pulse, each 100 µJ pulse shown in Figure 4-19 was presented at least 5 weeks apart. In the period between exposures, average daily postexposure baselines were measured and are shown in Figure 4-20. At this high-energy level, animals typically had considerable difficulty fully recovering from the exposure during the normal 30-min postexposure session. In Figure 4-19, similar to the recovery functions shown in Figure 4-17, this animal appeared to regain its preexposure acuity baseline for the first three exposures within 15 to 20 min of exposure. But, unlike the recovery to 50 µJ pulses, this animal exposed to 100 µJ pulses was unable to maintain its preexposure baseline in subsequent daily postexposure testing in spite of the fact that no additional exposures were made.

Figure 4-19. Changes in visual acuity immediately following each of four separate 100-µJ exposures. This animal was exposed over a several weeks to high-energy, 532-nm Q-switched pulses from a Nd:YAG (neodymium-doped yttrium aluminum garnet) laser. Each exposure was a single Q-switched pulse presented coaxial with the gap in threshold Landolt ring (on-axis) and created a 250-µm diameter spot on the retina. Only one exposure was made per session. Postexposure acuity was measured using high-luminance backgrounds against blackened Landolt rings. Postexposure acuity was plotted against the animal’s preexposure baseline for each of the four separate exposures. The abscissa represents time after exposure; the ordinate represents average postexposure acuity. The recovery function following the first exposure is plotted with squares, the second exposure is plotted with diamonds, the third exposure is plotted with triangles, and the fourth exposure is plotted with circles.

Postexposure testing continued for this animal for 5 weeks before each reexposure; this process was repeated five times until eventually the animal failed to recover during the 30-min postexposure session. For example, after the first exposure, the animal appeared to fully recover within 6 min, but in the days that followed demonstrated a subtle but consistent depression in acuity (see Figure 4-20). Several months later, this animal’s acuity remained stabilized and depressed at 0.75 (min of arc)-1. At this point, the animal was exposed to a second 100 µJ pulse. Again, its immediate postexposure acuity appeared to return to its previously reduced baseline in approximately 14 min. After 24 h, the animal’s baseline acuity level again shifted from 0.75 (min of arc)-1 to 0.6 (min of arc)-1.

This animal’s acuity was followed for another 5 weeks before a third exposure was made. The immediate deficit produced by a third exposure was again similar to those of the first two exposures and quickly recovered to its previously depressed baseline in approximately 15 min before dropping to a stable baseline of approximately 0.4 (min of arc)-1. After another 5-week period of almost daily testing, the animal was exposed to a fourth 100 µJ pulse. Following the fourth exposure, the animal was unable to regain its previous stabilized acuity within the 30-min test session. After still another delay of 5 weeks, this animal was exposed to a fifth and final 100 µJ pulse (not shown). The reaction to this exposure was somewhat similar to that of the fourth exposure in that the animal was unable to regain its immediate preexposure acuity during the 30-min postexposure session and in subsequent testing remained somewhat stable at approximately 0.4 (min of arc)-1. These lingering effects for each of the five separate 100 µJ pulses represent this animal’s average postexposure acuity over a 5-month period and demonstrate a growing visual deficit with each 100 µJ pulse.

Long-term changes in visual acuity were followed in this animal after the fifth and final 100-µJ, Q-switched pulse. Figure 4-21 shows the gradual improvement change in this animal’s acuity over a period of several years. More than 3 years later, this animal’s acuity of 0.9 (min of arc)-1 was still depressed almost 40% from its original preexposure baseline of 1.45 (min of arc)-1, but was significantly better than the 0.4 (min of arc)-1 level noted in the weeks immediately following this final exposure. Acuity in this animal’s control eye remained normal and consistent during this entire period of postexposure testing.

Figure 4-20. Mean weekly postexposure acuity following each of five 100-µJ pulses. Each curve represents the average weekly acuity measured daily over a period of 5 weeks. Visual acuity was derived under high-luminance conditions; no laser exposures were made during each of the 5-week postexposure periods shown. Blue squares represent the average postexposure acuity following the first exposure, red squares represent the average postexposure acuity following the second exposure, triangles represent the average postexposure acuity following the third exposure, diamonds represent the average postexposure acuity following the fourth exposure, and circles represent the average postexposure acuity following the fifth exposure. Postexposure acuity is plotted on the ordinate in (min of arc)-1.

Figure 4-21. Long-term postexposure changes following high-energy exposure. Average weekly visual acuity for one animal exposed to five separate 100-µJ pulses. All exposures were presented on-axis. Each data point (diamonds) repre-sented mean weekly acuity measured in (min of arc)-1 and the vertical bars through each data point represent the range of variability (minimal and maximal) of these test sessions. Visual acuity was measured using high-luminance, achromatic backgrounds against darkened Landolt rings (high-acuity criterion) and plotted on the ordinate in (min of arc)-1.

Complete spectral acuity curves were also derived for this subject’s control and exposed eyes using both high (photopic) and low (scotopic) luminance conditions. Figure 4-22 represents the spectral acuity curves using a high-acuity criterion. Interestingly, spectral acuity showed less of a maximum deficit than achromatic acuity. Using achromatic targets, this animal’s maximum acuity in the exposed eye was 0.9 (min of arc)-1 relative to 1.4 (min of arc)-1 in the control eye, whereas chromatic acuity in the exposed eye was 0.8 (min of arc)-1 versus 1.1 (min of arc)-1 in the control eye. For the exposed eye, the shape of its spectral acuity curve, however, was somewhat flat across the entire visible spectrum while in the control eye; and this animal’s spectral acuity peaked between 480 and 520 nm. Overall, the two spectral curves for the control and exposed eyes overlapped considerably, except in the short-wavelength region of the spectrum where the short-wavelength sensitivity in the exposed eye was approximately 30% reduced from that of the unexposed eye. Not shown here are the spectral acuity curves for low-acuity criterion (low-luminance conditions). Under these luminance levels, the spectral curves for the control eye wer also flat across most of the visible spectrum and to that extent were similar to the curve shown here for the exposed eye. The spectral curve for the exposed eye under these reduced luminance conditions (low-acuity criterion) was greatly depressed; the criterion was difficult to derive at the spectral extremes, leaving measurements available only for midspectrum background targets.

Figure 4-22. Postexposure spectral acuity. Postexposure acuity for an animal exposed to five separate 100-µJ Nd:YAG (neodymium-doped yttrium aluminum garnet) laser pulses that produced long-term deficits in acuity. Acuity was measured using different chromatic backgrounds equated for equal energy against darkened Landolt rings. Diamonds represent the spectral acuity of the unexposed (or control) eye (OD; oculus dextrus [right eye]); squares (OS; oculus sinister [left eye]) represent the exposed eye. Each data point represents the mean acuity for this spectral background tested over a period of approximately 1 month.

Fundus examination of exposed eyes was routinely performed and often showed punctate lesions in both the fovea and parafovea in those animals with permanent functional losses. Retinal optical coherence tomography scans in these animals showed retinal thinning and NFL loss in the macula and papillomacular bundle. Fluorescein angiography typically showed leakage at the punctate foveal damage site within the foveal vascular zone.

DISCUSSION

The visual deficits that were elicited by laser exposure are consistent with what would be expected with temporary or permanent foveal loss. Exposures presented outside the fovea produced little or no effect on maximum photopic visual acuity. Exposure of wide regions of the fovea or macula by large-diameter spots or by repetitive, small-diameter pulses led to immediate and often sustained decreases in visual acuity. Typically, the animal’s visual acuity dropped immediately after exposure to a maximum deficit that remained depressed for several minutes before gradually returning to its preexposure level. The magnitude of the initial deficit appeared related to the area of retinal involvement, whereas the duration for full recovery was more dependent on the energy rather than the size of the exposure.

Consistent with the nature of our visual task, exposure to single Q-switched pulses of minimal spot diameters produced little or no acuity deficits. Irradiation of very small foveal regions (<50 µm) would not be expected to disrupt enough photoreceptors and/or neural pathways in any one region to seriously limit the processing of incoming visual information. Even for energy densities significantly above the ED_50, multiple pulses presented over several exposure ses-sions or within the same exposure session would be necessary to produce damage in a large enough region to alter an animal’s ongoing photopic acuity. The only exception might be transient changes that could result from exposures powerful enough to induce retinal bleeding and thereby obstruct the light pathway as it travels through the ocular media. At energy levels near the ED_50, both single and multiple Q-switched pulses did temporarily impede the ability of the animal to consistently maintain a baseline photopic acuity, perhaps suggesting changes in the opacity within the eyeball. Although large-diameter exposures and more pulses per exposure produced larger and more sustainable visual deficits, it was only the combination of these factors that elicited a permanent deficit in visual acuity.

A relatively wide range of different retinal spot sizes (50–825 µm) was used in this study, and these variations in the size of the exposure did produce initial deficits of varying degrees. Typically, the larger the spot size, the greater the initial deficit and, to some extent, the longer the time required for full recovery. The same relationship was generally true for the number of Q-switched pulses. Single, 15 ns pulses normally had only a minimal impact on the ability of the animal to maintain its preexposure baseline unless the spot size was large (>200 µm). These brief laser pulses would allow a highly motivated observer the ability to “look” around the affected regions and still maintain maximum visual performance. Consistency might be a problem, however, and with single Q-switched pulses, we did observe subtle changes in discrimination errors (false positives and misses) and response times that were not characteristic for the subject. This was especially the case when intense, but extremely small, punctate exposures were made within the fovea. On the one hand, bleeding and involuntary eye movements possibly affected the ability of even highly motivated animals to consistently maintain the discriminanda on functional rather than irradiated or clouded regions of the fovea. On the other hand, multiple Q-switched pulses, even for these small spot sizes, typically elicited more sizable initial deficits that required longer recovery times. Larger diameter multiple pulses produced even larger visual deficits and required still more time for full recovery.

Increasing the power density of individual pulses generally produced longer recovery times and, in some cases, produced prolonged deficits that extended beyond the typical 30-min postexposure test session. Multiple Q-switched pulses at energy levels 10× below the ED_50 produced only transient deficits in immediate postexposure acuity. These deficits were reminiscent of the deficits we observed for long-duration expo-sures (millisecond time domain) below the ED_50 or for Q-switched pulses (nanosecond time domain) above the ED_50 where neuropathological effects would be expected. However, if the area of retinal exposure was small (50–100 µm), due either to the number of pulses presented and/or the diameter of the exposure site, little change was noted either to the animal’s immediate or long-term postexposure visual acuity regardless of the exposure energy used. Even for initial exposures at energy levels that were significantly above the ED_50 (10× to 100×), remarkably little decrement in visual acuity was often noted. In several cases, single Q-switched pulses of larger retinal diameter (>100 µm) produced more pronounced visual deficits that were similar in nature to the transient deficits produced by large-diameter, longer duration (either millisecond CW exposures or multiple nanosecond Q-switched) pulses. When significant areas of the fovea were involved, an immediate drop in baseline photopic acuity resulted, and what followed was a gradual recovery that often lasted 45 min or longer. Both the magnitude and duration of the observed visual deficits were related to the amount of retinal area involved (exposure spot size) and to the number of Q-switched pulses presented.

With larger spot sizes, the exposure energy clearly influenced the duration of the initial deficit, as well as the likelihood of full recovery within the remaining time of the test session. The impact of multiple expo-sures under this condition often became prolonged and sometimes permanent for Q-switched pulses above the ED_50. Unlike millisecond time-domain exposures, no similar cumulative effect was noted for repeated nanosecond time-domain exposures at energy levels significantly below the ED_50. The lack of any corresponding cumulative impact for Q-switched pulses is noteworthy. Although high-energy exposures often produced transient acuity shifts, our results suggested that for the smallest diameter and shortest duration exposures, the functional criterion may be limited in defining a permanent effect, even when minimal neuropathy may be present. However, we have noted significant initial effects and possibly subtle longer-term changes in discrimination errors, especially when multiple punctate exposures within the fovea are made. These less conspicuous effects could possibly reflect more global dysfunction when briefly presented discriminable targets fall on “altered” retinal regions. The consequences of repeated exposures within these transitional energy zones may be particularly important in understanding these changes. The demonstration of any transitional zone between temporary and permanent functional changes for nanosecond time-domain exposures similar to that found for millisecond time-domain exposures would suggest the possibility of increased susceptibility of exposed tissue to permanent damage, especially in situations involving brief, but repeated, low-level energy exposures.

The transient effects observed in this study at energy levels below the ED_50 and below those that might cause edema suggest that single, isolated Q-switched pulses can have a significant impact on an animal’s immediate postexposure acuity, even if the consequence is not permanent. The time course of these transient effects suggests reversible receptor or photochemical alterations that may bypass the normal time parameters of visual adaptation. Still unresolved is the possibility that repeated nanosecond time-domain exposures within the same retinal region might ultimately become additive and eventually produce permanent functional changes similar to those that we have demonstrated for millisecond time-domain exposures. If that were the case, over time these transient visual deficits might blossom into significant permanent functional loss with minimal initial warning. Such changes would likely not be immediately apparent through an ophthalmoscope, but might be observable if visual functioning was carefully tracked.

The energy required to produce a threshold functional deficit for the nonhuman retina in the millisecond time domain (CW exposures) approximated damage thresholds using morphological criteria; and, in some cases, especially when using repeated exposures or large spot sizes, was somewhat lower than that found using nonfunctional criteria.29,30 Pathology thresholds for nanosecond time-domain exposures are even lower than for millisecond time-domain exposures and may be the result of higher peak powers produced by these briefer pulses.[31] Such concentrations of energy can create, in addition to a thermal component, acoustic damage when they interact with the retina. In comparison to longer-duration exposures, this acoustic or mechanical insult may be sufficient to rupture tissue membranes at much lower energy levels than is possible in the millisecond time domain. In relation to the function of retinal tissue, Q-switched pulses are deposited within the neural layers of the retina before photoreceptors are normally able to respond. These rapid deliveries of light energy could temporarily short circuit the full response of the photoreceptor system and bypass its normal adaptation function. However, because the pulse is still sufficient to cause morphological damage, alterations in permanent visual function might still occur. Due to its limited temporal and spatial domains, repeated nanosecond exposures may be required to influence large enough areas necessary to produce a significant overall functional effect.

Using exposures in the millisecond time domain, we have shown that regardless of the size of the spot on the retina, even larger areas of involvement typically occur because of the smearing effect of involuntary eye movements. Somewhat independent of the differences in exposure energies used, the immediate and often transient acuity deficits that resulted from millisecond time-domain exposures were larger than those shown here using nanosecond time-domain exposures. Given the differences in spatial characteristics of these two types of exposures, repeated exposures over different sessions would more likely irradiate the same retinal regions when large-diameter, longer-duration (millisecond time domain) exposures are used. With minimal diameter Q-switched pulses of limited spatial extent, repeated exposures in either the same or different exposure sessions would have a much lower likelihood of exposing the same retinal region. Thus, the lack of any cumulative impact observed when using Q-switched pulses at energy densities below the ED_50 for nanosecond time-domain exposures, but not for the millisecond time-domain exposures, could be explained on the basis of nonoverlapping sites and not strictly by differences in the delivery of energy over time.

In our previous studies using millisecond time-domain exposures, permanent acuity deficits were noted following repetitive exposures at energies below the MPE.[24] Recent ophthalmoscopy on one animal suggests that these types of cumulative functional deficits, even at levels below the MPE, can be associated with distinct pathology in the eye. Although in the current study, no similar cumulative functional effect was noted for low-energy, Q-switched pulses, a distinct cumulative effect was evident for small spot exposures at energy densities above the MPE. Similar to lower-energy and longer time-domain exposures, repetitive high-energy Q-switched pulses produced longer and longer recovery times until evidentially a permanent functional deficit was observed. Unlike the millisecond time-domain exposures, however, the size of the initial deficit with repeated exposures did not significantly change when high-energy nanosecond time-domain exposures were made. This suggests that even small-diameter, high-energy, Q-switched pulses can produce a significant dazzle effect independent of any permanent change that it might produce.

These results may be consistent with other functional studies using slightly different exposure conditions. For example, it has been demonstrated that repeated extended source exposures slightly above the MPE for a single-extended source exposure induce a bull’s-eye maculopathy that imaged confocally; these results suggested a primary or secondary retinal nerve fiber defect. However, in this case, no permanent loss in high-contrast grating acuity was observed.[32] Visual targets in that study did not exceed a Snellen acuity of 20/40, whereas in our studies animals normally achieved preexposure photopic acuity levels better than 20/15 when using Landolt ring targets. The deficits noted in our studies are above the maximum acuity range previously noted.

Of particular interest in our results was the consistent temporary enhancement in acuity (hyperacuity) that followed each acuity deficit produced by low-energy, Q-switched exposures. Hyperacuity was routinely observed following either single or multiple 0.1 µJ, Q-switched pulses and, like the preceding acuity deficit, this enhancement was also not sustainable. The cause of this hyperacuity is difficult to discern, but it might be significant that it was only obvious with on-axis exposures and with low-energy exposures that produced small and transient deficits. A similar enhancement effect might not be expected in off-axis exposures where neural networking and spacing between cells are different. Exposing the fovea to intense light might eventually disinhibit the areas within and around the central fovea by fatiguing the retina’s lateral inhibition mechanisms. The sensitivities and recovery times for this neural inhibitory mechanism and that of the photochemical process in the receptor cell could be different and could possibly account for this apparent enhancement.[33]

SUMMARY

In conclusion, several hypotheses were made and empirically supported. First, light-induced damage to the retina disrupts visual performance, as well as retinal physiology. The type and magnitude of the functional alteration appear related to the loca tion and degree of the retinal insult. Structural damage to photoreceptors should affect an organism’s fine-resolution capability through changes in the organism’s inherent color, brightness, and contrast sensitivities. These changes should be especially distinct if foveal areas are involved. Damage to areas outside the fovea may disrupt scotopic and peripheral vision, but would not be easily detected unless more complex visual field testing is performed. Using our performance paradigm, only foveal damage would disrupt photopic acuity, although scattered damage throughout the parafoveal region should increase within-session variability. Typically, we have defined these parafoveal and peripheral exposures as misses; in reality, the animal’s retina was likely exposed, but not in the region where photopic acuity would be altered. This notion is supported by the limited acuity changes produced when our exposures were purposely made off-axis from the animal’s fixation point.

Second, the size of the irradiated retinal area should directly influence the magnitude of the observed visual deficit. As previously stated, irradiation of very small regions of the fovea still permits a highly motivated observer to develop alternative viewing strategies that could effectively allow him/her to look around isolated dysfunctional regions and maintain a high-acuity criterion. Larger spot sizes or multiple exposures within the same region would make this strategy less effective. Also, exposing larger retinal zones increases the probability of a “successful” foveal exposure because a larger retinal region is irradiated, which increases the probability that at least some portion of the central fovea will be involved. Exposing the animal to a single pulse (nanosecond duration) of a relatively small spot diameter (<100 µm) evokes only a small lesion even at the highest power densities and therefore elicits only minimal acuity shifts that might appear transient in nature. Edema, bleeding, and other damage and repair mechanisms are often delayed, and their impact would not be immediately obvious.

Somewhat unexpected was the lack of consistent and large-scale deficits when relatively large-diameter (100–500 µm), single Q-switched pulses were presented. These very brief exposures produced only small observable deficits for both high- and low-acuity criterion. It is likely, however, that exposures of this brief duration (15 ns) did not allow for involuntary eye movements to produce enough “smearing” of the exposure and therefore increased the probability that the exposure site was not consistently centered within the fovea. Hence, below the ED_50, our paradigm appeared unable to fully delineate transient acuity deficits in spite of the fact that some temporary or even semipermanent damage might have occurred. Using more spatially complex targets or more sensitive measures of contrast sensitivity and/or color vision could delineate subtle functional changes not observed in the current study. Repetitive Q-switched pulses were shown to summate their individual effects and create significant transient shifts in immediate postexposure acuity, even for those energy levels significantly below the MPE. Fewer, larger-diameter exposures should produce the same overall effect as would longer-duration, single exposures from a CW laser. Furthermore, repeated low-energy exposures within the same retinal region, even if delayed by hours or days, may increase the long-term susceptibility of that particular tissue to insult. If the nature of nanosecond exposures is consistent with that observed for millisecond exposures, these individual exposures can be presented beyond the time needed for full functional recovery to any one exposure. In both nanosecond and millisecond exposures, we have noted within the transitional zone that repetitive exposures that initially produce only minimal baseline shifts can increase the variability of the animal’s postexposure acuity. This more erratic behavior was normally temporary, lasting only several days or weeks, and might be the result of ongoing repair mechanisms within the affected tissue. With time, variability should decrease and acuity improve as the repair mechanisms proceed, as surrounding unaltered photoreceptors migrate into the area now devoid of active photoreceptors, and/or as the animal learns to compensate by improving its fixation ability to stabilize the critical features of the target on unaltered portions of the retina.

Shifts in postexposure acuity noted in our study could also be explained by an initial edema within or surrounding the exposed tissue. Swelling of the retina tissue would alter photoreceptor orientation, spacing, and possibly neural functioning. These changes could clearly alter the ability of the exposed animal to resolve spatial detail. If swelling occurred, the initial acuity defi cit would be expected to grow in time, stabilize, and possibly then decrease depending on the time course of the edema. Combined with ocular clouding, due to even minor hemorrhages that could develop from low-energy exposures, transient acuity deficits could also have resulted from increased light scatter that created a blurred image within an otherwise intact neural encoding system. As the hemorrhage dissipated over time, acuity would have then returned to normal. These optical changes in image clarity should be more transient than those caused by encoding problems associated with photoreceptor repair.

Even more immediate and transient postexposure acuity changes could be explained by a dazzle effect. Its time course could correspond to the normal regeneration of pigments or could be prolonged depending on any reversible actinic insult that might also accompany the exposure. Psychological variables associated with even temporary blindness might also adversely impact the organism’s normal viewing and decision-making strategies. Changes in the ratio of false alarms to correct detection and misses to correct rejections might signal shifts in the organism’s confidence level and strategies used to complete the task. Ultimately, however, in forced-choice tasks where there is a high payoff for positive performance, observers should develop strategies to maximize their perceived rewards. Following laser exposure, such strategies should involve altered points of fixation to maximize the use of retinal regions with the highest ongoing sensitivities. Our data clearly support the notion that our animals did engage in defensive behavior that maximized their existing visual sensitivities because their visual acuity did not drop to zero after exposure, but rather quickly stabilized at new levels consistent with the resolution power of the parafovea.

Research to address ocular damage in the workplace should extend beyond the problem of treatment intervention to include training strategies for alternative viewing of critical target features. Studies of this type provide unique opportunities to generate immediate postexposure visual performance under a wide array of exposure conditions both below and above the ED_50. There is potential value in the opportunity to train personnel to minimize the impact of potentially damaging light through strategies that support continuation of visually guided missions. These strategies are important not only for those with pathology, but also for those who might be only temporarily disabled by laser irradiation. Data from studies of this kind could also be used to further delineate the impact of dazzle, changes in the integration of neural retinal circuits, minute enzyme changes within irradiated tissue, and changes in ocular opacity that might not otherwise be evident by traditional ophthalmoscopic examination. We would not expect that these data would be inconsistent with the morphological data, but they may reveal more subtle effects—including photochemical and neural processes—that could equally degrade visual performance.

Acknowledgments

This research was supported in part by a contract to Ohio Wesleyan University from the US Army Medical Research Detachment, Walter Reed Army Institute of Research, Brooks Air Force Base, Texas.

The death of Dr Harry Zwick was a tremendous personal and professional loss. Dr Zwick’s lifelong dedication to advancing our understanding of the visual system and his commitment to his research program and fellow researchers were without parallel.

In conducting the research described in this chapter, the investigators adhered to the Guide for the Care and Use of Laboratory Animals, as promulgated by the Committee on Revision of the Guide for Laboratory Animal Facilities and Care, the Institute of Laboratory Animal Resources, and the National Academy of Sciences–National Research Council.

REFERENCES

1. Curcio CA, Sloan KR Jr, Packer O, Hendrickson AE, Kalina RE. Distribution of cones in human and monkey retina: individual variability and radial asymmetry. Science. 1987;236:579–582.

2. Roorda A, Metha AB, Lennie P, Williams DR. Packing arrangement of the three cone classes in primate retina. Vision Res. 2001;41:1291–1306.

3. Ham WT Jr, Geeraets WJ, Mueller HA, Williams RC, Clarke AM, Cleary SF. Retinal burn thresholds for the helium-neon laser in the rhesus monkey. Arch Ophthalmol. 1970;84:797–809.

4. Powell JO, Bresnick GH, Yanoff M, Frisch GD, Chester JE. Ocular effects of argon laser radiation. II. Histopathology of chorioretinal lesions. Am J Ophthalmol. 1971;71:1267–1276.

5. Robbins DO, Zwick H. Changes in spectral acuity following brief laser (647 nm) exposure. In: Vierriest G, ed. Colour Vision Deficiencies V. Bristol, England: Adam Hilger Press, Ltd.; 1980: Chap 2.

6. Zwick H, Bedell RB, Bloom KB. Spectral and visual deficits associated with laser irradiation. Mod Probl Ophthalmol. 1974;13:299–306.

7. Zwick H. Visual functional changes associated with low-level light effects. Health Phys. 1989;56:657–663.

8. Tso MOM. Photic maculopathy in rhesus monkey. A light and electron microscopic study. Invest Ophthalmol. 1973;12:17–37.

9. Custis PH, Gagliano DA, Zwick H, Schuschereba ST, Regillo CD. Macular hole surgery following accidental laser injury with a military range finder. Proc SPIE. 1996;2674:166–174.

10. Stuck BE, Zwick H, Molchany JW, Lund DJ, Gagliano DA. Accidental human laser retinal injuries from military laser systems. Proc SPIE. 1996;2674:7–20.

11. Marshall J. Structural aspects of laser-induced damage and their functional implications. Health Phys. 1989;56:617–624.

12. Marshall J. Blinding laser weapons. Br Med J. 1997;315(7120):1392.

13. Zwick H, Ness JW, Molchany JM, Stuck BE, Loveday J. Utilization of scanning laser ophthalmoscopy in laser induced human retinal nerve fiber layer damage. Proc SPIE. 1998;3246:144–147.

14. Zwick H, Stuck BE, Dunlap W, Scales DK, Lund DJ, Ness JW. Accidental bilateral Q-switched neodymium laser exposure: treatment and recovery of visual function. Proc SPIE. 1998;3254:80–89.

15. Zwick H, Ness JW, Molchany JM, Stuck BE, Loveday J. Neural motor ocular strategies associated with the development of a pseudofovea following laser-induced macular damage and artificial macular occlusion: is the fovea replaceable?J Laser Appl. 1998;10:144–147.

16. Zwick H, Stuck BE, Scales DK, Brown J, Ness J. Longitudinal evaluation of selected human laser eye accident cases. Proc SPIE. 2001;4246.

17. Ramon Y, Cajal S. Degeneration and Regeneration of the Nervous System. May RM, trans. New York, NY: Haffner Publishing Co; 1928. Vol 2.

18. Houle JD. Demonstration of the potential for chronically injured neurons to regenerate axons into intraspinal peripheral nerve grafts. Exp Neurol. 1991;113:1–9.

19. Tom VJ, Steinmetz MP, Miller JH, Doller CM, Silver J. Studies on the development and behavior of the dystrophic growth cone, the hallmark of regeneration failure, in an in vitro model of the glial scar and after spinal cord injury. J Neurosci. 2004;24:6531–6539.

20. Brittis PA, Silver J. Multiple factors govern intraretinal axon guidance: a time-lapse study. Mol Cell Neurosci. 1995;6:413–432.

21. Inman DM, Steward O. Ascending sensory, but not other long-tract axons, regenerate into the connective tissue matrix that forms at the site of a spinal cord injury in mice. J Comp Neurol. 2003;462:431–449.

22. Marshall J, Hamilton AM, Bird AC. Histopathology of ruby and argon laser lesions in monkey and human retina. A comparative study. Br J Ophthalmol. 1975;59:610–630.

23. Robbins DO, Zwick H, Bearden BD, Evans BS, Stuck BE. Visual acuity changes in rhesus following low level Q-switched exposures. Proc SPIE. 1997;2974:94–104.

24. Robbins DO, Zwick H. Subthreshold functional additivity occurring at the transition zone between temporary and permanent laser-induced visual loss. Proc SPIE. 1996;2674:44–52.

25. Pizzorusso T, Medini P, Berardi N, Chierzi S, Fawcett JW, Maffei L. Reactivation of ocular dominance plasticity in the adult visual cortex. Science. 2002;298:1248–1251.

26. Robbins DO, Zwick H, Holst GC. Functional assessment of laser exposures in awake, task-oriented, rhesus monkeys. Mod Probl Ophthalmol. 1974;13:284–290.

27. Robbins DO, Zwick H, Holst GC. A method for producing foveal retinal lesions. Behav Res Meth Instr. 1973;5:457–461.

28. Robbins DO, Zwick H, Leedy M, Stearns G. Acute restraint device for rhesus monkeys. Lab Animal Sci. 1986;36:68–70.

29. Robbins DO. Analysis of Retinal Function Following Laser Irradiation. Fort Detrick, MD: US Army Medical Research and Development Command; 1992. Final Report Contract DAMD17-83-C-3172 and DAMD17-88-C-8032.

30. Zwick H, Robbins DO, Stuck BE, et al. Small-spot laser exposure effects on visual function. Proc Int Soc Opt Eng. 1990;1207:71–88.

31. Zwick H, Robbins DO, Reynolds SB, et al. Effects of small spot foveal exposure on spatial vision and ERG spectral sensitivity. In: Drum B, Moreland JD, Serra A, ed. Color Vision Deficiencies X. Dordrecht, The Netherlands: Kluwer Academic Publishers; 1991: 581–597.

32. Rhodes JW, Zuclich JA, Zwick H, et al. Bullseye-gap maculopathy associated with repeated large spots, Q-switched laser exposure. Paper presented at: Annual Meeting of the Association for Research in Vision and Ophthalmology; May 1–6, 1994; Sarasota, FL.

33. Zwick H, Gagliano DA, Zuclich JA, Stuck BE, Lund DJ, Glickman RD. Confocal scanning laser evaluation of repeated Q-switched laser exposure and possible retinal NFL damage. Proc SPIE. 1995;2391:634–639.

Chapter 5

LASER GLARE EFFECTS ON VISUAL PERFORMANCE

PETER ALAN SMITH, PhD * Technical Fellow, Science Applications International Corporation, Tri-Service Research Laboratory, 4141 Petroleum Road, Joint Base San Antonio, Fort Sam Houston, Texas 78234

INTRODUCTION

Units of Measurement

NORMAL VISUAL ADAPTATION

Mechanical Mechanisms

Photochemical Mechanisms

Neurophysiological Processes

TEMPORARY CHANGES IN VISUAL SENSITIVITY

Glare

Factors Affecting Laser Glare Effects

Glare Recovery

Factors Affecting Visual Recovery Time

Transient Effects of Laser Exposure

SUMMARY

INTRODUCTION

There have been many studies of the threshold energy required for laser-induced ocular damage. However, exposure to a visible laser that does not produce irreversible ocular damage can still result in substantial visual impairment through temporary mechanisms, such as glare and flash blindness. Visual deficits like these can disrupt visual performance and thus compromise the safety and success of military operations. The severity of laser glare and subsequent visual recovery depends on a number of factors, including parameters of laser exposure, presence of intervening optical materials, and requirements of the visual task.

Units of Measurement

Optical radiation can be described by two systems of terms and measurements: (1) radiometric quantities and (2) photometric quantities. The radiometric system is a physical system that can be applied throughout the electromagnetic spectrum. The photometric system is used only to describe visible radiation (ie, electro-magnetic radiation in the range of wavelengths from approximately 400 to 700 nm).

Radiometric Quantities

In the context of this chapter, radiometric quantities are used only in relation to the characteristics of laser radiation. The radiometric quantities (and units) referred to here are

- radiant energy (J),

- radiant power (W),

- radiant exposure (energy per unit area of

- absorbing source, J • m-²), and

Safe exposure limits are generally defined in terms of radiant exposure and irradiance.

Photometric Quantities

Although laser sources are usually described in terms of radiometric quantities, these give no indication of the effectiveness of the source as a stimulus for vision. The photometric system was developed to describe optical radiation in terms of its ability to elicit a response from the visual system. The basic unit of photometry is the lumen (lm), which is the photometric equivalent of the watt (W). Under photopic conditions, 1 W of radiant flux at 555 nm is, by definition, equivalent to 683 lm of luminous flux.[1] This wavelength is the peak of the sensitivity of the eye under photopic viewing conditions. The relative sensitivity of the eye to other wavelengths is defined by the International Commission on Illumination[2] (CIE) as the relative photopic spectral luminosity function, Vλ, for a standard observer (Figure 5-1). This function is given a value of unity at its maximum of 555 nm. For a laser with a radiant power (flux) of P in W at 555 nm, the luminous power (flux [in lm]) will be 683 × P lm. To generalize to any laser wavelength, λ, the luminous flux, ϕv, is calculated as:

Figure 5-1. The CIE photopic spectral luminosity curve for the standard observer. The curve has a peak sensitivity at 555 nm and declines toward zero at 400 and 750 nm. CIE: International Commission on Illumination

where

P

=

radiant power at this wavelength, and

Vλ

=

value of the relative spectral luminosity function at this wavelength.

NORMAL VISUAL ADAPTATION

The human visual system is capable of retaining its ability to detect a change in visual stimulation (sensitivity to light) over a wide range of illumination levels (Figure 5-2). Adaptation refers to the processes by which the system maintains sensitivity to changes in illumination. The mechanisms by which the human eye and visual system adapt to light can be grouped into three gross divisions: (1) mechanical, (2) photochemical, and (3) neurophysiological.

Figure 5-2. Visual function in relation to the normal range of light intensities confronting the human eye.

Mechanical Mechanisms

Mechanical adaptation mechanisms include the constriction of the pupil of the eye and, in extreme cases of intense light exposure, the blink reflex, and the natural aversion response to bright lights.

Pupillary Constriction

The iris controls the aperture of the refracting system (the pupil) of the eye. The iris acts as a diaphragm. It constricts or dilates through the opposing action of two sets of muscles: (1) the sphincter pupillae and (2) the dilator pupillae. Pupil size is thus governed by the refractive state of the eye and in response to the average brightness of the scene being viewed.3,4 In an adult human, maximum pupil diameter in the dark is approximately 8 mm, although larger pupil diameters have been documented.[5] Current laser safety standards accept a value of 7 mm as a worst-case maximum pupil diameter. The pupil has a complex response to bright light exposure,[6] but on prolonged exposure will generally constrict to a minimum pupil diameter of approximately 2 mm.

The amount of light that enters the eye is directly proportional to the area of the pupil. Pupil diameter range (2–8 mm) allows for a 16-fold change in pupillary area. For a large change in illumination, pupillary constriction and dilation response times are fairly slow, reported at 0.2 and 0.5 s, respectively.[6] These response times are wholly inadequate to protect the human eye from intense light sources.

Although the pupil plays a useful role in the adaptation of the eye to changes in luminance level, it clearly lacks the dynamic range to support changes much beyond an order of magnitude. The pupil assumes a greater role in image formation in the eye. Optical aberrations are much greater in the periphery of the cornea and the lens.7,8 Pupillary constriction excludes light that passes through the peripheral portions of these structures. Constriction also serves to increase depth of focus and occurs synergistically with accommodation for near objects. Under normal lighting conditions, the operating diameter of the pupil is between 2 and 4 mm.

Blink Reflex

Reflexive blinking can be evoked by almost any peripheral stimulus. The two most functionally significant reflexes are (1) the sensory blink reflex (which is caused by corneal stimulation) and (2) the optical blink reflex (which is caused by bright lights). Only the optical blink reflex is relevant to protecting the eye from overexposure to visible light. The latency of the optical blink reflex depends on the magnitude of the stimulus, but for the brightest lights would typically occur at about 250 ms.[9] Indeed, safety standards for some visible lasers (class 2) apply a 250 ms exposure time on the premise that aversion response (which includes the optical blink reflex) will limit exposure to this period of time.[10]

The blink reflex plays a very important role in protecting the eye. However, even when the eyelids are shut, the human eye can perceive the brightness of an external scene. Although detailed vision is not possible, changes in illumination level are still apparent. The human eyelid has a transmission ranging from approximately 0.3% in the blue region of the spectrum to 5.6% in the red region.[11] With regard to the normal processes of visual adaptation, however, the blink reflex is of little value when the eyelids are closed. In this state, the light level to which the visual system must adapt is greatly attenuated, and useful vision is lost until the lid reopens.

Photochemical Mechanisms

The presence of a steady level of illumination on a retinal photoreceptor bleaches a portion of the retinal photopigment and reduces the number of pigment molecules that remain in an unbleached, active state. This depletion of photopigment contributes to a loss in sensitivity with increasing field intensity. Under steady-state conditions, the increase in threshold should be inversely proportional to photopigment content. For example, halving the number of available molecules would be expected to double the threshold intensity. However, Aguilar[12] and Stiles[13] demonstrated that the visual system loses at least five to six log units of sensitivity before the photopigment is depleted by even a few percent. Within the range of normally encountered intensities, pigment depletion plays a small role in adaptation. At high luminance, however, pigment depletion accounts for all of the loss in sensitivity.[14]

If a light source is sufficiently bright, the subjective sensation may last much longer than the stimulus itself. It is this persistence that causes a moving light to be seen as a line or a flickering light to appear fused when the rate of flicker is sufficiently high. Remnants of past stimulation are known as afterimages and may continue for a relatively long period of time. Studies of afterimages have shown that they are the result of persistent photopigment changes that follow bleaching.15,16 The luminance of a surface judged to be exactly as bright as an afterimage has been shown to be proportional to the fraction of the photopigment that remains bleached.[17] Additional discussion of afterimages will appear later in this chapter.

Neurophysiological Processes

Although pupillary constriction and the depletion of photopigment both alter the adaptive state of the visual system, neurophysiological adaptation mechanisms exert more functionally significant effects. These processes are known as spatial and temporal induction and summation.

Spatial induction, or simultaneous contrast, refers to the observation that the effect of light falling on a given portion of the retina is generally not confined to the stimulated retinal elements. For example, a gray square viewed against a black background will appear as almost white, whereas the same gray square seen against a white background will appear to be much darker. The white surround has the effect of depressing the sensitivity of the entire retina, which makes the gray appear darker. The effect of temporal induction, or light adaptation, is similar. If the entire retina is stimulated with white light, its sensitivity to a subsequent second stimulus will be reduced.

Ricco’s law of areal or spatial summation states that when a stimulus is small and brief, the visual system shows complete summation over space and time.[18] For small test stimuli, there is an inverse relationship between the area of the stimulus and the intensity required for its detection. Bloch[19] showed that a similar relationship exists between stimulus duration and threshold. Bloch’s law of temporal summation states that the threshold remains the same as long as the product of stimulus intensity and duration (ie, the number of quanta) is held constant. This is true for stimulus durations shorter than a critical period of about 100 ms.[14] For slightly longer exposures, there occurs a phenomenon known as brightness enhancement, or the Broca-Sulzer effect, whereby a brief flash of light may appear to be brighter than a steady light of equivalent luminance.

TEMPORARY CHANGES IN VISUAL SENSITIVITY

Transient decrements in visual performance may be caused by artificial light sources at exposure levels that are lower than the levels necessary to cause permanent retinal damage. Unfortunately, the literature is inconsistent with respect to nomenclature used to describe these effects. Terms such as glare, dazzle, flash blindness, and afterimages are widely used, but are ill-defined and often used interchangeably.

Glare

Glare can be described as the hindrance to vision that is caused by too much light. Glare has been formally defined as any degree of light falling on the retina in excess of that which enables an individual to see clearly. In other words, glare is caused by any excess light that hinders rather than helps vision.[8] If glare is sufficiently intense, it can temporarily reduce the sensitivity of the visual system even after the source of glare is removed from the field of view. For example, a photographic flash often causes temporary flash blindness and afterimages. These phenomena are a function of retinal and visual pathway processes that will be discussed in more detail later in this chapter.

Glare phenomena have been differentiated into a variety of subcategories. As early as 1922, the Illumination Engineering Society of New York charged a subcommittee with investigating the subject of glare to “furnish a sound foundation for definite research regarding the matter.”20(p743) Based on the nature of the light source and particular types of resulting visual interference, three types of glare were identified:

1. veiling glare,

2. dazzle glare, and

3. scotomatic glare.

More recently, Vos[21] defined three expressions of glare as:

1. Disability glare refers to a masking effect that occurs when one or more bright lights are in close proximity to the object under view. Light scatter from the optic media results in the superimposition of a veil of light on the image of viewed object. This, in turn, reduces the object’s contrast and thus its visibility. Although absolute foveal illumination is increased, the concomitant reduction in image contrast makes detailed discrimination more difficult.

2. Discomfort glare refers to the distracting effect of a peripheral light source in the field of view. This phenomenon involves the same configuration as disability glare, but the effect is different. Discomfort glare does not necessarily impair the visibility of objects. Rather, the emphasis here is on the distracting effect. Discomfort glare is typically associated with bright light sources, such as road luminaries or ceiling spots, that attract attention and catch one’s gaze. This causes visual discomfort, but is not due to light overexposure.

3. Dazzling glare refers to the effects of an excessively bright field of view (eg, sunlight, snow, sky) that causes one to squint, avert gaze, don sunglasses, or take some other action to avoid the light. Overexposure to light may even be painful. If present, the pain probably originates in the sphincter muscle of the iris, which may spasm in an effort to overconstrict. The retina of the eye itself has no pain receptors.

Equivalent Background Luminance Concept

This concept (or equivalent veiling luminance) was developed in an effort to extrapolate the effect of a disability glare source to a wide variety of visual tasks. It was first introduced by Cobb[22] and later elaborated by Holladay,23,24 and the initial application was in relation to glare from car headlights. These studies showed that in the presence of a glare source, vision is impaired just as if a veil of light was cast over the objects in the field of view. The visual effect of the source could be described by superimposing an external luminous field onto the scene. The effect could thus be expressed in terms of steady luminous field intensity or “equivalent background,” which has an equivalent effect on target visibility. Equivalent background produces a contrast threshold elevation identical to that produced by the glare source.

Similar effects have been shown with afterimages. The contrast of a visual target viewed through an afterimage is reduced just as if a physical luminous background had been superimposed on the affected portion of the visual scene. Crawford[25] established a relationship between the equivalent background luminance and elapsed time for detection of a variety of simple targets following flashes of various energies. By measuring the background luminance for threshold detection of any target configuration at a given illuminance level, Crawford was able to predict the recovery time for that target following a known flash energy. The value of the equivalent background luminance technique lies in its predictive capability through its generalizability to other target conditions.

A great deal of evidence supports the equivalent background hypothesis in the human rod system,17,26–28 and further studies have extended the hypothesis to cone functions.29,30

The application of the equivalent veiling luminance technique to afterimage research has been largely limited to the studies performed by Miller.31–33 In the first of these studies, Miller[31] alluded to the fact that equivalent background may be useful to predict recovery times. In her later studies, she realized the full benefits of the technique and was able to predict recovery times from afterimage brightness measurements.

Factors Affecting Laser Glare Effects

Retinal Light Distribution

In a perfect optical system, the light from a laser would be seen by the eye as if it were coming from a point source. This would mean that only a small portion of the visual field would be affected. In reality, however, the eye may not be able to form a perfect image of the laser source. This is due to the scattering properties of the atmosphere, intervening optical materials, and the ocular media of the eye itself. If the scatter is of sufficient magnitude, the image will appear as a sharp, intense central peak surrounded by widely scattered radiation.

Intraocular Scatter. Although in principle the light from a point source should be imaged on the retina as a point, in reality focused rays do not all converge on the retina as a single spot. Optical imperfections (eg, spherical and chromatic aberrations, diffraction effects, and refractive errors) cause blurring.34-37 Retinal image quality is further degraded by stray light from intraocular scatter, which spreads approximately 8% of the incident light.[38] The cornea, lens, and fundus appear to contribute in approximately equal proportions to the total amount of intraocular scatter.

Several investigators have sought to understand the relationship between glare luminance and glare angle (radial distance from the center of the source image). Indeed, the equivalent veiling luminance technique was originally used to establish the luminance of the glare source as a function of glare angle, θ.[23] Later, Stiles[39] extended the use to calculate the equivalent veiling luminance and then used this value to estimate the resultant reduction in image contrast on the retina. In general, a glare spread function can be expressed as follows:

where

θ

=

the glare angle (degrees)

Lveil

=

the veiling glare luminance (cd . m-2),

Eglare

=

the glare illumination in the pupil plane (lux), and

K and n

=

constants.

The product of E . f(θ) gives the glare luminance in cd . m-2.

In the earliest studies of Holladay[23] and Stiles,[39] K = 10 and n = 2. This yielded the so-called Stiles-Holladay formula (Lveil/Eglare = 10/θ²). Early studies measured glare spread from 5° to 25°. Subsequent studies over different angular domains have found slightly different values for K and n, the most notable being a steepening of the relationship for small glare angles (< 5°).

Estimates of the extent of laser glare must therefore begin with attention to how the laser light is distributed on the retina. The precise shape of the retinal distribution has been a topic of great concern in applied vision work related to veiling glare. There have been concerted efforts to quantify retinal distribution. Most notable among these are the works of Vos.36,40–46 In a recent review, Vos published the Small Angle Disability Glare Equation,[21] with a validity domain for glare angles between 0.1° and 30°, which was developed for, and adopted by, the CIE.[47] The equation is expressed by relating the equivalent luminance of the veiling glare in cd . m-2, Lveil to the incident illumination from the glare source, Eglare. This describes a radially symmetric distribution of light on the retina as a function of angular distance, θ (in degrees), from the center of the source:

This formula is valid for young healthy observers up to about 30 years of age. Variation in the glare spread function due to age (in the typical range for military personnel) is small. Figure 5-3 shows the relationship between glare angle and relative intensity based on a 30-year-old observer. Beyond approximately 0.1°, glare falls off rapidly with angle, and the shape of the curve is essentially that shown by Campbell and Gubisch,[35] characterized by a width (full-width, half-maximum) of <1 min of arc. Stray light from the cornea and lens decreases with increasing wavelength while that from fundus reflectance or transillumination of the iris and sclera increases with increasing wavelength.48,49 As a consequence, stray light reaching the retina has little wavelength dependence.[50] There is an effect of pupil size, but this can be regarded as a second-order effect.[45] Intraocular scatter increases with age[40] as light scattering in the lens of the eye increases,[51] and the CIE function allows for this. Disability glare also increases in diseased eyes because opacities in the cornea and lens produce an increase in stray light.[52] In patients with early cataracts, increased lenticular light scattering has been shown to impair contrast sensitivity when the contrast sensitivity function is measured in the presence of a bright light source. This occurs even if visual acuity is unaffected.[53]

Extraocular Scatter. Target visibility through a transparency (eg, vehicle windscreens, visors, spectacles) depends on the way the transparency scatters light.54,55 The introduction of additional scattered light from a glare source can reduce visibility even further.56,57 In this context, the atmosphere itself may also be regarded as a transparency that scatters light,[58] although recent studies with laser light have shown that this scatter may be significantly less than in the eye itself.

Figure 5-3. The CIE Small Angle Disability Glare Equation.

Quantitative data are rare concerning stray light scatter from typical optical transparencies. Allen[54] used a photographic technique to measure the scattering properties of car windscreens. To compare various windscreens, he used a veiling luminance index based on the veiling luminance factor at 5.3°, the value chosen to represent the typical geometry of approaching headlights in a driving situation where the index for the eye is 0.42. The value for car windscreens varied with windscreen condition. For a typical used wind-screen, the value was about twice the value obtained for the eye. Allen also investigated the shape of the scatter curve from 3° to about 15°, and showed that it was qualitatively similar to that of the human eye. Although he attempted to study the effect of veiling luminance on visual performance in a driving situation, he did not attempt to correlate the glare index itself with performance.

Forward scatter from optical surfaces is often referred to as “haze,” but this term is used rather loosely in the literature. The American National Standard test method for haze and luminous transmittance of transparent plastics defines haze as the ratio of scattered light to the total amount of light emerging from an optical surface.[59] Acceptable levels for spectacles and windscreens are on the order of 1% to 6%. However, the relationship between haze and visual performance remains poorly understood.[55]

To determine the extent of laser-induced veiling glare on visual function, it is necessary to describe the distribution of light in the retinal image of the laser source (glare spread function). The shape of this distribution will depend on the scattering properties of the optical media through which the laser beam has passed. Scatter functions for the ocular media are well established, but those for extraocular scatter are not.

Visual Task Parameters

In broad terms, the parameters that make a visual task easier or more visible are those that will mitigate the effect of a glare source and reduce the time that is necessary for task performance to recover. These beneficial parameters include task luminance and the size and contrast of target stimuli. Generally, an increase in any of these parameters will tend to reduce both the immediate glare effect and subsequent recovery times.

Task Luminance. Hill and Chisum[60] studied the time taken to detect acuity gratings following flash exposure and demonstrated that display luminance level has a significant effect on detection time.[60] As display luminance is increased, recovery times are reduced (down to a minimum value). Because the target stimulus must be viewed through a fading afterimage, this effect arises from the competing effects of the afterimage and task parameters. Increasing display luminance serves to increase the contribution of the display to the retinal image. This improves stimulus contrast and hence visibility. At high display luminance, the upper limit for optimal viewing of the display is approached. There appears to be little difference in recovery time for different adapting luminance levels.

Although other studies have recognized the importance of task luminance as a factor in determining recovery times,61,62 they have not gathered systematic data relevant to this parameter. Studies that have specifically adjusted display luminance as a primary independent variable32,63,64 have found that as display luminance is reduced, recovery times increase at an increasing rate. This occurs down to a display luminance that represents the absolute threshold for the discrimination of the visual task.

Display luminance is an extremely important variable. Increasing the luminance of the display can significantly reduce recovery time. Of course, there will be a logical limit to this method of improvement because extreme increases may begin to interfere with the visual process itself.[22]

Target Size and Contrast. The size and contrast of a target stimulus can exert a profound effect on recovery time. Recovery times are longer for small acuity letters and low-contrast gratings.[31] In general, the greater the inherent difficulty of a visual task, the more time will be needed to recover the ability to perform that task. Recovery times for threshold stimuli are much longer than are those for supra-threshold stimuli.

Glare Recovery

Although the eye is extremely good at adapting to large changes in ambient illumination, adaptation problems can occur when the changes are large and occur over a short time period. When the eye is illuminated by an intense light source, visual effects do not terminate immediately after the light source is removed. Rather, they persist as transient loss of visual sensitivity for a definite time interval. In many situations, this effect may not cause any difficulties. However, serious problems may occur if the observer must perform a detailed visual task.

Although the exact mechanism of afterimage production is not fully understood, since an afterimage can be formed in an eye made temporarily anoxic by pressure on the globe, afterimages almost certainly originate in the photoreceptors.[65] The afterimage may result from the persistence of photoproducts that are produced by the bleaching of visual pigments.[66]

Afterimages persist following exposure of the eye to a bright flash. The afterimage appears immediately in the visual field as a bright area of the same size and shape as the original flash field. This may prevent the observer from perceiving detail in the same portion of the visual field. The afterimage will eventually fade, and normal visual function will then return. In this case, recovery time refers to the time interval between the flash and restoration of a given level of visual function.

As afterimages persist and fade, they undergo qualitative changes. If the eye is placed in darkness immediately after exposure, the afterimage appears initially as an image of the originating source itself. Its color and brightness will be similar to those of the stimulating source. On continued observation, color and brightness of the afterimage will begin to change. These changes are also apparent when the afterimage is viewed against an illuminated field.

Variations in the appearance of afterimages have given rise to a number of descriptive terms in the literature. Positive afterimage refers to a visual image that has the same relative brightness relations as the original stimulated field. The positive afterimage is believed to result from intense bleaching of retinal photopigment. This results in the imposition of a luminous veil on the visual image, thereby reducing its perceived contrast.25,32,33

A negative afterimage differs in that its brightness relation is opposite that of the original field. Afterimages may also be described as homochromatic or complementary. (For a detailed description of afterimages, see Brown.[67])

The interference in vision that results from afterimages has been referred to as flash blindness.[68] However, used in this way, the term is somewhat misleading. Rather than being blinded, the subject experiences a temporary reduction in the ability to see a visual stimulus in what is typically a limited portion of the visual field. A more appropriate description of this effect might be transient localized visual desensitization. Recovery of visual threshold has been tracked by matching the intensity of an external light to the perceived brightness of its afterimage.32,33,69 The time that is needed for task performance recovery is usually less than the time it takes for an afterimage to disappear completely or for the eye to regain its preexposure level of sensitivity or adaptation. Under normal conditions, the eye operates at suprathreshold levels of adaptation. This means that an observer is often able to “see through” an afterimage sufficiently well to distinguish the required level of detail.

Due to the extreme but very necessary safety considerations involved with direct viewing of laser sources, there have been relatively few studies of laser effects on visual function. However, the nature of visual recovery has been studied extensively in human subjects using various types of noncoherent flash sources.31–33,60,68,70–74 Studies using a variety of techniques (eg, fundus reflectometry and evoked potentials) have shown that there are two mechanisms responsible for the rapidly changing sensitivity of the eye following exposure to intense flashes: (1) the photochemical effect and (2) the neural effect. Because this chapter is primarily concerned with overall system response, the following discussion will be limited largely to psychophysical studies of afterimage recovery.

There have been many studies of the change in visual function that follows a small change in adapting luminance level at relatively low levels of light intensity. These effects are generally described as light and dark adaptation. In some respects, research into these changes can be regarded as precursors to the study of laser flash recovery, which involves exposure to high-intensity photic stimuli. The transient effects of intense light exposure have been studied to address three main areas of concern: (1) clinical application, (2) occupational hazards, and (3) basic visual function.

Clinical Studies

The most common clinical test involving intense light exposure is the photostress recovery test of macular function. Historically, this test employed an attenuated light coagulator and assessment of retinal response using a test, such as reading Landolt C’s on the Goldmann-Weekers adaptometer.[75] Later studies have proposed the use of a simple penlight and Snellen chart.[76]

The purpose of the photostress test is to determine if the retina is diseased. The test imposes a full-field photic stress across the retina. Physiologically, the intense light source bleaches a significant proportion of the visual pigments, producing a transient state of insensitivity. Return of retinal sensitivity, and hence visual function, depends not only on neural mechanisms, but also on the regeneration of visual pigments in the retina.[14] Ocular disease that affects photoreceptor outer segments or pigment epithelium causes a delay in photopigment regeneration and leads to a slower recovery of visual function, whereas no such delay is observed for diseases of the optic tract. The photostress test has thus been useful as a means to determine whether reduced visual function is due to macular disease or optic neuropathy. Patients with maculopathies—such as central serous retinopathy, macular degeneration, or retinal detachment—show prolonged recovery times. Patients with optic neuritis, glaucoma, or retinal edema associated with contusion usually show normal recovery times.

Occupational Studies

In most occupations, overexposure to visible radiation is not a common risk factor. However, such accidents can occur in certain vocational situations. Early research in this area concentrated on problems arising from exposure to the flash of an atomic explosion. More recently, research has focused on the potential hazards to both military and civilian personnel from the uncontrolled use of lasers.77,78 Lighting engineers have also shown some interest in problems associated with heterogeneous illumination in the workplace.[79]

Due to the practical nature of the problem, occupational studies are usually designed around everyday tasks. In general, these studies follow the same basic paradigm. The experimental subject is required to perform a realistic visual task. The subject is then exposed to a bright flash of light. Investigators then observe and measure the time required for the subject to return to a given criterion level of accuracy on the original task. Because dark adaptation is not of interest, viewing conditions are usually photopic, or at least mesopic, and hence involve cone function. Studies of this kind have documented recovery times ranging from as short as a few seconds to as long as 2 min.[61]

The luminous flux from a nuclear detonation is capable of producing retinal burns, flash blindness, and afterimages. Early studies established that retinal burns are unlikely at survival distances, although the flash exposure will still be considerable.[62] This conclusion led to a plethora of psychophysical studies. For obvious reasons, criterion tasks were designed to test vision in the aviation environment. Tasks involved reading key instruments or warning lights61,72,80 and detection of grating pattern orientation.60,70,73,74 Severin et al[75] even adapted the photostress recovery test to study this problem.[81] More recently, Wang et al measured recovery time as the time needed for a moving grating pattern to induce an optokinetic nystagmus.[82]

Basic Vision Research

The study of flash blindness and afterimages has attracted much interest in vision research. There may be some truth in the conclusion of Davson that “although they have attracted a lot of interest, little of fundamental value has emerged from their study.”7(p146) Nevertheless, our understanding of the problem of afterimages has been improved by the application of basic principles of vision science. These principles also serve as a foundation for the present study. In particular, the concept of equivalent background luminance has been of great value to afterimage research.

Factors Affecting Visual Recovery Time

Researchers have used a variety of techniques to study afterimage recovery. For this reason, it is extremely difficult to compare results directly across studies. Recovery time depends on many variables, in particular task type and adapting flash parameters. The most important parameters of the adapting flash are flash intensity and duration, field size, and spectral content.

Flash Intensity and Duration

In terms of threshold effects on the eye, it is generally accepted that total energy is the determining variable for all exposures shorter than a critical duration of about 100 ms.[19] This is the Bunsen–Roscoe law of reciprocity, which states that the threshold remains the same as long as the product of stimulus intensity and duration is held constant. Bloch’s law states that this same relationship applies to the intensity of visual sensation for exposures above the threshold.[19] It is unknown whether the same is true for the high-intensity and suprathreshold adaptation effects involved in the generation of prolonged afterimages.

Fry and Alpern[83] studied recovery using flash durations from 3 s to 3 ms. They concluded that recovery time was determined by total flash energy (ie, the product of adapting flash intensity and flash duration). However, the experimental task involved parafoveal (low) acuity and measures taken no earlier than 10 to 15 s after the flash exposure.

A similar study that used a foveal vision task reached the same conclusion; recovery time depended largely on total flash energy.[60] The greater the total flash energy, the more time was needed for subjects to detect the orientation of acuity gratings. At constant flash energy, recovery was unaffected by the duration of flashes ranging from 33 to 165 µs. However, the authors noted that recovery time was almost doubled when flash duration at constant energy was increased from 165 µs to 9.8 ms.

Miller[31] also studied the influence of flash energy on recovery times needed for observers to identify a dimly lit test letter. In this case, when the integrated retinal illuminance of the flash exposures was varied from 5.9 to 7.5 log troland-seconds (log td-s), visual recovery times varied from 14 to 109 s. However, Miller found no significant differences for flash durations from 40 µs to 1.4 ms. Later, Chisum[72] observed no systematic variation in recovery times for flash blindness exposures from 100 µs to 8.5 ms, and concluded that there exists a complex interaction between flash total luminance and duration. A strict reciprocity relationship may not hold for very short flashes, although the magnitude of the variation she observed was small (<10%).

A possible explanation for these apparently conflicting observations can be found by considering the work of Hagins,84,85 who demonstrated that for flash durations of about <1 ms, it was not possible to bleach more than about half of the retinal photopigment. Williams[86] later hypothesized that this effect may be a consequence of unstable intermediate bleaching products that are isomerized back by the light itself.

Thus, there is reasonable evidence that, within certain limits, flash blindness recovery time is governed by total flash energy. Specifically, the greater the flash energy, the longer the recovery. The interaction between flash intensity and duration is complex, and strict reciprocity may not always apply. There remain some unresolved conflicts in the published body of experimental data.

Flash Source Size and Location

The visual angle subtended by the flash will determine the size of the retinal image of the source. This, in turn, will define the size of the resultant afterimage. The location of the afterimage is determined by the location of the flash source in the visual field. Although the location of the flash source itself is fixed in visual space, its afterimage is fixed in retinal space and will move with the eye.

Perhaps the most extensive and controlled study of the effect of flash field size and location on afterimage recovery was that performed by Chisum.[70] She measured the time to detect the orientation of high-contrast gratings that required foveal (20/60) acuity. Flash field sizes were 0.5°, 1°, 2°, 4°, 6°, 8°, and 10°. They were located on the optical axis or at the separation between the edge of the flash field and the optical axis (0.5°, 1.0°, 1.5°, and 2.0°). For the on-axis flashes, Chisum found that recovery times increased as the visual angle subtended by the adapting flash was increased from 0.5° to 2.0°. No further increase was seen as the visual angle was increased from 2° to 10°. Recovery times decreased as the flash field was moved away from the optical axis.

Most of these results can be explained by the degree of overlap with the fovea. The fovea subtends a visual angle on the order of 2°.[8] For flashes that subtend an angle less than 2°, some of the fovea will be unexposed. The unexposed portion of the fovea can be used to complete the visual task (ie, by looking around the afterimage). As field size approaches 2°, the unexposed area of the fovea becomes smaller, making it more difficult to avoid the afterimage. At 2°, the entire fovea is exposed, and recovery time will be unaffected by any additional increase in field size. For off-axis exposures, recovery times will also increase as the degree of overlap between the flash field and the fovea is increased.

Cushman[80] investigated the effect of flash field size using a criterion task that required subjects to read cockpit instruments. He tested flash field sizes of 1°, 3°, 5°, 10°, and 15°. He found that recovery time increased with increases in visual angle subtended by the source. However, the shape of this increase varied with the specific visual requirements of different cockpit instruments. In general, the most rapid changes (between 1° and 5°) were observed for instruments that required foveal vision. For less visually demanding instruments, changes were less dramatic, suggesting the involvement of parafoveal vision.

Therefore, if a central adapting flash subtends 2° or more, the entire fovea will be exposed. In this situation, it will not be possible to perform a foveal (ie, high-acuity) vision task by looking around the flash afterimage. Instead, the subject will have to wait until the afterimage has faded to the extent that it no longer prevents viewing of the task display. Flash fields smaller than 2° may spare some of the fovea, in which case the subject may be able to look around the afterimage. Relatively less demanding visual tasks may be performed by using parafoveal vision to avoid the afterimage.

Flash Spectral Content

In most of the studies described herein, investigators used a xenon flash lamp or some other conventional lamp as a light source. The light from these lamps has a broad spectrum and appears as white light to the observer. Very few studies have been done to test the possible effects of flash source spectrum (color) on visual recovery.

Wang et al[82] used narrow-band filters with a xenon flash tube to investigate the effects of the spectral content of the flash source. Using a recovery task that required a significant amount of dark adaptation, they found that variation in recovery time for equal energy flashes closely matched the scotopic spectral sensitivity (Vλ) curve. This study confirmed that the important factor in determining recovery time is flash total luminous energy (ie, radiant energy weighted by the appropriate spectral sensitivity curve).

Transient Effects of Laser Exposure

Although few human studies have been conducted to investigate visual recovery after exposure to non-damaging light from a laser source, safety concerns have limited most studies to the use of animal subjects. There are always ethical concerns about the use of animals in experimentation, and there are also well-known problems associated with extrapolating from animal models to human behavior. These problems notwithstanding, studies of this type have applied both behavioral and electrophysiological techniques. Although useful, both techniques present certain drawbacks.

Behavioral research techniques in this field are often cost-prohibitive because of the need for extensive subject training. Electrophysiological methods avoid this requirement, but suffer from a variety of other problems. For example, although signal characteristics may be closely correlated with the perception of the test stimulus, the nature of this relationship is not well understood. This raises questions concerning the extrapolation from electrophysiological data to visual performance or capability. In addition, electrophysiological response amplitudes are extremely low for foveal stimuli and visual stimuli presented at threshold.

Most studies of laser-induced transient visual deficits have used the monkey as a model. There is a strong similarity between the visual system of the monkey and that of human beings. Most such studies have applied electrophysiological techniques, such as electroretinography or visual-evoked potentials (VEPs), to track recovery. Although these studies probably monitor visual decrements related to prolonged afterimages, they are usually referred to as studies of flash blindness.

As with conventional light sources, the size of the laser-induced retinal afterimage depends on the size of the flash source. Collimated visible laser light entering the eye will be focused on the retina as an extremely small spot, approximately 0.1° (25 µm) in diameter.[87] Because visual disturbance is reduced if the afterimage subtends less than 2°, significant transient visual decrements are not expected as the result of laser exposure. Indeed, experiments using VEPs in rhesus monkeys have failed to demonstrate a flash effect from single Q-switched ruby (20 ns, 694 nm) laser exposures, even at doses that produced retinal lesions.[88] One could argue that this is because of an inefficient wavelength (Vλ < 0.008). However, similar results have been reported using much more efficient argon (250 ms, 514 nm, Vλ = 0.61) and Q-switched, frequency-doubled neodymium:YAG (yttrium aluminum garnet; 532 nm, Vλ= 0.86) lasers.

Previc et al89,90 measured the amplitude of the steady-state VEP response following flashes from argon and doubled neodymium:YAG lasers. By expanding the beam to 3°, these investigators were able to show significant recovery times, measured as the latency of VEP amplitude reduction to preexposure baseline. The authors demonstrated several phenomena, all of which were consistent with flash recovery factors discussed previously in this chapter. Specifically, recovery time increased with flash energy and was dependent on test stimulus spatial frequency in a manner consistent with stimulus visibility as predicted by the baseline VEP. No effects were observed when the laser was allowed to form a minimal image on the retina, or if its exposure was not foveal. Finally, Previc et al90 demonstrated reciprocity between flash intensity and duration; recovery times were similar for 20 ns and 100 ms flashes of constant energy.

In one of few behavioral studies, Rhodes and Garcia[91] trained monkeys to perform a visual detection task and exposed them to Q-switched laser flashes at 530, 694, and 1,060 nm at exposure levels up to the maximum permissible exposure.The beam was expanded to form a large (12.5°) spot centered on the fovea. Only the 530 nm wavelength produced a significant impairment of visual performance, an effect consistent with the spectral efficiency of laser wavelengths. Recovery was quickest for less demanding visual tasks and could be improved by increasing the contrast of the stimulus. No flash effect was observed when the image size was reduced to a minimal spot. Once again, all of these effects are consistent with those reported in human studies of flash recovery from conventional light sources.

These animal studies suffer from a distinct lack of quantitative information, so it would be very difficult to use their findings as a basis for predicting human visual performance effects. However, these findings are valuable because they

- confirm that recovery from laser exposure is qualitatively similar to that from conventional light,

- support the case that results from studies of recovery from conventional flash sources in human subjects that are often more quantitative, and

- can be used to predict the temporary effects of laser exposure.

SUMMARY

Laser glare and subsequent visual recovery depend on a number of variables. These include the parameters of the laser itself, the presence of intervening optical materials, and the visual task that must be performed. The extent of resulting visual decrement is not a simple binary function. For example, effects may manifest as a loss of high-acuity vision close to the center of the source image or as an increase in visual search time due to the persistence of a transient relative scotoma. The size of the scotoma will be relative to the parameters of the visual target; the scotoma will be much bigger for threshold stimuli than for suprathreshold stimuli. Although resulting visual deficits may be dangerous in very dynamic situations involving occupational tasks that require high levels of vigilance and fast response times (eg, piloting an aircraft or driving a vehicle), they may exert little or no practical effect on performance in other tasks that are more stable or pose less risk when compromised by temporarily slowed response.

It is not a trivial challenge to conduct an overall assessment of the transient effects of laser exposure on visual function and operator performance. It is not possible to derive a single estimate of the amount of laser energy that would be required to cause a problem in any particular situation. However, there are indirect estimation techniques that can be used to link the experimental data in a conceptual framework that can in turn be used to assess the transient effects of laser exposure on visual performance.92,93 The conceptual framework expresses visual impairment in terms of object contrast degradation during and after laser exposure. The impact of laser exposure can then be assessed by using the degraded visual scene as input to a contrast-based model of visual perception.

In considering previous studies of the transient effects of intense light exposure, it is difficult to relate results across tasks and studies. To overcome this problem, it is vital to apply the equivalent luminance technique. This technique allows the expression of experimental findings in terms of an equivalent reduction in image contrast rather than as a reduction in visual sensitivity.[94] In addition, this technique simplifies the prediction of the effect of light exposure on visual performance by using the observation that detection probability can be related to image contrast.[95] The equivalent luminance technique also helps to relate the results of a dynamic situation (eg, instantaneous brightness of a fading afterimage) to a specific condi- tion of steady-state adaptation.

To estimate the effect of laser glare on vision, one must begin by calculating the brightness distribution of light on the retina. This calculation must represent all of the scattering media for a given set of observation conditions. Glare spread equations for the eye, windscreens, and atmosphere can be used to construct a complete luminance profile of the laser source retinal image. For pulsed laser sources operating at frequencies > 30 Hz, glare effect can be taken as equivalent to a continuous wave source with the same time-averaged illumination.

To anticipate the effect of the glare source on the visual scene as a whole, the effective contrast (Ce) of elements in the visual scene can be reduced by adding the glare luminance profile on a point-by-point basis across the image of the scene. At any given glare angle, veil θ, a veiling glare of luminance, L, will be introduced, where Lveil is a function of glare angle. Target contrast is viewed with this veiling glare superimposed on the target and background. This will reduce the target contrast in a systematic way. For small, well-defined targets viewed against a uniform background, target contrast, Ctarget, is given by:

Mathematically, glare luminance, Lveil, can be added to the background luminance and target luminance terms to give the reduced target contrast in the presence of glare:

where

Lbackground

=

luminance of the background and

Ltarget

=

luminance of the target.

that reduces to:

Glare can be included in this formula by substituting the appropriate glare spread function, Eglare · f(θ), for Lveil , as follows:

The glare spread function will depend on the scenario under consideration. It could represent only the eye or the eye and the atmosphere. It may need to include an intervening optical transparency. In addition, the scattering properties of any optical transparency will depend on the condition of the transparency itself. Contaminants such as dirt, scratching, mist, and rain will increase scatter considerably.[54]

When glare spread function has been determined, glare luminance can be added on a point-by-point basis across the retinal image of the visual scene. In this way, glare effect is expressed as a reduction in contrast of elements in the visual scene. The degraded image can then be used as the visual scene input to a contrast-based model of visual perception such as ORACLE[96] or VIDEM.[95] These models are used to assess a variety of visual performance factors and could additionally be used to predict the effect of a glare source on vision.

If a light source is sufficiently intense, exposure may result in flash blindness and subsequent formation of an afterimage. This chapter did not specifically consider short duration flash blindness in the context of a full-field loss of visual function and visual disorientation. Indeed, many so-called studies of flash blindness are actually studies of afterimage recovery. The body of available literature serves to demonstrate how an afterimage may impair visual performance, especially for high-acuity visual tasks. The afterimage acts as a relative scotoma. Although the afterimage improves rapidly with time, even a small, short-lived scotoma may be troublesome in some situations. Studies involving simulated scotomas have shown that to impair visual search time for a visual target subtending 10 min of arc, the area affected by the afterimage must be foveal and must subtend an angle greater than 2°. For more visually demanding tasks, search times may be increased with a smaller scotoma.[97]

The degraded visual scene can be used as input to a contrast-based model of visual performance. However, it is necessary for such assessments to include the time element that represents fading of the afterimage. An additional question is whether the reciprocity of intensity (Bloch’s law) holds for Q-switched lasers whereby energy can be deposited in nanoseconds. Brindley[98] has demonstrated that reciprocity holds for the threshold detection of low-luminance flashes shorter than 1 ms. In addition, Previc et al89,90 showed that visual deficits after equal total energy flashes of 100 ms and 20 ns duration followed a similar time course. As a first approximation, this evidence would seem to support the working assumption that Bloch’s law holds even with very short flashes.

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Chapter 6

THE EFFECTS OF NONDAMAGING LEVELS OF LASER ENERGY ON VISION AND VISUAL FUNCTION

JAMES W. NESS, PhD, * Colonel, Medical Services Corps, US Army; Professor of Discipline, Photonics Research Center, US Military Academy, 601 Cullum Road, West Point, New York 10996 and JONATHAN M. NESS, BS † Chemical Engineer, Argos, Summerville, South Carolina 29486

INTRODUCTION

ENTOPTIC LIGHT-LIMITING RESPONSES

Photic Blink Reflex

Spot Size to Intensity Relationship in Photic Blink Reflex

Pupillary Responses, Partial and Monocular Lid Closure, and Eye Movement

Effects on the Resolving Power of the Eye

MODELING INTRAOCULAR SCATTER

SCATTER MODEL VALIDATION

Blaser Visual Pursuit System

Photoreceptor Bleaching and Performance

Light-Limiting Strategies Revealed in Patterns of Afterimages

Pupillary Response and Performance

Assessment of Performance and the Entoptic Scatter Model

CONCLUSION

INTRODUCTION

In 2014, Colonel James W. Ness (chapter author) received a call from a colleague in Afghanistan who was concerned about a “retinal laceration” diagnosis his driver received subsequent to a laser exposure at a checkpoint in the vicinity of Kabul. During the lead-up to the Afghan national elections, tensions were palpable. Checkpoints had been established randomly throughout Kabul. Nevertheless, “blue” (US and North Atlantic Treaty Organization [NATO]) convoys had been instructed to move rapidly around Kabul to avoid the placement of magnetic bombs on their vehicles while in traffic. Returning from an evening meeting between military commanders and local officials at about 19:30 local time, the colleague’s three-vehicle movement approached a random but poorly marked checkpoint. Seeing the convoy swerving around the checkpoint, the Afghan guard, following the rules of escalation of engagement, illuminated the lead driver’s windshield with a green laser at a distance of about 15 to 10 meters and closing. The driver’s left eye was exposed, and the driver reported feeling a sudden pain and something like a “snap” sensation. Unable to see and extremely disoriented, the driver immediately pulled over and swapped seats with his troop commander, who had occupied the front seat. The convoy then moved to the nearest forward operating base with an aid station. Care at an aid station includes triage, treatment, and evacuation, with care provided by a physician or physician assistant. There are no ophthalmic assets at this level of care.

While on the phone, Colonel Ness asked the colleague to detail the parameters of his driver’s exposure, from which retinal dose could be estimated and escalating concerns about the perceived hazard could be addressed. Given the initial “retinal laceration” diagnosis, the driver’s complaint of eyes watering for 2 days after exposure, and the need to keep one eye covered for 24 hours to mitigate light sensitivity symptoms, Colonel Ness advised his colleague that the driver should have a fundus exam. A trip to Bagram Air Base was encouraged.

In the meantime, Colonel Ness collaborated with a colleague from the laser safety community to estimate retinal dose based on the exposure information he gathered from his colleague in Afghanistan reporting the incident. Given the reported parameters and known official issue of laser interdiction systems to NATO forces, the laser source was assumed to be a B.E. Meyers Green Laser Interdiction System (GLIS), commonly used at checkpoints.[1] At the high setting, the GLIS has an output power of 200 mW at 532 nm with a beam divergence of 7 mrad. With the reported ambient light conditions, a pupil diameter of 3.5 mm was estimated. The report of the incident also stated that the beam was scanned across the vehicle’s windshield, so the exposure duration chosen was 0.1 second.

Excluding the “dirty windshield” at 10 m from the source, the total intraocular energy (TIE) was estimated to be 0.5 mJ, or a total intraocular power of 5 mW, corresponding to a radiant exposure of 5 mJ/cm^2 at the cornea. The maximum permissible exposure (MPE) for a t = 0.1 s exposure, given by the formula 1.8 t^75, is 0.32 mJ/cm^2 at the cornea.[2] Visual disruption and likelihood of injury are estimated as follows: a glare effect is expected out to about 68 m from the source, the nominal ocular hazard distance (NOHD) is 14 m from the source, and there is a 50% chance of retinal damage (ED_50) at a distance of 5 m from the source (see Chapter 9, Laser-Induced Ocular Effects in the Retinal Hazard Region, this volume).[2]

Six days after the incident, given persistent complaints of light aversion consistent with photoallodynia, the soldier was taken to Bagram Air Base for the encouraged ophthalmologic assessment. The exam revealed no ophthalmologic anomalies. Notwithstanding this clinical finding, it was a significant exposure that disabled the driver, causing the crew to break the seal of the vehicle to swap drivers, and exposing the occupants to the threat of small arms fire.

This incident highlights multiple factors involved in a laser ocular exposure, which define the impact on soldier survivability. These factors include the laser source, the visual task, the ambient light conditions, and, beyond the biophysics, the individual concerns over perceived hazard.3,4 The latter modulates the soldier’s and command’s reactions to the event, influencing “return to duty” determinations, which in turn impact unit readiness.

Perceived hazard phenomenon and laser-induced ocular damage are discussed in detail in other chapters in this volume (see Chapter 7, Psychological and Operational Impacts of Military Lasers, and Chapter 9, Laser-Induced Ocular Effects in the Retinal Hazard Region). This chapter will focus on entoptic laser effects that cause visual disruption but do not cause tissue damage. Many laser incidents involve exposures that temporarily disrupt vision. These incidents typically involve the use of handheld laser pointers, which are often implicated in illuminating aircraft cockpits,[5] moving vehicles, and the faces of individuals such as performers and athletes.[6] Effects on the visual system depend on the retinal illuminance,[7] retinal location affected, extent of retinal area affected, effects of photolysis on retinal neural elements,[8] ambient light-induced visual function adaptation, and degree of forward scatter on the retina.9,10 In healthy eyes, some intraocular backscatter does occur, but the effect on vision is nominal, mainly influencing the number of photons that reach the retina.[11]

When assessing the question of laser-induced damage, only the portion of the laser beam directly focused on the retina is considered because this is the area associated with the highest incident energy per unit area. However, along with the beam’s directed-energy umbra is an associated penumbra, which is defined by forward scatter of the beam as it passes through ocular media to the retina. Because this chapter’s focus is on vision and visual performance, a model for the effects of bright laser sources on visual function is presented that includes the effect of forward scatter. The model is derived from a Monte Carlo method developed by Jacques and Wang in 1995 for modeling light transport in tissue.[11] The model was adapted by Jonathan M. Ness (chapter author) and is validated against a series of studies that induced retinal light-limiting ocular responses to study the effects of bright laser light on pursuit tracking.[12]

ENTOPTIC LIGHT-LIMITING RESPONSES

Induced retinal light-limiting ocular responses of the healthy eye involve two physiologic mechanisms: (1) cortically mediated light-limiting responses and (2) a subcortically mediated photic blink reflex. The photic blink reflex is differentiated from the startle blink response, which is a binocular response to unexpected, transient noxious stimuli (eg, loud noise, touching, and visual loom),13,14 and from the light aversion response, photoallodynia.[15] Photoallodynia is excluded because it is a syndrome that manifests subsequent to intense bright light exposure, which involves trigeminal sensitization.[16] The postexposure tearing in the case of the driver indicates a trigeminal sensitization. Tearing reflex is governed by the fifth (trigeminal) cranial nerve.[17]

Photic Blink Reflex

There is a continuum of light-limiting responses in the human eye, ranging from pupillary responses to photic blink reflex. Light-limiting responses, save the photic blink reflex, serve to maintain visually guided behavior by mitigating the entoptic effects of bright light on vision. Exposure to extremely bright light sources that subtend a significant retinal area will induce the photic blink reflex, a subcortically mediated reflex that has two myogenic components affecting the orbicularis oculi muscle via the seventh (facial) cranial nerve.14,17 The first component is a blink onset component that is 30 milliseconds in duration with an average onset latency of 50 milliseconds from stimulus onset. This component is referred to as R50 and is followed by a second burst around 80 milliseconds from stimulus onset, referred to as R80. The R80 impulse persists for about 100 milliseconds, with persistence dependent on light intensity. The behavioral referent for the photic blink reflex described in the literature is a “screwing up of the eyes”[18] caused by the contraction of the orbicularis oculi, which is a sphincter muscle.

The impulse for the photic blink reflex appears to arise when light stimulates melanopsin in intrinsically photoreceptive retinal ganglion cells (ipRGCs). Signals from the ipRGCs serve as primary input for nonvisual photo-regulated physiology such as the pupillary light reflex, blink reflex, irradiance detection, photo-entrainment of circadian rhythms, and, in mice, light suppression of diurnal locomotor activity.19,20 The photic blink reflex is inhibited by a centrally governed (cortical) tonic levator palpebrae superioris contraction innervated by the third cranial (oculomotor) nerve. The contraction maintains upper eyelid opening and provides voluntary control over eyelid opening and closing. The tension between the subcortical mechanism of the photic blink reflex and the central mechanisms of the light-limiting response determines the continuum of behavioral outcome from nominal pupillary constriction to prolonged eye closure. An intermediary “squinting response” is an orbicularis oculi contraction of the lower lid, with the upper lid remaining open.

Light intensity incident on the retina peaking at 490 nm drives the nonvisual subcortical mechanism, and luminance (perceived brightness) drives the cortical mechanism.21 A visual photo-regulated inhibitory circuit links the cortical and subcortical mechanisms by way of the ipRGCs. Thus, ipRGCs are influenced by the entire visual spectrum and, in this way, are considered irradiance detectors.21,22

In visual photo-regulated physiology, rods and cones depolarize in on- and off-light channels, whereas the nonvisual photo-regulated physiology of ipRGCs responds only to light-on channels. The ipRGCs have an inhibitory circuit from the rod and cone light-on channel. The implication is that the degree of bleaching of the photo elements of the on-circuit determines the inhibition of the ipRGCs. The higher the retinal illuminance and the greater the affected retinal area, the greater the bleaching and the weaker the inhibitory signal, and thus the greater the ipRGC light suppression signal for induction of photic blink reflex.

Bleaching is determined by retinal illuminance measured in log_10 Td·sec (troland-seconds). A troland is a measure of the amount of light energy reaching the retina, normalized to retinal sensitivity for transducing that energy. For a source duration longer than 1 second at a retinal illuminance of 6.8 log_10 Td·sec, the fraction of unbleached pigment is 50%, with complete opsin bleaching at 8.0 log_10 Td·sec.[23] In a synthesis of research on the photic blink reflex as induced by an incoherent source, Stuck supports the hypothesis that in order to reliably stimulate a photic blink, the source must illuminate a retinal area greater than the rod-free zone at about 6 log_10 Td·sec.[24] As the light source was moved in eccentricity from the fovea to the periphery, the latency to blink in response to source onset increased. This increase appeared to correspond to the time the eye responded with a saccade to move the source from the peripheral eccentricity to central fixation. Thus, latency to elicit a photic blink appeared dependent on recruitment of the rod and cone system, since photic blink latency differences across eccentricity correlated with saccade velocity to central fixation.

Spot Size to Intensity Relationship in Photic Blink Reflex

Few studies can be found that relate laser retinal spot size to intensity in inducing the photic blink response. Regardless, there is considerable debate as to whether the blink reflex should be included as a safety factor in exposure to bright laser light.25,26 This section is a metaanalysis of refereed journal articles from which retinal spot size, retinal illuminance, and probability of blink may be estimated.

Visible laser light produces high retinal illuminance but relatively small focused spots, which are on the order of 50 to 100 µm. Because of their small spot size, laser sources are unlikely to elicit the photic blink reflex. The studies reviewed here show that the onset of the light source elicits light-limiting behaviors to maintain visual function, which in turn mitigates induction of the photic blink reflex. That mitigation results in about a 15% chance of a blink within 250 milliseconds of light onset, with 5% of those blinks likely spontaneous and, thus, not elicited.

Figure 6-1. Probability of photic blink as related to retinal illuminance, retinal spot size, retinal location, and wavelength based on data from an accident case and from three experimentally controlled exposures.1–3 (1) Reidenbach H-D, Hofmann J, Dollinger K. Active physiological protective reactions should be used as a prudent precaution safety means in the application of low-power laser radiation. In: Magjarevic R, Nagel JH, eds. World Congress on Medical Physics and Biomedical Engineering. IFMBE Proceedings. 2006;14:1, 2690–2693. (2) Stamper DA, Lund DJ, Molchany JW, Stuck BE. Binocular and monocular laser glare effects on eye blink and tracking performance. Paper presented at: 25th Annual Lasers on the Modern Battlefield Conference; February 2004; Brooks City-Base, TX. (3) Gerathewohl, S, Strughold H. Motoric responses of the eyes when exposed to light flashes of high intensities and short duration. Aviat Med. 1953;24:200–207.

Figure 6-1 shows data from the accident case described at the beginning of this chapter and from three laboratories where researchers have explored the photic blink reflex.26–28 This figure indicates wavelength dependence; wavelengths closer to peak luminous efficiency (550 nm) are associated with a higher probability of eliciting a photic blink. The apparent anomaly is the parafoveal exposure at 635 nm. However, peak luminous sensitivity in the parafovea is 507 nm, and, thus, a 635 nm stimulus is a less efficient stimulus for parafoveal receptors than for foveal receptors.

Figure 6-1 depicts a retinal illuminance relationship with the probability of a blink increasing with retinal illuminance. There is also an apparent spot-size relationship as indicated in comparing the 514.5 nm and 532 nm spot sizes with that of the accident case. The accident case retinal spot size is 30% and 60% greater than that of the 514.5 nm and 532 nm experimentally controlled exposures, respectively. Note that the retinal illuminance for the incoherent source, estimated at 5.75 log_10 Td·sec, is about three orders of magnitude less than the accident case. However, like the accident case, the exposure was delivered as an intense flash, which would reduce opsins to about 45% of the baseline.[8] Moreover, the diameter of the retinal spot produced by the incoherent source encompasses the entire macula (≈2,800 µm). Those produced by the laser sources are on the order of 100 µm (or about ¹⁄₂₈ the diameter of the macula and ⅓ the diameter of the fovea).

Although the parameters of spot size and illuminance are identified as likely important to the induction of a photic blink, the relationships are far from clear and require further systematic investigation. From the blink data shown in Figure 6-1 and the breadth of oculomotor light-limiting behaviors in response to bright light reported in the referenced studies, it appears that given the small spot sizes of a focused beam, a quintessentially visual organism engaged in visually guided behavior tends not to blink. Although the focused beam for the accident case was well within the fovea, there were significant postflash sequelae, suggesting that the spot size contributed to the induction of the postflash sequelae. The increase in spot size was likely due to intraocular scatter, which is not accounted for in the NOHD calculation (see Chapter 9, Laser-Induced Ocular Effects in the Retinal Hazard Region, this volume).

Moreover, given the intensity, an appreciable number of pigmented molecules likely received a second quantum hit, disrupting reestablishment of active protein sites on the photoreceptor.[29] Thus, recovery of visual function in the accident case would involve not only recovery of opsin, but also recovery of the active sites that hold the opsin. This effect, called the 𝛳 effect, is described by Rushton.[8] Recovery in this case is likely proportional to the number of photons delivered by the source, rather than to the amount of visual pigment bleached.[29]

Pupillary Responses, Partial and Monocular Lid Closure, and Eye Movement

Short of the induction of the photic blink response, the visual system exhibits a breadth of retinal light-limiting behaviors. These behaviors include pupillary reflex, eye movement, closing one eye, squinting, and blinking. The pupillary reflex is governed by the ipRGCs specifically associated with the R80-myogenic impulse.[30] The pupillary reflex is also centrally governed, influenced by true luminance scene changes as well as by changing visual illusions of brightness.[31]

The pupillary reflex and blink reflex show a summation of a binocular signal due to the crossing visual ascending pathways of the nasal retinal ganglion cells.14,32 An equivalent monocular sensation of brightness reported under binocular viewing requires an order of magnitude increase in light intensity, provided the stimulus is on for more than 1 second.[32] Under binocular exposure conditions, a light-limiting behavioral response is to close one eye.

The eye is constantly moving, with eye movements contributing to the smear of energy on the retina. Under deliberate fixation of a diffraction-limited spot at optical infinity, eye movements produce about a 50 µm diameter spot on the retina. Viewing a focal target for longer than 1 second, the spot increases to 150 µm with the inclusion of head movement.[33] Accounting for head and eye movement, peak radiant power is reduced by one-thirtieth of the expected power for the no-movement case.[33]

Effects on the Resolving Power of the Eye

Fixation on target distinctive features is contrast dependent, with the eye focusing on areas of high contrast and features that are spatially resolvable by the eye. With a masking bright light source, the fixation tends to move off of the source to a target area resolvable by the eye (see Chapter 5, Laser Glare Effects on Visual Performance, this volume). By virtue of redirecting fixational gaze, the relative luminous efficiency of the source decreases as a function of its distance from the pupil center.[34] Viewing a source at the margin of a 3 mm pupil reduces luminous efficiency by 20%, making the source appear less bright. For laser exposures longer than 1 second, the viewer can adjust fixation to eccentric viewing of the target, which preserves visually guided behavior by diminishing the perception of source brightness. In this way, the masking bright light source contributes to reducing sensitivity of the eye not only through bleaching opsins, but also through inducing the movement of target fixation from the masked target to some other associated feature of the target resolvable by the eye.

In the visual photo-regulated physiology, ambient light levels and degree of photolysis determine the recovery of visual function and persistence of afterimages. The affected retinal area determines the suppression of visual function. Figure 6-2 shows contrast sensitivity (1/% contrast) as a function of target size for four conditions of stabilized opacity in the visual field. The opacity simulates effects of afterimages and of masking bright light sources on the resolving power of the eye. The “No Scotoma” condition shows visual function within normal limits under typical photopic viewing conditions. The “5° Foveal” condition simulates the effect of an afterimage centered on the fovea, occluding the central 5° of vision. The “2° Parafoveal” condition simulates the effect of an afterimage outside the macula, occluding 2° of peripheral vision. The “5° Relative” condition simulates the effect of a masking bright light source centered on the fovea, reducing contrast by 5% in the central 5° of vision.

Figure 6-2 also shows that relative to the “No Scotoma” condition, the central occlusions had a greater effect on high- to mid-spatial frequencies, whereas the peripheral occlusion had a greater effect on low- to mid-spatial frequencies. Note that regardless of retinal position, all occlusions induced a significant suppression of sensitivity in the mid-spatial frequencies. This tendency may implicate that mid-spatial frequency sensitivity is a result of a neural integration of peripheral and central retinal signals along the visual pathway.35,36

Figure 6-2. Contrast sensitivity as a function of target size for four conditions of stabilized opacity in the visual field.

MODELING INTRAOCULAR SCATTER

When viewed intrabeam, a laser source appears as a small bright spot surrounded by a halo of diffuse light (Figure 6-3). This section introduces a model of intraocular scatter to define the extent of the penumbra of retinal illuminance surrounding the umbra, or small bright spot. This intraocular scatter is separate from scene glare. Scene glare, as depicted in Figure 6-3, is caused by reflections from a glare source incident with the scene, which disrupts scene contrast (see Chapter 5, Laser Glare Effects on Visual Performance, this volume)

Laser-induced intraocular scatter is wavelength dependent for viewing angles less than 4°.[10] A viewing angle of 4° equates to a retinal extent of about 70 mrad, or about twice the extent of the rod-free zone (Figure 6-4). The focused beam of the laser described in the accident case was about 0.4°, which equates to a retinal extent of about 7 mrad.[10] Although the effects of scattering are minimized in the optics of the cornea and lens, and through waveguide at the retina, the optics of the eye leave longitudinal chromatic aberration uncorrected.[37] Thus, the wavelength results in differential effects on image quality. For wavelengths greater than 600 nm, there is increasing diffusion, which increases the spread of the point-spread function, defocusing the image.[10] For wavelengths less than 600 nm, there is an increasing effect of scatter.[10] Ginis and colleagues report that, at a viewing angle within 0.5°, the effect of straylight can be five times higher in the red segment of the visual spectrum (> 600 nm) than in the green (500–575 nm), implicating the role of straylight in chromatic induction.10 For example, there is a tendency to see a red hue in the glare from white light sources.

Figure 6-3. Laser glare veiling a target acquired through targeting optics. The veiling glare is from a laser source mounted on an armored vehicle directed at the viewing optics of a tube-launched, optically tracked, wire-guided missile system targeting the armored vehicle.

Figure 6-4. (a) The diameter in µm of the fovea, rod-free area, and macula, and their respective angular subtenses in mrad. (b) Optical coherence tomography (OCT) image showing a full retinal thickness cross-section of scanned retina.

TABLE 6-1
DISTANCE AND TISSUE LAYER THICKNESS USED TO PREDICT INTRAOCULAR SCATTER

Boundary layer

Thickness of tissue (mm)

Distance from front of cornea (mm)

Cornea

0.5

0.5

Aqueous/anterior chamber

3.1

3.6

Lens capsule 1

0.01

3.61

Crystalline lens

3.58

7.19

Lens capsule 2

0.01

7.2

Vitreous humor

17.2

24.4

Macula lutea/Henle fibers

0.03

24.43

Retina

0.47

24.9

RPE

0.02

24.92

RPE: retinal pigment epithelium

To estimate the effective spot size of a laser source on the retina, which includes scattering and diffuse reflectance, the contribution of each boundary layer of the eye to the path of a photon was computed from cornea to retinal pigmented epithelium. Table 6-1 shows each of the boundary layers used in the model, with the associated tissue thicknesses and distance from the corneal surface. The model incorporates each layer’s refractive index, coefficient of absorption, scatter coefficient, and anisotropy. Absorption, scatter, and anisotropy are wavelength dependent. As a photon interacts with each layer, the algorithm determines if there is a drop in the energy weight of the photon and then determines its deflection angle and azimuth of travel.

Figure 6-4 shows the extent of retinal structures as a reference for Figure 6-5. Figure 6-5 depicts the illuminance, through the layers of the eye, as a heat map of the laser power incident at the cornea for the reported accident case and for the 514.5 nm controlled experimental exposure reported by Stamper and colleagues.[38]

Figure 6-5 also illustrates the effect of scatter on retinal spot size (it does not show the extension of the retinal spot due to retinal smearing produced by head and eye movements). The figure shows a focusing of the beam in the lens and a broader area of high illuminance in the anterior chamber, producing considerable veiling glare. Within the vitreous, there is relatively broader scatter due to the lower anisotropy associated with the vitreous. At the boundary of the vitreous and the retina, there is a significant energy absorption that defines the umbra of absorption due to the focused beam (red spot) and the penumbra of absorption due to scatter (yellow to green annuli).

The illuminance of the umbra for the 514.5 nm beam[38] (see Figure 6-5, left panel) is 9.3 log_10 Td, and that of the 532 nm beam associated with the accident case (see Figure 6-5, right panel) is 9.87 log_10 Td. The corneal irradiance of the 532 nm beam is an order of magnitude greater than that of the 514.5 nm beam. The 514.5 nm focused spot is 50 µm for 3.0 seconds, and that of the 532 nm spot is 122 µm for 0.1 seconds. These differences contribute to the extent of the respective associated penumbras due to intraocular scatter.

In addition, Figure 6-5 shows that the extent of the penumbra out to 6 log_10 Td for the 514.5 nm beam is 2,600 µm. This equates to a 5 mm^2 retinal area. The extent of the penumbra out to 6 log_10 Td for the 532 nm beam is 4,000 µm. This equates to a 12 mm^2 retinal area, which is twice the area produced by the 514.5 nm source and equivalent to that of the incoherent source (see Figure 6-1). Given the increased retinal area affected by the 532 nm source due to intraocular scatter, the probability of blink is estimated to be greater than the probability associated with the incoherent source (see Figure 6-1).

5 log10 Td illuminance penumbra around the 514.5 nm focused beam spot and 532 nm focused beam spot are 2,607 μm and 4,000 μm, respectively. (1) Stamper D, Lund D, Molchany J, Stuck B. Laser-induced afterimages in humans. Percept Motor Skills. 2000;91:15–33." />

Figure 6-5. Light scatter around the focused beam (red) traveling from the cornea to the retina for a 514.5 nm, 0.5 mW/cm^2 controlled exposure reported by Stamper et al1 and for a 532 nm, 5 mW/cm^2 accident case exposure. Focused beam spot sizes for the 514.5 nm beam and the 532 nm beam are 50 µm and 122 µm, respectively. The > 5 log_10 Td illuminance penumbra around the 514.5 nm focused beam spot and 532 nm focused beam spot are 2,607 µm and 4,000 µm, respectively. (1) Stamper D, Lund D, Molchany J, Stuck B. Laser-induced afterimages in humans. Percept Motor Skills. 2000;91:15–33.

In Figure 6-5, the penumbra was estimated out to over 6 log_10 Td illuminance, based on Rushton’s finding[23] that 50% of the opsins are depleted, from an adaptive state baseline, at a retinal illuminance of 6.8 log_10 Td·sec. In general, the opsin bleaching for a given retinal illuminance follows a Weber-Fechner constant, from which contrast sensitivity and the duration and intensity of afterimages can be predicted.39,40

SCATTER MODEL VALIDATION

In 1979, when a team of vision scientists at Letterman Army Institute of Research was confronted with the question of how intense, sub-injury threshold laser light might affect soldier performance, they chose to study the effects of laser-induced visual disruption on pursuit-tracking behavior. Tracking behavior is visually guided and also involves the integration of other sensory inputs (eg, proprioceptive and vestibular) to maintain orientation. The scientists recognized that laser disruption to visually guided behavior would be expected to cause performance deficits, but that individuals may be able to compensate and adapt to the visual disruption. Disruption of the visual signal was predicted to alter sensory integration and to induce behavior (eg, blinking, pupil constriction, and eccentric viewing) that would limit retinal illuminance. To test their predictions, the research team developed the Blaser system.41–43

Blaser Visual Pursuit System

In 1985, Peter O’Mara, David Stamper, David Lund, Richard Levine, Bruce Stuck, and Edwin Beatrice conducted the first purposeful, nonclinical study of human laser exposure.[44] Volunteers engaged in a pursuit-tracking task were exposed to low levels of visible laser light (below the MPE level). The results provided timely answers concerning the relationship between laser source and target parameters, and their effects on visual performance. The investigators found that when equal amounts of laser energy from 514.5 nm argon-ion (Ar) and 632.8 nm helium-neon (HeNe) lasers were presented to volunteers as they performed a pursuit-tracking task, the 514.5 nm laser light (near the peak of the photopic sensitivity curve) was relatively more disruptive. Continuous wave (CW) laser exposures were also compared to repetitively pulsed (RP) lasers exposures. For RP durations of up to 30 Hz, the CW mode of presentation was the more disruptive.

Figure 6-6 is a schematic showing the current version of the Blaser tracking simulator, which includes an option for binocular or monocular viewing.[45] The Blaser scene subtends a visual angle of 12.7° and can be adapted to accommodate ambient lighting and figure/ground contrast for the tracking task. The tracked target is a ¹⁄₃₅ scale model tank that subtended 2° (35 mrad) of visual angle. The target moved alternately left-to-right and right-to-left in a fixed arc, at 0.28° per second angular velocity at a simulated distance of 2 km. To maintain velocity and simulated distance, the model tank was moved along an HO-gauge model train track. A square aiming patch housed the detector that measured tracking accuracy. The patch subtended 2 mrad with a black center dot about 1 mrad in visual angle. The desert camouflaged model tank was set against a desert scene background. The beam from the Ar (514.5 nm) laser source was brought into the eyepiece through a fiber optic cable. Exposures were limited to approximately 40% of the MPE, with a retinal illuminance of 9.1 log_10 Td over a 50 µm retinal diameter focal spot.[46]

Photoreceptor Bleaching and Performance

Light energy incident on the retina is transduced as chemical energy through absorption of photons by opsins in the photoreceptors. The absorption leads to bleaching of the opsin, which in turn generates an electrical potential. Through a complex of enigmatic neural entanglements well beyond the scope of this chapter, the transmitted electrical pulse durations, rates, and intensities manifest as conscious visual perception. For light sources that do not induce a flash photolysis effect,[8] the extent of opsin bleach depends upon retinal illuminance as well as retinal exposure duration.

Figure 6-6. A Blaser tracking simulator with binocular viewing capability used at the Walter Reed Army Institute of Research in the 1990s.[1] (1) Stamper D, Lund D, Molchany J, Dembrowsky, Boneta O, Stuck B. Validation of the Blaser II Laboratory Tracking System. Silver Spring, MD: Walter Reed Army Institute of Research; 1997. Technology Report 97–001.

Figure 6-7. Photopic (cone) and scotopic (rod) bleaching and recovery Rushton curves for a 532 nm accident case exposure and a 514.5 nm Blaser exposure. Penumbra annuli around the focused beam umbra associated with 6, 7, and 8 log_10 Td (see Figure 6-5) show degree of bleaching and time to return to baseline. Note that the 532 nm source duration is 0.1 seconds for both accident case curves, and the 514.5 nm source duration is 3 seconds for both Blaser curves.

Figure 6-7 shows the cone bleaching and recovery curves for the 532 nm accident case exposure (left panels) and for the 514.5 nm Blaser exposure (right panels). The upper charts are the photopic recovery curves and the lower charts are the scotopic curves. Each chart shows percent opsin remaining or bleached as a function of time. The curves show laser onset at 100 seconds and plot bleaching and recovery for the retinal areas associated with 6, 7, and 8 log_10 Td retinal illuminance. The difference in bleaching efficiency is related to the amount of time the retinal area was illuminated. The 532 nm source illuminated the retina for 0.1 seconds, and the 514.5 nm source illuminated the retina for 3 seconds. The graph for the 514.5 nm exposure indicates that the retinal area inclusive of 7 log_10 Td bleaches op-sins to within 50% of baseline. The associated retinal diameter (as described in Figure 6-5) is 127 µm, which corresponds to a visual angular subtense of 7.25 mrad. The Blaser target subtended 35 mrad, which is about five times that of the visual angular subtense associated with 50% opsin bleaching for the 514.5 nm source.

Light-Limiting Strategies Revealed in Patterns of Afterimages

Figure 6-8 depicts the pattern of afterimages as recorded on an Amsler grid from volunteers who were exposed to the 514.5 nm source for 3 seconds during a pursuit-tracking task in the Blaser simulator. The figure indicates three strategies used to maintain tracking performance. Figure 6-8a depicts a strategy to maintain fixation on the aiming point. This strategy would yield significant retinal smearing due to head and eye movement over the 3-second exposure.33,47 The expected effect of smearing is to increase the 127 µm spot by 150 µm, producing a total spot size diameter of 277 µm. Because bleaching is dependent on exposure time, the movement would interrupt dwell time on any given retinal spot until revisited. Average dwell time for a given fixation over the 3-second exposure is 0.15 seconds.[33] Thus, the opsin bleaching and recovery would be consistent with the function for the 532 nm photopic function (0.1 s exposure) and would follow the same afterimage persistence timeline as described for the blinking strategy (Figure 6-8b).

Figure 6-8. Illustrations of the differing patterns of afterimages reported (a) when an observer stared at a laser without blinking, (b) when the observer repeatedly blinked when the laser was on, and (c) when the observer made a rapid eye movement away from and back to the target aiming point.

Figure 6-8b depicts the afterimages from a volunteer who reported “rapidly blinking” during the laser exposure.[38] Latency for a blink response, at its limit, is 250 milliseconds.[48] Over 3 seconds, at a rate of four per second, there should be about 12 spots given a constant blink rate. Figure 6-8b shows 11 afterimage spots with an angular subtense between 7 and 10 mrad. The spot left of the bore evacuator at the fore of the turret is over the aiming point, which is the spot of best fixa-tion on the aiming point. This spot measures 7 mrad as predicted in Figure 6-5 (left panel, 7 log_10 Td spot). A nominal effect of smearing of the spots is expected due to head and eye movement. The shorter effective exposure times would likely result in bleaching and recovery function closer to 8 log_10 Td curve for the 532 nm photopic condition (see Figure 6-7). The curve predicts that the time to recover 50% of the bleached opsins is 70 seconds, which is about the time the afterimage should persist under photopic conditions.[40] Time to fully recover to baseline is 300 seconds. Note that in the scotopic curves for all three cases, if the volunteers close their eyes (effectively producing a scotopic background condition), the reintegration of the afterimage with eye closure is predicted to occur up to 400 seconds postexposure.40,49

Figure 6-8c depicts a saccade to inferior-temporal space relative to and away from the source. Thus, the source was placed in the superior-nasal visual field. As described earlier in this chapter, viewing the source in this manner reduces luminous efficiency by 20%. The exposure was a monocular right-eye exposure, which in retinal space would mean that the laser source was placed on the inferior-temporal retina. Curcio and Allen reported that “densities in nasal retina exceed those at corresponding eccentricities in temporal retina by more than 300%; superior exceeds inferior by 60%.”50(p5) Thus, as a result of the eye movement, the laser source was placed in a relatively low receptor area. The saccade is estimated to be about 40 mrad, which is beyond the rod-free area around the fovea (see Figure 6-4), resulting in the illumination of a 700 µm path of photoreceptors from the fovea along the inferior-temporal path shown in Figure 6-8. Given the distance, the saccade would include about a 200-millisecond onset and take about 70 milliseconds to travel the distance and return.[51] The width of the streak is consistent with the spot size estimate from the scatter model. However, since saccadic eye movements were not reported in the Blaser study, it is difficult to assess retinal effects beyond inferences from spot sizes as reported in Figure 6-8.

Pupillary Response and Performance

Associated with the onset of the laser is a concomitant, compensatory change in vision that diminishes retinal illuminance and glare. Glare effects end with glare source termination (see Chapter 5, Laser Glare Effects on Visual Performance, this volume). However, the effects of retinal illuminance persist, with retinal function recovering per the opsin recovery depicted in Figure 6-7. The effect of the laser is dependent on the adaptive state of the eye and characteristics of the laser source.[52] As shown in Table 6-2 and Figure 6-8, the calculated retinal illuminance is greatest at the onset of the source and diminishes with light-limiting pupil adaptations and oculomotor behavior.

Table 6-2 shows pupillary changes for 0.1- and 3-second exposures for photopic and scotopic ambient conditions. These data confirm the effect of binocular summation in the pupil response as considered in the earlier discussion of light-limiting behavior. In response to source onset and at recovery, the pupil diameters at baseline are smaller for the binocular versus the monocular exposures.

TABLE 6-2
PUPIL DYNAMICS IN RESPONSE TO LASER OCULAR EXPOSURE DURATION, AMBIENT LIGHT CONDITIONS, AND VIEWING CONDITIONS

Bright

Dim

Monocular

Binocular

Monocular

Binocular

Duration (s)

0.1

3.0

0.1

3.0

0.1

3.0

0.1

3.0

Baseline (mm)

6.3

6.5

5.2

5.6

7.3

7.3

7.0

7.0

Minimum (mm)

3.9

2.9

3.5

2.5

4.5

2.9

3.5

2.9

Recovery (mm)

5.7

5.3

4.6

4.2

6.2

5.5

4.9

4.7

RPE: retinal pigment epithelium

Pupil constrictions in response to source onset limits retinal illuminance. For example, the dim-light monocular-viewing condition for the 0.1-second exposure results in pupil constriction from the baseline diameter of 7.3 mm to 4.5 mm. In turn, this change limits light onto the retina and changes retinal illuminance from 9.9 log_10 Td to 9.5 log_10 Td. For the 3-second exposure, the pupil constricted to 2.9 mm, resulting in a reduction of retinal illuminance to 9.1 log_10 Td.

Figure 6-9 shows the mean performance of volunteers engaged in the Blaser pursuit-tracking task. Exposure conditions and retinal spot sizes for the 0.1- and 3-second exposure durations are as previously described in this chapter. There were robust effects for exposure time and ambient light conditions. Time off target was about twice that for the dim-light conditions compared to that of the bright-light conditions. Comparing pulse durations within viewing (binocular or monocular) and ambient light (bright or dim) conditions, the 3-second exposure produced about a 4-fold increase in time-off-target scores compared to the 0.1-second scores. Time off target was shorter for binocular viewing compared to monocular viewing, with the differences particularly pronounced under dim-light conditions.

From the data reported in Table 6-2, the effect of summation in the binocular case resulted in smaller pupil sizes, effectively limiting light to the retina. As the performance data suggest, the smaller pupil size is associated with improved performance for the binocular condition compared to that of the monocular condition. The reported data are averaged. The data do not indicate that a light-limiting strategy of closing one eye occurred in the binocular case. The pupil constriction data in Table 6-2 show the expected difference between monocular and binocular pupil constriction, predicted by nasal pathway summation.

Assessment of Performance and the Entoptic Scatter Model

Assessing the performance data based on opsin recovery functions (see Figure 6-7), the data show that recovery of pursuit tracking is not well explained by opsin recovery. Time-off-target measures began with the onset of the source and continued until the target was reengaged. Thus, to assess opsin recovery, the duration of the laser exposure was subtracted from the total time off target. For bright-light conditions, the effects of opsin recovery are nominal, given tracking was lost for less than a second. In the bright-light conditions, opsins were bleached to about 45% of baseline, and the bleaching seemed to have little postflash effect on performance. For the dim-light condition for the monocular 3-second exposure, the estimated 4 seconds time off target from source offset (≈7 s total time off target; 3-s exposure) yields a 6% opsin recovery to baseline. Under the dim-light condition, opsins were bleached to about 65% of baseline. Note from the previous eye-movement discussion that the opsin recovery curves are based on a 0.1-second exposure (see Figure 6-7). Similar to the bright-light condition, data for the dim-light condition suggest that opsin recovery was nominally related to the return of pursuit-tracking performance.

Figure 6-9. Mean performance of volunteers engaged in a Blaser pursuit-tracking task. Average total time off target as a function of viewing condition, laser exposure duration, and ambient lighting conditions.

The time-off-target data seem to be most parsimo-niously explained by two factors: (1) a glare event and (2) the induction of a retinal relative scotoma (afterimage). The disruption due to the glare event would last as long as the laser was on. The induction of a relative scotoma depends upon retinal illuminance as described in Figures 6-5, 6-7, and 6-8. In this case, the source produced a central relative scotoma on the order of 127 µm on the retina, corresponding to 7.25 mrad or about 0.4° of visual angle. The scotoma likely affected the ability to resolve mid- to high-spatial frequency targets as described in the curve showing the suppression of the resolving power of the eye for the 5° central relative scotoma (see Figure 6-2). The Blaser target subtended 2° of visual angle, which equates to 0.5 cycles per degree or a low spatial-frequency target. The low spatial-visual channel is mainly governed by parafoveal pathways associated with the magnocellular visual pathways.[53] Although the aiming point is a foveal-resolved target, the aiming point, as referenced by the extent of the tank and its position in the reticle, is resolvable in the parafovea. Together with the smooth track of the target, the recovery of the sensory integration of the visually guided behavior likely accounts for the relatively short latency from laser source offset to recovery of tracking performance. In this way, the bleached patch of opsins and associated afterimage predict overall resolving power of the eye and, thus, the effect on performance.

Taken together and when normalized across expo-sure times and ambient light conditions, these data show a constant ratio as predicted in a Weber-Fechner relation (Figure 6-10). The data support the fact that sensation is dependent upon changes in source radiance relative to ambient radiance. The sensation is the underpinning for the perception and behavioral changes. The regression shows a constant in the rela-tionship between effect on visual performance and ratio of laser radiance to ambient radiance. This constant ratio is about 0.45. The caveat is that the correlation coefficient of the curve that fits these data is R^2 = 0.35. This is likely due in part to the varied light-limiting behaviors used to maintain tracking, which would affect the outcome of pursuit-tracking performance. Also, Weber’s law is applied liberally in that the task is intersensory. Visually guided behavior is guided by vision and dependent on visual function, but not uniquely predicted by it. Head and eye movements are coordinated through the inner ear, and motion of the track is aided through proprioception. Despite these caveats, there is a significant underlying visual-sensory mechanism that governs the data, evincing Weber’s law.

Figure 6-10. Graph of data from the Blaser pursuit-tracking task. Time off target is normalized to exposure duration as a function of log_10 laser radiance normalized to ambient radiance. The regression line suggests an underlying constant ratio that follows Weber’s constant.

CONCLUSION

The overarching finding is that a quintessentially visual organism, when engaged in visually guided behavior, will tend not to blink in response to bright light. To induce a photic blink, a significant area of the macular region has to be illuminated to greater than or equal to 6.8 log_10 Td·sec. Based on the data presented in this chapter, it is estimated that this area must at least broach the rod-free zone of central vision (see Figure 6-4; > 500 µm diameter). The focused beam of a laser is typically on the order of 100 µm. Associated with the umbra of the focused beam is its penumbra. The size of the penumbra determines the opsin bleaching of the retina, which in turn depends on wavelength, power incident at the cornea, and ambient lighting conditions. Compared to the experimentally controlled exposures depicted in Figure 6-1, the retinal illuminance of the focused beam associated with the accident case exposure was equivalent to experimentally controlled exposures as reported by Stamper and by Reidenbach.12,26

The difference between the accident case and the experimentally controlled exposures is the retinal area affected as predicted by forward scatter. The spot sizes resulting from the addition of the penumbra for the controlled experiments were well within the limit of the rod-free zone, even when accounting for retinal smearing due to head and eye movements. Factoring in the penumbra for the accident case yields a spot size larger than the rod-free zone. For retinal illuminance greater than 7 log_10 Td·sec (6.8 log_10 Td·sec for 50% opsin bleach), the diameter of the illuminated spot for the accident case was 694 µm. The sequelae associated with this exposure were consistent with symptoms of photoallodynia. Exposure in the accident case was dangerously close to the exposure dose associated with a 50% chance of producing a minimally visible retinal lesion (ED_50), whereas the experimentally controlled exposures were 40% less than the MPE. The experimental data show a significant repertoire of adaptations to limit light on the retina so as to maintain visually guided behavior. This point is best made by Reidenbach, who advocates a proactive approach to incorporating these behavioral adaptations into the safety standards.[26]

There is the potential that the accident case exposure resulted in what Rushton described as a 𝛳 effect.[8] From the calculations described by Rushton,[8] the accident case would have received successive quantal hits with average time between successive hits per molecule, about 10 milliseconds over the 100-millisecond exposure. The exposure would have bleached opsins to within 45% of baseline and deformed active-site proteins. The latter effect is unique to the flash photolysis process. The outcome would be a significant increase in latency to recovery of visual function because, along with opsin recovery, active sites must recover conformity to accept the opsin. The biochemical changes have a cascading effect on processes such as lateral inhibition[54] and diffusion of the chemicals that underlie formation of afterimages.[55] Flash photolysis effects, along with those of spot size, may explain the induction of symptoms of photoallodynia experienced by the convoy driver.

The major contribution of this chapter to the assessment of laser tissue interaction is the forward scatter model, which was based on the model developed by Jacques and Wang.[11] The model allows for quantifica-tion of forward scatter on the retina, which is critical for the assessment of performance-related metrics in laser ocular exposure. The model showed that the ocular system is very efficient in directing photons to the retina and, although scatter does occur, it is centrally directed. For many of the posterior tissue boundaries, the model used bovine coefficients of anisotropy, absorption, and scatter. Thus, this model can certainly be improved upon. The model includes a Henle fiber layer to account for absorption in the blue spectrum. However, wavelengths in that range were not run; the study’s objective was to explain the accident case sequelae in contrast to the outcomes of experiments that studied light-limiting behaviors in the context of visually guided behavior. Without the scientists’ work in the Blaser program, validation of the forward scatter model would not have been possible; this fact points to the relevance of their work today.

Lasers are currently used and will continue to be used as less-than-lethal means in the de-escalation of violence, particularly in postconflict operations[56] as was described in the accident case from Kabul, Afghanistan. However, the use of lasers as visual disruptors requires a reassessment of beam divergence and power to effectively induce the desired visually disruptive effect. The glare effects are disruptive and last as long as the laser is on. The effects of the induced relative scotoma depend on retinal illuminance and spot size, which in turn depend on viewing conditions, laser output power, and beam divergence. The desired effects are determined by rules of engagement and relevant tactical distances. These effects could range from psychological (eg, “There is a laser spot on me!”; “I am being targeted!”) to the symptoms described in the accident case that caused the crew to breach the seal of their vehicle. The available science now allows researchers to reliably model these effects for the appropriate implementation of lasers as less-than-lethal resources in postconflict operations. In these types of operations, the goal is to consolidate the win of the kinetic effort by promoting stability, but the ability to promote stability depends on the ability to limit lethal force where possible. As visual disrupters, lasers provide soldiers another resource to limit lethal force and thus promote stability in postconflict operations.

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24. Stuck BE. The blink and the blink reflex. Bioeffects Data, Supplement 1. Classified, Unclassified. In: Beatrice ES, Penetar DM, eds. Handbook of Laser Bioeffects Assessment, Volume 1. Presidio of San Francisco, CA: Letterman Army Institute of Research; 1984: S23–S28. Classified, Secret.

25. Reidenbach H-D, Hofmann J, Dollinger K, Seckler M. A critical consideration of the blink reflex as a means for laser safety regulations. In: Proceedings of the 11th International Congress of the International Radiation Protection Association. May 23–28, 2004; Madrid, Spain. http://irpa11.irpa.net/pdfs/8c5.pdf. Accessed October 16, 2017.

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Chapter 7

PSYCHOLOGICAL AND OPERATIONAL IMPACTS OF MILITARY LASERS

GEORGE R. MASTROIANNI, PhD, * Professor Emeritus, US Air Force Academy, Colorado 80840 and JAMES W. NESS, PhD † Colonel, Medical Services Corps, US Army; Professor of Discipline and Program Director of Engineering Psychology, Department of Behavioral Sciences and Leadership, US Military Academy, 601 Cullum Road, West Point, New York 10996

INTRODUCTION

IMMEDIATE PSYCHOLOGICAL EFFECTS

Suppressive Effects of Laser Use

Psychological Effects of Laser Exposure

CASE STUDIES

The Importance of Preexisting Knowledge About Lasers

Psychosomatic Responses to Suspected Laser Exposure

Functional Somatic Syndrome?

A More Effective Response to Laser Injury

PREPARING FOR THE FUTURE

Planning for the Psychological Aspects of Laser Casualties

Immediate, Appropriate Care

Accurate Information About Laser Injury and Recovery

Positive Therapeutic Relationship

CHALLENGES

Issues of Scale

Role of the Media

Politics of Laser Injuries

SUMMARY

Training

Surveillance

Media Relations

INTRODUCTION

The human combatant is and always has been the most important system on the battlefield. Weapons, equipment, supplies, tactics, and doctrine are all essential, but they are all brought to bear on the enemy by the capability and will of individual human beings who act alone or in concert with others. Lasers have been present on the battlefield for many years, largely as components of rangefinders and target-designating systems. Laser-based systems dramatically improve accuracy and thus have helped to reduce civilian casualties and collateral damage. However, because lasers are now widely distributed with air, land, and sea forces, they have also become a nearly ubiquitous source of potential harm.

Until now, battlefield lasers have been confined largely to adjunctive roles in rangefinders and designators. Widespread intentional use of lasers as antipersonnel weapons has not occurred, and the purposeful use of lasers in this role has been proscribed by international agreement.[1] In the future, directed-energy weapons systems, including lasers, will be even more widely used to support fire-control and training systems. Lasers may yet be developed for use as antimateriel weapons or, despite the current ban on their intentional use against human beings, as antipersonnel weapons.

Comparatively few cases of injury (perhaps a few hundred) have resulted from exposure to lasers in military and nonmilitary settings. The most well-known cases involve the sometimes intentional, sometimes inadvertent exposure of pilots to laser-directed aircraft cockpits; but ground troop exposures have also occurred, and some significant injuries have been sustained. Unavoidably, service members will encounter lasers on the modern battlefield, and some service members will be injured by them. To manage this threat effectively, it is crucial that we understand its potential psychological impact and how warfighters may respond.

It might well be argued that, to date, as much or more psychological than physical harm has been done by real and potential accidental exposure to lasers in the military and in commercial aviation. Tragic accident cases, mainly involving short-distance exposure to Q-switched laser pulses of high power and short duration, have resulted in severe retinal damage and permanent visual disability. Fortunately, such cases have been rare. More common are exposures that cause immediate visual disruption (glare, afterimage, or flash blindness), but that leave no permanent trace in the exposed person’s eye and no permanent damage to vision. However, in some cases, laser exposures have resulted in significant disability despite the lack of any known organic mechanism. Where no biological basis can be found, such consequences must be psychological. This is not to say that reported symptoms are not real or that the person who experiences such symptoms is in any sense weak, stupid, crazy, or a malingerer. Rather, it is simply the case that challenging and dangerous conditions inherent to military life or in commercial flying can interact with human psychology, sensory experience, and perception. This is made all the more likely by sensationalized and incorrect information or reports about lasers and their potential dangers.

In some respects, lasers can be usefully compared to chemical weapons.[2] Chemical weapons and lasers are both “unconventional.” Both can be invisible and undetectable until it is too late to defend against them, and both can cause significant injury. The prospect of an invisible and unfamiliar threat is frightening. Lasers superficially resemble the “death rays” of popular science fiction, and most people have relatively little experience with lasers projected over long distances. Lasers are extensively used in everyday technology, but often are not recognized by the average person. Chemical weapons are used militarily in much the same way they are employed in daily life, but our modern familiarity with insecticides and their effects is relatively recent.

The introduction of gas warfare had a significant psychological impact on soldiers in World War I, in part because the idea was new that one might be injured by something neither seen, heard, nor smelled. The Army’s response to this problem included the “gas chamber” exercise whose purpose was (and still is) to convince recruits that gas was a real threat and to build their confidence with the effective use of protective masks. In this exercise, trainees are brought into a chamber containing tear gas while wearing a gas mask. Then, they are required to remove the mask shortly before exiting the chamber. Thus, they receive a brief but compelling exposure to the noxious gas. The intended effect of this exercise is mainly psychological. The gas chamber exercise continues as a rite of passage for all members of the American military.

It has been proposed that service members may benefit from a laser training exercise conceptually similar to the gas chamber exercise.3,4 Like chemical weapons, lasers may be invisible yet potentially harmful. Their operational mechanisms are not readily apparent to untrained individuals, and laser protection requires specialized protective equipment. In 1995, the International Committee of the Red Cross (ICRC; Geneva, Switzerland) published a pamphlet supporting a campaign to ban “blinding weapons.”[5] To dramatize the threat, the pamphlet included sensational photos of chemical weapon victims from World War I.

Unfortunately, such emotional appeals ignore several important differences between battlefield lasers and chemical weapons. Lasers contribute precision to the battlefield, and precision ultimately helps to reduce unnecessary suffering. Chemical weapons offer no such benefit. Chemical weapons are by their nature indiscriminate, whereas lasers are by their nature highly discriminate. Regulations to discourage the legitimate use of lasers in combat might, therefore, have the unintended consequence of increasing unnecessary suffering.

There is a growing appreciation that psychological considerations are crucial to our understanding of modern combat and its consequences for combatants. Controversy over the health effects of Gulf War service helped to focus our attention on the psychological dimensions of modern warfare. The “signature wounds” of the Iraq War are posttraumatic stress disorder and traumatic brain injury, both of which pose unique diagnostic and treatment challenges involving the psychological dimensions of injury to the mind and brain. Individuals whose injuries are viewed as essentially psychological often struggle with stigma and may be mistreated by those who believe such injuries are merely imaginary. In recent years, the term posttraumatic stress disorder became the object of a vigorous campaign by General Peter Chiarelli, who argued that the name of the condition should be changed to posttraumatic stress injury.[6] An improved understanding of the potential psychological effects of military lasers may help us to manage more effectively the full range of health consequences for those exposed to lasers in the future.

In general, all modern wars have been associated with symptom clusters that appear as “syndromes,” but whose etiologies are confounding.7,8 For example, Jones et al[7] researched pension files of the British military from 1872 through 1991 and found three varieties of postcombat disorder:

1. debility syndrome—without psychological or cognitive symptoms associated with wars fought before 1918;

2. somatic syndrome—involving cardiorespira-tory symptoms (eg, rapid heart beat, shortness of breath, fatigue, etc) associated with World War I; and

3. neuropsychiatric syndrome—involving neurological and psychiatric symptoms (eg, depression, anxiety, headaches, etc) associated with World War II through the first Gulf War.

There was no single presentation of symptoms common across the various wars studied. Moreover, none of the syndromes identified could be linked to a definitive etiological agent, such as exposure to microbial agents, depleted uranium, chemical agents, or uniquely identifiable psychological trauma. This led researchers to implicate cultural factors (eg, common health fears, compensation, trends in diagnostic labeling, etc) as contributors to these unexplainable illnesses.[9]

IMMEDIATE PSYCHOLOGICAL EFFECTS

The psychological effects of lasers in military operations can be classified as either suppressive effects or exposure effects. Suppressive effects are changes in behavior or performance that result from the fact that lasers are or may be present on the battlefield. Exposure effects are those that result from actual exposure to lasers.[10]

Suppressive Effects of Laser Use

The mere threat of laser exposure may affect the behavior of service members and thus can have a profound impact on military operations. For example, vision is vital to situational awareness on the battlefield. If the enemy can disrupt the normal use of vision, performance on the battlefield may suffer. The threat of direct ocular exposure may motivate soldiers, sailors, or pilots to alter their visual search strategies, disrupt their scanning patterns, or otherwise modify their efforts to visually extract information from the combat environment. There is some evidence that exactly such effects may have occurred in the Falklands War in 1982 and perhaps contributed to the destruction of three Argentinian aircraft.[11] Likewise, performance may be degraded by the use of protective equipment or evasive maneuvers. The subject of laser eye protection is not considered at length in this volume, but there is an active and extensive ongoing research program to develop protective systems. Such systems have been fielded to protect pilots, vehicle crews, and dismounted soldiers. Laser eye protection is itself a complex and difficult issue, and will remain a dynamic problem.12–14

The use of military lasers (or simulated lasers) may also have significant suppressive effects by straining the military medical system. Wessely et al[2] described several incidents in which healthcare delivery systems were affected when large numbers of people sought medical help after a rumor or a suggestion that they may have been exposed to chemical weapons. In one case, 35 people in a Maryland subway station were sickened by an unknown substance that was later identified as window-cleaning solution sprayed under suspicious circumstances.[2] The appearance of harmless colored lights or eyesafe lasers might also easily be misinterpreted as potentially harmful on the battlefield. Large numbers of suspected laser injuries could impose a substantial burden on the battlefield triage and medical treatment system, even in the absence of any actual injuries.

Psychological Effects of Laser Exposure

The physical and medical effects of actual laser exposure have been dealt with extensively in other parts of this volume. Ocular laser injuries are rare, but reports of such injuries are numerous enough to describe their effects with some confidence.15,16 In general, such injuries occur without pain at the time of injury and afterward. Accident victims who report a “popping sound” or a “light blow” to the affected eye do not describe these acute effects as painful. Such exposures are not followed by a lengthy postinjury period of ocular pain, periorbital pain, corneal grittiness, or headache. Although patients may experience symptoms secondary to rubbing their eyes in response to real or perceived visual changes, some victims of severe laser retinal injury remain unaware that they have been injured until some time has passed. It is possible for a bright laser flash to cause fleeting visual effects without injury. Conversely, a laser may produce no perceptible flash (or a very mild one) and cause significant visual changes or even long-lasting and severe injury. Uncertainty may be confounded by delayed notification of known or possible exposure, or by conflicting alarms from laser warning sensors.

When laser injuries do occur, immediate and lasting psychological effects are possible. Immediate effects may include fear, panic, agitation, or shock. These acute effects would be expected to subside quickly as the patient receives care and reassurance from others. However, if complete recovery from exposure is not possible, psychological adjustment to lasting disability may be difficult. In principle, these effects are not different from those to be expected in the case of traumatic amputations or other severe battlefield injuries. What makes lasers different is the degree of uncertainty involved in assessing the severity of the injury and its likely course of recovery, and the possibility that a victim of laser injury may show no outward signs of injury. As is often the case for individuals who suffer with other “invisible” injuries, such as posttraumatic stress disorder and mild brain trauma, individuals who live with laser-related disabilities may discover that their injuries are poorly understood, regarded skeptically, or not taken seriously by others.[6]

Certain terms have a psychological saliency that focuses collective attention on a concept (eg, radiation, laser, posttraumatic stress disorder, anthrax) in a manner that can overshadow alternatives and exceptions to the collective idea of that concept. This forces a competition between the deliberate practice of determining etiology and those of the common prevailing understanding. For example, in the case involving Kapitan Man in 1997, discussed in detail in the following section, the then prevailing theme was a concern for the indiscriminant use of lasers as blinding weapons. This concern prompted a series of meetings by the International Conference of the Red Cross culminating in 1994 with an agreement on the prohibition on the indiscriminate use of lasers for the purpose of blinding.[17] In the case of the Kapitan Man, given the heightened concern over lasers, complaints by the crew concerning their eyes and a suspicious red dot on the photographs, and a paucity of cases lending to the lack of understanding of laser tissue interaction influenced an initial diagnosis of laser eye injury given by the attending optometrist. Alternative explanations and exceptions were not easily accepted, even though further evaluation proved the initial diagnosis as inconsistent with the associated events. For the Navy commander involved, the initial misdiagnosis and subsequent Congressional hearings played out into 2003 with the Navy rejecting an award for a Purple Heart.

The severity of the laser-related injury itself may not play a dominant role in determining psychological outcome. Rather, the psychological effects of laser exposure will probably depend on the interaction of several factors:

- the nature and severity of the symptoms themselves,

- the circumstances under which the exposure occurred,

- the victim’s cognitive appraisal of the impli-cations of exposure (determined by existing knowledge and beliefs about lasers, and by postexposure diagnosis and information), and

- individual personality differences and re-sponse tendencies (eg, coping skills).

Similar injuries may have very different psychological effects on various people. Psychological response may also be shaped by the physical and psychological states of the victim at the time of injury. Complex relationships among these factors are illustrated by analysis and comparison of case reports from the relatively few laser exposures that have been documented to date.

CASE STUDIES

Although cases of accidental laser exposure and injury have been relatively infrequent, case analysis supports the idea that a victim’s immediate response to laser injury may be most strongly influenced by his or her prior knowledge of lasers and laser injury mechanisms. Postinjury treatment and subsequent related events will significantly affect the character and intensity of long-term psychological response.

The Importance of Preexisting Knowledge About Lasers

Two cases (patients 1 and 2) reported in the literature support the hypothesis that preexisting knowledge of lasers affects initial response to laser-related injury. In each case, there occurred a relatively severe injury that led to permanent disability.

Patient 1: This patient was a laser scientist who was very knowledgeable about lasers and laser injury mechanisms.[18] He was accidentally exposed to a pulsed laser that produced an intraocular hemorrhage. He knew immediately that he had suffered a serious injury. However, at the time of this incident, few if any similar injuries had occurred or been documented in the literature. Little was known about the potential for recovery from laser injury. This patient experienced a powerful emotional reaction that he later described as worse than any reaction he had experienced as witness to horrific combat injuries in Vietnam.

Patient 2: This case offers a marked contrast in terms of immediate psychological response to laser eye injury.[19] A 21-year-old soldier was injured by a pulsed-laser rangefinder. He knew comparatively little about lasers or their potential consequences. The soldier sustained an injury that produced an immediate intraocular hemorrhage, but he reacted with relative calm. He observed blood in the vitreous humor of his eye and tried (unsuccessfully) to wash the blood away. He did not seek medical attention until several hours later.

Patients 1 and 2 both suffered immediate and obvious physical effects from their injuries, and both patients subsequently experienced substantial recovery. In each case, the initial resulting injuries were severe enough to produce significant, well-defined symptoms that could be directly and unambiguously attributed to the accidental laser exposure and its effects. Patient 1 experienced a profound, immediate, and disturbing psychological reaction. Patient 2 remained calm. Neither patient suffered lingering psychological effects.

Psychosomatic Responses to Suspected Laser Exposure

Laser exposures to the retina need not result in severe psychological reactions, but the potential for such reactions has long been recognized. In 1990, the US Army officially noted that “… soldiers who sustain minimal or even no injury from low-energy laser exposures may develop serious psychological problems and become ineffective in the performance of their duties.”20(p4) At least one case of possible military laser exposure may have led to just such severe psychological consequences.

Patient 3: This patient was a crewman aboard a helicopter conducting a photographic surveillance mission of a ship suspected of espionage activities.

Patient 4: This patient was a pilot operating the helicopter at the time of the incident. Several hours after returning to base, a photo analyst noted a red light in one of the surveillance photographs that had been taken during the mission. The analyst concluded that the red light was a laser. Alarmed, he immediately contacted the crew, explained his observation, and urged them to seek medical attention for their eyes. In response, the crewmembers reported to a local hospital emergency room. They became concerned that they had sustained severe eye injuries, and they reported this to their chain of command. Because of the sensitive nature of the surveillance mission, the case drew immediate and intense interest at the highest levels of government.[21] The case became the subject of Congressional hearings and also led to a civil lawsuit against the owners of the ship from which the laser was alleged to have been fired.22,23

The US Navy eventually concluded that no laser exposure had occurred in this case and that the red light apparent in the surveillance photo was actually a navigational lamp on the ship. However, there remains legitimate controversy among knowledgeable experts as to whether patient 3 was ever actually exposed to a laser. If a laser exposure did occur, it is nevertheless clear that any resulting ocular damage was minor and subtle. Patient 3’s visual acuity remains 20/20 in each eye. From a psychological point of view, however, the question of actual exposure is largely immaterial. Patient 3 reported persistent and severe symptoms of pain. Although his reported symptoms are not consistent with those that have occurred in cases of known exposure, patient 3 remains convinced that he was exposed to a laser and that his pain is the direct result of that exposure.

It is worth noting that several similar, but more severe, incidents have been documented involving laser irradiation of civilian police helicopters and commercial airliners. In most cases of actual laser exposure, aircrewmen perceived a bright flash and subsequent afterimage, and they responded by taking immediate evasive action. The affected crewmembers often experienced anxiety about the potential long-term effects of the incident. Some members were reluctant to seek medical help because they feared that doing so might jeopardize their flying qualification. However, in none of these cases has there occurred a postincident course characterized by long-term severe pain and disability such as that reported by patient 3.

A recent review of reports of aircrew exposed to lasers showed that adverse effects (defined as distraction/annoyance, glare, flash blindness, afterimages, operational problems, or pain/injury) occurred in about 11% of the incidents.[24] This contrasts with a rate of 60% in some simulator studies and may reflect the greater variability of exposure parameters under real-world conditions. Pain/injury was reported in approximately 2% of the incidents. The severity and duration of the symptoms associated with the pain/injury reports were not detailed.

Functional Somatic Syndrome?

There are many examples of putative medical disorders that seem to exist and persist in spite of medical and scientific evidence casting doubt on their organic origin. Barsky and Borus refer to these disorders as functional somatic syndromes and describe them as “characterized more by symptoms, suffering, and disability than by disease-specific, demonstrable abnormalities of structure or function.”25(p910) Examples may include multiple chemical sensitivity, Gulf War syndrome, or chronic whiplash, among others. Functional somatic syndromes may involve disagreement between the reporting patient and mainstream medical authorities with respect to the attribution of particular symptoms. The patient attributes symptoms to the putative syndrome. Medical authorities often do not.

Barsky and Borus argue that “somatic distress and medically unexplained symptoms have always been endemic to daily life, but the social and cultural characteristics of each era shape the expression, interpretation, and attribution of these symptoms.”25(p911) Medical history includes many disorders or syndromes that have flourished for periods of time, only to disappear or be replaced by other syndromes. Shorter[26] provides a fascinating history of these psychosomatic disorders. Barsky and Borus[25] assert that patients with such syndromes today are even less likely than their historical counterparts to respond to medical explanation and treatment. They believe this shift in patient responsiveness can be traced to three factors:

1. an overall decline in physician authority;

2. an influence of the mass media, including the Internet; and

3. contemporary medicolegal and financial interests related to compensation, disability, and legal damage claims.

These factors apply to military personnel and the population at large.

The term functional somatic syndrome would seem to be best applied when a large number of people are involved. However, given the role of mass media and the medicolegal system, the development of such syndromes can probably be set in motion today by a relatively small number of individuals. Indeed, Gulf War syndrome apparently began with national attention to reports from members of a relatively small Army Reserve unit. Although no such syndrome related to laser exposure has yet been named, the responses of patients 3 and 4 described previously suggest the possibility that underlying mechanisms at work in the development of such syndromes may have been a factor in the eventual unhappy outcome of their cases. It is certainly possible that conditions could conspire to create such reactions again, perhaps on a larger scale.

Barsky and Borus[25] identify four psychosocial factors that lead to the amplification of symptoms and thus set the stage for attribution of those symptoms to a functional somatic syndrome:

1. belief that one is sick,

2. future expectations and the role of suggestion,

3. sick role, and

4. stress and distress.

The case of patient 3 can be interpreted in terms of these four processes.

Beliefs

Many studies have shown that an individual’s beliefs about illness can exert a powerful effect on his or her symptoms and health. Patient 3’s beliefs about the connection between laser exposure and ocular symptoms may well have begun with incorrect or incomplete knowledge, and with faulty expectations about the future course of laser injuries. If so, his beliefs were probably strengthened by early, specialized examinations that revealed lesions in his right retina. These lesions were described as consistent with lesions that could result from laser exposure. Because accidental laser injury is rare, and because this particular case was so sensitive, the initial diagnostic findings were not broadly tested against the opinions of other knowledgeable specialists. Discussions about the case were limited to a relatively small circle of military laser experts who found themselves under extreme time pressure to report their findings. Experts in the field of laser injury have emphasized the difficulty of making a definite attribution of ambiguous retinal findings without lengthy, detailed, and highly sophisticated investigations.[27] In the case involving patient 3, the strong belief that laser exposure had occurred and caused detectable ocular damage may well have been at least partly iatrogenic.

Suggestion

The role of suggestion in the development of health symptoms has been extensively documented.[28] Patient 3 did not perceive his ocular symptoms as significant enough to require medical attention until he was phoned by the photographic analyst who had identified the red light in one of the mission photographs and concluded it was a laser. Additionally, some aspects of patient 3’s initial symptom reports may point to the possible role of suggestion or social transmission. On examination, patient 4 had no abnormal or pathological findings in either eye. Nonetheless, he later reported severe symptoms remarkably like those reported by patient 3. Although such symptoms (eg, headache, severe eye pain, head pain) may result from organic causes, they have also been reported as part of psychosomatic syndromes in the past.[26]

News reports of aircraft illuminations often contain inaccurate or exaggerated information. For example, a story appearing in the New York Post reporting the apprehension of a man who pointed a laser at commercial aircraft approaching LaGuardia airport began by describing the laser used as a “military-grade” laser, an ominous-sounding label with no real meaning. Like civilian lasers, military lasers vary in output characteristics according to their intended use. One of the officers who used his police helicopter to (successfully) lure the perpetrator to point the laser at his aircraft described the effects of the exposure this way: “You feel a strong tingle in your eyes. You have a burnt spot where you can’t see. It is very dangerous for any pilot to be blinded.”[29] “Tingling” is not a likely consequence of such exposure, and the “burnt” spot was most likely a temporary afterimage.

In an article for CNN, Marsh and Brumfield said of lasers in cockpits, “A direct hit can burn the cornea and that has put pilots in the hospital.”[30] The suggestion from the article is that ocular injuries severe enough to require hospitalization have ocurred as a result of cockpit laser exposures. In fact, corneal burns are highly unlikely in any cockpit scenario, because visible light passes through the cornea and is absorbed in the retina. Infrared lasers (not visible to the naked eye) could burn a cornea, but the cockpit windscreen would offer significant protection against such an injury. Retinal burns are possible in a cockpit exposure scenario, but we have been unable to find or document a single case in which a retinal burn has been verified.

The Sick Role

Adopting a sick role can produce secondary gain as sympathetic responses from others serve to reinforce and sustain sick behavior. Patients 3 and 4 received rapid and close attention from the media and from high levels of government. At least one media report portrayed the two military men as victims of Russian aggression and betrayal by the Clinton administration.[31] The supposed seriousness and permanence of the injuries reported by patients 3 and 4 conferred an air of significance to the case that surely would have been greatly diminished if the alleged victims had simply recovered in a day or so. Once the sick role is adopted, it cannot easily be relinquished without significant loss of standing.

Stress

Stress is well known to influence the perception of physical symptoms and their severity. People who experience chronic stress and/or acute stress that results from major life-changing events may perceive physical symptoms more negatively and more seriously than people who are not so stressed. As discussed previously, patients 3 and 4 found themselves in a very stressful situation. Patient 4 also experienced a major life-changing event when he lost his flying qualification, a devastating outcome for a pilot. Severe and chronic stress can produce somatic symptoms. Functional somatic syndromes provide apparently legitimate diagnostic labels for symptoms that may be due partially or wholly to stress. The possibility of laser exposure and its aftereffects may have provided a convenient and psychologically compelling explanatory outlet for the symptoms reported by patients 3 and 4.

The police officer who reported tingling and whom reporters described as injured32 was in fact exposed to laser illumination after an immensely difficult and presumably stressful chase at night, during which he maneuvered his helicopter to resemble an approaching jetliner specifically to provoke the laser exposure and identify its source location. The emotional and physiological arousal associated with such actions, which can only be described as heroic, might easily result in sensitization to a startling and feared stimulus.

A More Effective Response to Laser Injury

A few years after the incident involving patients 3 and 4, a similar incident occurred in Bosnia. Two aircrewmen, patients 5 and 6, observed a red light directed at them. Both men experienced visual disruption. There is little doubt among knowledgeable experts that these two crewmen were indeed exposed to a laser. Patients 5 and 6 both recovered fairly quickly from the incident. However, early media reports about the incident were incorrect in reporting its effects. Vinch erroneously reported that the crewmen had “sustained minor burns in their outer eye tissue, but are fully expected to recover.”33(p21) In fact, no such burns were sustained and would not have been possible in any of the most likely laser scenarios. Because visible laser light is not absorbed strongly by the cornea, it could only produce such burns with extremely high power, which would have also produced profound retinal effects. Infrared radiation is absorbed by the cornea, but would probably have produced immediate pain in the victim. Moreover, infrared radiation would have been partially or completely blocked by the victims’ night vision goggles.

Making reference to the earlier cases involving patients 3 and 4 as having suffered “permanent eye damage, Washington Times reporter Gertz21,31 also incorrectly reported that the two aircrewmen in Bosnia had “suffered eye burns.” In a report published in the Wall Street Journal, Ricks quoted an Army general as saying that patients 5 and 6 had suffered “mild-to-moderate burns” and further that there was “no indication of long-lasting effects such as retinal scarring, but it is too early to say. …”34(p8) Also disturbing was the imputation that (unnamed) “soldiers were disturbed by the lack of timely disclosure” and that the “Pentagon may not have wanted to call attention to the continuing U.S. mission on the eve of national elections in the U.S.”34(p8) Such media reports are troublesome because they exploit lack of knowledge in their sources, as well as their readers, and because they fuel suspicion and mistrust in victims and others. Information withheld or distorted for political purposes can worsen the pain and disability suffered by those who may (or may not) have been injured. Given the inconsistent and incorrect early media reports in this case, a negative psychological outcome could easily have resulted. Fortunately, it appears that no lasting damage was done.

Perhaps the most important lesson from these cases is that actual and possible laser injuries must be handled very carefully, with early attention to the possibility of psychological effects. In 1990, the US Army acknowledged the importance of stress management and reassurance:

Treatment following a laser injury is extremely important. Calm, professional treatment at each echelon of medical care is mandatory, including reassurance that the injury is not life-threatening and that chances for some, if not total recovery, are good. The potential psychological effects of lasers could be enormous. It is imperative that secondary gain be minimized by prompt return to duty of those individuals with temporary flash-blindness or noncritical (non-foveal) burns of the retina without hemorrhage. If an error is to be made, it should be on the side of return to duty of questionable injuries. Medical management of stress reactions for patients suffering from real or imagined laser injuries is like stress management of other injuries. Repeat the reassurance that symptoms will improve with rest, nutrition, hygiene, and the expectancy of an early return to the soldier’s unit.”20(p18)

Other chapters in this volume detail the painstaking research undertaken to explain the mechanisms of laser–tissue interaction and to develop effective therapies for physical laser-related injuries. Yet the cases illustrated here force us to recognize that even the most sophisticated scientific knowledge may be overcome by casual inaccuracies introduced and perpetuated by people who do not fully understand lasers and their potential effects on human beings.

PREPARING FOR THE FUTURE

To date, laser accidents and injuries involving military personnel have been extremely rare. If there were a shift toward the use of antipersonnel or antioptic lasers on the battlefield, we could expect to see an increase in casualties. Of course, it is impossible to estimate the magnitude or nature of the effects of weapons whose specific characteristics, strengths, and weaknesses are not yet known. The International Convention of the Red Cross on Certain Unconventional Weapons compared the indiscriminant use of lasers to that of the use of mustard gas in World War I. As with any ubiquitous agent used indisciminantly, there is often a reporting of symptoms that are a result of the risk communication rather than a direct result of exposure. Two processes seem to be involved in the evolution of symptom clusters associated with modern wars. One process is the rapid spread of notions concerning health-related problems. These health-related notions are best described as “memes” (a unit of cultural transmission or imitation).35,36 Memes are memorable, have strong psychological appeal, and speak to the concerns of a specific generation. They can replicate with relative high-copying fidelity (note consistency of symptom clusters within a war period) at sometimes alarming rates. The meme process spreads horizontally, within a generation or time-bounded category,6,37 and resonates with the presently held notions. As an example, Gulf War syndrome has been persistently attributed to toxin exposure,[38] which in turn has sustained arguments such as those concerning its possible relationship to a mycoplasma species infection. This attribution has been proven incorrect, but not before Gulf War I vet-erans were inappropriately treated with doxycycline as part of a clinical trial.[39] (In February 2001, the US Army Medical Research and Materiel Command con-ducted an external peer review of the Department of Defense-funded work on mycoplasma and found no putative role of Mycoplasma fermentans in the etiology of illness in veterans presenting with symptoms akin to chronic fatigue syndrome. Further, ethical concerns were raised in the use of a non-US Food and Drug Administration-approved technique used to enroll personnel in the course of antibiotic treatment.) The point is that as with any poorly understood symptom cluster or weapons that produce mass indiscriminant casualty, we might expect symptom reporting greater than what one would expect from those directly ex-posed.40,41

Planning for the Psychological Aspects of Laser Casualties

A review of injury cases yields a few basic heuristics to guide an effective response to laser casualties. These focus on the paramount importance of providing state-of-the-art medical and supportive care to victims of laser injury. From a psychological viewpoint, the special context that surrounds laser injuries must be recognized and carefully considered when plans are developed to deal with laser casualties.

Immediate, Appropriate Care

Fortunately, none of the cases reviewed here involved any significant or avoidable delay in the provision of medical care. The interval between battlefield injury and treatment has been dramatically reduced by advances in military medicine. Injured troops can now receive specialty care from well-trained, well-equipped military medical personnel very far forward in the combat zone. Faster treatment and a remarkable medical evacuation system have led to improved survival and faster return to duty. Service members are well aware of these advances, and they know they can expect excellent treatment. This helps to build and sustain morale and confidence. Service members must be confident that the military medical system is prepared to deal with laser injuries as effectively and efficiently as it does other types of combat-related injuries. It is important that the military medical system anticipates and be appropriately prepared for laser-related injuries.

First-line medical personnel must be appropriately trained and equipped to deliver relevant care for victims of laser injury. Certainly, there is much yet to learn about laser injuries and their treatment. However, from a psychological point of view, what matters most is that the injured service member understands that he or she is receiving state-of-the-art medical care. An injury victim can reach this determination by assessing the skill and confidence of healthcare providers. The best way to convince service members that they are being well cared for is to care for them well. This objective cannot be met without continuing research into the treatment of laser-related injuries.

Accurate Information About Laser Injury and Recovery

Victims of a traumatic injury will likely pay very close attention to all that is said about the injury and its prognosis. It is essential that commanders, health-care providers, and others provide laser injury victims with the most complete and accurate information that is available about their injuries and prospects for recovery. Injury victims will detect inconsistencies in the quality or character of such information and may attribute perceived discrepancies to incompetence or manipulation on the part of medical and military personnel.

Training is crucial to preparing service members for the stresses of deployment and combat. However, it is important to understand that informing service members about the potential for laser injury may have positive as well as negative consequences. There is the potential that by emphasizing the risks and hazards of battlefield lasers, we may create the possibility for misattribution of symptoms to laser exposure. It is likely that in any large-scale deployment, at least some returning service members will be affected by somatic complaints. We cannot discount the possibility that some will be misunderstood and misattributed. Nonetheless, the likely benefits of expanded awareness (by combatants) and readiness (of military medical personnel) would seem to outweigh these potential risks.

Positive Therapeutic Relationship

A number of factors may tend to heighten the sense of alarm experienced by victims of accidental exposure. Unfortunately, the “high-tech” and unfamiliar nature of lasers may tend to reinforce negative expectations concerning the seriousness of laser-related injuries. The popular portrayal of lasers and “death rays” in movies and books does little to relieve such fears. The exceptional nature of laser injuries might contribute to the intensity of psychological responses. Ironically, laser injuries would probably seem much less threatening if they were more common. The rarity of true laser injuries on the battlefield, and the military and (potential) legal issues associated with laser use necessarily involve military secrecy, intelligence, and security, which may add a further measure of cynicism and stress to an already complicated psychological circumstance.

Of course, we can only hope that laser injuries continue to be rare and that they become less frightening by the intelligent exercise of accurate information and effective treatment. If laser injury victims are well informed and treated well, the stage is set for positive outcomes. Even serious laser injuries to the retina may show a surprising degree of recovery. Less serious injuries often resolve quickly with little or no permanent disability. Soldiers should be given this fundamental information to relieve their fear of the unknown. Based on what is currently known and possible with respect to laser injury care and treatment, service members can feel reasonably confident that, in the unlikely event that they sustain a laser-related injury, they will receive appropriate and state-of-the-art care as quickly as possible, recover quickly, and return to duty. Soldiers should also be reassured that they will be given complete and accurate information about the nature of their injuries and prospects for recovery.

CHALLENGES

We face significant challenges in the treatment of laser injuries and in the development of effective strategies to minimize physical, functional, and psychological morbidity in laser injury victims. These challenges arise primarily from the potential requirement to respond to dramatic increases in the number of laser injuries that occur on the battlefield and from the new realities of the information age.

Issues of Scale

To date, battlefield laser-related injuries have been sufficiently rare and noteworthy that they have received extraordinary resources, attention, and care from specialists and experts. The cases reviewed in this chapter received extensive resources and fast attention and involvement from individuals at the highest levels of the US government. Patients were transported thousands of miles to receive special medical examinations. The case involving patients 3 and 4 set in motion a wide-ranging response that involved the military, the State Department, and the US Congress. The case involving patients 5 and 6 led to a temporary shutdown of night aviation training operations in Bosnia. Responses such as these may have military, legal, or political importance, but they also have implications for the psychological status of laser accident victims. This raises the question of how our responses might or should differ in the unfortunate event that laser-related injuries become more common on the battlefield.

One potentially effective response would be to establish a medical surveillance program (periodic ophthalmic examinations) for vulnerable military personnel. Such a program would

- contribute to our knowledge of laser hazards on the battlefield,

- support improved individualized treatment decisions in cases of suspected laser injury, and

- enable more thorough and accurate assess-ment of postinjury disabilities.

An ophthalmic surveillance database would be particularly helpful because virtually every ophthalmic examination reveals abnormalities of some sort. Although most such abnormalities are trivial, many (eg, “window defects”) are consistent with clinical findings that might also be expected to occur after laser exposure. Thus, the availability of a preinjury baseline examination would be quite helpful to identify preexisting defects that should not be considered as evidence of laser exposure. This would also help to reduce diagnostic uncertainty, which can have important psychological consequences for victims of laser injury.

The US Air Force has adopted an aggressive surveillance program for certain pilots, but the program is currently limited to a relatively small number of individuals. On one hand, the costs of broad medical surveillance would be much higher. On the other hand, such a program may significantly reduce the costs that would be associated with treating and compensating large numbers of laser-injured troops.

Role of the Media

Media reports of most incidents have been worrisome. Knowledgeable experts would disagree with much of the information contained in most media reports. For example, news reports about patients 3 and 4 generally do not acknowledge doubt as to whether a laser exposure ever really occurred, but instead report as fact that patients 3 and 4 are permanently disabled due to their alleged exposure.21,28,31 Similarly, reports about patients 5 and 6 describe the presence of “corneal burns” and ocular damage, in spite of the fact that no such findings were ever made. More recent reports almost always include the false assertion that pilots in cockpit laser exposure scenarios have suffered injuries or burns, leaving readers with the impression that such serious injuries have also occurred in the incidents being reported.

Journalists are limited by the space, time, and people available to them as resources. Competition is intense for air time or column inches of print space; therefore, reporters develop short, hard-hitting stories that will demand attention. Information readily available to the reporter in the aftermath of an incident often comes from the pilots themselves or from law enforcement authorities. Neither necessarily possesses the expertise necessary to fully and clearly explain what happened or what may not have happened. Understanding a real-world laser exposure incident requires

- sophisticated knowledge of the type of laser used and its output characteristics (eg, power, beam divergence, wavelength, and pulse characteristics),

- the angle from which the beam was directed into the cockpit, and

- whether the pilot viewed the beam on- or off-axis and for how long.

Complex calculations based on these and other parameters can then estimate the probable laser expoSeesure. Understanding the medical consequences of laser exposure is similarly complicated, though here the past should offer some comfort: very few laser incidents in cockpits result in any adverse consequence for the pilot.[24] An unknown, but small, proportion of this 2% may experience short-term changes in visual function that most commonly resolve quickly. Permanent disability is highly unlikely.

Politics of Laser Injuries

Inaccurate media coverage may be the result of many factors, including politics. For example, the incident involving patients 3 and 4 became a cause célèbre among certain individuals and organizations already firmly opposed to the foreign policy of the Clinton administration. As a result, patients 3 and 4 were portrayed by some as heroic soldiers who had been betrayed by political interests in foreign policy. This simplistic presentation left little room for a full and fair discussion of the manifold ambiguities of the incident itself. Unfortunately, the resulting controversy may have contributed substantially to the continuing disability of two men who might otherwise have quickly and fully recovered from their symptoms.

Inaccurate press has also been fueled by humanitarian campaigns to regulate the use of laser weapons. The ICRC (Washington, DC) published a book and a pamphlet titled Blinding Weapons, which contain reports of a series of meetings convened by the ICRC more than 20 years ago. The pamphlet is a campaign brochure. It presents a photograph of poison gas victims from World War I, with the caption, “Gas 1918 … Lasers 1999?” The dramatic text of the pamphlet begins as follows: “Sudden, endless, inescapable darkness. You cannot walk, eat, work, or read without help … ever again. You do not know how you look, and you will never see your children smile. Day and night merge into one. … There will be no recovery, only coping for the rest of your life with the effects of a split-second attack on your eyes.”5(p1)

The ICRC devoted considerable effort to its campaign to ban blinding weapons and assembled an extensive documentation of the devastating consequences of blindness. The campaign was predicated on the beliefs that

1. lasers used to specifically attack human vision could produce large numbers of military personnel who would be immediately blinded;

2. even weapons designed to produce only temporary effects must be expected to cause blindness notwithstanding their intended effect; and

3. a regulatory regime could be instituted that would proscribe intentional blinding, but permit “legitimate” uses of lasers.

The profound psychological effects of blindness hold a prominent place in the ICRC reports and serve as an important justification of its campaign.

Because we have no experience with lasers used purposely as weapons, it is difficult to evaluate the assumptions that underlie the ICRC campaign. We do know that after many years of laser use, some few hundred reported laser accidents have yet to produce a result even similar to that so vividly described by the ICRC’s pamphlet. We also know that despite the widespread use of lasers on the battlefield in adjunctive roles, very few injuries have occurred. Whether lasers used as weapons would have the devastating effects predicted by the ICRC is simply unknown.

The politics of lasers are relevant to their psychological impact. To the extent that politics are presented through the media, discussions of military lasers in the media help to establish and reinforce beliefs, expectations, and fears among service members and their families. When such discussions portray laser-related injuries as having unavoidably serious and permanent effects (eg, blindness), this sets the stage for dissonance between preexisting beliefs and more accurate information that may later be delivered by medics and physicians who care for victims of injury. Injury victims may thus experience confusion, fear, and ultimately doubt and suspicion that in turn can have serious negative psychological consequences. Functional somatic syndromes may also be reinforced through media attention that is driven by individual or organizational political efforts and interests.

SUMMARY

Three specific areas emerge as potential opportunities for immediate action:

1. training,

2. surveillance, and

3. media relations.

Training

Probably the most important theme to emerge from this chapter is the criticality of information and trust. When victims of laser injury are well informed about the nature of laser injuries and prospects for recovery, they will be well positioned to cope with the medical and visual challenges that may be involved in recovery. Complete and accurate information will help to relieve troops of the unnecessary complications associated with mistrust, suspicion, and anger. Beliefs matter. Our best opportunity to affect beliefs is during training. Soldiers at every level should be familiarized with lasers and their role in modern warfare, hazards associated with their use, the nature of possible laser-related injuries, and the prospects and promise of treatment.

Surveillance

A carefully targeted surveillance program would make it possible to document the preexisting and postincident ocular status of troops who are most vulnerable to accidental laser exposure. Information from such a surveillance program would also directly support the needs of researchers who continue to investigate laser injury mechanisms and consequences. Individual information would support individualized treatment and, additionally, would provide extremely valuable data for the adjudication of any medicolegal claims that may arise from such injuries.

Media Relations

It is incumbent upon us to ensure that accurate information be transmitted to the public sector as quickly as possible. Misleading information can be harmful. Moreover, the Internet makes it possible to store information (accurate or inaccurate) that may then be retrieved and repeated for many years, contributing to the impression that there exists a pattern of consistent evidence. Although journalists bear the ultimate responsibility for the accuracy of their coverage, we must also accept our responsibility to provide reporters with scientifically valid information, a balanced perspective, and knowledgeable guidance.

Although staggering advances in the technology used in warfare have transformed the face of modern conflict, combat remains an intensely personal affair. The ever-increasing sophistication of military technology should not blind us to the human characteristics of the men and women who operate advanced military devices and systems. On the battlefield, the service member is our most precious resource. Thus, it is essential that we understand how the presence of lasers on the modern battlefield may affect the psychological well-being, effectiveness, and readiness of those who serve.

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27. Mainster MA, Sliney DH, Marshall J, Warren KA, Timberlake GT, Trokel SL. But is it really light damage? Ophthalmology. 1997;104(2):179–180.

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29. Celona L, Sheehan K, Prendergast D. Three pilots injured after man points laser at jets. New York Post (Metro), March 10, 2015. http://nypost.com/2015/03/10/man-busted-for-pointing-laser-at-jets-in-nyc/. Accessed October 15, 2015.

30. Marsh R, Brumfield B. Nearly 4,000 laser attacks annoyed, injured U.S. pilots last year. CNN.com website, February 12, 2014. http://www.cnn.com/2014/02/12/us/pilots-laser-attacks/. Accessed October 15, 2015.

31. Gertz B. Betrayal: How the Clinton Administration Undermined National Security. Washington, DC: Regnery Press; 1999.

32. Gertz B. Laser weapons called threat to allied pilots over Serbia. The Washington Times. April 12, 1999:1–4.

33. Vinch C. Lasers under the gun. European Stars & Stripes. November 8, 1998:21.

34. Ricks T. U.S. force in Bosnia curtailed flights after aviators were injured by lasers. The Wall Street Journal. November 2, 1998:8.

35. Dawkins R. The Selfish Gene. New York, NY: Oxford University Press; 1976.

36. Ness J. Communicating the risk of weapons of mass casualty. Combating Terrorism Center Biodefense Rep. 2006;1:10–12. https://www.files.ethz.ch/isn/26330/ctc_biodefense_rep_june_06.pdf. Accessed July 11, 2017

37. Sterelny K. Memes revisited. Br J Philos Sci. 2006;57:145–165.

38. Nicolson G, Berns P, Nasralla M, Haier J, Nicolson N, Nass M. Gulf War illnesses: chemical, biological, and radiological exposures resulting in chronic fatiguing illnesses can be identified and treated. J Chronic Fatigue Syndr. 2003;11:135–154.

39. Nicolson G, Nicolson N. Doxycycline treatment and Desert Storm. JAMA. 1995;273:618–619.

40. Government Accounting Office. Gulf War Illness: Preliminary Assessment of DoD Plume Modeling for U.S. Troops’ Exposure to Chemical Agents. Washington, DC: US GAO; June 2003. Report GAO-03-833T. Testimony Before the House Subcommittee on National Security, Emerging Threats, and International Relations; Committee on Government Reform.

41. Doswald-Beck L, ed. Blinding Weapons: Reports of the Meetings of Experts Convened by the International Committee of the Red Cross on Battlefield Laser Weapons, 1989–1991. Geneva, Switzerland: International Committee of the Red Cross; 1993.

Section III

LASER-INDUCED INJURY
THRESHOLDS

Prior to heading on a night patrol, SPC Jameson Gurley of the 229th Military Police Company, 336th Military Police Battalion, 49th Military Police Brigade, tests a dazzler, or a laser sighting on his weapon, the night before Iraq’s general election, March 7, 2010. The 229th was stationed at Baghdad’s Provincial Directorate of Police headquarters as an additional entity. (Photo by SPC Edward Siguenza, 49th Military Police Brigade.)
Reproduced from: https://www.dvidshub.net/image/257957/iraqi-elections-baghdad.

Chapter 8

OCULAR EFFECTS OF ULTRAVIOLET LASER RADIATION

JOSEPH A. ZUCLICH, PhD * Senior Scientist/Consultant, Science Applications International Corporation, 1100 Northwest Loop 410, Suite 700, San Antonio, Texas 78213

INTRODUCTION

Military Relevance

General Background

ABSORPTION PROPERTIES OF OCULAR TISSUES

CORNEAL EFFECTS

Clinical Observations—Photokeratitis

Action Spectra

Photoablation

Pulsewidth Dependence

Cumulative Effects

LENS EFFECTS

Transient Clouding and Cataracts

Lens Fluorescence

RETINAL EFFECTS

Photochemical Effects—Morphology

Veiling Glare

SUMMARY

INTRODUCTION

The consequences of exposure to ultraviolet (UV) radiation are known to include acute and chronic effects in the cornea, lens, and retina of the primate eye. The purpose of this chapter is to describe the nature of the various UV laser-induced ocular pathologies and to discuss the operative mechanisms of damage in each case. Understanding of damage mechanisms and delineation of the exposure parameters to which each ocular tissue is the most sensitive have helped guide development of many military and biomedical applications of lasers described in this volume.

Military Relevance

The development of the laser in the late 1950s to early 1960s coincided historically with early successes in the manned space program, which spurred military and biomedical interest in understanding bioeffects of UV radiation at dose levels encountered in the extraterrestrial environment. The UV laser offered compelling advantages over the use of conventional sources of light such as arc lamps or high-power searchlights. Lasers provided the means to deliver intense, carefully directed exposures to in-vitro and in-vivo targets while allowing accurate diagnostic measurements of exposure parameters. Thus, as UV-emitting lasers first became available in the 1970s, researchers used them to supplement and complement ongoing investigations of biological effects of UV radiation.

As research and development yielded a greater variety of UV lasers, military interest continued to evolve and expand. The US Navy provided early support for the development of UV/short-visible wavelength lasers that might be used in undersea communications. Excimer lasers, now widely used for corrective refractive surgery, have been studied extensively as a means to preserve and enhance the visual performance of pilots, other specialized aircrew, and combat personnel. Low-level, portable UV laser systems are widely used in photo-therapeutic and germicidal applications. Some remote bio-detection systems utilize a tripled neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (355 nm) to identify a variety of specific aerosol agents. Diode lasers with near-UV/blue wavelength outputs can induce a veiling glare that results from the fluorescence of the ocular lens; this is a possible way to disrupt visual performance without causing permanent ocular injury.

General Background

Proteins and nucleic acids are the molecular building blocks of living tissue; they are largely transparent to visible and near-infrared wavelengths but can have strong absorption bands in the UV range. At UV wavelengths, photons may be sufficiently energetic to excite electrons of absorbing bio-molecules from the inert ground state to a highly reactive state. Before relaxing back to the ground state, the excited molecules may react with neighboring molecules to form a “photoproduct” that is not innate to the cell. The photoproduct is often disruptive to normal cell functioning and may eventually lead to cell death. The macroscopic observation of an abnormality and any physical sensation or other manifestation of the photodamage may be delayed, typically for several hours beyond the time of the UV exposure. Depending on the location and extent of damage, the resulting pathology may be described as a “lesion,” “erythema,” “inflammation,” or “burn.”

In order to understand the nature, extent, and recovery of laser-induced injury to the eye, and to establish protection and guidance for others (eg, military personnel) who may be exposed, careful dose-response data in nonhuman primates described effects of UV radiation on the cornea, lens, and/or retina. In each case, the primary target tissue is determined by the specific combination of exposure parameters (wavelength, peak power, pulsewidth, pulse repetition frequency, and total energy delivered).1,2 Effects may be acute or chronic, and the implicated mechanism of damage may be photochemical, photoablative, or thermal. The photochemical damage mechanism described above is most specific to UV wavelengths. Photoablative and thermal processes, also prevalent throughout other regions of the wavelength spectrum, are described elsewhere in this volume.

ABSORPTION PROPERTIES OF OCULAR TISSUES

Figure 8-1 depicts a schematic cross-sectional view of the primate eye, illustrating the passage of a collimated laser beam through the pupil and focused on the retina. The UV absorption properties of the components of the ocular medium (cornea, aqueous, lens, and vitreous) are illustrated in Figure 8-2 (calculated from the data of Boettner and Dankovic3). As can be seen, far-UV wavelengths (200–300 nm) are strongly absorbed by the cornea and do not penetrate deeper into the eye. Near-UV radiation (300–400 nm) is largely transmitted by the cornea but strongly absorbed by the lens, which serves to protect the retina from ambient environmental UV radiation. The aqueous and vitreous humors have absorption spectra that run parallel to that of the cornea, but with lower absorption coefficients for UV and visible wavelengths due to relatively lower cellular and higher aqueous contents. The composite transmission spectrum of the primate ocular medium (Figure 8-3) is calculated from the absorption properties of its individual components.[3] Little incident UV radiation is transmitted through the ocular medium to reach the retina. However, at ~320 nm and again at ~400 nm, approximately 1% of the corneal incident radiation does reach the retina and is absorbed by its cellular constituents.

Figure 8-1. Schematic cross-sectional view of the primate eye.

Figure 8-2. Ultraviolet absorption spectra of ocular components of the primate eye. The absorption spectra for the rhesus and human eyes are virtually identical.
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

From the ocular component absorption properties as described above, it is anticipated that the cornea will be the primary if not the only target tissue affected by far-UV wavelengths. Within the range of ~320 to ~400 nm, the lens is generally the primary tissue affected by near-UV radiation. Given that the focusing power of the eye more than offsets transmission losses through the ocular medium, the small percentage of UV radiation that reaches the retina at ~320 and ~400 nm could also have consequences for retinal tissue. The remaining sections of this chapter will consider, in turn, the corneal, lenticular, and retinal effects observed following exposure to UV laser radiation.

Figure 8-3. Transmission spectrum of rhesus ocular medium for near-ultraviolet radiation. The solid line represents direct transmission. The dashed line represents total (direct plus forward scattered) transmission.
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

CORNEAL EFFECTS

Clinical Observations—Photokeratitis

Figure 8-4 illustrates a clinical manifestation of UV-induced photochemical damage to the cornea of a rhesus monkey.[4] The clouding observed on the right side of the cornea developed over a period of 24 hours following UV irradiation of a circular area 2 mm in diameter. The UV source was a krypton-ion laser emitting at ~350 nm. At this wavelength, the radiant exposure required to induce an observable clouding was ~60 J/cm^2. Although this effect is wavelength dependent, it is not related to the coherent properties of the laser radiation. The same irradiance threshold can be obtained using a conventional source (eg, mercury arc lamp) filtered to yield a comparable wavelength.

Clinical reports of photokeratitis (snow blindness, exposure to welder’s arc, etc) indicate that suprathreshold whole-eye UV exposure may produce considerable discomfort and possibly severe pain, which begins several hours after exposure and persists for 24 hours or more.[5] In addition to the clouding shown in Figure 8-4, symptoms can include conjunctivitis, tearing, photophobia, and the sensation of sand or other granules in the eye. Generally, all symptoms resolve within 48 hours. For the threshold determination experiments referenced above,[4] UV exposures were limited to small areas covering the center of each cornea; following exposure, the behavior of the animal subjects was asymptomatic of eye irritation.

Figure 8-4. Corneal clouding (arrow) induced in a rhesus monkey following ultraviolet irradiation of a 2-mm diameter area of cornea by ultraviolet output of krypton-ion laser (350.7 and 356.4 nm). The bright reflection seen to the left of the lesion is due to the photographic flash.
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

Figures 8-5 and 8-6 are photomicrographs showing the cellular effects associated with the macroscopic UV-induced corneal clouding seen in Figure 8-4.[6] In Figure 8-5, the left edge of the photo shows normal tissue characterized by a regular array of basal cells and fairly even staining of the epithelial cells. The right half of the photo shows the edge of a corneal lesion, with the irradiated tissue exhibiting a significant thinning of the epithelium relative to the non-irradiated tissue. Thinning of the epithelium occurs as damaged surface epithelial cells break up and are sloughed into the tear layer. The premature breakup and sloughing of epithelial cell debris into the tear layer lead to the delayed physical discomfort experienced following a suprathreshold UV exposure. At the same time, the UV exposure causes an initial depression of cell division in the basal layer.7,8 Following a quiescent period generally lasting no more than 24 hours, there is increased mitotic activity until the epithelial cell population grows back to its normal level.

Figure 8-6 illustrates the central region of the lesion shown in Figure 8-5. Here, the basal cells of the epithelium are swollen and irregularly shaped. Heavy staining indicates radiation damage in the vast majority of the cells. In a subsequent experiment (not shown), the corneal tissue of a rhesus monkey subjected to an identical exposure was fixed at 48 hours (rather than at 18 h postexposure as shown in Figures 8-5 and 8-6). The resulting tissue in that case was essentially normal save for the thickness of the epithelial layer, which had not yet fully recovered.

Action Spectra

The action spectrum (threshold vs wavelength) for near-UV-induced corneal damage in the rhesus eye is plotted in Figure 8-7.[9] The action spectrum was determined by using an arc-lamp source filtered to bandwidths of 10 nm. Thresholds varied significantly over the near-UV wavelengths, ranging from ~10 J/cm^2 at 320 nm to over 300 J/cm^2 at 400 nm. When corrected for variation in corneal absorption,[3] the curve has a shape similar to that found for near-UV inactivation of bacteria.[10]

Figure 8-5. Photomicrograph of rhesus corneal tissue from an eye exposed to ultraviolet output of krypton-ion laser (350.7 and 356.4 nm). The tissue was fixed in glutaraldehyde in cacodylate buffer and stained with hematoxylin and eosin. This photo shows normal tissue (left) and the edge of a corneal lesion with irradiated tissue on the right.
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

The action spectrum for far-UV corneal damage is plotted in Figure 8-8. This plot is based on data from Pitts and colleagues, who showed closely similar curves for rabbit, monkey, and human subjects.5,11 The cornea exhibits maximum sensitivity to far-UV exposure at ~260 to 280 nm, where the threshold is ~5 mJ/cm^2. This wavelength region coincides with the first absorption bands of the aromatic amino acids of proteins and of the common bases of nucleic acids.[12]

Photoablation

Also plotted in Figure 8-8 are the corneal damage thresholds for ~20-ns pulses from XeC1, krypton fluoride (KrF), and argon fluoride (ArF) excimer lasers, at wavelengths of 308, 248, and 193 nm, respectively.13–15 The XeC1 and KrF excimer thresholds are in reasonable agreement with the action spectrum obtained using low-power conventional sources with exposure times in the order of seconds. However, the ArF threshold is 2 to 3 orders of magnitude below what would be anticipated by extrapolation of the action spectrum to 193 nm. This reflects the greater efficiency of a photoablative damage mechanism for the short-pulse, high-peak power excimer laser exposures relative to that of a photochemical mechanism, which dominates with long, low-power exposures.

Photoablation may be the most efficient tissue damage mechanism when exposure conditions create a photon flux that is large enough to overwhelm molecular bonding and thus produce an explosive dispersion of small fragments from the irradiated surface. If the laser radiation is also strongly absorbed by the irradiated tissue, little if any light penetrates beyond the small volume of ablated tissue. Hence, surrounding tissue will remain undamaged. However, a high absorption coefficient is not a requirement for an ablative surface process. Short-pulsewidth infrared and visible-wavelength lasers have also been used successfully to ablate ocular tissues via a plasma-mediated process that results from optical breakdown at the irradiated focal plane.[16] A typical ablation rate observed in corneal tissue is 1-µm depth of tissue ablated per 1 J/cm^2 of excimer laser radiation incident at the surface. By repetitive laser pulsing, a very precise and controlled tissue cutting process is achieved. Additional discussion of the photoablative process may be found in the work of Srinivasan and Trokel.17–19 A photomicrograph of a corneal cut observed after repetitive pulsing with ArF excimer laser radiation is pictured in a 1990 article by Zuclich.[20]

Figure 8-6. Center of the corneal lesion shown in Figure 8-5.
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

Figure 8-7. Action spectrum for near-ultraviolet-induced corneal damage in the rhesus monkey.

Figure 8-8. Action spectrum for far-ultraviolet-induced corneal damage in the rabbit. Open circles are excimer laser thresholds.
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

Figure 8-9. Log-log plot of corneal threshold as a function of pulsewidth. The dashed line represents a best fit to the experimental data. The solid line is the American National Standards Institute (ANSI) laser safety standard maximum permissible exposure (MPE) for near-ultraviolet laser radiation (315–400 nm). The horizontal solid-line segment represents the ANSI MPE for exposures >10^3 s, as it existed before the 1986 revision of the standard.
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

Pulsewidth Dependence

Commercially available UV sources cover very broad ranges of exposure parameters. These range from low-power continuous wave (CW) sources to short-pulsewidth lasers (nanosecond or less) with very high peak powers (megawatt or greater). Figure 8-9 demonstrates the variation in corneal threshold across 12 orders of magnitude of pulsewidth.[2] These data represent corneal lesions induced by krypton-ion and argon-ion laser radiation (350–360 nm), except for the point at 10 ns, which resulted from nitrogen laser radiation at 337 nm. The dashed line is an equal energy curve equivalent to a corneal radiant exposure of 60 J/cm^2. All of the thresholds, including those for single-pulse and multiple-pulse exposures, fall quite close to the equal energy line. Therefore, a reciprocity relationship exists between irradiance and pulsewidth. This provides quantitative evidence that a single-photon photochemical mechanism is operative over the entire range of pulsewidths examined at near-UV wavelengths. Functionally, this suggests that a UV hazard assessment can be determined in terms of radiant exposure (ie, total number of photons absorbed by the exposed tissue), and that within certain limits (discussed below), the threshold is dependent upon neither the rate at which the energy is delivered nor whether the UV dose is delivered by a single exposure or any sequence of repeated exposures.

For UV wavelengths other than ~350 nm, the corneal threshold at any given pulsewidth would be higher or lower than that shown in Figure 8-9, in ac-cordance with the wavelength dependence depicted by the action spectra (Figures 8-7 and 8-8). The solid line shown in Figure 8-9 is the American National Standards Institute (ANSI) maximum permissible exposure (MPE) for near-UV (315–400 nm) laser radiation.[21] This standard runs roughly parallel to the experimental data, allowing a margin of safety of a factor of 10 or more.

Cumulative Effects

Another aspect of UV-induced corneal damage that has been examined quantitatively is the cumulative effect of multiple pulses or repeated long exposures.[22] Multiple-pulse threshold data (see Figure 8-9) show that exposures have a net additive effect indicative of the total energy delivered. However, at some point, this additive effect levels off, which indicates that the cornea has a repair or recovery mechanism, or that it can replace damaged epithelial cells with a fresh supply of normal cells.

To quantify the cumulative effect for long or repeated exposures, corneal thresholds were determined for two identical exposures to ~350-nm radiation while time between the two exposures was varied.[22] Figure 8-10 shows the results of one such series of experiments. The point on the ordinate is the single-pulse corneal threshold for exposure to UV krypton-ion laser radiation. The remaining points are cumulative thresholds, that is, total energy doses from two identical subthreshold (if taken independently) exposures. The result is a monotonically increasing trend of cumulative threshold dose with time between exposures. The cumulative threshold approaches twice the single-pulse threshold for longer time intervals. This value would be the upper limit for the threshold if repair was completed between exposures. However, the thresholds for intervals of 5, 7, and 10 days between exposures fall ~10% short of twice the single-pulse threshold. This could indicate a small residual effect due to less-than-complete repair (during the time between exposures) or to enhanced corneal sensitivity related to the administration of drugs, radiation, or both during the initial exposures.

Figure 8-9. Log-log plot of corneal threshold as a function of pulsewidth. The dashed line represents a best fit to the experimental data. The solid line is the American National Standards Institute (ANSI) laser safety standard maximum permissible exposure (MPE) for near-ultraviolet laser radiation (315–400 nm). The horizontal solid-line segment represents the ANSI MPE for exposures >10^3 s, as it existed before the 1986 revision of the standard.
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

The solid line in Figure 8-10 represents a best fit to the data assuming that the trend of the corneal threshold (Th) is governed by an exponential repair process:

where k is the repair rate constant, c_1 and c_2 are fitting constants, e is the base of the natural logarithms (approximately 2.71828), and t is time. The rate of repair (k-1) found from a nonlinear regression calculation (yielding a least squares fit to the data) is equal to ~46 hours.[22] Knowing the rate constant, k, one can calculate the effective dose of any sequence of repeated exposures. This is important in any situation in which personnel would be exposed to UV radiation on successive days. With such a slow repair rate (46 hours), cumulative effects would occur from one day to the next.

Figure 8-11. Log-log plot of corneal threshold as a function of pulsewidth according to the exponential repair model. Curves are shown for 360 nm (dashed line) and 315 nm (dotted line) for comparison to the American National Standards Institute (ANSI) maximum permissible exposure (MPE) (solid line), which applies to the wavelength band from 315 nm to 400 nm. The horizontal solid line segment represents the ANSI MPE for exposures >10^3 s as it existed before being revised to reflect the quantitative repair rate determinations.
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

Figure 8-11 shows the behavior of the corneal threshold versus pulsewidth curve according to the exponential repair model. The curve levels off for exposure times greater than 10^5 seconds (>24 hours). Roughly speaking, there is a total additive effect of all exposures that occur within a given 24-hour interval. This additive effect tapers off for exposures separated in time by more than 24 hours. Recognizing the cumulative effect described above, the ANSI laser safety standard for near-UV radiation (315–400 nm) defines an MPE (solid line of Figure 8-11) that follows an equal energy dose for exposure durations from 10 seconds to 3 × 10^4 seconds (~8 hours).

TABLE 8-1
THRESHOLDS FOR TRANSIENT LENS OPACITIES IN THE RABBIT

Wavelength (nm)

Corneal Threshold (J/cm^2)

Lens Threshold (J/cm^2)

290

0.012

>3.0

295

0.02

0.75

300

0.052

0.15

305

0.07

0.30

310

0.055

0.75

315

2.25

4.5

320

7.25

12.6

325

18.0

>50

Data source: Pitts DG. A comparative study of the effects of ultraviolet radiation on the eye. Am J Optom Physiol Optics. 1978;50:19–35.

The proposed exponential repair model and the behavior of the threshold versus pulsewidth curve in Figure 8-11 are specific to the corneal epithelium. Different results may be found for other tissues that have different repair capacities or more complex (multiparametric) repair processes. However, Griess and Blakenstein examined the additive effect and repair following low-level (nonthermal), blue-light retinal exposures and have concluded that a simple exponential repair model applies in that case as well.[23] The rate of repair found for retinal tissue was ~96 hours compared to 46 hours for the corneal epithelium.

LENS EFFECTS

Transient Clouding and Cataracts

As was seen in Figure 8-2, most of the incident near-UV radiation is transmitted through the cornea and absorbed by the lens. Due to the “yellow pigment” found in primate lenses,[24] the lens has an absorption peak centered at 365 nm. Much evidence relates chronic or age-related cataract to long-term (lifetime) exposure to ambient UV, but discussion of this extensive body of epidemiological, biochemical, and histological evidence on chronic cataract is beyond the scope of this chapter. For more information on chronic cataract, see Waxler and Hitchens.[25]

Acute cataract induced via photochemical processes can occur following exposure to a narrow band of wavelengths from 290 to 325 nm. Table 8-1 compares the corneal and transient lens opacity thresholds for wavelengths in this range.[26] Depending on exposure dose, the lens clouding may be transient or permanent. Permanent opacities (cataracts) are observed following exposure to doses that are a factor of two or more above the transient lens opacity thresholds.[26] Therefore, the lens effect can represent a more serious injury than the corneal damage (which generally is repaired within 48 hours). For wavelengths shorter than ~295 nm, corneal absorption is sufficient to protect the lens. At wavelengths greater than ~325 nm, acute cataract induction via photochemical processes is not observed.

Figure 8-12. Cataracts (arrows) induced in rhesus monkey lens as a result of thermal insult from ultraviolet laser radiation. The cataracts are located at the anterior surface of the lens. Reflections can also be seen from the corneal surface, the posterior surface of the lens, and the lids (above and below). (a) Two cataracts induced by 10-ns pulses from nitrogen laser (337 nm). (b) Cataract induced by continuous wave radiation from argon-ion laser (351.1 and 363.8 nm).
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

There is, however, another type of lens hazard associated with lasers and other intense sources of wavelengths near the lens absorption band centered at 365 nm. At high irradiance levels, immediate thermal damage to the lens is possible because the incident energy is deposited primarily near the anterior surface of the lens. Examples of such acute cataracts are shown in Figure 8-12. The two bright opacities seen in Figure 8-12 (a) were induced in a rhesus lens by trains of 10-ns pulses from a nitrogen laser emitting at 337 nm.[4] The peak power of the 10-ns pulses was ~1 MW. The elongated shape of the lesions reflects the shape of the nitrogen laser beam. Figure 8-12 (b) shows an opacity induced by a CW argon-ion laser. In this case, the laser power was ~1 W at 351.1 nm and 363.8 nm (emitted simultaneously) with a beam diameter of ~2 mm. An exposure time of 1 second was sufficient to result in cataract formation.

Figure 8-13. Log-log plot of lens threshold as a function of pulsewidth. The solid line is the predicted thermal threshold for primate lens damage induced by 350-nm radiation.
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

This type of immediate lens opacity appears to be adequately described by a thermal damage mechanism. [4] On a plot of irradiance versus pulsewidth such as that seen in Figure 8-13, lens threshold data, although sparse, follow the solid line, which represents the damage threshold predicted by thermal model calculations. This trend contrasts with that of the corneal thresholds data, which follow the equal energy curve for exposure durations up to 10^5 seconds. The corneal and lenticular threshold versus pulsewidth curves are overlaid in Figure 8-14 to demonstrate that for long exposures, the corneal photochemical damage can be induced at much lower irradiance levels. For shorter exposures (1 s or less), there may be a greater hazard to the lens. However, it is important to note that there is no simple demarcation of lens and corneal susceptibility based on exposure duration. Corneal and lens thresholds exhibit different wavelength dependencies, reflecting the damage mechanisms operative in each case.

Figure 8-14. Overlay of lens thermal threshold versus pulsewidth curve of Figure 8-13 (solid line) and corneal photochemical threshold versus pulsewidth curve of Figure 8-9 (dashed line).
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

Lens Fluorescence

The development of “blue” diode lasers (here referring to diodes emitting at near-UV through short-visible wavelengths) and their potential widespread use in consumer electronics raised the prospect of escalating rates of ocular exposures and possible claims of eye injury or visual problems, even at non-injurious exposure levels. A similar scenario unfolded following the widespread dissemination of small, inexpensive (virtually throw-away) red diode lasers.27–30 In the case of “blue” diode lasers, however, there is an interesting variation with respect to the nature of potential visual disruption. Because the majority of incident radiation throughout the near-UV to blue wavelength range is absorbed by the lens, visual consequences arise not only from the small percentage of incident radiation that is transmitted directly to the retina (see Figure 8-3), but also (and primarily) from the blue-green lens fluorescence emission induced by this wavelength range. The fluorescing lens can be an intraocular source of veiling glare that is dispersed across the entire visual field. This effect may be intense enough to impair visual function.

Figure 8-15 illustrates the fluorescence spectrum recorded from an excised nonhuman primate lens upon excitation with 360 nm radiation (~10-nm bandwidth) from an arc-lamp source.[31] The trailing edge of the excitation envelope is seen at the left edge. When the excitation wavelength was varied across the range from 350 to 430 nm, the fluorescence spectrum retained the same general appearance, but its peak shifted to slightly longer wavelengths.31–33 Table 8-2 summarizes the results of spectroradiometer/photometer measurements of the fluorescence intensity as the exciting wavelength varied from 350 nm to 430 nm. It is readily seen that after equating for source irradiance, both fluorescence radiance and luminance remained relatively constant over this wavelength range. However, as the exciting wavelength was increased above 430 nm, fluorescence intensity dropped rapidly due to the increasing transmission of the lens.

Figure 8-15. Fluorescence of excised rhesus lens excited by 360-nm radiation from an arc-lamp source. Reproduced with permission from: Zuclich JA, Glickman RD, Menendez AR. In situ measurements of lens fluorescence and its interference with visual function. Invest Ophthalmol Vis Sci. 1992;33:410–415.

TABLE 8-2
FLUORESCENCE INTENSITIES MEASURED FROM EXCISED RHESUS LENSES

Excitation

Parameters

Emission Measurements

Wavelength (nm)

Irradiance (mW/cm^2)

Radiance (W/sr/m^2)

Luminance (cd/m^2)

350

0.019

4.5 × 10-4

0.034

360

0.092

9.6 × 10-4

0.16

400

0.054

5.3 × 10-4

0.13

430

0.064

6.2 × 10-4

0.18

cd: candela

sr: steradian

Reproduced with permission from: Zuclich JA, Glickman RD, Menendez AR. In situ measurements of lens fluorescence and its interference with visual function. Invest Ophthalmol Vis Sci. 1992;33:410–415. Copyright: Association for Research in Vision and Ophthalmology.

Figure 8-16. Peak spectral radiance (circles, left ordinate) and luminance (squares, right ordinate) of lens fluorescence as a function of continuous wave laser power. The slopes of regression lines fit to the radiance and luminance data both approximate 1.0 (actual: radiance = 0.984, r = 0.999; luminance = 0.956, r = 0.999).
CW: continuous wave
r: regression
sr: steradian
Reproduced with permission from: Zuclich JA, Glickman RD, Menendez AR. In situ measurements of lens fluorescence and its interference with visual function. Invest Ophthalmol Vis Sci. 1992;33:410–415. Copyright: Association for Research in Vision and Ophthalmology.

An in-vivo experiment was conducted to support the hypothesis that fluorescence veiling glare could reach visually debilitating levels in a living subject (anesthetized rhesus monkey).[31] A 413-nm krypton-ion laser was used as the exciting source, and a telephotometer was used to measure the lens fluorescence intensity as a function of excitation intensity. Figure 8-16 shows peak spectral radiance and photopic luminance, each plotted as a function of CW laser power. Both curves exhibit a slope of 1.0 (dashed lines) with no sign of saturation of the emitted fluorescence below the maximum exposure level of 18 mW. Higher exciting intensities were not used with the live subjects due to the risk of inducing thermal damage to the retina or lens. However, with excised lenses, the CW-laser intensity was taken as high as 100 mW. This yielded a fluorescence luminance of ~2,000 cd/m^2, again without saturation of the fluorescent chromophore.

Figure 8-17. Fluorescence spectra induced in younger (a) or older (b) lenses by three exciting wavelengths.

These findings were later extended to the human.[34] Fluorescence properties measured from human lenses (provided by participating eye banks) were qualitatively and quantitatively similar to those previously reported for nonhuman primates.[31] Typical fluorescence spectra induced by 360-, 400-, and 430-nm arc-lamp excitation are shown in Figure 8-17. Again, excitation wavelengths longer than the ~365-nm lens absorption peak resulted in a more red-shifted fluorescence. However, induced fluorescence had approximately the same luminous and radiant intensities for any exciting wavelength within the range of 350 to 430 nm. Figure 8-18 shows a plot of the peak wavelength of the fluorescence spectrum as a function of exciting wavelength. The only apparent deviation from a monotonically increasing function occurs for 450-nm excitation, where the fluorescence intensity was weak and assignment of a peak wavelength for the broad spectral output was problematic.

Figure 8-18. Variation of fluorescence peak wavelength as a function of exciting wavelength (averaged over all lenses).

Numerous investigators have examined the age dependence of absorption and scattering in the human lens and the consequent age dependence of the near-UV induced lens fluorescence. The age variation in transmission of the human lens is illustrated in Figure 8-19 by a spectral plot of the fraction of the incident radiation transmitted directly through the lens for three age categories.[34] These measurements were obtained with the radiometer detector head placed first at the position where the lens would be mounted and then directly behind the mounted lens. Thus, Figure 8-19 illustrates on-axis transmission/absorption spectra of human lenses. It shows that the young lenses had measurable transmission above ~390 nm and exhibited a rapidly increasing transmission for excitation ≥ 410 nm, whereas the older lenses were virtually opaque to wavelengths ≤ 405 nm and only rose to ~20% direct transmission at 450 nm.

Figure 8-19. Human lens transmission spectra for three age categories.

Figure 8-20. On-axis (solid lines) and 40° off-axis (dashed lines) fluorescence luminance measurements plotted as a function of exciting wavelength for each age category (nor-malized to 1-mW incident laser power).

Figure 8-20 shows the analogous (on-axis) plots of lens fluorescence luminance for the same three age categories. With excitation wavelengths ≥ 390 nm, measured luminous intensity increased rapidly with increasing wavelength. This is due primarily to the increasing direct transmission of the source. For shorter exciting wavelengths, where the contributions of the directly transmitted radiation are minimal, all age categories showed approximately the same fluorescence luminous intensity.

TABLE 8-3
COMPARISON OF LUMINOUS INTENSITIES FROM NONHUMAN PRIMATE LENSES AND HUMAN EYE BANK LENSES

Exciting Wavelength (nm)

Normalized Luminance Rhesus Lenses[*]

Normalized Luminance Eye Bank Lensesa[†] (cd/m^2 ÷ W/cm^2)

350

1.80

9.96

360

1.74

9.85

400

2.40

11.1

430

2.80

15.2

*From Table 8-2; luminance divided by irradiance of exciting source.

†Averaged across all lenses (all age categories).

Data source: Zuclich JA, Previc FH, Novar BJ, Edsall PE. Near-UV/ blue light-induced fluorescence in the human lens: potential interference with visual function. J Biomed Optics. 2005;10:44021-1-7.

Figure 8-20 also depicts off-axis luminance of the three age categories as measured at 40° from the axis of irradiation. In contrast to the on-axis measurements, the off-axis results show little dependence upon excitation wavelength. The luminance data were also strikingly similar to the nonhuman primate results reported in Table 8-2. This can be seen in Table 8-3, where the luminance values from Table 8-2 are normalized versus the respective source irradiances to yield a relatively constant ratio (central column of Table 8-3). Analogous results from the eye-bank lenses (averaged across all age categories) show virtually the same trend (right-hand column of Table 8-3). It is noted that normalized lens luminance is ~5 times higher in the human lens than in the nonhuman primate lens; however, this is not considered a sufficient basis to conclude that either fluorescence efficiency or visual disruption is greater in the human. (Experimental approaches used for human and nonhuman subjects were not entirely analogous; different detecting instruments, aperture sizes, and detector head placements were used).

RETINAL EFFECTS

Photochemical Effects—Morphology

The hazard to the retina from laser radiation or from any other effectively collimated source is that the focusing power of the eye can result in a much higher power density at the back of the eye than was incident at the cornea. For UV wavelengths, this retinal hazard is mitigated but not necessarily eliminated by strong absorption by the ocular medium.

The lens is the primary ocular filter of near-UV radiation, and it effectively cuts off transmission to the retina at the short wavelength end of the visible spectrum. However, an important feature of the lens absorption spectrum (see Figure 8-2) is the small window centered at ~320 nm. At this wavelength, the cornea is not strongly absorbing. Thus, a small amount of UV (~1% of a direct transmission) can reach the retina (see Figure 8-3). It has been shown that the retina is considerably more sensitive to wavelengths near this narrow transmission window than to longer UV wavelengths, which overlap the lens absorption band centered at ~365 nm.[35] This potential retinal hazard was identified with a helium-cadmium (He-Cd) laser that emits at 325 nm. At exposure levels well below the corneal threshold for 325 nm (14 J/cm^2), darkly pigmented spots developed (over a period of several hours) on the exposed retina of a rhesus monkey (Figure 8-21).[35] Lesion diameters were typically 50 to 100 µm. The time frame of development closely resembled that for the slowly developing corneal clouding described previously and is also comparable to the development of skin erythema induced by UV radiation. Retinal lesions maintained their darkly pigmented appearance for at least several months (as long as the exposed subjects were monitored).

Figure 8-21. Retinal lesions induced in maculae of rhesus eyes exposed to the 325-nm output of a helium-cadmium laser. (a) Three-by-three array of macular lesions induced with a constant laser power (20 mW) but varying exposure times. (b) Two-by-four array of macular lesions induced with varying laser powers (< 20 mW).
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

TABLE 8-4
COMPARISON OF OCULAR THRESHOLDS FROM HELIUM-CADMIUM AND KRYPTON-ION LASERS

Corneal Threshold

Retinal Threshold

Laser Source

Radiant Exposure (J/cm^2)

>Energy Dose (J)

>Radiant Exposure (J/cm^2)*

>Energy Dose (J)*

Helium-cadmium-UV (325 nm) < 1% transmitted to retina

14

0.28

3.61 × 10-1

7.6 × 10-3[†]

Krypton-UV (350.7 and 356.4 nm) < 1% transmitted to retina

67

0.89

> 670

> 8.9

Krypton-blue (476 nm) ~60% transmitted to retina

-

-

4.4 × 10-2

2.5 × 10-3[†]

*incident at cornea

†comparable pulsewidths (350 ms)

—: no data

Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

The lesions shown in Figure 8-21 were induced during experiments in which both laser power and exposure time were varied. It was found that there was a total energy requirement (and not a peak power threshold) necessary to induce the darkly pigmented retinal lesions.[35] This evidence suggests a photochemical mechanism of damage.

Table 8-4 compares the retinal threshold for 325-nm radiation (0.36 J/cm^2) to the corneal threshold for the same wavelength and to the corresponding thresholds for two other wavelengths. The efficiency of the 325-nm UV photons is striking compared to the other cases. In the 350- to 360-nm region, near the lens absorption peak, argon-ion or krypton-ion laser radiation induced no observable retinal effect even with exposures well in excess of corresponding corneal thresholds. Compared with the blue laser emission (> 60% of the incident radiation transmitted to the retina), the 325-nm photons (~1% transmission) are more effective in inducing retinal damage.

Retinal sensitivity to UV wavelengths is further demonstrated by the data of Ham et al,[36] who measured retinal thresholds in the aphakic rhesus eye for a number of visible and UV wavelengths. Their results are summarized in Table 8-5, where the numbers shown in the right-hand column demonstrate the relative retinal sensitivity without the filtering effect of the ocular lens. The shorter the wavelength, the more efficient the retinal photochemical damage mechanism. Note that the 325-nm wavelength is probably close to the shortest wavelength for observation of any retinal effect. At shorter wavelengths, the absorption of the ocular media begins to overwhelm all other factors.

TABLE 8-5
RETINAL THRESHOLDS FOR ULTRAVIOLET EXPOSURES IN THE APHAKIC RHESUS

Wavelength (nm)

Energy at Cornea (J)*

Calculated Retinal Irradiance (W/cm^2)

488[†]

-

0.77

405

0.41

0.15

380

0.24

0.081

350

0.20

0.054

325

0.23

0.05

*100-s exposures

†normal (phakic) eye

—: no data

Data sources: (1) Ham WT, Mueller HA, Ruffolo JJ, Guerry D, Guerry RK. Action spectrum for retinal injury from near-ultraviolet radiation in the aphakic monkey. Am J Ophthalmol. 1982;93:299–306. (2) Ham WT Jr, Mueller HA, Sliney DH. Retinal sensitivity to damage from short wavelength light. Nature. 1976:260;153–155.

Figure 8-22. Morphology of retinal damage induced by the 325-nm output of a helium-cadmium laser. (a) Light micrograph (× 850) of a lesion resulting from a 0.95 J/cm^2 exposure (incident at cornea). Necrotic inner segments are seen separated by intact cells. (b) Electron micrograph (× 21,000) of tissue subjected to a 3 J/cm^2 exposure (incident at cornea). A degenerating photoreceptor outer segment is seen adjacent to receptors, which are normal in appearance.
Reproduced with permission from: Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

The morphology of UV laser-induced retinal lesions in the phakic eye is illustrated in Figure 8-22.[37] Figure 8-22 (a) is a light micrograph of a section of rhesus retina that was exposed to a suprathreshold dose of 325-nm laser radiation 24 hours before fixing the tissue. Exposure durations were on the order of 1 second, and exposures were confined to the macula. Several instances of necrosis of photoreceptor inner segments are observable, as well as loss of adjacent nuclei in the outer nuclear layer. Figure 8-22 (b) is an electron micrograph of similarly exposed tissue, showing a degenerating photoreceptor outer segment adjacent to apparently normal cone segments on either side. These histologic studies thus identify the photoreceptors as the primary site of retinal damage. The retinal pigment epithelium (RPE) and other retinal layers appear normal. By contrast, Ham et al[36] observed significant damage to the RPE as well as to photoreceptors in the aphakic rhesus retina exposed to near-UV radiation for 100-second and 1,000-second periods.

Retinal radiant exposures calculated using best estimates of retinal image size and transmission of the ocular medium at 325 nm are comparable for the threshold in the phakic eye (see Table 8-4) and that reported by Ham et al in the aphakic eye (see Table 8-5). However, it should be noted that the exposure times differed by ~3 orders of magnitude; this factor may account for differences noted in the pathology. Although the implications for visual function are not fully understood, it is important to stress that the near-UV exposures did induce photoreceptor damage and that the funduscopically observed retinal lesions (darkly pigmented spots) were permanent in nature.

Veiling Glare

As noted previously, near-UV to blue wavelengths (360–430 nm) can induce a blue-green fluorescence in the primate lens. The measured luminance of that fluorescence can be sufficient to interfere with visual function. Lens fluorescence is dispersed over the entire visual field, imposing a “veiling glare” that reduces the contrast of the perceived view. A unique experiment used visual evoked potentials (VEPs) to provide an objective measure of the visual deficit associated with the fluorescent glare induced in live subjects by low-level laser radiation.[31] The VEPs were recorded from anesthetized rhesus monkeys with scalp electrodes placed over the foveal projection area of the visual cortex. The anesthetized subject (with a dilated pupil) viewed a stimulus monitor projected to the eye from a pellicle beam-splitter set in front of a fundus camera. The center of the projected stimulus field was aligned along the optic axis of the fundus camera. The subject’s fundus was viewed on a television monitor using only the infrared component of the fundus camera’s viewing light. This was done to avoid disrupting the dark-adaptation state. During the VEP recording session, 413-nm krypton-ion laser radiation was introduced by directing the collimated beam through the pupil at an angle of 45° to the optic axis of the fundus camera (and the subject’s visual axis). The small percentage of laser radiation transmitted through the ocular medium[38] was incident on the peripheral retina at a spot well off the field of view of the fundus video monitor. Laser power incident at the cornea was 0.5 to 1.5 mW in a 5-mm diameter beam.

Laser exposure conditions for the VEP experiment were chosen to approximate the safety standard MPE levels for exposure to a visible wavelength laser21,39 while minimizing the possibility of a direct glare effect. The exposure wavelength had a low luminous efficiency (0.002) and the collimated beam was directed 45° off axis, where the predicted glare effect is negligible.[40]

Figure 8-23 depicts VEP amplitude plotted as a function of stimulus contrast with and without CW-laser radiation. In the absence of lens fluorescence effects, the two response curves should coincide. Instead, in the presence of the laser radiation, the VEP amplitudes were reduced for all values of stimulus grating contrast. Similar results were generated in each of three VEP recording sessions with two rhesus subjects. Observed reductions in VEP amplitude were attributed to the fluorescence glare.

Data from excised human lenses provide an objective distinction between contributions to the veiling glare that arise from direct transmission of the exciting source radiation versus those attributable solely to the induced lens fluorescence. Zuclich et al[34] performed luminance measurements and generated CIE (International Commission on Illumination) chromaticity diagrams for both on-axis and 40° off-axis directions relative to the axis of the incident radiation. In each case, the chromaticity coordinates were plotted for three exciting wavelengths (390, 410, and 430 nm) and for each of three age categories (< 20 years, 20–45 years, and > 45 years). The results are shown in Figure 8-24 (on-axis) and Figure 8-25 (off-axis). For the on-axis measurements, color appearance reflected the relatively strong direct transmission contributions for each age group. An exception was noted only for the older lenses at the shortest exciting wavelength (390 nm), where direct transmission was minimal. By contrast, the off-axis measurements demonstrated similar fluorescent color appearances for all ages with 390-nm and 410-nm excitation, but began to reflect contributions from direct transmission of the exciting light for wavelengths as long as 430 nm. Again, the results seen in Figure 8-25 are consistent with higher transmission through the younger lenses.

Figure 8-23. Effect of laser-induced lens fluorescence on visual evoked potential.
Reproduced with permission from: Zuclich JA, Glickman RD, Menendez AR. In situ measurements of lens fluorescence and its interference with visual function. Invest Ophthalmol Vis Sci. 1992;33:410–415.

Observed similarities in luminous intensities and color appearance imply that lens fluorescence and consequent glare disruption could be a comparable problem for all age categories. This was somewhat surprising since lens absorption increases and broadens with age, and so might the induced fluorescence intensity. On the other hand, the young lens is already virtually opaque (transmission < 1%) at 360 to 390 nm, and any increase in absorption beyond that level would not result in a significant incremental increase in induced fluorescence. Even at longer exciting wavelengths, where young lenses have significantly greater transmission, age-related incremental increases in induced luminance and radiance are less than a factor of 2.

Furthermore, induced lens fluorescence is generated in a cylindrical (or conical) volume as incident radiation penetrates into the lens. Therefore, even if the younger lens generates a somewhat lower fluorescent intensity, more of that fluorescence emanates from deeper within the lens. Hence, the fluorescence “source” is closer to a detector positioned behind the lens. Because emitted fluorescence must cross through intervening lens tissue before reaching the detector, and because it is more highly absorbed and scattered by older lens tissue, luminous intensity measured from the younger lens would be reduced less than that measured for the older lens. Taking this argument one step further, the insitu scenario replaces the photometer or radiometer with the innate detector (the retina). Thus, it is inferred that the resultant visual response would be reduced less in the young lens than would otherwise be expected solely on the basis of the lower induced-fluorescent intensity.

Figure 8-24. International Commission on Illumination (CIE) chromaticity diagram showing on-axis measurements for three exciting wavelengths and three age categories.
Reproduced from: Zuclich JA, Previc FH, Novar BJ, Edsall PE. Near-UV/blue light-induced fluorescence in the human lens: potential interference with visual function. J Biomed Optics. 2005;10:44021-1-7. Published under Creative Commons (CC BY 4.0)-Gold Open Access (https://creativecommons.org/licenses/by/4.0/legalcode).

Figure 8-25. International Commission on Illumination (CIE) chromaticity diagram showing 40° off-axis-measurements for three exciting wavelengths and three age categories.
Reproduced from: Zuclich JA, Previc FH, Novar BJ, Edsall PE. Near-UV/blue light-induced fluorescence in the human lens: potential interference with visual function. J Biomed Optics. 2005;10:44021-1-7. Published under Creative Commons (CC BY 4.0)-Gold Open Access (https://creativecommons.org/licenses/by/4.0/legalcode).

SUMMARY

Corneal, lenticular, and retinal damage effects resulting from UV laser radiation have been described. Ranges of exposure parameters for which each of the ocular tissues is the primary target site have been identified, and in each case, the resultant UV-induced ocular pathology has been discussed. The ranges of exposure parameters suggested as capable of inducing acute effects are, necessarily, only rough guidelines because many factors individually and collectively influence the relative sensitivity of exposed ocular tissues.

Long-term (lifetime) cumulative exposures to ambient UV radiation also contribute to chronic ocular conditions such as cataracts and macular degeneration. Exposure to low-level (subacute) doses from UV lasers or non-coherent UV sources, even if they result in no apparent short-term deleterious ocular effects, may contribute to the long-term UV cumulative “load” and thereby exacerbate the chronic consequences of UV exposure. Therefore, it falls to promulgators of laser safety standards to judiciously review evidence for the myriad reported acute and chronic consequences of UV exposures and adopt an appropriately conservative posture toward safety considerations for UV laser sources.

REFERENCES

1. Zuclich JA. Ultraviolet laser radiation injury to the ocular tissues. In: Court LA, Duchene A, Courant D, eds. CorneProceedings of the First International Symposium of Laser Biological Effects and Exposure Limits. Cedex, France: Commissariat a I’Energie Atomique; 1988: 256–275.

2. Zuclich JA. Ultraviolet-induced photochemical damage in ocular tissues. Health Phys. 1989;56:671–682.

3. Boettner EA, Dankovic D. Ocular Absorption of Laser Radiation for Calculating Personnel Hazards. University of Michigan Final Report, Contract F41609-74-C-0008. Brooks Air Force Base, TX; US Air Force School of Aerospace Medicine; 1974.

4. Zuclich JA, Connolly JS. Ocular damage induced by near-ultraviolet laser radiation. Invest Ophthalmol. 1976;15:760–764.

5. Pitts DG, Tredici TJ. The effects of ultraviolet on the eye. Am Ind Hyg Assoc J. 1971;32:235–246.

6. Zuclich JA. Ultraviolet induced damage in the primate cornea and retina. Curr Eye Res. 1984;3:27–34.

7. Breschke W, Friedenwald JS, Moses SG. Effects of UV irradiation on the corneal epithelium. J Cell Comp Physiol. 1945;26:147–164.

8. Friedenwald JS, Breschke W, Crowell J, Hollender A. Effects of ultraviolet irradiation on the corneal epithelium II: Exposure to monochromatic radiation. J Cell Comp Physiol. 1948;32:161–173.

9. Kurtin WE, Zuclich JA. Action spectrum of oxygen-dependent near-ultraviolet induced corneal damage. Photochem Photobiol. 1978;27:329–333.

10. Mackay D, Eisenstark A, Webb RB, Brown MS. Action spectrum for lethality in recombinationless strains of salmonella typhimurium and escherichia coli. Photochem Photobiol. 1976;24:337–343.

11. Pitts DG. A comparative study of the effects of ultraviolet radiation on the eye. Am J Optom Arch Am Acad Optom. 1970;50:535–546.

12. Steiner RF, Weinryb I, eds. Excited States of Proteins and Nucleic Acids. New York, NY: Plenum Press; 1971.

13. Zuclich JA, Blankenstein MF. Ocular effects of ultraviolet and infrared laser radiation. In: Effects of Laser Radiation on the Eye, Vol II. Brooks Air Force Base, TX: US Air Force School of Aerospace Medicine; 1984. Technical Report SAMTR-84-10.

14. Zuclich JA, Blankenstein MF. Corneal threshold for the ArF excimer laser. In: Effects of Laser Radiation on the Eye, Vol IV. Brooks Air Force Base, TX: US Air Force School of Aerospace Medicine; 1985. Technical Report SAM-TR-85-13.

15. Taboada J, Mikesell GW, Reed RD. Response of the corneal epithelium to KrF excimer laser pulses. Health Phys. 1981;40:677–683.

16. Stern D, Schoenline RW, Puliafito CA, Dobi ET, Bimgruber R, Fujimoto JG. Corneal ablation by nanosecond, picosecond, and femtosecond lasers at 532 nm and 625 nm. Arch Ophthalmol. 1989;107:587–592.

17. Srinivasan R. Ablation of polymers and biological tissue by ultraviolet lasers. Science. 1986;234:559–565.

18. Trokel SL, Srinivasan R, Braren, B. Excimer laser surgery of the cornea. Am J Ophthalmol. 1983;96:710–715.

19. Krueger RR, Trokel SL, Schubert HD. Interaction of ultraviolet laser light with the cornea. Invest Ophthalmol Vis Sci. 1985;26:1455–1464.

20. Zuclich JA. Ultraviolet laser effects on the cornea. Proc SPIE. 1990;1207:48–58.

21. American National Standards Institute. American National Standard for Safe Use of Lasers. Orlando, FL: Laser Institute of America; 2000.

22. Zuclich JA. Cumulative effects of near-UV induced corneal damage. Health Phys. 1980;38:833–838.

23. Griess GA, Blankenstein MF. Additivity and repair of actinic retinal lesions. Invest Ophthalmol Vis Sci. 1981;20:803–807.

24. Cooper GF, Robson JG. The yellow colour of the lens of man and other primates. J Physiol. 1969;203:411–417.

25. Waxler M, Hitchens VM. Optical Radiation and Visual Health. Boca Raton, FL: CRC Press; 1986.

26. Pitts DG. A comparative study of the effects of ultraviolet radiation on the eye. Am J Optom Physiol Optics. 1978;50:19–35.

27. Luttrull JK, Hallisey J. Laser pointer-induced macular injury. Am J Ophthalmol. 1999;127:95–96.

28. Sell CH, Bryan JS. Maculopathy from handheld diode laser pointer. Arch Ophthalmol. 1999;117:1557–1558.

29. Sethi CS, Grey RH, Hart CD. Laser pointers revisited: a survey of 14 patients attending casualty at the Bristol Eye Hospital. Br J Ophthalmol. 1999;83:1164–1167.

30. Zuclich JA, Stolarski DJ. Retinal damage induced by red diode laser. Health Phys. 2001;81:8–14.

31. Zuclich JA, Glickman RD, Menendez AR. In situ measurements of lens fluorescence and its interference with visual function. Invest Ophthalmol Vis Sci. 1992;33:410–415.

32. Zuclich JA, Shimada T, Loree TR, Bigio I, Strobl K, Nie S. Rapid non-invasive optical characterization of the human lens. Lasers Life Sci. 1994;6:39–53.

33. Zuclich JA. In vivo measurements of optical properties of the human lens. Proc SPIE. 1994;2134B:99–112.

34. Zuclich JA, Previc FH, Novar BJ, Edsall PE. Near-UV/blue light-induced fluorescence in the human lens: potential interference with visual function. J Biomed Optics. 2005;10:44021-1-7.

35. Zuclich JA, Taboada J. Ocular hazard for UV laser exhibiting self-mode locking. Appl Optics. 1978;17:1482–1484.

36. Ham WT, Mueller HA, Ruffolo JJ, Guerry D, Guerry RK. Action spectrum for retinal injury from near-ultraviolet radiation in the aphakic monkey. Am J Ophthalmol. 1982;93:299–306.

37. Schmidt RE, Zuclich JA. Retinal lesions due to ultraviolet laser exposure. Invest Ophthalmol Vis Sci. 1980;19:1166–1175.

38. Boettner EA. Spectral Transmission of the Eye. University of Michigan Final Report Air Force Contract F41(609)-2966. Brooks Air Force Base, TX: US Air Force School of Aerospace Medicine; 1967.

39. International Electrotechnical Commission. Safety of Laser Products–Part 1: Equipment Classification, Requirements, and User’s Guide. Geneva, Switzerland: IEC; 2001.

40. Vos JJ. Disability glare—a state of the art report. CIE J. 1984;3:39–52.

Chapter 9

LASER-INDUCED OCULAR EFFECTS IN THE RETINAL HAZARD REGION

DAVID J. LUND, BA, * Research Biophysicist (retired), US Army Medical Research Detachment, 7965 Dave Erwin Drive, Brooks City Base, Texas 78235 and BRIAN J. LUND, PhD † Research Physicist, Ocular Trauma, US Army Institute of Surgical Research, 3698 Chambers Pass, Joint Base San Antonio, Fort Sam Houston, Texas 78234-7767

INTRODUCTION

BACKGROUND

WAVELENGTH DEPENDENCE

EXPOSURE DURATION

REPETITIVE PULSES

SUMMARY

INTRODUCTION

Researchers have actively investigated the interaction of laser radiation with retinal tissue in vivo for well over 40 years. A majority of the research has been funded by the Department of Defense primarily because of capability and need. Immediately after the first successful operation of a ruby laser, the US Army proceeded to adapt the device for use as a rangefinder. The laser presented an elegant solution to an old problem, but also presented a new, poorly understood problem. Military tacticians already fully understood and could fully exploit the consequences of directing a high-velocity projectile. The parameters of safe operation of traditional munitions were understood and drummed into new recruits in basic training. By contrast, the new laser could be fired repeatedly at an individual with no discernible effect, unless that individual was standing in the wrong place and looking in the wrong direction. In that case, the consequences of exposure could be devastating. The parameters of safe laser operation were not understood because the potential for harm had not yet been measured. Initial guidance was borrowed from studies that had been conducted in the 1950s and were designed to determine the retinal hazard of the nuclear fireball. But the laser was clearly different than other light sources; to resolve safety issues, it would be necessary to perform bioeffects experiments using the laser itself as a source. The military had the lasers, the applications, and the need to ensure the safety of its troops. Both the US Army and the US Air Force established multidisciplinary research teams in the late 1960s to initiate bioeffects experiments to determine the eye hazard posed by the lasers available at that time. Data developed by these teams provided a basis for the first standards for the safe use of lasers.

Since that time, researchers have continued to study the potential for damage of ever more sophisticated lasers using more sophisticated dosimetry and diagnostics. The total number of groups and individual investigators involved is small; the database of thresholds for laser-induced retinal damage is substantial, but by no means complete. A primary purpose of laser bioeffects research is to establish parameters for safe use and to serve as a basis for the establishment of safety guidelines. Laser safety guidelines are, in effect, an empirical model based on the trends of threshold data, which enables the computation of a maximum permissible exposure (MPE) for any given combination of laser parameters. The original guidelines were formulated around a rudimentary database and drew heavily on knowledge of the optical and physical characteristics of the eye, and from physical theories about how light interacts with matter in general and with biological tissue in particular.1–3 The original guidelines have proven quite durable. Provisions of the guidelines have been adjusted and/or incremented to represent a growing body of supporting data, but many of the basic provisions for exposure time and wavelength dependence are essentially unaltered.

A secondary purpose of laser bioeffects research is to reach a point in which the database itself is sufficient. Based on existing data, it would seem useful to construct an empirical model that is capable of predicting the ED_50 (exposure dose having a 50% probability of producing the criterion response) for all exposure configurations. To the extent that such a model is successful, data are understood to be sufficient and self-consistent. Where the model is not successful, data are understood to be inadequate or contradictory. The model should, therefore, point to deficiencies in the available dataset and, by extension, to deficiencies in the provisions of the safety guidelines.

BACKGROUND

The eye is the most vulnerable part of the body to visible and near-infrared (NIR) laser radiation. This is because the eye can concentrate incident light on the absorbing layers of retinal tissue that lie at the focus of the eye’s optical system3–6 (Figure 9-1). In the relaxed, normal eye, a collimated laser beam is focused into a small retinal image where the concentrated energy can induce thermal, mechanical, and photochemical processes that alter the retinal tissue.6–9

Researchers have accumulated a substantial body of dose–response data by introducing carefully controlled and measured energy into the eye of anesthetized animals, and evaluating the exposed retinas for resulting alterations. A number of metrics have been used to determine the presence of alteration. The more sensitive metrics, such as measures of visual function and microscopic evaluation of excised tissue, are resource intensive; these metrics are utilized sparingly to place a lower bound on the range of introduced energy capable of producing retinal change. The primary metric continues to be the presence of a minimum visible lesion (MVL) detected via ophthalmic examination after exposure. Two methods have been used to estimate the introduced energy that is required to produce the MVL. Some researchers placed a graduated range of exposures on the retina and approximated threshold energy as the average of the lowest energy that produces the criterion effect, and the highest energy that does not produce the criterion effect. More commonly, researchers have placed an array of exposures over a range of introduced energies (Figure 9-2), correlated the response (presence or absence of an MVL) to the introduced energy for each exposure (Figure 9-3), and computed the probability of producing the criterion response as a function of introduced energy using the statistical technique of probit analysis.10,11 The principal products of the probit analysis are the ED_50, and the slope that can be given either as the slope, b, of the probit curve at the ED_50 or as the ratio ED_50/ED_84, where ED_84 is that dose having an 84% probability of producing the criterion response. The two are related: b = [log_10(ED_50/ED_84)]-1.

Figure 9-1. An incident laser beam is concentrated by the optics of the eye onto the retina. Light passes through the clear ocular media and the sensory retina before impinging on the retinal pigment epithelium (RPE) and the choroid. The retinal pigment epithelium is a monolayer of cells containing strongly absorbing melanin granules.

The ED_50 is not a threshold; in fact, it may not be possible to determine a true threshold for these effects. The ED_50 should, however, be related to the threshold in a manner that is persistent across exposure parameters and therefore serves as a fair and viable basis for safety guidelines. For the remainder of this chapter, ED_50 will be the label for not only the product of a probit analysis, but also for the estimated dose for production of an MVL determined by other estimation techniques.

Figure 9-2. An array of laser exposures of varying incident energy in the retina of a rhesus monkey. The laser wavelength was 532 nm, and the exposure duration was 100 ms. Some exposures resulted in visible alteration while others did not.

The ED_50 for laser-induced threshold damage is dependent on a number of factors. Inherent to the laser are wavelength, pulse duration, and pulse repetition rate. The experimental configuration determines the retinal irradiance area and profile, the exposure duration, and the number of pulses. The investigator chooses the criterion for determination of retinal alteration. The scope of this chapter encompasses only the retinal MVL as determined by ophthalmic examination. The visibility of laser-induced retinal alteration varies with the interval between exposure and observation. Early researchers used 5- to 15-min observation times before standardizing on a 1-h end-point. More recently, investigators have augmented the 1-h endpoint with a second observation at 24- to 48-h postexposure. The later observation typically results in a lower ED_50. Early researchers used the rabbit as the animal model, but later adopted the rhesus monkey as a closer match to the human eye. Within the primate eye, the central area of the retina, known as the macula, is generally more sensitive to laser-induced alteration than are the more peripheral paramacular retinal areas. A single experiment, with exposures placed in both macular and paramacular retinal areas of the rhesus eye and with observation endpoints of 1 h and 24 h postexposure, can yield four distinct ED_50 values, the lowest of which is the ED_50 for macular alteration observed 24 h after exposure. The remainder of this chapter concerns the wavelength dependence of the ED_50, the exposure duration dependence of the ED_50, and the nature of the effects of repetitively pulsed retinal exposures.

Figure 9-3. The probability of producing a minimum visible lesion (MVL) as a function of the incident energy. Exposures producing an MVL are placed on the probability = 1.0 axis. Exposures not producing an MVL are placed on the probability = 0 axis. The red line shows the probability of producing an MVL determined by dividing the number producing an MVL by the total number of doses in a range of incident energy. The green line is the probability of producing an MVL as determined by probit analysis of the data. The dashed line (on the green line) is the probability obtained by setting α = ED_50 (dose having a 50% probability of producing the criterion response) and B = b – 1 in the logistic ogive (equation (9)). b is the slope of the probit fit.
TIE: total intraocular energy

WAVELENGTH DEPENDENCE

Threshold-level laser-induced thermal retinal damage is localized to the retinal pigment epithelium (RPE), a monolayer of cells within the retina containing melanin granules (see Figure 9-1). Melanin is a very strong absorber of optical radiation to the extent that most of the radiation incident on the retina is absorbed in a 5 µm layer of melanin granules. The absorbed energy results in significant tissue heating and thermal damage even for very low levels of energy incident at the cornea.

Assuming that the temperature required for threshold damage is not dependent on the wavelength of the incident radiation, an action spectrum for thermal retinal damage can be approximated based on the wavelength-dependent transmittance through the preretinal ocular media and absorption within the retina.1,6,12 Transmittance of the preretinal ocular media has been measured by a number of investigators.13–19 The transmittance of the media, cornea, aqueous, lens, and vitreous was measured separately for each of the component parts after dissection of the eye. The tissue was necessarily “dead” with attendant changes in transmission and, more importantly, scatter of the transmitted light. Scattered light becomes very important for the determination of retinal irradiance in that it removes light from the focused beam, thus reducing the retinal irradiance. The primary source of scatter in the transmitted radiation is the cornea, and scatter in the cornea is sensitive to the integrity of its structure. Typically, the transmission of the tissue is measured in a spectrophotometer configured to collect all the transmitted radiation; thus, the measured quantity is the total transmission through the tissue. Transmission of the eye, based on these measurements, will overstate the irradiance at the retina. Alternately, the direct transmission of the ocular tissues is determined by collecting only the portion that remains collimated after traversing the tissue and thus will converge to a focus in the intact eye. Data from these studies have been collected and used as the basis for a consistent set of ocular transmittance tables published by the Commission Internationale de l’Éclairage (CIE).[20] The CIE tables of direct transmission of the rhesus eye are used in this chapter (Figure 9-4a). The choice of rhesus monkey is deliberate; essentially all available laser-induced retinal damage thresholds have been determined in that species, and the intent is to compare the theoretical action spectrum to the experimental data.

a

b

Figure 9-4. (a) Direct (green line) and total (red line) transmission (Tλ) of the preretinal ocular media of the rhesus eye. (b) Absorption (Aλ) of light in the retina by H_2O (blue line), oxyhemoglobin (red line), and retinal pigment epithelium (green line).

Energy reaching the retina is absorbed in the retina and choroid. The percentage of light absorbed in the RPE has been measured for the human, rabbit, and rhesus monkey. The values for RPE absorption used in this analysis (Figure 9-4b) are represented by the equation:

where s is the absorption length, and the absorption coefficient is given by αλ = α_0(λ_0 ⁄ λ)3.5.

The absorption length, s, is 5 µm and α_0 is set to 4,100 cm-1 at the wavelength_0 of 380 nm. This form provided a reasonable fit to the experimentally determined absorption of the RPE.21–23

Before reaching the RPE in the macula and the region around the macula, light must traverse the neural retina that contains layers of capillaries having an average diameter of 5 µm.[24] The absorption of incident radiation in 5 µm of hemoglobin is equal to the absorption in the RPE for the wavelength range around 440 nm (see Figure 9-4b). Figure 9-5 is representative of the retinal appearance after exposure to blue wavelength laser pulses of 3.5-ns duration with the laser beam focused by the eye to ~25 µm diameter at the retina; this demonstrates the high incidence of retinal hemorrhage for such exposures. For exposure wavelengths from 410 to 450 nm, the hemorrhage resulted from rupture of capillaries in the neural retina, and the ED_50 for the production of such hemorrhage was nearly the same as the ED_50 for the production of RPE injury at the same wavelength (Figure 9-6). For wavelengths longer than 450 nm, the hemorrhage was subretinal, resulting from the rupture of Bruch’s membrane at the RPE/choriocapillaris interface; the ED_50 for such a hemorrhage was much higher than the ED_50 for production of RPE injury.

Figure 9-5. An array of laser exposures of varying incident energy in the retina of a rhesus monkey demonstrating a high incidence of retinal hemorrhage. The laser wavelength was 430 nm, and the exposure duration was 3.5 ns.

At wavelengths longer than 1,300 nm, light absorption by H_2O in the sensory retina is as great as that absorbed in the RPE. The H_2O-absorbed energy can produce laser-induced thermal damage in all layers of the retina[25] (Figure 9-7).

The energy absorbed by the RPE, Qr(λ), is:

where

Qp(λ)

=

the energy at the cornea within the area of the pupil,

T(λ)

=

the transmission of the preretinal ocular media at wavelength λ,

A(λ)

=

ARPE(λ) + AH20(λ) is the absorption of the retina at wavelength λ, and

Tb(λ)

=

the transmission of hemoglobin (where a 5 µm absorption path is assumed).

Rearranging,

The absorbed energy, Qrλ, required to produce thermal tissue damage varies as a function of the diameter of the irradiated area on the retina. Given a collimated laser beam incident at the cornea, the diameter of the irradiated area at the RPE varies with the wavelength of the incident light because of chromatic aberration (Figure 9-8).26,27

Figure 9-6. A comparison of the ED_50 (dose having a 50% probability of producing the criterion response) for produc-tion of a minimum visible lesion (green line) in the retinal pigment epithelium to the ED50 for production of a retinal hemorrhage (red line) for laser retinal exposure in 3.5-ns duration pulses to laser radiation at wavelengths from 410 to 570 nm.
TIE: total intraocular energy

Figure 9-7. Laser-induced retinal injury in the rhesus monkey after exposure to a 20-ns duration pulse having a wavelength of 1,319 nm. High absorption of laser energy by the H_2O in the retina resulted in damage in all retinal layers.

Figure 9-8. Chromatic-aberration-induced variation of the laser beam diameter at the retinal pigment epithelium (RPE) (dλ) of the rhesus eye for a collimated beam incident at the cornea. Blue, green, and red wavelengths are imaged at different retinal planes.

The threshold for laser-induced retinal damage becomes larger as the irradiated area of the retina be-comes larger (see Chapter 10, Dependence of Retinal Thermal Injury Threshold on Size and Profile of Laser). Therefore, a spot size-dependent term must be inserted into equation (3).

where

k

=

Qr_0/d_0,

Qr_0

=

the required energy for a minimum spot size,

dλ

=

the chromatic aberration-induced diameter at wavelength λ.

The value of the exponent X and therefore (dλ)X is time dependent. X varies from a value of 2 (nanosecond to microsecond-duration exposures) to a value of 1 (1-s du-ration and longer exposures). This relationship is com-plicated by uncertainty over the value of d_0. Although the optical quality of the eye will allow the incident laser radiation to be focused to a diameter at the RPE as small as 5 to 7 µm under optimum conditions,[28] research suggests that the threshold for retinal injury does not decrease for image diameters <70 µm29–31 (Figure 9-9).

Figure 9-9. The dependence of ED_50 (dose having a 50% prob-ability of producing retinal injury) on the retinal diameter (d) for 7-ns duration, 532-nm laser exposures.
Circles: measured values of the ED_50. Dashed lines: trend lines fitted to the data. HC: Radiant exposure measured at the cornea.

Experimental data relative to the wavelength de-pendence of the ED_50 for retinal damage have been reported in the literature.12,32–39 Data are shown in Figure 9-10. The corresponding Qp(λ) curve was fit to each dataset by choosing the value of k to match the data at a single wavelength and choosing the value of X appropriate for the exposure duration. The value of d_0 was set to 40 µm except where the data were collected for larger retinal irradiance diameters. Over a broad range of exposure conditions, threshold laser-induced retinal damage can be fitted to curves derived from the assumption that the threshold injury is a thermal event driven by the laser energy absorbed in the RPE. Data shown include exposure durations from 3.5 ns to 16 s, wavelengths from 410 to 1,319 nm, and retinal irradiance diameters from the minimum the eye will produce to 350 µm. Equation (4) produces a curve that matches the wavelength dependence of the data in all cases.

For most of the parameter space shown in Figure 9-10, laser-induced thermal injury is the dominant and limiting injury mechanism determining the laser hazard to the eye. When the wavelength is shorter than 550 nm and the exposure is longer than 10 s, laser irradiation can produce photochemical injury to the retina at doses significantly lower than those required to produce thermal injury.6,33,36 These pho-tochemical injury levels are omitted from Figure 9-10 for clarity.

Figure 9-10. Wavelength dependence of ED_50 (dose hav-ing a 50% probability of producing retinal injury) for laser-induced retinal alteration with Qpλ matched to each dataset. t is the exposure duration, and d is the diameter of the irradiated retinal area. Violet lines: t = 16 s, d = 350 µm; blue lines: t = 1 s, d = 350 µm; green lines: t = 0.1 s, d = 30 µm; orange lines: t = 600 µs, d = 30 µm; and red lines: t = 3.5 ns, d = 30 µm.
TIE: total intraocular energy

The ability to produce retinal lesions has been re-stricted to the wavelength range wherein the preretinal ocular transmission is ≥1%. Lesions have been produced in normal rhesus monkey eyes at 325 nm[40] and at 1,330 nm41,42 near the short- and long-wavelength limits for retinal damage. Increasing the corneal dose to compen-sate for the preretinal loss does not extend the retinal damage range. Laser-induced alteration to the preretinal tissue limits the energy transmitted to the retina.

The eye is vulnerable to injury from laser radiation at wavelengths longer than 1,400 nm. The injury site is shifted to the cornea and lens, and the doses required to produce injury are higher because the incident radia-tion is no longer concentrated on the absorbing tissue by the optics of the eye. Although the database for laser-induced corneal injury is sparse compared to the data available for retinal thresholds, enough is avail-able to match to a curve based on the 95% absorption depth of corneal tissue.[42] A continuation of injury level is seen through the transition from retinal injury to corneal injury at 1,400 nm, with a range at which both retinal and corneal injuries are possible (Figure 9-11).

Figure 9-11. ED_50 (dose having a 50% probability of producing retinal injury) for laser-induced ocular injury after exposure to nanosecond-duration laser irradiation. The thresholds are presented as corneal radiant exposure. When the injury site is the retina, the incident energy is averaged over a 7-mm diameter area at the cornea. The injury site is the retina for wavelengths shorter than 1,300 nm and the cornea for wavelengths longer than 1,400 nm. At 1,319 nm, both the cornea and the retina can be injured, but the threshold for retinal injury is lower. The American National Standards Institute’s 2014 maximal permissible exposure for nanosecond-duration exposures is shown in ANSI Z136.1-2014 (American National Standard for the Safe Use of Lasers).
Green circles: measured retinal injury thresholds. Red triangles: measured corneal injury thresholds. Blue line: the 2014 maximum permissible exposure for ns-duration exposures. HC: Radiant exposure measured at the cornea.

The MPE as provided in the 2007 and earlier editions of the laser safety standards was more than two orders of magnitude higher than the experimentally derived ED_50 at 1,330 nm. The safety factor was larger than necessary. Zuclich et al [41] proposed an adjustment of the wavelength dependence of the MPE for wavelengths between 1,250 and 1,400 nm to provide a better fit to the ED_50 data. In 2013, the International Commission on Non-Ionizing Radiation Protection[43] (ICNIRP) ac-cepted a modified version of that proposal that was then adopted in the 2014 editions of the American National Standards Institute (ANSI) Z136.1 (Safe Use of Lasers)[44] and the International Electrotechnical Com-mission (IEC) 60825-1 (Safety of Laser Products).[45] In Figure 9-12, data are compared to both the 2007 and the 2014 forms of the MPE.

EXPOSURE DURATION

The ED_50 for in vivo laser-induced thermal retinal damage as a function of exposure duration is shown in Figure 9-13. For exposure durations of longer than a few microseconds, laser-induced retinal injury results from thermal coagulation of the retinal tissue; this is well explained by thermal models incorporating thermal conductivity of the tissue and the Arrhenius integral to signify damage due to denaturation of proteins.

A large body of data, supported by the thermal damage models, shows that for t greater than a few microseconds, the ED_50 varies as t3/4 , where t is the exposure duration. For exposures shorter than a few microseconds, the energy is deposited in times shorter than the thermal relaxation time of retinal tissue, leading to thermal confinement; thus, the energy required to produce a damaging temperature rise is independent of the duration of the exposure. Ex vivo experiments designed to expose the RPE in retinal explants demonstrated that, for short-duration laser exposures, the threshold for laser-induced cell death correlates to the appearance of microcavitation (bubbles) around melanin granules superheated by incident laser irradiation.46–51 Cell death almost al-ways followed the induction of a bubble in the cell. Gerstman[52] showed theoretically that microcavita-tion occurred at lower incident irradiance than that required for Arrhenius thermal damage for pulses of duration between 1 ns and 1 µs. Experiments designed to distinguish between thermally induced damage and microcavitation-induced cell death showed that, for pulse durations of less than about 50 µs, the threshold-level damage mechanism transitions from thermal denaturation of proteins (as modeled by the Arrhenius integral) to a damage mechanism based on the formation of microcavitation bubbles around the melanosomes in the RPE. Figure 9-14 includes microcavitation-induced threshold values for laser exposure in retinal explants from several studies.46,47,49,53–59 The time dependence of these data is consistent with that of the in vivo data represented in Figure 9-13. Injury mechanisms for exposure dura-tions shorter than 1 ns are discussed in Chapter 12, Ultrashort Laser Pulses and Their Bioeffects.

Figure 9-12. Wavelength-dependent ED_50 (dose having a 50% probability of producing the criterion response) data for nanosecond-duration laser exposures (green) and for 0.1-s duration laser exposures (red) in the rhesus eye. Qpλ has been fit to the data. The 2007 (long dashed lines) and the 2014 (short dashed lines) minimal permissible exposures are shown for each exposure duration.
TIE: total intraocular energy

Figure 9-13. The time dependence of the ED_50 (dose having a 50% probability of producing retinal injury) for visible wavelength, laser-induced retinal damage. The 2007 (dashed line) and the 2014 (solid line) maximum permissible exposures for visible laser ocular exposure are included for comparison. Red circles: measured values of the ED_50.
TIE: total intraocular energy

Recent experimentally determined laser-induced retinal injury threshold studies have been concentrated on determining the ED_50 based on the detection of an MVL at 24-h postexposure for macular exposures in the rhesus monkey eye. For visible wavelength expo-sures of duration ranging from 3 to 100 ns, new data were within a factor of two to three times the MPE as provided by the 2007 standards.31,60–62 The margin of safety was inadequate, considering the experimental uncertainties associated with the ED_50 for short-pulse, collimated beam ocular exposure. In 2013, ICNIRP[43] accepted a recommendation to reduce the MPE for exposure durations below 5 ns by a factor of 2.5 to provide a larger safety margin that was then adopted in the 2014 editions of ANSI Z136.1[44] and IEC 60825- 1[45]. The MPE, as provided by both the 2007 and 2014 guidelines, is included in Figure 9-13.

Figure 9-14. The ED_50 (dose having a 50% probability of producing retinal injury) for thermally induced ex vivo (retinal explant) exposures. For pulse durations of less than about 50 µs, the damage mechanism at threshold level changes from a thermal mechanism that can be well modeled by the Arrhenius integral to a damage mecha-nism based on the formation of microcavitation around the melanosomes in the retinal pigment epithelium. Circles: measured values of the ED_50. HR: Radiant exposure at the retina.

REPETITIVE PULSES

Laser safety guidelines provide three rules to be considered in the determination of the MPE for expo-sure to repetitive pulsed lasers. Rule 1 simply states that no single pulse can exceed the MPE for exposure duration equal to the duration of the particular pulse. This is easily understood, because if a single pulse has enough energy itself to cause injury to the retina, it does not matter if any other pulses come before or after. Rule 2 essentially says that if a number of pulses are deliv-ered in an exposure time T, the average power in the pulsed beam shall not exceed the MPE for an exposure of duration T. This rule protects against injury due to accumulated photochemical damage mechanisms, as well as the buildup of heat in the retina. Rule 3 states that the exposure for any single pulse in the train of pulses shall not exceed the single-pulse MPE multiplied by a multiple-pulse correction factor CP. The purpose of Rule 3 is to protect against thermal injury caused by the buildup of heat from a series of subthreshold pulses.

The form of CP has been rethought after the identi-fication of microcavitation as a laser-induced retinal injury mechanism, and there is debate within the laser bioeffects research community as to whether or not Rule 3 can be eliminated entirely. In the 1983 edition of ANSI Z136.1, the multiple-pulse correction factor for Rule 3 was set to CP = n–1/4, where n is the number of pulses in the exposure.[63] The exposure limit for a multiple-pulse exposure is then given by

where MPE(n.p.) is the maximum permissible exposure for the repetitive-pulse train consisting of n pulses and is expressed as an energy per pulse. MPE(s.p.) is the maximum permissible exposure for a single pulse from the same laser. This form for the multiple-pulse correction factor was continued through the 2007 edi-tion of ANSI Z136.1.

The n–1/4 relationship was first articulated by Stuck et al[64] based on an empirical fit to data reported in the literature. Laser-induced retinal injury threshold data for repetitive-pulse ocular exposures obtained from the literature42,64–68 appear to confirm that the ED_50, expressed as energy per pulse, is well represented by a derating factor that varies as n–1/4 (Figure 9-15). This relationship can be expressed as:

The relationship of equation (6) is independent of the wavelength, pulse duration, or pulse repetition frequency of the laser. Models based on a thermal damage mechanism cannot readily explain this result. Additivity of effect requires that each pulse must some-how sensitize the exposed retina, such that it becomes more susceptible to damage with each successive and cumulative pulse. Buildup of heat within the retina means that later pulses will require less energy to raise the temperature of the retina to the critical temperature that causes thermal damage. For a low pulse repeti-tion frequency (or large interpulse spacing), diffusion of heat will allow the retina to cool, thus lessening the heat buildup. The fact that the n–1/4 dependence is independent of the interpulse spacing essentially rules out thermal memory as the mechanism.

Figure 9-15. Laser-induced retinal injury threshold data for repetitive ocular exposures derived from the literature. The ED_50 (dose having a 50% probability of producing retinal injury), expressed as energy per pulse, is plotted as a func-tion of the number of pulses, n.
TIE: total intraocular energy

Menendez et al[69] proposed a probability-summation model for predicting the threshold for a train of pulses based on the dose–response statistics for a single pulse. The model assumes that each pulse is an inde-pendent trial, that is, earlier pulses neither “sensitize” nor “harden” the retina to subsequent pulses. For the special case of a beam that consists of identical pulses (energy, pulse duration), the probability of a retinal response to each individual pulse can be assumed identically equal to p. In this case, the probability P(n) of inducing a retinal response after n pulses can be shown to be

where P(n) = 0.5 for an ED_50-level exposure. The response probability for each pulse of an ED_50-level exposure to n pulses can then be determined by solv-ing equation (7) for p:

Menendez et al[69] assumed the single-pulse response probability was adequately described by the logistic ogive:

where

D

=

the dose (pulse energy),

α

=

the ED_50 pulse energy for a single-pulse expo-sure, and

β

=

related to the steepness of the dose–response curve.

Solving for D gives the pulse energy corresponding to the single-pulse response probability, p, obtained from equation (8):

As shown in Figure 9-3, when α = ED_50 and β = b – 1, where b is the slope of the probit curve, the logistic curve yields a relationship between dose and prob-ability nearly identical to that predicted by the probit fit for 0.05 < p < 0.95.

Lund and Sliney[70] showed that, for a large number of pulses, the probability summation model led to the approximate relationship:

where b is the slope of the probit fit to the single-pulse, dose–response data. Equation (11) relates the ED_50(n.p.), expressed as energy per pulse in a pulse train, to the ED_50(s.p.) for a single pulse as a function of the number of pulses in the train and the slope (b) of the probit fit for a single-pulse exposure.

The mean value of the slope (b) of the probit fit is 4.8, as computed by the ProbitFit program[11] for more than 150 single-pulse threshold studies. Substituting b = 4.8 in equation (11) effectively reproduces equation (6). The probability summation model can explain the apparent success of the CP = n-1/4 relationship. The unsettling thing about equation (11) is that ED_50(n.p.) continues to decrease at the same rate as a function of n for an extremely large number of pulses, resulting in unreasonably small threshold values.

Equation (11) was derived with the aid of math-ematical approximations, and assumed that the single-pulse dose–response data followed the logistic curve. However, the ED_50 values for laser-induced injury are typically inferred from exposure data using probit analysis, in which the dose–response curve is assumed to follow a log-normal distribution10,11:

In this equation, the probit value, Y, is given by:

where

x

=

log_10(pulse energy);

µ

=

log_10(ED_50(s.p.)), the base-ten logarithm of the ED_50 pulse energy for a single-pulse exposure; and

σ

=

the standard deviation of the log-normal distribution.

Equation (13) is a linear equation for Y as a function of x, and probit analysis involves finding the slope b and intercept a of the line Y = bx + a that best fits the dose–response data. The standard deviation of the single-pulse retinal response distribution is then given by σ = 1/b, and the ED_50 = 10–a/b.

Lund et al29,71 examined multiple-pulse exposure data using probit analysis in conjunction with the probability summation model. For an n-pulse exposure, the per-pulse retinal response probability may be determined from equation (8). The probit value Y corresponding to this single-pulse response probability p is a function of the number of pulses n (equation (8)), and Y = Y(n) is also a function of n. The per-pulse energy at threshold, ED_50(n.p.) for an n-pulse exposure can then be calculated from the single-pulse ED_50 by solving equation (13):

Inserting x = log10(ED_50(n.p.)) and µ = log_10(ED_50(s.p.)) gives

Equations (11) and (15) relate the ED_50(n.p.), expressed as energy per pulse in a pulse train, to the ED_50(s.p.) for a single pulse as a function of the number of pulses in the train and the slope (b) of the probit curve for a single-pulse exposure.

Figure 9-16. Comparison of the multiple-pulse correction factor (CP) for b = 24 (typical of explant exposures; green lines), b = 8 (typical of large spot in vivo exposures; red lines), and b = 5 (typical of the data of figure 9; blue lines). b = 1/σ is the slope of the probit fit to the data. Dotted lines: CP = n-1/(b-1) (equation 11). Solid lines: CP = 10Y(n)/b (equation 15).

The values of b and therefore CP = f(b) are in part a measure of experimental uncertainties in determining the single-pulse ED_50. Figure 9-16 compares the CP as a function of n for a range of values of b for the exact solution and the approximate solution. Experimental uncertainties are reduced in threshold studies that use retinal explants as their model57,72 and in the in vivo threshold studies wherein the diameter of the exposed retinal area is large.29,71

Figure 9-17 shows repetitive-pulse exposure threshold data obtained in retinal explant studies,46,54 whereas Figure 9-18 shows repetitive pulse exposure threshold data obtained in large retinal irradiation diameter studies.29,71 Data represented in these plots show that the experimentally determined value of CP falls off much slower than n–1/4 when experimental uncertainties are reduced. A derating factor computed via equation (15) better matches the data and has the property that the ED_50(n.p.) decreases more slowly with increasing n.

It is not simple to translate equation (15) into a derating factor easily incorporated into the standards. Equation (11) is of the form already used to define the derating factor CP. However, it requires a choice of the value of β (or b). For the 1983 standard, the choice was effectively made to set β = 4 based on available data. New data and analysis suggest that this value is too low and results in overly conservative values of the MPE for large n. Lund and Sliney[70] and Sliney and Lund[73] argued that if indeed the value of the derating factor CP was largely a function of experimental uncertainties, then the reduction afforded by this derating factor was already built into the MPE via the fact that the MPE was purposely set to a fraction of the ED_50 to account for experimental uncertainties. Further reduction was therefore unnecessary, and CP should be set to 1.0 for most exposure conditions. This suggestion motivated reevaluation of existing data and encouraged new studies. Given the required reduction of the single-pulse MPE for exposure durations shorter than a few microseconds, the value CP = 1 was found to provide a MPE level safe for essentially all of the credible available repetitive-pulse data.

Figure 9-17. Repetitive-pulse exposure threshold data obtained in retinal explant studies by Brinkmann et al in 2000 (see reference 46) (green symbols) and by Roegener et al in 2004 (see reference 54) (red symbols).
HR: Radiant exposure at the retina

Based on these considerations, the most recent guidelines for safe use of lasers44,45,74 contain a revised formulation that sets the value of CP = 1 for most repetitive-pulse exposures.

Figure 9-18. Repetitive-pulse exposure threshold data obtained in vivo for 7-ns duration, 532-nm laser exposure of retinal areas having diameters of 30 (green symbols), 100 (red squares), and 500 µm (orange triangles) (see reference 29).
HR: Radiant exposure at the retina

SUMMARY

The laser safety guidelines are, in effect, an empirical model that enables the computation of MPE for any given combination of laser parameters. Bioef-fects research establishes the parameters for safe use of lasers and provides a basis for the establishment of guidelines. Although the bioeffects database is extensive and for the most part fully supports the safety guidelines, there are areas in which our understanding of specific damage mechanisms continues to evolve or in which the bioeffects data are not yet accurately reflected in the safety guidelines. The threshold for laser-induced threshold damage is dependent on a number of factors. Inherent to the laser are its wavelength, pulse duration, and pulse repetition rate. The experimental configuration determines the retinal irradiance area and profile, the exposure duration, and the number of pulses. This chapter outlines our current understanding of how the threshold varies in each case with each of these parameters.

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18. Ambach W, Blumthaler M, Schopf T, et al. Spectral transmission of the optical media of the human eye with respect to keratitus and cataract formation. Doc Ophthalmol. 1994;88:165–173.

19. Dillon J, Zheng L, Merriam J, Gaillard E. Transmission spectra of light to the mammalian retina. Photochem Photobiol. 2000;71:225–229.

20. Commission Internationale de l’Éclairage. CIE 203-2012, A Computerized Approach to Transmission and Absorption Characteristics of the Human Eye. Vienna, Austria: Commission Internationale de l’Éclairage; 2012.

21. Birngruber R, Hillankamp F, Gabel VP. Theoretical investigations of laser thermal retinal injury. Health Phys. 1985;48(6):781–796.

22. Gabel VP, Birngruber R, Hillenkamp F. Die lichtabsorbtion am augenhintergrund. Munich, Germany: Geselschaft fur Strahen- und Umweltforschung; 1976. GSF-Bericht A55.

23. Gabel VP, Birngruber R, Hillenkamp F. Visible and near infrared light absorption in pigment epithelium and choroid. In: International Congress Series No. 450: XXIII Concillium Ophthalmologicum Kyoto. Amsterdam, The Netherlands: Oxford-Excerpta Medica; 1978.

24. Lund DJ, Edsall PR, Stuck BE. Ocular hazards of Q-switched blue wavelength lasers. Proc SPIE. 2001;4246:44–53.

25. Lund DJ, Edsall PR, Stuck BE. Ocular hazards of Q-switched near-infrared lasers. Proc SPIE. 2003;4943:85–90.

26. Vincelette RL, Welch AJ, Thomas RJ, Rockwell BA, Lund DJ. Thermal lensing in ocular media exposed to continuous wave, near-infrared radiation: the 1150–1350 nm region. J Biomed Optics. 2008;13(5):054005.

27. Thomas RJ, Vincellete RL, Clark CD, Stolarski J, Irvin LJ, Buffington GD. Propagation effects in the assessment of laser damage thresholds in eye and skin. Proc SPIE. 2007;6435:64350A.

28. Birngruber R, Dreschel E, Hillankamp F, Gabel VP. Minimum spot size on the retina formed by the optical system of the eye. Int Ophthalmol. 1979;1(3):175–178.

29. Lund BJ, Lund DJ, Edsall PR. Damage threshold from large retinal spot size repetitive-pulse laser exposures. Health Phys. 2014;107(4):292–299.

30. Lund DJ, Edsall PR, Stuck BE, Schulmeister K. Variation of laser-induced retinal injury with retinal irradiated area: 0.1 s, 514 nm exposures. J Biomed Opt. 2007;12(2):06180.

31. Zuclich JA, Edsall PR, Lund DJ, et al. New data on the variation of laser-induced retinal damage threshold with retinal image size. J Laser Applic. 2008;20(2):83–88.

32. Connolly JS, Zuclich JA, Nawrocki DA, et al. Research on the Effects of Laser Radiation. Brooks Air Force Base, TX: Technology Incorporated; 1975. US Air Force School of Aerospace Medicine Contract F41609-73-C-0016. Second Annual Report.

33. Ham WT Jr, Mueller HA, Ruffolo JJ, Clarke AM. Sensitivity of the retina to radiation damage as a function of wavelength. Photochem Photobiol. 1979;29:735–743.

34. Ham WT Jr, Mueller HA, Sliney DH. Retinal sensitivity to damage from short wavelength light. Nature. 1976;260:153–155.

35. Lund DJ, Beatrice ES. Near infrared laser ocular bioeffects. Health Phys. 1989;56(5):631–636.

36. Lund DJ, Stuck BE, Edsall PR. Retinal injury thresholds for blue wavelength lasers. Health Phys. 2006;90(5):477–484.

37. Onda Y, Kameda T. Studies of Laser Hazards and Safety Standards. Part 2. Retinal Damage Thresholds for Helium-Neon Lasers. Fort Detrick, MD: Technological Research and Development Institute, Japan Defense Agency, and US Army Medical Intelligence and Information Agency; 1979. Translation no. USAMIIA-K9991.

38. Onda Y, Kameda T. Studies of Laser Hazards and Safety Standards. Part 3. Retinal Damage Thresholds for Argon Lasers. Fort Detrick MD: Technological Research and Development Institute, Japan Defense Agency, and US Army Medical Intelligence and Information Agency; 1979. Translation no. USAMIIA-K9992.

39. Zuclich JA, Griess GA, Harrison JM, Brakefield JC. Research on the Ocular Effects of Laser Radiation. Brooks Air Force Base, TX: US Air Force School of Aerospace Medicine; 1979. Report SAM-TR-79-4.

40. Zuclich JA, Connolly JS. Ocular damage induced by near-ultraviolet laser radiation. Invest Ophthalmol. 1976;15(9):760–764.

41. Zuclich JA, Lund DJ, Stuck BE. Wavelength dependence of ocular damage thresholds in the near-IR to far-IR transition region: proposed revisions to MPEs. Health Phys. 2007;92(1):15–23.

42. Lund DJ, Stuck BE, Beatrice ES. Biological Research in Support of Project MILES. Presidio of San Francisco, CA: Letterman Army Institute of Research Institute; 1981. Report 96.

43. International Commission on Non-Ionizing Radiation Protection. Revision of guidelines on limits of exposure to laser radiation of wavelengths between 400 nm and 1.4 mm. Health Phys. 2000;29(4):431–440.

44. American National Standards Institute. ANSI Z136.1-2014: American National Standard for the Safe Use of Lasers. Orlando, FL: Laser Institute of America; 2014.

45. International Electrotechnical Commission. IEC 60825-1: Safety of Laser Products. Part 1. Equipment Classification, Requirements and Users Guide. 3.0 ed. Geneva, Switzerland: IEC; 2014.

46. Brinkmann R, Hüttmann G, Roegener J, Roider J, Birngruber R, Lin CP. Origin of retinal pigment epithelial cell damage by pulsed laser irradiance in the nanosecond to microsecond time regimen. Lasers Surg Med. 2000;27:451–464.

47. Kelly MW. Intracellular Cavitation as a Mechanism of Short-Pulse Laser Injury to the Retinal Pigment Epithelium [PhD thesis]. Medford, MA: Tufts University; 1997.

48. Kelly MW, Lin CP. Microcavitation and cell injury in RPE cells following short-pulsed laser irradiation. Proc SPIE. 1997;2975:174–179.

49. Lin CP, Kelly MW, Sibayan SAB, Latina MA, Anderson RR. Selective cell killings by microparticle absorption of pulsed laser radiation. IEEE J Sel Top Quantum Electron. 1999;5(4):963–968.

50. Roegener J, Lin CP. Photomechanical effects—experimental studies of pigment granule absorption, cavitation and cell damage. Proc SPIE. 2000;3902:35–40.

51. Roider J, El Hifnawi E, Birngruber R. Bubble formation as primary interaction mechanism in retinal exposure with 200 ns laser pulses. Lasers Surg Med. 1998;27(5):451–464.

52. Gerstman B. Theoretical modeling of laser-induced explosive pressure generation and vaporization in pigment cells. Proc SPIE. 2000;3902:41–53.

53. Payne DJ, Thomas R, Elliot JJ, et al. Cavitation thresholds in the rabbit retina pigmented epithelium. Proc SPIE. 1999;3601:27–31.

54. Roegener J, Brinkmann R, Lin CP. Pump-probe detection of laser induced microbubble formation in retinal pigment epithelium cells. J Biomed Opt. 2004;9(2):367–371.

55. Lee H, Alt C, Pitsillides CM, Lin CP. Optical detection of intracellular cavitation during selective laser targeting of the retinal pigment epithelium: dependence of cell death mechanism on pulse duration. J Biomed Opt. 2007;12(6):064034.

56. Schüle G, Rumohr M, Hüttmann G, Brinkman R. RPE damage thresholds and mechanisms for laser exposure in the microsecond-to-millisecond time regimen. Invest Ophthalmol Vis Sci. 2005;46(2):714–719.

57. Schulmeister K, Husinski J, Seiser B, et al. Ex vivo and computer model study on retinal thermal laser-induced damage in the visible wavelength range. J Biomed Opt. 2008;13(5):054038.

58. Neumann J, Brinkmann R. Cell disintegration by laser-induced transient microbubbles and its simultaneous monitoring by interferometry. J Biomed Opt. 2006;11(4):041112.

59. Alt C, Pitsillides V, Roegner J, Lin C. Monitoring intracellular cavitation during selective targeting of the pigment epithelium. Proc SPIE. 2003;4951:48–55.

60. Lund BJ, Lund DJ, Edsall PR. Laser-induced retinal damage threshold measurements with wavefront correction. J Biomed Opt. 2008;13(6):064011.

61. Lund BJ, Lund DJ, Holmes ML. Retinal damage thresholds in the 1 ns to 100 ns exposure duration range. In: Proceedings of the International Laser Safety Conference, San Jose, California, 14–17 March 2011. Orlando, FL: Laser Institute of America; 2011: 183–186.

62. Cain CP, Toth CA, DiCarlo CD, et al. Visible retinal lesions from ultrashort laser pulses in the primate eye. Invest Ophthalmol Vis Sci. 1995;36(5):879–888.

63. American National Standards Institute. ANSI Z136.1-1983: American National Standard for the Safe Use of Lasers. Cincinnati, OH: Laser Institute of America; 1983.

64. Stuck BE, Lund DJ, Beatrice ES. Repetitive Pulse Laser Data and Permissible Exposure Limits. San Francisco, CA: Letterman Institute of Research; 1978. Report 58.

65. Griess GA, Blankenstein MF, Williford GG. Ocular damage from multiple-pulse laser exposure. Health Phys. 1980;39:921–927.

66. Zuclich JA, Blankenstein MF. Additivity of Retinal Damage for Multiple Pulse Laser Exposures. Brooks Air Force Base, TX:US Air Force School of Aerospace Medicine; 1988. Report TR-88-24.

67. Ham WT Jr, Mueller HA, Wolbarsht ML, Sliney DH. Evaluation of retinal exposures from repetitively pulsed and scanning lasers. Health Phys. 1988;54(3):337–344.

68. Cain CP, Noojin GD, Stolarski DJ, Rockwell BA. Visible lesion thresholds from multiple pulse near infrared ultrashort laser pulses in the retina. Health Phys. 2002;86(6):855–862.

69. Menendez AR, Cheney FE, Zuclich JA, Crump P. Probability-summation model of multiple laser-exposure effects. Health Phys. 1993;65(5):523–528.

70. Lund DJ, Sliney D. A new understanding of multiple-pulsed laser-induced retinal injury thresholds. Health Phys. 2014;106(4):505–515.

71. Lund BJ, Lund DJ, Edsall PR, Gaines VD. Laser-induced retinal damage threshold for repetitive-pulse exposure to 100-ms pulses. J Biomed Opt. 2014;19(10):105006.

72. Lund DJ, Lund BJ. The determination of laser-induced injury thresholds. In: Proceedings of the International Laser Safety Conference, Albuquerque, New Mexico, 23–26 March 2015. Orlando, FL: Laser Institute of America; 2015: 69–73.

73. Sliney DH, Lund DJ. Do we overstate the risk of multiple pulsed exposure? In: Proceedings of the International Laser Safety Conference, Reno, Nevada, 23–26 March 2009. Orlando, FL: Laser Institute of America; 2009: 93–97.

74. International Commission on Non-Ionizing Radiation Protection. Guidelines on limits of exposure to laser radiation of wavelengths between 180 nm and 1000 nm. Health Phys. 2013;105(3):271–295.

Chapter 10

DEPENDENCE OF RETINAL THERMAL INJURY THRESHOLD ON SIZE AND PROFILE OF LASER IMAGE

DAVID J. LUND, BA* Research Biophysicist (Retired), US Army Medical Research Detachment, 7965 Dave Erwin Drive, Brooks City-Base, Texas 78235 ; RICHARD C. HOLLINS, DPhill † Senior Fellow, Cyber and Information Systems Division, Defence Science and Technology Laboratory, Porton Down, Salisbury, SP4 0JQ, United Kingdom ; and KARL SCHULMEISTER, PhD‡ Consultant on Laser and Optical Radiation Safety, Seibersdorf Laboratories, Seibersdorf, Austria

INTRODUCTION

BACKGROUND

Issues of Laser Safety

Image Size

Influence of Refractive Errors on Image Size

Image Diameter

LASER SAFETY GUIDELINES

HISTORICAL EMPIRICAL BASIS FOR LASER SAFETY GUIDELINES

PHYSICAL MODELS AND CALCULATIONS

Simple Models

Computer Models

Model Results

Variations to Fit the Small Spots

Images With Complex Profiles

DISCUSSION AND CONCLUSIONS

SUMMARY

INTRODUCTION

The relationship between the threshold for thermally induced injury of the retina and the size and shape of the retinal image (area of laser exposure) has been a topic of discussion for many years. For lasers in the retinal hazard wavebands, this question is central to the understanding and application of laser safety exposure limits. However, the relevant experiments and their interpretations are problematic, and the evolution of experimental techniques has generated an assortment of datasets that are difficult to reconcile. Safety standards have contained anomalies that are not explicable by physical models, and their accuracy has been questioned in light of data that have become available over the past 15 years. This chapter reviews experimental techniques used in these studies, study data, relevant physical models, and previous and current safety standards. After much debate, our understanding has converged toward a revision of the dependence of the exposure limits on image size.

Several issues complicate the interpretation of in-vivo threshold data involving different image sizes. Image size at the retina is not directly measurable, so it must be inferred from the measured characteristics of the incident beam (the laser beam to which the eye has been exposed) and assumptions about the optical quality and transparency of the eye and its state of accommodation (whether it is focused on a near or far object). Errors may be introduced at this stage, particularly for small images. Moreover, lesion observation is influenced by lesion size, which may differ from the size of the laser image itself. As the image size is adjusted, the observed dependence of the injury threshold can be influenced by all of these issues. Thus, it becomes difficult to accurately identify trends in the injury threshold. In-vitro experiments1–4 enable better control over the size of the image and the detection of lesions, but questions remain about whether these data correctly reflect the dependencies of in-vivo laser–tissue interactions.[5]

The understanding of the laser–tissue interaction has itself been revised, particularly for short laser pulses (see Chapter 12, Ultrashort Lasers and Their Bioeffects, this volume). As pulse duration is reduced to below ~10 µs, bubble generation and other mechanical processes begin to accompany the thermally induced reactions that cause injuries from longer pulses.6,7 Serious attempts to model the injury threshold’s dependence on image size have been confined to thermal processes,[4] and even then, some difficulty remains in reconciling the models with all of the parametric dependences, especially for small image sizes.

In the past, safety standards have been based largely on in-vivo experiments done before 1980. These early studies, conducted in a number of laboratories, covered a wide variety of wavelengths and pulse durations. However, image diameters addressed in each study were usually confined to just two or three widely separated data points. Findings revealed some anomalies, so substantial safety margins were built into the safety standards to compensate. More recent experiments have investigated significant wavelengths and pulse durations in greater detail, with closer-spaced image sizes. These more stringent experiments indicate deficiencies in the previous safety standards. Under certain exposure conditions, safety margins have been eroded or even eliminated by differences between the parametric dependences apparent in the new data and those built into the earlier standards. This chapter will consider these issues with attention to laser safety, emphasizing the use of advanced models and improved experimental techniques to resolve dataset differences.

BACKGROUND

Issues of Laser Safety

Retinal image size is heavily influenced by exposure conditions, and for a given intraocular power, retinal irradiance varies according to the inverse square of the image diameter. Direct ocular exposure to a well-collimated, coherent beam usually produces a small, tightly focused retinal image. However, when, for example, a beam is scattered by a diffusing screen, it produces a much larger retinal image whose size is determined by geometrical optics rather than by the coherence of the beam. The area of the resulting image can vary by a factor greater than 1,000. Between these two extremes, a range of image sizes is possible, controlled by the divergence and coherence of the incident beam and by the state of accommodation of the eye. The resulting wide variety of image sizes can be produced in controlled experiments or by accidental exposures on the battlefield or elsewhere.

The study of the relationship between retinal image size and light-induced retinal injury thresholds is important to safety for several reasons. First, scaling laws are built into safety standards. Experimental and theo-retical studies are essential to test our understanding of underlying processes. Second, a better understanding can provide a “bridge” between safety standards for lasers and incoherent light sources. The two sets of standards should merge seamlessly as the size of the retinal image varies. Finally, there is potential protec-tive benefit. Ocular hazard can be reduced considerably by degrading the focusability of the beam.

Image Size

Image size, or more precisely the diameter of the irradiated area on the retina and the distribution of irradiance or radiant exposure across that diameter, is by far the least accurately quantified and understood variable affecting the threshold for laser-induced retinal damage. Parameters of the laser beam incident at the cornea can be precisely controlled and measured, and the laws of geometric optics and physical optics can be applied to the transmission of the beam through the ocular optics. However, because the eye is a biological system, it is capable of perturbing the transmitted beam and the distribution of irradiance at the retina in unexpected and unrecognized ways.

For direct intrabeam exposures of anesthetized animals accommodated to infinity (focused on a far object), the diameter, D, of the retinal image is controlled principally by the divergence, α, of the intraocular beam. The relationship between D and α is illustrated most easily for the so-called “Maxwellian view” exposure geometry, in which the beam is brought to a focus at the pole of the ocular system, as shown in Figure 10-1.

In this case, all rays are effectively undeviated, and the size of the image on the retina is

where f is the effective focal length of the eye. In prac-tice, this simple geometry is never used in exposure experiments due to the risk of unwanted injury at the focus of the beam. Instead, experiments use a “modified Maxwellian view” geometry, in which the focus is usually positioned a distance, Z, in front of the eye, as shown in Figure 10-2, where Z is often adjusted so that the incident beam at the pupil has a diameter of 3 to 4 mm.

Figure 10-1. The “Maxwellian view” exposure geometry for irradiation of large retinal areas.

If the refractive state of the eye is adjusted to focus distant objects, the retina will be one focal length away from the pole, and the simple construction shown in Figure 10-2 shows that despite displacement Z, the size of the retinal image is still given by equation (1). In general, the image in the focal plane of a lens is directly related to the far-field irradiance distribution of the beam passing through the lens. Because the angle subtended by the far-field irradiance profile is the di-vergence, the angular subtense, α, of the image in the focal plane of the lens is also equal to the divergence.

Influence of Refractive Errors on Image Size

Refractive errors have their maximum influence in the “smallest image” case. If the state of accommodation is not adjusted for optimum focus of the collimated beam, the resulting retinal image will be enlarged. According to simple geometrical optics, an otherwise perfect eye that exhibits an error in optical power, 𝚫P, in its anesthetized state will, for a collimated input beam, produce a retinal image of diameter

where dbeam is the diameter of the incident beam, and f_0 is the optical length of the eye (which is not equal to its focal length because of the refractive error). For a typical rhesus monkey exposure in which dbeam = 3 to 4 mm, f_0 = 13.5 mm, and 𝚫P = 0.25 diopter, Dmin is predicted by equation (2) to be about 10 to 13 µm.

Figure 10-2. Modified “Maxwellian view” geometry for irradiation of large retinal areas with limited radiant exposure at the cornea. D: diameter; f: effective focal length of the eye; Z: focus distance in front of eye; α: angular subtense of the source.
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For modified Maxwellian view exposures, the refractive error is usually less important. It modifies the image size to

The fact that 𝚫P appears in a minor linear term in equation (3) means that positive and negative refractive errors can compensate for each other in the statistical distribution among different subjects. This contrasts with the “smallest image” case, where refractive errors of either sign can only increase the image size. The Z𝚫P term becomes most important for small images, because these involve the maximum values of Z. For example, for exposures with α = 5 mrad, Z might be ~0.5 m in order to make dbeam ~3 mm at the pupil. If 𝚫P lies within ±0.25 diopter, then Z𝚫P will be in the range ±0.13 for individual subjects, and averaging over subjects will probably reduce the effect on the average image diameter to less than ±10%. The corresponding retinal irradiance would not be affected by more than ±20%. Refractive errors rapidly become much less important for larger images.

Refractive errors vary from subject to subject, and most animal studies minimize their impact through preexposure ophthalmic screening. Skilled ophthalmologists can determine the refractive error to a precision of ±0.25 diopter, and they normally accept errors estimated within the range ±0.25 diopter. Most of the eyes accepted for study therefore have errors no greater than ±0.25 diopter, although a small proportion may have errors of up to ±0.5 diopter. Care is taken in the selection of subjects to ensure that each statistical threshold determination includes eyes with positive and negative refractive errors. It should be noted that refractive errors determined by ophthalmic screening do not necessarily map exactly into exposure experiments because laser energy absorption may occur deeper in the retina. Nevertheless, a refractive error of 0.25 diopter would move the focus axially by 45 µm, considerably greater than the thickness of the retinal pigment epithelium (RPE).8,9

Image Diameter

The smallest retinal images are produced using a collimated beam. Equation (1) can no longer be used to determine the image size, which in these cases is limited by other issues. In the real eye, optical aberrations increase the retinal image over the diffraction limit.9–11 In spite of considerable study, the minimum image size is still a topic of debate.

Several approaches have been used to measure the image size produced at the retina by a collimated incident laser beam. Invasive techniques allow a direct measure of the spot size by effectively placing a detector at the plane of the retina. These techniques have produced results ranging from 7 to 13 µm in the rabbit[12] and from 8 to 40 µm in the rhesus monkey.13,14

Figure 10-3. The dependence of ED_50 on D for a range of exposure durations and laser wavelengths. Orange: 150 fs at 1,060 nm; violet: 5 ns at 532 nm; blue: 3 µs at 590 nm; green: 100 ms at 514 nm; red: 0.125 s, 0.5 s, and 1 s at 633 nm.
Data sources: (1) Cain CP, Toth CA, Noojin GD, et al. Visible lesion threshold dependence on retinal spot size for femto-second laser pulses in the primate eye. J Laser Applications. 2001;13(3):125–131. (2) Zuclich JA, Edsall PR, Lund DJ, et al. New data on the variation of laser-induced retinal damage threshold with retinal image size. J Laser Applications. 2008;20(2):83–88. (3) Zuclich JA, Edsall PR, Lund DJ, et al. Variation of laser-induced retinal damage threshold with retinal image size. J Laser Applications. 2000;12(2):74–80. (4) Lund DJ, Edsall PR, Stuck BE, Schulmeister K. Variation of laser-induced retinal injury with retinal irradiated area: 0.1 s, 514 nm exposures. J Biomed Opt. 2007;12(2):06180. (5) Ham WT Jr, Geeraets WT, Mueller HA, Williams RC, Clarke AM, Cleary SF. Retinal burn thresholds for the helium-neon laser in the rhesus monkey. Arch Ophthalmol. 1970;84:797–809.

Photographic techniques simultaneously image the laser on the retina and an object of known size (such as a wire or bead inserted into the eye) or, alternatively, retinal blood vessels, which are measured after enucleation of the eye. In three animal studies, the laser image on the retina so measured has been reported to be 40 µm15,16 and 50 ±25 µm.[17] Other researchers have reported an image size based on the size of the retinal lesion resulting from exposure. However, this approach is problematic because the lesion changes with time due to metabolic response to the injury; the resulting lesion may be larger than the laser image.

Historically, the distribution of light in human retinal images has been estimated by measurement of the line spread function, modulation transfer function, or point spread function.18–21 These measurements show that at least a portion of the retinal image can be as small as 6 µm, corresponding to an angular resolution of 0.35 mrad. However, this high-resolution component is surrounded by a broader scattered component. The available data suggest that the smallest retinal images are ~20 µm.22,23 Most recently, techniques have evolved to measure the wave-front aberration errors of human eyes. Retinal image diameters have been estimated using ray-tracing software in a model eye incorporating these wavefront errors. Retinal image diameters as low as 6 µm are estimated for eyes with the least refractive error.11,24

The above discussion shows that estimates of the image diameter in in-vivo experiments are likely subject to uncertainties that should be assessed carefully in light of what is known about the incident beam and exposure conditions. Many authors assign a nominal image diameter of ~25 µm to collimated-beam laser exposures in monkey subjects. Recent data suggest that the minimum diameter could be as large as 80 to 100 µm, based on the observation that the incident energy at the cornea required to produce retinal damage does not continue to decrease with D below that diameter (Figure 10-3).25–27 Sliney et al cite several factors that may cause the minimum achieved spot size to be greater than the expected values.[9] These factors include small-angle forward scatter of the laser beam within the eye, which distributes the energy over a larger diameter than expected at the retina; larger than predicted uncompensated aberrations of the eye of the anesthetized monkey; and limited capability of the investigator to detect retinal alteration contained within diameters less than 100 µm unless additional energy is introduced to produce a more severe and therefore more visible alteration. The combined effect of these factors might be significant.

LASER SAFETY GUIDELINES

Before 1986, the maximum permissible exposure (MPE) for viewing an extended laser source was expressed in units of source radiance or source-integrated irradiance, and was constant for any given combination of wavelength and exposure duration.[28] Retinal irradiance is proportional to the source radiance.23,29 Thus, the retinal irradiance at the MPE was a constant that required the total energy incident on the retina to vary directly with the area of retinal image; that is, the MPE, expressed as energy incident on the cornea within the area of the ocular pupil (total intraocular energy [TIE]), varied according to the formula MPE(TIE) = kD^2, where k is a constant relating the MPE at D = D_0 to the value D_0. This simple provision was confounded by the idea that αmin, the limiting angular subtense that divides intrabeam (point-source) viewing from extended source viewing, was a function of exposure duration, reaching a minimum of 1.5 mrad at 18 µs, and increasing for both shorter and longer duration pulses. The rationale for such behavior by αmin was unclear for durations shorter than 18 µs, though it was justified by the evocation of eye movements for longer exposure durations. When the 1986 standard was drafted, there was strong sentiment to do away with radiance formulations. As a result, in the 1986 and subsequent standards prior to the 2014 edition, the extended-source MPE was defined as irradiance or radiant exposure at the cornea. This was given as the product of the point-source MPE and a correction factor proportional to the diameter of the irradiated area on the retina; that is, MPE(TIE) = kD for retinal diameters less than ~1.7 mm.30–32

By definition, a point source subtends a limiting visual angle, αmin, of 1.5 mrad. The MPE for a source subtending a larger visual angle, α, is obtained by multiplying the point-source MPE by a correction factor (CE in American National Standards Institute [ANSI] and International Commission on Non-Ionizing Radiation Protection [ICNIRP] standards, C_6 in the International Electrotechnical Commission [IEC] standard) that is a function of α. The angular or spatial distribution of the beam is the measurable parameter, but the diameter of the irradiance profile at the retina determines the damaging potential of a given quantity of energy incident on the retina. The retinal irradiance diameter D may be calculated from the source visual angle as D = αfe, where fe is the effective focal length of the eye in air. For a given value of α, D is smaller in the monkey eye (fe = 13.5 mm), which is used in injury threshold studies, than in the human eye (fe = 17 mm), for which the standards pertain. When the intent is to compare the MPE to injury thresholds experimentally determined in the monkey eye, it is useful to express CE as a function of D (Table 10-1, Figure 10-4). Dmin is the retinal irradiance diameter in the human eye calculated for the limiting visual angle, αmin, and Dmax is the retinal irradiance diameter in the human eye calculated for αmax = 100 mrad. In the 1986 and subsequent standards before the 2014 edition, CE, C_6 and the MPE were directly proportional to D between 25 and 1,700 µm for the case of the human eye. (It should be noted that Table 10-1 and Figures 10-4 and 10-5 presented here are specific to the 2007 editions of the ANSI and IEC safety standards. The 2014 edition of the standards produced a different set of tables and figures. The discussion of the relationship between retinal radiant exposure and corneal radiant exposure remain relevant to the 2014 standards.)

TABLE 10-1
DEPENDENCE OF CORRECTION FACTOR CE ON THE ANGULAR SUBTENSE AND THE RETINAL IRRADIANCE DIAMETER

α [*]

CE

D

CE

α < αmin

1

D < 25 mm

1

amin< α <amax

α/amin

25 mm < D < 1,700 mm

D/25

α > αmax

α^2/(αmin × αmax)

D > 1,700 mm

D^2/(25 × 1,700)

*αMIN = 1.5 mrad; αMAX = 100 mrad

α: angular subtense of the source

D: diameter (specifically, retinal irradiance diameter)

Figure 10-4. The dependence of the source-size correction factor CE on diameter, D.

Laser exposure limits (MPEs) are defined in terms of radiant exposure or irradiance at the position of the cornea. The TIE can be derived when the MPE is multiplied by the area of a 7 mm diameter pupil, a value equivalent to the energy that enters the eye. In this sense, MPEs are defined in corneal space. The TIE is a useful measure of the dose in bioeffects studies in that the experiment is usually designed so that the laser beam incident at the cornea is smaller than the pupil, and the TIE can be and is directly measured. On the other hand, when in-vivo data are to be compared to in-vitro data or to the computed results of thermal models of laser-induced retinal injury, a more useful quantity is the retinal radiant exposure, HR. For a perfect eye, the retinal radiant exposure is related to the incident energy at the cornea by the relationship

where Tλ is the transmission of the preretinal ocular media at the wavelength of exposure, D is the retinal image diameter assuming circular symmetry, and TIE is the energy incident at the cornea within the area of the pupil. CE (or C_6) shows a different dependency upon α and D when the exposure is expressed as retinal radiant exposure (Figure 10-5). Note also that while investigators can measure the angular distribution of the beam entering the eye, they cannot directly measure the irradiance diameter at the retina. The spatial distribution of energy or power at the retina (retinal spot size and irradiance profile) is a computed quantity that requires assumptions about the size and focal length of the eye, the optical quality of the eye, and the transparency of the preretinal ocular media. Large retinal area exposures are made in Maxwellian view, and α, the angle subtended by the retinal irradiance profile, is assumed equal to q, the divergence angle of the incident beam.

Figure 10-5. Blue: General dependence of the maximum permissible exposure (MPE) values, when specified as corneal levels, as a function of α when αmax equals 100 mrad. Red: General dependence of the MPE values when specified as retinal radiant exposure, as a function of α. Because D = fα, where f is the focal length of the eye (17 mm in the human eye), the same general dependencies of the MPE are obtained as a function of D when Dmax = 1,700 µm, as shown in Figure 10-4.
α: angular subtense of the source
D: retinal irradiation diameter
HR: radiant exposure

HISTORICAL EMPIRICAL BASIS FOR CURRENT LASER SAFETY GUIDELINES

Experimental studies relating retinal irradiance, retinal image diameter, and retinal injury were initiated before the invention of the laser, motivated originally by the need to understand how thermal energy might be hazardous to the eyes of those who viewed nuclear detonations. Early investigators33–35 used high-intensity broadband light sources to induce retinal burns in rabbit and nonhuman primate retinas, and found that retinal injury thresholds varied as a function of exposure duration and retinal area. When the ruby laser became available, investigators incorporated this new light source to explore laser-induced retinal injury for pulse durations not available from broadband sources. Based on studies using a Q-switched ruby laser to irradiate large retinal areas, Ham et al concluded that 0.07 J/cm^2 at the retina was sufficient to produce retinal injury.[36] In experiments designed to produce small retinal spots limited only by the optics of the eye, Vassiliadis et al reported that 0.9 J/cm^2 at the retina was required to produce retinal injury.[37] These discordant results spurred further studies designed to better characterize the relationship between irradiated area and injury threshold.

Beatrice and Frisch[16] reported data that indicated the threshold TIE varied with D for exposures to continuous wave (CW) argon lasers and Q-switched ruby lasers. Other studies10,38-46 conducted through the 1980s tended to support this notion (Figure 10-6). In the late 1990s, Zuclich and Lund initiated a series of studies to examine the ocular protection afforded by nonlinear devices.25,27,47 The studies included measuring the threshold for retinal alteration over a range of retinal irradiance diameters for exposure to 5 ns, 532 nm Nd:YAG laser irradiation and to 3 µs, 590 nm flashlamp-pumped dye laser irradiation. The data from these studies showed that the threshold TIE varied according to D^2 when D was larger than ~ 80 µm (Figure 10-7). These results were supported by the results of injury threshold studies for ultrashort lasers, which also showed that threshold TIE varied with D^2.[48]

These disparate results motivated researchers to gather all available data relating the radiant exposure required to produce retinal damage to the diameter of the irradiated area on the retina from reports of studies designed to obtain dose-response data for light irradiation of retinal tissue in vivo and in vitro. The collected data are tabulated in Tables 10-2 through 10-16. These data are expressed in units of radiant exposure (J/cm^2) at the retina as determined by equation (4). In all cases, the retinal image diameter has been computed at the point where the radiant exposure fell to 1/e of the peak radiant exposure, and the diameter has been adjusted to the appropriate value for a 13.5 mm focal length eye (in rhesus monkeys) or a 10 mm focal length eye (in rabbits).

Most commonly, the retinal response was observed using an ophthalmic instrument such as an ophthalmoscope, fundus camera, or slit-lamp biomicroscope. This equipment does not allow the investigator to directly observe the induced retinal alteration for near-threshold exposures, but it does allow observation of the biological or metabolic response to the induced damage (which is not instantaneous but develops over time following the exposure). Early studies used a minimum visible lesion (MVL) detectable at 5 minutes postexposure as the endpoint for determining the presence of a retinal response. Most subsequent studies reported 1-hour and/or 24-hour MVL endpoints. Some investigators employed fluorescein angiography as an indicator of retinal alteration. While the nonhuman primate is the current model of choice, many of the early studies used the rabbit as an animal model, no-tably studies that exposed retinal tissue to broadband radiation from a xenon lamp.

Figure 10-6. The dependence of ED_50 on diameter, D, show-ing data available prior to 1990 upon which the correction factors CE and C_6 were based before 2013.
Data sources: (1) Vassiliadis A, Rosan RC, Zweng HC. Research on Ocular Thresholds. Menlo Park, CA: Stanford Research Institute; 1969. https://apps.dtic.mil/dtic/tr/fulltext/u2/700422.pdf. Accessed December 12, 2018. (2) Beatrice ES, Frisch GD. Retinal laser damage thresholds as a function of the image diameter. Arch Environ Health. 1973;27:322–326. (3) Beatrice ES, Shawaluk PD. Q-Switched Neodymium Laser Retinal Damage in Rhesus Monkey. Philadelphia, PA: Frankford Arsenal; 1973. Report No. M73-9-1. (4) Borland RG, Brennan DH, Marshall J, Viveash JP. The role of fluorescein angiography in the detection of laser-induced damage to the retina: A threshold study for Q-switched neodymium and ruby lasers.
Exp Eye Res. 1978;27:471–493. (5) Goldman AI, Ham WT Jr, Mueller HA. Ocular damage thresholds and mechanisms for ultrashort pulses of both visible and infrared laser radiation in the rhesus monkey. Exp Eye Res. 1977;24:45–56. (6) Greiss GA, Blankenstein MF, Williford GG. Ocular damage from multiple-pulse laser exposure. Health Phys. 1980;39:921–927. (7) Ham WT Jr, Geeraets WT, Mueller HA, Williams RC, Clarke AM, Cleary SF. Retinal burn thresholds for the helium-neon laser in the rhesus monkey. Arch Ophthalmol. 1970;84:797–809. (8) Lund DJ, Beatrice ES. Ocular hazards of short-pulse argon laser irradiation. Health Phys. 1979;36:7–11. (9) Zuclich JA, Blankenstein MF. Additivity of Retinal Damage for Multiple Pulse Laser Exposures. San Antonio, TX: KRUG International; 1988. US Air Force School of Aerospace Medicine Report No. TR-88-24. (10) Lund DJ. Variation of ED_50 With Retinal Irradiance Diameter - 850 nm Erbium Laser. San Francisco, CA: Letterman Army Institute of Research; 1977. Laboratory Notebook U0023-G. (11) Lund DJ. Variation of ED_50 With Retinal Irradiance Diameter - 599 nm Flashlamp-Pumped Dye Laser. San Francisco, CA: Letterman Army Institute of Research; 1979. Laboratory Notebook U0023-G.

Many of the datasets consisted of only two points. One was a small retinal irradiation diameter determined by the ability of the eye to focus a collimated incident beam, generally recorded at 25 to 30 µm. The second data point was at a larger irradiation diameter, between 150 and 900 µm. Due to the uncertain determination of the minimum irradiance diameter, such datasets are less reliable than those that present data for more than two image diameters.

It is difficult to draw any conclusions concerning the true relationship between the ED_50 (the dose, expressed as TIE or HR, having a 50% probability of causing retinal injury) and the retinal irradiance diameter by simple examination of this body of data (Figure 10-8). Each dataset can be approximated by an equation of the form:

The values of S relate the retinal radiant exposure to the retinal irradiance diameter at the ED_50. The results of thermal model calculations show that it is an oversimplification to fit each dataset with a single value of S^4; nonetheless, S so derived has utility in understanding the collected data. The value of S for a dataset is not changed when all values of D are multiplied by a constant, such as an adjustment to the eye focal length or an adjustment from the 1/e^2 to 1/e diameter definition.

The value of S varies with the exposure duration (Figure 10-9). From thermal considerations, the ED_50 is expected to be independent of the irradiation diameter (S = 0) for exposure durations shorter than a few microseconds when thermal conduction is not a factor. As the exposure duration increases, the value of S will decrease as thermal conduction becomes increasingly more important.

Figure 10-3 shows all datasets that include a value for the ED_50 at or near a retinal diameter of 100 µm, as well as data for larger and smaller retinal irradiance diameters. Collectively, these datasets show an effective minimum retinal irradiance diameter below which the ED_50, expressed as TIE, no longer decreases as the irradiated area decreases. The effective minimum irradiance diameter is significantly larger than the minimum diameters discussed in the background section.

The analysis of the data quite clearly shows that the ED_50 does not simply vary with either the diameter or the area of the retinal image. In fact, the ED_50 varies with the irradiance diameter in a more complex manner, dependent upon the exposure duration. The collective data called into question the pre-2013 formulation of CE and C_6 and, to a degree, the value of αmin. Thermal models of laser-induced retinal injury are useful to increase understanding of the dynamics of this dependence.

PHYSICAL MODELS AND CALCULATIONS

Simple Models

Laser-induced thermal retinal damage is initiated when incident radiation is absorbed in the melanin-granule layer of the RPE. From a purely physical viewpoint, the melanin granule layer can be viewed as a thin (5–10 µm), highly absorbing layer of large lateral extent immersed in a non-absorbing media with the thermal properties of water. Radiation is incident normal to the plane of the layer. The aspect ratio of the retinal region heated by the la-ser is an important factor controlling the expected time–temperature history of the irradiated area. For large images, the heated portion of retina behaves as a thin disc, and any cooling occurs by heat flow perpendicular to the disc. All regions of a large, flat-topped image have equivalent exposure and dissipation opportunities, so the energy required to cause injury is proportional to the area of the image, as expressed by the safety standards for α > αmax. The large-image injury threshold can be described by a retinal irradiance that is independent of image size. For very small images, the diameter and thickness of the heated region become quite comparable, and dissipation can occur in three dimensions. The threshold retinal irradiance is therefore higher than for the large-image value.

Figure 10-7. The ED_50 for retinal injury induced by exposure to 5 ns, 532 nm laser pulses (blue) compared to the pre-2013 maximum permissible exposure (red).
Data source: Zuclich JA, Edsall PR, Lund DJ, et al. New data on the variation of laser-induced retinal damage threshold with retinal image size. J Laser Applications. 2008;20(2):83–88.

TABLE 10-2
TABULATION OF LASER-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER: HELIUM-CADMIUM LASER

Retinal diameter (μm)

50

125

327

Wavelength (nm)

Endpoint

Duration (s)

T

Retinal site

S

Retinal radiant exposure (J/cm^2)

442

1 h vis

1

0.4

extramacula

-1.13

177

37.2

12.6

442

48 h vis

1

0.4

extramacula

-0.96

145

31.5

12.6

442

1 h vis

5

0.4

extramacula

-1.14

611

117

39.1

442

48 h vis

5

0.4

extramacula

-1.04

591

106

39.1

442

1 h vis

16

0.4

extramacula

-1.41

-

386

99.1

442

48 h vis

16

0.4

extramacula

-0.82

-

75.1

34.1

442

48 h vis

100

0.4

extramacula

0.045

-

22.8

23.8

—: no data

1 h vis: retinal injury detected via ophthalmoscopic examination 1 hour after exposure

48 h vis: retinal injury detected via ophthalmoscopic examination 48 hours after exposure

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

Data source: Lund DJ, Stuck BE, Edsall PR. Retinal injury thresholds for blue wavelength lasers. Health Phys. 2006;90(5):477–484.

TABLE 10-3
TABULATION OF LASER-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER: HELIUM-CADMIUM LASER

Retinal diameter (μm)

30

50

100

200

252

327

378

598

616

Data source

Wavelength (nm)

Endpoint

Duration (s)

T

Retinal site

S

Retinal radiant exposure (J/cm^2)

1

514

1 h vis

0.0005

0.55

extramacula

-0.64

—

—

—

—

0.273

—

—

—

0.154

1

514

1 h vis

0.012

0.55

extramacula

-0.78

—

6.16

—

—

—

—

—

—

0.875

2

488

1 h vis

0.0135

0.52

extramacula

-1.54

19.9

—

—

1.07

—

—

—

—

—

2

488

1 h vis

0.08

0.52

extramacula

-1.37

76.5

—

11.7

4.50

—

—

—

—

—

3

458

1 h vis

0.1

0.46

extramacula

-1.17

—

26.2

—

—

—

2.89

—

—

—

3

458

48 h vis

0.1

0.46

extramacula

-1.10

—

24.6

—

—

—

3.10

—

—

—

4

514

1 h vis

1.0

0.55

extramacula

-1.12

—

154

—

—

—

—

15.4

9.83

—

—: no data

1 h vis: retinal injury detected via ophthalmoscopic examination 1 hour after exposure

48 h vis: retinal injury detected via ophthalmoscopic examination 48 hours after exposure

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

Data sources: (1) Lund DJ, Beatrice ES. Ocular hazards of short-pulse argon laser irradiation. Health Phys. 1979;36:7–11. (2) Vassiliadis A, Rosan RC, Zweng HC. Research on Ocular Thresholds. Menlo Park, CA: Stanford Research Institute; 1969. https://apps.dtic.mil/dtic/tr/fulltext/u2/700422.pdf. Accessed December 12, 2018. (3) Lund DJ, Stuck BE, Edsall PR. Retinal injury thresholds for blue wavelength lasers. Health Phys. 2006;90(5):477–484. (4) Beatrice ES, Frisch GD. Retinal laser damage thresholds as a function of the image diameter. Arch Environ Health. 1973;27:322–326.

TABLE 10-4
TABULATION OF LASER-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER: ARGON AND NEODYMIUM:YTTRIUM-ALUMINUM-GARNATE (ND:YAG) LASERS

Retinal diameter (μm)

20

69

136

281

500

562

1,013

1,018

2,012

Data source

Laser

Wavelength (nm)

Endpoint

Duration (s)

T

Retinal site

S

Retinal radiant exposure (J/cm^2)

1

argon

514

1 h vis

0.1

0.55

macula

-0.92

217

26.0

7.31

3.92

—

1.83

—

1.14

—

1

argon

514

1 h vis

0.1

0.55

extramacula

-0.95

294

28.1

8.10

4.06

—

1.88

—

1.18

—

1

argon

514

24 h vis

0.1

0.55

macula

-0.85

184

20.6

6.70

3.17

—

1.91

—

1.11

—

1

argon

514

24 h vis

0.1

0.55

extramacula

-0.77

215

21.9

6.44

3.56

—

2.08

—

1.31

—

2

Nd:YAG

532

1 h vis

0.1

0.57

extramacula

-0.18

—

—

—

—

2.00

—

1.51

—

1.57

2

Nd:YAG

532

24 h vis

0.1

0.57

extramacula

-0.38

—

—

—

—

2.20

—

1.74

—

1.30

—: no data

1 h vis: retinal injury detected via ophthalmoscopic examination 1 hour after exposure

24 h vis: retinal injury detected via ophthalmoscopic examination 24 hours after exposure

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

Data sources: (1) Lund DJ, Edsall PR, Stuck BE, Schulmeister K. Variation of laser-induced retinal injury with retinal irradiated area: 0.1 s, 514 nm exposures. J Biomed Opt. 2007;12(2):06180. (2) Lund DJ. The new maximum permissible exposure: A biophysical basis. In: Barret K, ed. Laser Safety: Tools and Training. 2nd ed. Boca Raton: CRC Press;2014: 145–175.

TABLE 10-5
TABULATION OF LASER-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER: NEODYMIUM:YTTRIUM-ALUMINUM-GARNATE (ND:YAG) AND DYE LASERS

Retinal diameter (μm)

22

25

76.7

77.4

88.4

289.7

326.6

614.3

1,177

1,617

Laser

Wavelength (nm)

Endpoint

Duration (s)

T

Retinal site

S

Retinal radiant exposure (J/cm^2)

Nd:YAG

532

1 h vis

7 × 10-9

0.57

macula

0.052

—

0.152

0.0284

—

0.011

—

0.016

0.011

0.0133

—

Nd:YAG

532

24 h vis

7 × 10-9

0.57

macula

0.070

—

0.075

0.0074

—

0.0069

—

0.0074

0.0095

0.0081

—

Nd:YAG

532

1 h vis

7 × 10-9

0.57

extramacula

-0.28

—

0.426

0.041

—

0.051

—

0.028

0.017

0.026

—

Nd:YAG

532

24 h vis

7 × 10-9

0.57

extramacula

-0.29

—

0.243

0.030

—

0.021

—

0.0093

0.015

0.0087

—

Dye

590

1 h vis

3 × 10-6

0.62

macula

0.028

1.452

—

—

0.166

—

0.068

—

—

—

0.071

Dye

590

24 h vis

3 × 10-6

0.62

macula

-0.18

0.555

—

—

0.156

—

0.057

—

—

—

0.042

Dye

590

1 h vis

3 × 10-6

0.62

extramacula

-0.12

2.267

—

—

0.266

—

0.125

—

—

—

0.103

Dye

590

24 h vis

3 × 10-6

0.62

extramacula

-0.13

1.582

—

—

0.223

—

0.083

—

—

—

0.066

—: no data

1 h vis: retinal injury detected via ophthalmoscopic examination 1 hour after exposure

24 h vis: retinal injury detected via ophthalmoscopic examination 24 hours after exposure

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

Data source: Zuclich JA, Edsall PR, Lund DJ, et al. New data on the variation of laser-induced retinal damage threshold with retinal image size. JLA. 2008;20(2):83–88

TABLE 10-6
TABULATION OF LASER-INDUCED INJURY THRESHOLDS IN RETINAL EXPLANTS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER: NEODYMIUM:YTTRIUM-ALUMINUMGARNATE (ND:YAG) LASER

Retinal diameter (μm)

30

50

82

200

211

325

500

Data source

Laser

Wavelength (nm)

Endpoint

Duration (s)

T

Retinal site

S

Retinal radiant exposure (J/cm^2)

1

HeNe

633

24 h vis

0.02

0.65

extramacula

-1.72

—

26.2

11.2

—

—

—

—

1

HeNe

633

24 h vis

0.125

0.65

extramacula

-1.15

—

97.7

38.6

—

13.0

—

—

1

HeNe

633

24 h vis

0.250

0.65

extramacula

-0.73

—

106

42.5

—

23.4

—

—

1

HeNe

633

24 h vis

0.5

0.65

extramacula

-0.75

—

197

73.2

—

37.0

26.2

—

1

HeNe

633

24 h vis

1.0

0.65

extramacula

-0.76

—

321

127

—

61.5

44.7

—

1

HeNe

633

24 h vis

3.0

0.65

extramacula

-1.19

—

—

—

—

171

104

—

2

Krypton

647

1 h vis

0.1

0.65

macula

-1.08

91.9

—

—

5.38

—

—

1.99

—: no data

1 h vis: retinal injury detected via ophthalmoscopic examination 1 hour after exposure

24 h vis: retinal injury detected via ophthalmoscopic examination 24 hours after exposure

HeNe: helium-neon

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

Data sources: (1) Ham WT Jr, Geeraets WT, Mueller HA, Williams RC, Clarke AM, Cleary SF. Retinal burn thresholds for the helium-neon laser in the rhesus monkey. Arch Ophthalmol. 1970;84:797–809. (2) Zuclich JA, Blankenstein MF. Additivity of Retinal Damage for Multiple Pulse Laser Exposures. San Antonio, TX: KRUG International; 1988. US Air Force School of Aerospace Medicine Report No. TR-88-24.

TABLE 10-7
TABULATION OF LASER-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER: RUBY AND DYE LASERS

Data source

Laser

Wavelength (nm)

Endpoint

Duration (s)

T

Retinal Site

S

1

Ruby

694

1 h vis

4 × 10-8

0.67

E&M

-1.31

1

Ruby

694

1 h fluor

4 × 10-8

0.67

E&M

-1.02

2

Ruby

694

1 h vis

3 × 10-8

0.67

extramacula

-1.04

3

Ruby

694

1 h vis

1.7 × 10-3

0.67

extramacula

-0.42

4

Ruby

694

5 min vis

2 × 10-3

0.67

extramacula

-0.061

5

Dye

599

1 h vis

4 × 10-7

0.64

extramacula

-1.02

—: no data

1 h vis: retinal injury detected via ophthalmoscopic examination 1 hour after exposure

1 h fluor: retinal injury detected via fluorescein angiography 1 hour after exposure

5 min vis: retinal injury detected via ophthalmoscopic examination 5 minutes after exposure E&M: extramacula and macula

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

The extent to which heat can conduct away from the image is an important factor in the transition between the large-image and small-image extremes. According to diffusion theory, during the time, t, of the exposure, heat can conduct a distance

where k is the thermal conductivity of the tissue, ρ the density, and C the specific heat. Assuming that all these parameters exhibit values close to those of water, some 30 µs is required for heat to escape from a small (20 µm) retinal image, and some 10 s would be required for a diffusion distance of 1 mm. For exposures longer than 30 µs, a significant range of D exists for which D < X. When, for a given pulse duration, D < X, then radial cooling affects the center of the irradiated spot dur-ing the pulse duration, which results in a lower temperature, and thus a higher retinal radiant exposure for threshold injury is required as compared to cases where there is no radial cooling. This produces a 1/D dependence of retinal injury thresholds. If, for a given pulse duration, D > X, then the center of the irradiated spot is not affected by radial cooling during the pulse duration, and therefore the threshold in terms of retinal radiant exposure does not depend on the diameter, D. For pulse durations less than ~30 µs, this condition is met for all spot sizes. This time regime is referred to as the thermal confinement regime.

Computer Models

Computer models to estimate the temperature rise in retinal tissue were first written in efforts to understand the retinal hazard of intense broadband optical sources. Algorithms evolved to incorporate more realistic descriptions of energy deposition in retinal tissue and to include transient thermal events. Available computer models for laser-induced thermal retinal injury differ in the definition of the heat source. One definition, used by Takata, assumes absorption following Beer’s law in homogeneous RPE and choroid layers and solves the heat flow equations numerically with a finite difference method.[49] Homogeneous models provide a useful description of long-exposure durations, but are less successful for sub-100 µs exposures. In reality, power absorption within the RPE is not uniform; the strongly absorbing melanin is concentrated into small (~1 µm) granules called melanosomes, which are dispersed within a relatively transparent medium. On the microsecond timescale, the tissue temperatures are determined by the size and absorption of the melanosomes, and the rate of conduction from the granules into the surrounding tissue. For short exposures, the temperature proximal to the melanosomes rises considerably higher than a continuum model would predict.

TABLE 10-7 (continued)
TABULATION OF LASER-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER: RUBY AND DYE LASERS

Retinal diameter (μm)

30

35

40

135

150

350

392

446

716

891

1,026

1,350

10,000

Retinal radiant exposure (J/cm^2)

1.52

—

—

—

0.183

—

—

—

—

—

—

—

—

0.275

—

—

—

0.053

—

—

—

—

—

—

—

—

—

—

0.901

—

—

—

—

0.045

—

0.022

—

—

—

—

—

26.7

—

—

—

—

—

—

—

—

—

2.56

—

—

—

0.748

—

0.702

—

—

0.709

—

—

0.636

—

—

0.344

—

—

—

—

0.030

—

—

—

0.011

—

—

Data sources: (1) Borland RG, Brennan DH, Marshall J, Viveash JP. The role of fluorescein angiography in the detection of laser-induced damage to the retina: A threshold study for Q-switched neodymium and ruby lasers. Exp Eye Res. 1978;27:471–493. (2) Beatrice ES, Frisch GD. Retinal laser damage thresholds as a function of the image diameter. Arch Environ Health. 1973;27:322–326. (3) Vassiliadis A, Rosan RC, Peabody RR, Zweng HC, Honey RC. Investigations of Retinal Damage Using a Q-switched Ruby Laser (AD489476). Menlo Park, CA: Stanford Research Institute; 1966. (4) Allen RG, Bruce WR, Kay KR, et al. Research on Ocular Effects Produced by Thermal Radiation. Brooks Air Force Base, TX: US Air Force; 1967. Final Report AF41(609)-3099, AD659146. (5) Lund DJ. Variation of ED_50 With Retinal Irradiance Diameter - 599 nm Flashlamp- Pumped Dye Laser. San Francisco, CA: Letterman Army Institute of Research; 1979. Laboratory Notebook U0023-G.

Granule models were developed to deal with this shortcoming.50–54 Power absorption is assumed to be confined to the granules, and heat subsequently diffuses into the surrounding tissue, where criteria are applied to predict whether cell death will occur. In recent years, the most widely used version has been that of Thompson and Gerstman,[54] which builds on several of the earlier models. Theirs is a single-granule model, in the sense that a single solution of the heat diffusion equation is used for all granules. Provided that the incident laser power has a flat-topped temporal profile of finite duration, then an analytical solution can be found for the time-dependent temperature distribution Ti(r,t) at radius r from the ith granule. The temperature distribution around an array of granules is calculated by linear superposition of the individual solutions, taking into account the relative positions of the individual granules. Apart from this superposition process, thermal interaction between different granules is neglected. The model can accommodate laser images of different sizes and profiles by scaling the single solution Ti(r,t) according to the local irradiance at the location of each granule. The Thompson-Gerstman model successfully describes the dependence of ED_50 on exposure duration across a very wide range. However, it is currently a thermal damage model only and cannot account for microcavitation bubbles, which appear to result in lower damage levels in comparison to purely thermally induced damage. In-vitro data show that microcavitation bubble formation leads to lower damage thresholds for exposures shorter than ~10 µs.6,7 When optical and thermal properties are set to equivalent values, both the Takata model[49] and the Thompson-Gerstman model result in identical thresholds for pulse durations longer than ~10 µs.[55]

Current models include the Arrhenius integral to determine an endpoint for damage.[56] The Arrhenius model attributes cell death to a hypothetical chemical reaction with a temperature-dependent rate given by

where E is the activation energy of the reaction, R is the molar gas constant, and A is a multiplying rate constant with the dimensions of inverse time. The progress of this reaction is integrated over the entire heating cycle induced by the laser exposure, and the injury threshold is determined by the minimum incident laser energy that makes the time-integrated reaction equal to unity at some point within a cell, or within a certain given area comparable to the concept of MVL. This damage criterion takes some account of both the amplitude and the duration of the temperature excursion, and provides a basis for modeling of both long and short exposures.

TABLE 10-8
TABULATION OF LASER-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER: NEODYMIUM:YTTRIUM-ALUMINUM-GARNATE (ND:YAG), ND:GLASS, AND ERBIUM:YAG LASERS

Retinal diameter (μm)

25

30

60

100

175

362

460

875

Data source

Laser

Wavelength (nm)

Endpoint

Duration (s)

T

Retinal site

S

Retinal radiant exposure (J/cm^2)

1

Nd:YAG

1,064

1 h vis

1.5 × 10-8

0.57

extramacula

-0.57

—

—

8.65

2.30

—

—

0.623

—

2

Nd:YAG

1,064

1 h vis

1.6 × 10-8

0.57

extramacula

-0.66

—

4.47

—

—

—

—

—

0.485

2

Nd:YAG

1,064

24 h vis

1.6 × 10-8

0.57

extramacula

-0.68

—

3.60

—

—

—

—

—

0.359

3

Nd:Glass

1,059

1 h vis

1.5 × 10-8

0.57

E&M

-0.81

—

10.9

—

—

2.59

—

—

—

3

Nd:Glass

1,059

1 h fluor

1.5 × 10-8

0.57

E&M

-0.80

—

3.79

—

—

0.796

—

—

—

4

Erbium:YAG

850

1 h vis

1.8 × 10-7

0.72

extramacula

-1.11

1.79

—

—

—

—

0.092

—

—

—: no data

1 h vis: retinal injury detected via ophthalmoscopic examination 1 hour after exposure

1 h fluor: retinal injury detected via fluorescein angiography 1 hour after exposure

24 h vis: retinal injury detected via ophthalmoscopic examination 24 hours after exposure

24 h fluor: retinal injury detected via fluorescein angiography 24 hours after exposure

E&M: extramacular and macular

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

Data sources: (1) Cain CP, Toth CA, Noojin GD, et al. Visible lesion threshold dependence on retinal spot size for femtosecond laser pulses in the primate eye. JLA. 2001;13(3):125–131. (2) Goldman AI, Ham WTJ, Mueller HA. Ocular damage thresholds and mechanisms for ultrashort pulses of both visible and infrared laser radiation in the rhesus monkey. Exp Eye Res. 1977;24:45–56.

TABLE 10-9
TABULATION OF LASER-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER: TITANIUM:SAPPHIRE (TI:SAPH) AND NEODYMIUM:YTTRIUM-ALUMINUM-GARNATE (ND:YAG) LASERS

Retinal diameter (μm)

30

48

70

102

224

304

378

445

512

804

Data source

Laser

Wavelength (nm)

Endpoint

Duration (s)

T

Retinal site

S

Retinal radiant exposure (J/cm^2)

1

Ti:Saph

1,060

1 h vis

1.5 × 10-13

0.57

macula

-0.43

—

0.0724

0.0267

0.0223

0.0240

—

0.0194

—

—

0.0091

1

Ti:Saph

1,060

24 h vis

1.5 × 10-13

0.57

macula

-0.41

—

0.0315

0.0148

0.0146

0.0104

—

0.0100

—

—

0.0061

1

Ti:Saph

1,060

1 h fluor

1.5 × 10-13

0.57

macula

-0.26

—

—

0.227

0.0384

0.0146

—

0.0163

—

—

0.0212

1

Ti:Saph

1,060

24 h fluor

1.5 × 10-13

0.57

macula

-0.37

—

—

0.181

0.0516

0.0175

—

0.0179

—

—

0.0230

2

Nd:YAG

1,065

24 h vis

3 × 10-11

0.57

macula

-0.18

0.702

—

—

—

—

1.19

—

0.373

0.328

—

—: no data

1 h vis: retinal injury detected via ophthalmoscopic examination 1 hour after exposure

1 h fluor: retinal injury detected via fluorescein angiography 1 hour after exposure

24 h vis: retinal injury detected via ophthalmoscopic examination 24 hours after exposure

24 h fluor: retinal injury detected via fluorescein angiography 24 hours after exposure

E&M: extramacular and macular

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

Data sources: (1) Cain CP, Toth CA, Noojin GD, et al. Visible lesion threshold dependence on retinal spot size for femtosecond laser pulses in the primate eye. JLA. 2001;13(3):125–131. (2) Goldman AI, Ham WTJ, Mueller HA. Ocular damage thresholds and mechanisms for ultrashort pulses of both visible and infrared laser radiation in the rhesus monkey. Exp Eye Res. 1977;24:45–56.

TABLE 10-10
TABULATION OF LASER-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER IN THE RABBIT*: RUBY, DYE, AND HELIUM-NEON LASER

Data source

Laser

Wavelength (nm)

Endpoint

Duration (s)

T

S

1

Ruby

694

5 min vis

1.6 × 10-8

0.67

-1.95

2

Ruby

694

5 min vis

3 × 10-8

0.67

-0.73

3

Dye

593

15 min vis

6 × 10-7

0.63

-1.78

3

Dye

593

15 min vis

6 × 10-7

0.63

-1.15

3

Dye

593

24 h vis

6 × 10-7

0.63

-1.21

3

Dye

593

24 h fluor

6 × 10-7

0.63

-1.40

4

HeNe

633

1 h vis

10

0.65

-1.56

4

HeNe

633

24 h vis

10

0.65

-1.56

*Retinal site not applicable in rabbits

—: no data

5 min vis: retinal injury detected via ophthalmoscopic examination 5 minutes after exposure

15 min vis: retinal injury detected via ophthalmoscopic examination 15 minutes after exposure

1 h vis: retinal injury detected via ophthalmoscopic examination 1 hour after exposure

1 h fluor: retinal injury detected via fluorescein angiography 1 hour after exposure

24 h vis: retinal injury detected via ophthalmoscopic examination 24 hours after exposure

24 h fluor: retinal injury detected via fluorescein angiography 24 hours after exposure

HeNe: helium-neon

S: slope of the spot-size dependence. The retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

Model Results

Both the homogeneous absorber model and the granule model have been used to predict the spot-size dependence of the injury threshold.55,57,58 The computational results obtained by Schulmeister et al[4] are of special significance for two reasons. First, they present an exhaustive examination of the dependence of computed retinal injury thresholds upon retinal irradiance diameter over a range from 30 µm to 2,000 µm, and upon exposure duration over the range from 1 µs to 1 s. Second, the computational results were directly compared to and validated by injury thresholds resulting from laser exposure of bovine retinal explants in vitro over a range of irradiance diameters from 23 µm to 2,000 µm and exposure durations from 100 µs to 2 s.[4] Table 10-16 lists these in-vitro retinal injury thresholds. Figure 10-10 shows the in-vitro injury threshold data and computational results obtained with the Thompson-Gerstman model. The thermal model results were obtained by providing a retinal irradiance diameter and radiant exposure profile as input data and allowing the program to obtain a solution for the threshold radiant exposure. A top-hat (constant irradiance) beam profile was assumed, as well as a square-wave temporal pulse shape. The computed thresholds, expressed as retinal radiant exposure, vary inversely to the diameter of the irradiated area for small spots and are independent of the irradiance diameter for large spots. The range of transition between the two zones in terms of retinal spot diameter is a function of the exposure duration. A breakpoint (Bp) can be obtained as the point of intersection of lines projected from the two zones (Figures 10-10 and 10-11).

Figure 10-12 compares the thermal model predictions (optimized to model rhesus monkey macular thresholds for a wavelength of 532 nm) to the data for those exposure durations where data are available. Considering that part of the data represents incoherent radiation exposures in rabbit eyes, the model predicts the trend of the data reasonably well for exposure durations as short as 3 µs. Laser-induced retinal injury for exposure durations shorter than a few microseconds does not result from thermal denaturation of tissue, but rather is induced by superheating the melanosomes, leading to bubble formation, followed by cell death. As noted, current thermal models are not adequate to predict tissue injury based on these interaction mechanisms.

TABLE 10-10 (continued)
TABULATION OF LASER-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER IN THE RABBIT*: RUBY, DYE, AND HELIUM-NEON LASER

Retinal diameter (μm)

8

30

50

70

100

150

180

260

286

350

400

520

572

800

1,000

Retinal radiant exposure (J/cm^2)

483

—

11.1

—

—

2.32

—

—

—

—

0.260

—

—

0.050

—

—

—

0.409

—

0.341

—

0.234

—

—

0.153

—

0.0347

—

0.0493

0.0606

—

—

—

—

—

—

—

—

0.0862

—

—

—

0.0251

—

—

—

0.455

—

0.121

—

—

—

—

0.0271

—

—

—

0.0104

—

—

—

0.677

—

—

—

—

—

—

0.0459

—

—

—

0.0189

—

—

—

0.891

—

—

—

—

—

—

0.0399

—

—

—

0.0140

—

—

—

—

—

—

504

—

—

178

—

—

—

—

—

20

—

—

—

—

—

471

—

—

166

—

—

—

—

—

20.2

—

Data sources: (1) Bergqvist T, Kleman B, Tengroth B. Retinal lesions produced by Q-switched lasers. Acta Ophth. 1966;44:853–863. (2) Ham WT Jr, Geeraets WT, Williams RC, Guerry D III, Mueller HA. Laser radiation protection. In: Proceedings of the First International Congress of Radiation Protection. New York, NY: Pergamon Press; 1968:933–943. (3) Courant D, Court L, Abadie B, Brouillet B. Retinal damage thresholds from single-pulse laser exposures in the visible spectrum. Health Phys. 1989;56(5):637–642. (4) Davis TP, Mautner WJ. Helium Neon Laser Effects on the Eye. Los Angeles, CA: EG&G Inc, Santa Monica Division; 1969. Report C10659233.

TABLE 10-11
TABULATION OF INCOHERENT RADIATION-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER IN THE RABBIT*: XENON ARC LAMP, 1967 STUDY

Retinal diameter (μm)

53

67

90

180

260

540

1,080

Wavelength (nm)

Endpoint

Duration (s)

T

S

Retinal radiant exposure (J/cm^2)

400–900

5 min vis

0.00017

0.65

-0.17

—

—

0.686

0.457

0.383

0.423

0.415

400–900

5 min vis

0.0004

0.65

-0.47

—

—

1.35

0.845

0.615

0.533

0.403

400–900

5 min vis

0.001

0.65

-0.46

3.82

—

1.97

—

1.02

0.706

0.642

400–900

5 min vis

0.004

0.65

-0.12

5.40

5.19

5.28

4.67

—

—

—

400–900

5 min vis

0.01

0.65

-0.37

8.92

7.85

7.27

2.30

1.75

1.53

1.13

400–900

5 min vis

0.02

0.65

-1.53

15.8

11.1

—

—

—

—

—

400–900

5 min vis

0.04

0.65

-0.59

22.9

15.4

15.8

4.45

3.89

1.93

1.69

400–900

5 min vis

0.1

0.65

-0.76

40.3

29.7

29.3

9.32

7.12

3.21

2.55

400–900

5 min vis

0.25

0.65

-0.97

84.0

67.2

60.4

22.2

13.0

5.74

3.95

400–900

5 min vis

1.0

0.65

-1.00

—

—

209

68.4

49.2

20.7

11.9

400–900

5 min vis

4.0

0.65

-1.07

—

—

783

242

175

68.9

37.9

400–900

5 min vis

10

0.65

-1.16

—

—

1,900

578

409

151

76.1

*Retinal site not applicable in rabbits.

—: no data

5 min vis: retinal injury detected via ophthalmoscopic examination 5 minutes after exposure

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

Data source: Allen RG, Bruce WR, Kay KR, et al. Research on Ocular Effects Produced by Thermal Radiation. Brooks Air Force Base, TX: US Air Force; 1967. Final Report AF41(609)-3099, AD659146.

TABLE 10-12
TABULATION OF INCOHERENT RADIATION-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER IN NONHUMAN PRIMATES: XENON ARC LAMP

Retinal diameter (μm)

110

220

310

640

1,300

Wavelength (nm)

Endpoint

Duration (s)

T

Retinal site

S

Retinal radiant exposure (J/cm^2)

400–900

5 min vis

0.004

0.65

E&M

0.15

—

1.35

1.00

1.47

—

400–900

5 min vis

0.01

0.65

E&M

-0.49

7.40

2.95

1.73

3.31

—

400–900

5 min vis

0.02

0.65

E&M

-0.31

11.2

5.26

3.38

4.84

4.30

400–900

5 min vis

0.04

0.65

E&M

-0.30

13.0

7.33

4.07

5.00

5.81

400–900

5 min vis

0.1

0.65

E&M

-0.63

33.3

12.9

9.20

6.83

6.60

400–900

5 min vis

0.25

0.65

E&M

-0.74

76.8

24.6

12.3

14.1

10.2

—: no data

5 min vis: retinal injury detected via ophthalmoscopic examination 5 minutes after exposure

E&M: extramacular and macular

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

Data source: Allen RG, Bruce WR, Kay KR, et al. Research on Ocular Effects Produced by Thermal Radiation. Brooks Air Force Base, TX: US Air Force; 1967. Final Report AF41(609)-3099, AD659146.

TABLE 10-13
TABULATION OF INCOHERENT RADIATION-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER IN THE RABBIT*: XENON ARC LAMP, 1958 STUDY

Retinal diameter (μm)

Retinal diameter (μm)

180

240

360

710

710

1,100

1,100

Wavelength (nm)

Endpoint

Duration (s)

T

S

Retinal radiant exposure (J/cm^2)

400–900

5 min vis

0.025 (.02–.03)

0.65

-0.74

—

—

7.41

5.95

—

3.71

3.13

400–900

5 min vis

0.05 (.027–.057)

0.65

-0.62

—

11.8

—

7.72

6.29

4.25

—

400–900

5 min vis

0.1 (.09–.11)

0.65

-0.96

—

20.6

—

9.18

—

4.45

—

400–900

5 min vis

0.19 (.14-–24)

0.65

-1.25

52.4

41.5

—

9.45

—

5.92

—

*Retinal site not applicable in rabbits.

—: no data

5 min vis: retinal injury detected via ophthalmoscopic examination 5 minutes after exposure

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

Data source: Ham WT Jr, Wisenger H, Schmidt FH, et al. Flash burns in the rabbit retina as a means of evaluating the retinal hazard from nuclear weapons. Am J Ophthal. 1958;46:700–723.

TABLE 10-14
TABULATION OF INCOHERENT RADIATION-INDUCED RETINAL INJURY THRESHOLDS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER IN THE RABBIT*: XENON ARC LAMP, 1962 STUDY

Retinal diameter (μm)

700

1,000

2,000

4,000

Wavelength (nm)

Endpoint

Duration (s)

T

S

Retinal radiant exposure (J/cm^2)

400–900

5 min vis

0.023

0.65

—

—

—

—

2.67

400–900

5 min vis

0.027

0.65

—

—

—

1.90

—

400–900

5 min vis

0.084

0.65

—

—

2.445

—

—

400–900

5 min vis

0.111

0.65

—

—

2.69

—

—

400–900

5 min vis

0.116

0.65

—

—

—

2.96

—

400–900

5 min vis

0.151

0.65

—

—

—

2.80

—

400–900

5 min vis

0.43

0.65

—

5.97

—

—

—

400–900

5 min vis

0.441

0.65

—

6.34

—

—

—

400–900

5 min vis

0.466

0.65

—

6.47

—

—

—

400–900

5 min vis

0.53

0.65

—

6.91

—

—

—

400–900

NA

0.1 (projected)†

NA

0.12

3.24

2.61

2.83

3.78

*Retinal site not applicable in rabbits.

†Values in this row were projected from values in previous rows on the assumption that the ED_50 varies proportionally to t3/4, where t is the exposure duration.

—: no data

5 min vis: retinal injury detected via ophthalmoscopic examination 5 minutes after exposure

NA: not applicable

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

T: transmittance of the eye

Data source: Jacobson JH, Cooper B, Najac HW. Jacobson JH, Cooper B, Najac HW. Effects of Thermal Energy on Retinal Function. Wright- Patterson Air Force Base, OH: Aerospace Medical Division; 1962. Air Force Systems Command Report AMRL-TDR-62-96.

TABLE 10-15
TABULATION OF LASER-INDUCED INJURY THRESHOLDS IN RETINAL EXPLANTS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER: TITANIUM:SAPPHIRE (TI:SAPH), RUBY, AND NEODYMIUM:YTTRIUM-ALUMINUM-GARNATE (ND:YAG) LASERS

Retinal diameter (μm)

20

40

44

86

100

135

200

273

Data source

Laser

Wavelength (nm)

Endpoint

Duration (s)

S

Retinal radiant exposure (J/cm^2)

1

Nd:YAG

532

Cell death

1 × 10-10

0

0.045

0.042

—

—

0.041

—

0.045

—

2

Ruby

694

Cell death

2.85 × 10-8

0

0.114

—

—

—

—

0.114

—

—

3

Ti:Saph

1,055

Cell death

7 × 10-9

-0.52

—

—

2.74

1.83

—

—

—

1.05

—: no data

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

Data sources: (1) Roegener J, Lin CP. Photomechanical effects - experimental studies of pigment granule absorption, cavitation and cell damage. SPIE. 2000;3902:35–40. (2) King RG, Geeraets WT. The effect of Q-switched ruby laser on retinal pigment epithelium in vitro. Acta Ophthalmol. 1968;46:617–631. (3) Mills BM, Connor TM, Foltz MS, et al. Microcavitation and spot size dependence for damage of artificially pigmented hTERT-RPE1 cells. SPIE. 2004;5319:217–223.

TABLE 10-16
TABULATION OF LASER-INDUCED INJURY THRESHOLDS IN RETINAL EXPLANTS AS A FUNCTION OF THE RETINAL IRRADIANCE DIAMETER: NEODYMIUM:YTTRIUM-ALUMINUMGARNATE (ND:YAG) LASER

Retinal diameter (μm)

23

73

120

200

288

549

894

1,508

2,000

Data source

Endpoint

Duration (s)

Retinal radiant exposure (J/cm^2)

532

Cell death

0.0001

0.789

0.293

0.284

0.319

0.301

—

—

—

—

532

Cell death

0.001

2.03

0.719

0.747

—

0.700

0.712

—

—

—

532

Cell death

0.01

11.1

3.51

2.13

—

1.86

2.00

1.56

1.62

—

532

Cell death

0.1

90.4

19.3

12.0

—

6.24

4.63

4.50

4.05

—

532

Cell death

0.655

439

117

68.6

—

24.9

—

11.1

—

8.72

532

Cell death

2.0

—

—

187

—

—

41.8

—

—

22.0

—: no data

S: slope of the spot-size dependence; the retinal radiant exposure (HR) is related to the retinal diameter (D) by the equation HR = kDS

Data source: Schulmeister K, Husinski J, Seiser B, et al. Ex vivo and computer model study on retinal thermal laser-induced damage in the visible wavelength range. J Biomed Opt. 2008;13(5):054038.

Variations to Fit the Small Spots

Kennedy et al attempted to fit the thermal models to the available data for spot sizes less than 100 µm by adjusting the input parameters.[59] They found that the granule model alone was unable to account for the full extent of the experimentally observed departure of ED_50 (TIE) from a square-law dependence for small image sizes using plausible parameter values. In this study, measures that would improve the quality of the fit included the following: (1) Assignment of greater thickness to the RPE layer within which the laser energy is absorbed. This thickness controls the value of the image diameter where heat conduction out of the layer changes from a 1-dimensional process to a 3-dimensional process, and this is what ultimately controls the dependence of ED_50 on image size. (2) Assignment of larger diameters to the smallest of the retinal images to account for the possibility that the irradiated diameter in the rhesus monkey eye was larger than expected. The smallest images would need to be assigned diameters of at least 30 to 40 µm.

Figure 10-8. The variation of ED_50 for laser-induced retinal injury (retinal radiant exposure, J/cm^2) with the retinal ir-radiance diameter. These data, tabulated in Tables 10-2 to 10-16, included exposure durations from femtoseconds to kiloseconds and wavelengths from 400 nm to 1,100 nm.
HR: radiant exposure

Figure 10-9. The exposure duration dependence of the slope, S, of ED_50 versus diameter, D. Each point is the value S ob-tained by fitting the data of a single line in Figure 10-8 to an equation of the form

where Hr = radiant exposure and k is a constant relating HR at D = D_0 to the value D_0.

Figure 10-10. (a) Damage threshold values for bovine in-vitro samples plotted as retinal radial exposure for exposure dura-tions of 0.1, 1, 10, 100, 655, and 2,000 ms (starting at the bottom) (b) Computer model threshold data with tighter spacing of data (exposure durations of 0.01, 0.1, 0.315, 1.0, 3.16, 10, 31.6, 100, and 316 ms, starting at bottom) and larger ranges than the experimental threshold data. A breakpoint, Bp, is obtained from the projected points of intersection.
Data source: Schulmeister K, Husinski J, Seiser B, et al. Ex vivo and computer model study on retinal thermal laser-induced damage in the visible wavelength range. J Biomed Opt. 2008;13(5):054038.

Schulmeister et al4,60 performed thermal model calculations based on three possible interpretations for the observed spot size dependence for small spots. Under the first interpretation, lesions can only be detected ophthalmoscopically if they have some minimum size that might be larger than previously assumed. To explain the experimental spot size dependence, the MVL dimension would need to have a diameter of ~70 µm. The model can account for this by determining the damage threshold with the criterion that an area with a diameter of at least 70 µm must have values of the damage integral larger than 1. The experimentally determined threshold then constitutes a super-threshold compared to the real threshold for an undetectable smaller lesion. Alternatively, an MVL is commonly described as a subtle darkening of the exposure site, which may plausibly result from changes in the essentially transparent sensory retina overlying the RPE. It is also plausible that the threshold for a visible change in the sensory retina might differ from the threshold for a visible change in the RPE. This can be accounted for in the model by evaluating the integral damage in the sensory retina anterior to the RPE layer. A spot-size dependence trend akin to the one seen in the experimental data is found. Or, finally, a larger than expected irradiance diameter at the RPE could be caused by intra-retinal scattering in the sensory retina before the radiation reaches the RPE.

Till et al proposed a damage model that describes the injury process as a combination of thermal and nonthermal processes.[58] Their model differs fundamentally from the longstanding Arrhenius model in that only the initial insult to the tissue is described by a thermal process; the formation of a lesion is controlled by cell chemistry that occurs during the minutes and hours following laser exposure. Typically, in-vivo MVLs are detected ophthalmoscopically an hour or more after exposure. On the other hand, in-vitro studies with eye explants and viability staining indicate that RPE cells die immediately following laser exposure.60,61 In-vitro threshold values in the pulse duration range of 100 µs to 2 s and spot sizes in the intermediate range compare very well with injury thresholds predicted by the thermal model based on the Arrhenius integral, using the same model parameters that also fit the nonhuman primate thresholds.4 This model was later refined using a finite element method and validated against available rhesus monkey threshold data.[62]

Figure 10-11. The breakpoint, Bp, as a function of exposure duration.
Data source: Schulmeister K, Husinski J, Seiser B, et al. Ex vivo and computer model study on retinal thermal laser-induced damage in the visible wavelength range. J Biomed Opt. 2008;13(5):054038.

Figure 10-12. A comparison of the thermal model results optimized for macular rhesus thresholds for 530 nm exposures to the data for those exposure durations where data were available in Tables 10-2 through 10-16. The red line represents the thermal model calculations. The data include thresholds for extramacular exposures in the rhesus eye and incoherent radiation exposures in the rabbit eye.

Images With Complex Profiles

Animal experiments usually produce either a top-hat or a Gaussian beam profile at the retina. For these two profiles, the parameter “diameter” is relatively well defined. A top-hat profile has a clearly defined diameter. If the diameter of a Gaussian beam profile is defined at the points where the irradiance drops to 1/e times the peak irradiance, then the Gauss-ian profile has the same peak radiant exposure as a top-hat profile with the same diameter. The ED_50 for top-hat and Gaussian beams are the same to within a factor of 1.3, depending on the pulse duration and spot size (personal communication from Mathieu Jean, Seibersdorf Laboratories, Seibersdorf, Austria, ca 2010). However, such well-behaved retinal irradiance profiles are not always realized in real-world exposure scenarios. Thus, it is useful to define the “diameter” of the retinal irradiance profile in a general way. The ED_50s for thermally induced damage of the retina and the MPEs scale with a diameter. However, this diameter should not be understood in the sense of an optical diameter, but rather as a thermally effective parameter, a scaling factor for the thermal damage threshold. In this sense, the ideal diameter definition for a given arbitrary retinal irradiance profile would produce a thermally effective diameter, Deff, such that the damage threshold is the same as the threshold for a top-hat profile with the diameter Deff. This would ensure that the MPE, when given as the small spot value with a multiplication factor containing Deff, would scale in the same way as the thresholds scale. Currently, no criterion yields accurate results for all profiles and pulse durations.

Approaches to the development of such a criterion have been suggested. Schulmeister[55] proposed extending the multiple source criteria of IEC 60825-1 to include general irradiance profiles. This technique examines the entire profile to find the sub-area of the profile having the most restrictive combination ratio of (power within an area)/(diameter of area). In practice, this technique lends itself to the evaluation of digital camera images in which the signal of each pixel is characteristic of the local irradiance. This criterion was adopted in the second edition of the IEC standard.[32]

A related semi-empirical technique based on the concept of encircled energy provides a means to adapt the available injury threshold data (for flat-topped disc images) to describe images with complex profiles, provided they are circularly symmetric.[63] The technique compares the energy contained in circular portions of the complex image (the “encircled energy”) against the experimentally determined ED_50 energy for a disc-shaped image of equal diameter. Another related approach is taken by Riehl et al,[64] who propose a technique wherein the retinal irradiation distribution is convoluted by a circular filter and the maximum of the convolution is compared to the MPE for the diameter of the filter.

DISCUSSION AND CONCLUSIONS

The preceding analysis of the relationship of laser-induced retinal injury to the diameter of the irradiated area on the retina as evidenced by bioeffects data and thermal models leads to the conclusion that the formulation of CE and C_6 in the 2007 editions of the guidelines30,32 was not accurate. The empirical and thermal models suggest that the value of αmax should vary with exposure duration, and the in-vivo bioeffects data challenge the value of αmin.

It was shown that the thermal model, the explant in-vitro data, and the in-vivo data all support definition of a breakpoint, Bp, separating the small-spot regime from the large-spot regime that varies with exposure duration. It is recognized that the transition from small- to large-spot regime is gradual rather than abrupt as implied by a breakpoint; still, the defined Bp is useful. The Bp is the value of D that separates the zone in which the ED_50, expressed as HR, varies as D-1 from the zone in which the ED_50 is independent of D. In terms of the TIE, this is equivalent to the point separating the zone in which the ED_50 varies with D from the zone in which the ED_50 varies with D^2. Because D is proportional to α, this is also the definition of αmax. Thus, the observation that Bp varies with the exposure duration is an observation that the value of αmax should also vary as a function of the exposure duration. Based on the observed form of Bp, Schulmeister et al proposed the formulation shown in Table 10-17 and Figure 10-13 for αmax as a function of exposure duration.65,66 Note that the minimum value of αmax is set at 5 mrad, while αmin continues to be equal to 1.5 mrad. Because the formulation of CE would remain unchanged, the MPE would always scale with α in the range from 1.5 to 5 mrad (Figure 10-14).

TABLE 10-17
PROPOSED TIME DEPENDENCE OF THE MAXIMUM ANGULAR SUBTENSE*

t

αmax (mrad)

<625 ms

5

625 ms–0.25 s

200 t0.5

>0.25 s

100

*The angular subtense (amax) of an extended source beyond which additional subtense does not contribute to the hazard.

t: exposure duration

Data sources: (1) American National Standards Institute. Safe Use of Lasers. Orlando, FL: Laser Institute of America; 2014. ANSI Z136.1- 2014. (2) International Electrotechnical Commission. Safety of Laser Products, Part 1: Equipment Classification and Requirements. 3rd ed. Geneva, Switzerland: IEC; 2014. IEC 60825-1-2014. (3) Guidelines on limits of exposure to laser radiation of wavelengths between 180 nm and 1000 nm. Health Phys. 2013;105(3):271–295.

Figure 10-13. A proposed dependence of the maximum angular subtense (αmax) on exposure duration. This proposal was accepted by the American National Standards Institute, International Commission on Non-Ionizing Radiation Pro-tection, and International Electrotechnical Commission in 2013 and 2014.

Given this formulation, the value of αmax is 5 mrad for exposures less than 625 µs, and the MPE at αmax is 3.3 times the point-source MPE. Unfortunately, this produces values for the MPE that for certain cases are essentially equal to the experimental ED_50 (Figure 10-15). This brought into question the value of the pre-2013 MPE at αmin.

Figure 10-14. Impact on correction factor CE (C_6 in IEC) for different pulse durations when the maximum angular sub-tense (αmax) is time dependent.

Figure 10-16 shows that the pre-2013 guidelines provided a margin of safety for 0.1 s exposures, even given the possibility that the point-source ED_50 might be lower than that obtained through in-vivo experiments. There is no compelling reason to change the form of CE for CW exposures. On the other hand, the pre-2013 guidelines did not provide a safety margin for 5 ns, 532 nm exposures. It is evident that the provisions of those guidelines must be adjusted for short-pulse exposures. As noted above, an indicated adjustment would change the form of CE such that the MPE for short-pulse exposures varied with D_2 for D > 85 µm (5 mrad) (see Figure 10-14). Such a change results in MPEs that are a better fit to the data for D > 85 µm, but it creates a problem with safety margins.[26] To provide a margin of safety for large Ds, while at the same time maintaining the point-source MPE at the current level, would require that Dmin be increased to 80 to 100 µm (Figure 10-17). This formulation is supported by the in-vivo threshold data, but not by thermal models or in-vitro threshold data, and it is difficult to reconcile with the known visual acuity of primate eyes.

Figure 10-15. The effect of setting the maximum angular sub-tense (αmax) at 5 mrad for exposure durations below 625 µs. The resulting maximum permissible exposure would be almost equal to the ED_50 data of Zuclich et al[1] for retinal ir-radiance diameters greater than 85 µm (5 mrad).
(1) Zuclich JA, Edsall PR, Lund DJ, et al. New data on the variation of laser-induced retinal damage threshold with retinal image size. J Laser Applications. 2008;20(2):83–88.

Figure 10-16. A comparison of the dependence of ED_50 on irradiance diameter for in-vivo exposures (monkey eyes) and in-vitro exposures (retinal explants). Shown are 24-h endpoint ED_50 data for 514 nm, 0.1 s duration macular expo-sures in monkeys (open green circles)1; cell death endpoint ED50 data for 532 nm, 0.1 s duration exposures in retinal explants (closed green circles)2; 24-h endpoint ED50 data for 532 nm, 5 ns duration macular exposures in monkeys (open red circles)3; and cell death endpoint ED_50 data for 532 nm, 100 ps duration exposures in retinal explants (closed red circles).4 The pre-2013 maximum permissible exposure for 0.1 s exposure duration (solid green line) and for 5 ns and 100 ps exposure duration (solid red line) are included for comparison.
(1) Lund DJ, Edsall PR, Stuck BE, Schulmeister K. Variation of laser-induced retinal injury with retinal irradiated area: 0.1 s, 514 nm exposures. J Biomed Opt. 2007;12(2):06180. (2) Schul-meister K, Husinski J, Seiser B, et al. Ex vivo and computer model study on retinal thermal laser induced damage in the visible wavelength range. J Biomed Opt. 2008;13(5):054038. (3) Zuclich JA, Edsall PR, Lund DJ, et al. New data on the variation of laser-induced retinal damage threshold with retinal image size. J Laser Applications. 2008;20(2):83–88. (4) Roegener J, Lin CP. Photomechanical effects—experimental studies of pigment granule absorption, cavitation and cell damage. SPIE. 2000;3902:35–40.

In-vivo bioeffects data certainly suggest that the value of αmin might be set too low. The data in Figure 10-3 strongly suggest that the ED_50 (TIE) does not decrease with α for αs less than ~5 mrad, and setting the value of αmin to 5 mrad would be a better fit to the in-vivo data. Note that in order to make such a change in αmin, it is essential both to understand why the ED_50 reaches a minimum at that value, and to rule out as causal any experimental limitation that might not be operant for human exposure. In-vitro experiments with eye explants or cell cultures show that the threshold for damage at the RPE level does continue to decrease with irradiance diameter below 100 µm when all the uncertainties associated with imaging through the preretinal ocular media are removed (see Figure 10-16). These factors, which were discussed in the preceding sections, might operate differently in the optically immobilized eye of an anesthetized animal than in the fully active and accommodating eye of an alert young human. Lund et al addressed the role of uncompensated aberrations in the eye of the anesthetized animal during in-vivo injury threshold experiments by using an adaptive-optics–based wavefront correction system incorporated into the exposure configuration.[67] A wavefront analyzer detected the aberrations of the animal eye and drove an adaptive optics mirror to pre-distort the laser beam to compensate for those aberrations. In theory, a near-diffraction–limited spot size should result at the retina, and, if the retinal injury thresholds were purely radiant-exposure dependent, the injury threshold would be reduced by an order of magnitude compared to the threshold in the uncompensated eye. However, the experimental results produced an injury threshold reduction of only about 30%. The authors concluded that the fact that the measured injury thresholds did not decrease for irradiance diameters below 100 µm was not a result of uncompensated aberrations, but rather was likely due to difficulty in detecting the very small areas of injury in vivo unless the radiant exposure was substantially increased.

Figure 10-17. Possible changes to the ns-to-ms-duration maximum permissible exposure (MPE) to reflect the D^2 dependence of thresholds for large irradiance diameters while providing a margin of safety at all irradiance diameters: (a) an increase in Dmin (αmin) or (b) a decrease in the point-source MPE. This was the basis for the 2014 revision of the American National Standards Institute and International Electrotechnical Commission standards. Macular ED_50 data (blue) is for 5 ns exposures at 532 nm.1 The pre-2013 MPE is shown in red. Proposed changes to the MPE are shown in green.
(1) Zuclich JA, Edsall PR, Lund DJ, et al. New data on the variation of laser-induced retinal damage threshold with retinal image size. J Laser Applications. 2008;20(2):83–88.

If the value of Dmin remains at 25 µm, then the value of the point-source MPE in the nanosecond-pulse–duration regime must decrease substantially. This choice is supported by thermal models and by the in-vitro data. A reevaluation and augmentation of the in-vivo ED_50 values for point-source exposures in the 1 ns to 1,000 ns time range also supports the need to decrease the point-source MPE by a factor of ~3 in this exposure duration range.[68]

After considering the new data and interpretations summarized in this chapter, ICNIRP[69] chose to adopt the time-varying αmax in the form proposed by Schulmeister65,66 and shown in Table 10-17 and Figure 10-14. At the same time, ICNIRP accepted the need to decrease the value of the 0.01 ns to 5 µs MPE at αmin by a factor of 2.5 to provide a more adequate safety margin for short-pulse exposures. Together, these changes provide a much better match of the MPE to the ED_50 data over all exposure durations.[70] The changes adopted by ICNIRP have been accepted by both ANSI and IEC and are incorporated into the latest editions of ANSI Z136.1[71] and IEC 60825-1.[72]

SUMMARY

For lasers in the retinal hazard wavebands, the relationship between the threshold for thermally induced injury of the retina and the size and shape of the retinal image is centrally important to the un-derstanding and application of laser safety exposure limits. Early safety standards assumed that the retinal injury threshold varied with the square of the diam-eter of the beam on the retina; therefore, the standards said that the MPE should vary with the square of the angle subtended by the beam on the retina. However, further laser-induced injury threshold studies led to the perception that the retinal injury threshold varied directly with the diameter of the beam on the retina; therefore, the safety standards were revised to provide guidance that the MPE should vary directly with the angle subtended by the beam on the retina. From a theoretical point of view, neither of these formulations was satisfactory.

This chapter reexamined the relevant old and new bioeffects data relating the laser-induced retinal injury thresholds to the diameter of the laser beam on the retina, and noted that injury threshold varied with the square of the diameter for short-duration exposures but varied directly with the diameter for longer-duration exposures. Thermal models of laser-induced retinal injury provided a better understand-ing of the dynamics of this dependence and led to the formulation of a time-varying αmax. This in turn effectively provided a transition from a diameter-squared dependence of the MPE for short-duration exposures to a diameter dependence of the MPE for longer-duration exposures. This new formulation, which has been incorporated into the latest editions of the laser safety standards, provides a consistent relationship between the MPE and laser-induced injury thresholds.

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70. Lund DJ. The new maximum permissible exposure: A biophysical basis. In: Barret K, ed. Laser Safety: Tools and Training. 2nd ed. Boca Raton, FL: CRC Press; 2014: 145–175.

71. American National Standards Institute. Safe Use of Lasers. Orlando, FL: Laser Institute of America; 2014. ANSI Z136.1-2014.

72. International Electrotechnical Commission. Safety of Laser Products, Part 1: Equipment Classification and Requirements. 3rd ed. Geneva, Switzerland: IEC; 2014. IEC 60825-1-2014.

Chapter 11

RETINAL THERMAL DAMAGE AND OCULAR MOTION

BRIAN J. LUND, PhD * Research Physicist, Ocular Trauma, US Army Institute of Surgical Research, 3698 Chambers Pass, Joint Base San Antonio, Fort Sam Houston, Texas 78234-7767

INTRODUCTION

NATURE OF EYE MOVEMENTS DURING STEADY GAZE

EYE MOVEMENT PATTERN DURING FIXATION ON A LASER SOURCE

Measurements at the US Army Medical Research Detachment

Eye Movement Plots

Fixation Ellipse: Measure of the Extent of the Eye Movement Pattern

Diode Study: Growth of Fixation Ellipse, Effect of Wavelength

Laser Study: Intensity Effect

DISTRIBUTION OF ENERGY AT THE RETINA: RETINAL RADIANT EXPOSURE PATTERN

Modeling the Retinal Heating Pattern: The RHME (Retinal Heating, Moving Eye) Program

Simulation Results: A Look at Retinal Heating During a Long-Duration Exposure

RETINAL HEATING DURING FIXATION ON A LASER SOURCE

Modeling the Retinal Heating Pattern: The RHME (Retinal Heating, Moving Eye) Program

Simulation Results: A Look at Retinal Heating During a Long-Duration Exposure

ESTIMATING THERMAL DAMAGE THRESHOLDS FROM SIMULATION RESULTS

SUMMARY

INTRODUCTION

The human eye is never completely stationary. There are always some small-scale movements present, even when an individual is fixing his or her gaze on a small, well-defined target.1,2 These movements are of interest to the laser bioeffects research community because they impact the distribution of energy deposited in the retina during a long-duration exposure (eg, >100 ms) to a laser beam.

The guidelines for safe ocular exposure to lasers, expressed as maximum permissible exposure (MPE) limits, are based on damage threshold (ED_50) data obtained using anesthetized animals. The eyes of the test animals are artificially immobilized to control the location of the retina exposed to the laser beam. However, in an alert subject, the image of the beam moves about an extended region of the retina in response to eye movements. This means that energy from the laser is deposited in a region of the retina that is larger than the diameter of the beam, and the peak of the deposited energy distribution (radiant exposure distribution) will be less than would be experienced in a stationary eye.

The motion of the eye can also lead to a complex heating pattern in the retina. A particular location in the retina that is being directly irradiated by light from the laser will absorb energy from the beam and be heated. If an eye movement causes the laser spot to move away from this retinal location, it will have an opportunity to cool.

For short, single-pulse exposures, the eye may be treated as a stationary platform. But, for longer-duration exposures to continuous-wave (CW) lasers, ignoring the effects of eye movements may lead to an overly pessimistic assessment of damage probability and unnecessarily restrictive safety limits. Indeed, eye movement measurements performed at the US Army Medical Research Detachment (USAMRD) of the Walter Reed Army Institute of Research[3] played an important role in the decision to increase the MPE levels in 20004,5 (Figure 11-1).

This chapter describes a research program conducted to investigate eye movements as a mitigating factor in preventing the onset of thermal damage from a long-duration laser exposure. It will begin with a brief description of the nature of small-scale eye movements, followed by a discussion of experiments to record eye movements that occur during deliberate fixation on a laser source. The retinal radiant exposure pattern is examined. Taking eye movement data as input, a computer simulation is used to study the nature of the heating pattern in the retina during a long-duration laser exposure. An Arrhenius integral damage model is used in conjunction with the results of the computer simulation to estimate the thermal damage threshold for a moving eye. Although the dependence of the damage threshold on the beam spot size is an important topic of current research, this chapter will focus on small-beam spot sizes expected from a laser exposure.

104 s) viewing of a continuouswave laser source (from the American National Standards Institute [ANSI] Z136.1)." />

Figure 11-1. Change in the maximum permissible exposure (MPE) for long-duration (>10^4 s) viewing of a continuous-wave laser source (from the American National Standards Institute [ANSI] Z136.1). The MPE is expressed as irradiance at the cornea, EC.
Data sources: American National Standards Institute (ANSI). Safe Use of Lasers, Standard Z136.1. Orlando, FL: Laser Institute of America; 1993 & 2000.

NATURE OF EYE MOVEMENTS DURING STEADY GAZE

The movement pattern of the eye during steady gaze has been of considerable interest to vision researchers since the 1950s, when the first accurate recordings with high enough resolution to characterize the spatial and temporal natures of the movements became available (see Ditchburn,1 Kowler,2 and references therein). Data from these measurements were used in developing and assessing models of the human visual processing system, particularly how a stable gaze was obtained and subsequently maintained. In this chapter, eye movements are of interest because they cause the beam spot (during a long-duration laser exposure) to move about an extended region of the retina. The resulting heating pattern will be different from the pattern expected in a stationary eye, leading to (perhaps) a lower risk for a thermal injury to occur.

The motion of the eye during steady gaze is complex and nondeterministic.[1] Kinematically, the eye is described by its orientation in space, and by the direction and speed of its motion. Knowledge of the current state of the eye cannot be used to predict its state at a future time in anything other than a statistical sense. However, measurements of eye motion reveal the occurrence of several typical patterns. These patterns allow us to describe eye movements as they occur during a fixation task using three general classes of motion1,2: (1) drifts, (2) saccades, and (3) tremors.

Drifts are periods of fairly slow movement, in which the center of the gaze slowly shifts on average by about 2.5 min of arc (0.73 mrad). Using an effective focal length of the human eye of fe = 17 mm, such a rotation will move an image a distance of 12.4 µm on the retina. The speed of these drifts is usually in the range of 2 to 8 min of arc per second (0.58 to 2.3 mrad per second).

Saccades, or flicks, are sharp movements, usually of several minutes of arc, occurring over a few tens of milliseconds. The displacement caused by an involuntary saccade during fixation is usually <10 min of arc (2.9 mrad or 49 µm on the retina) and rarely>30 min (8.7 mrad, 148 µm on the retina). Saccades are observed to occur at intervals ranging from about 0.2 s to several seconds, with a mean frequency of 1.6 per second.

Superimposed on the other movements are high-frequency oscillations known as tremors. Tremors have characteristics reminiscent of random noise. The peak-to-peak amplitude of the oscillations is generally well under 1 min of arc (0.29 mrad), with frequencies typically in the range of 30 to 80 Hz.

For most individuals, movement of the eye during steady gaze can generally be described by this drift, flick, drift, flick pattern, with a tremor superimposed. However, the frequency and size of flicks, and the duration of the drift periods between flicks, can vary significantly from person to person. Researchers studying eye movements and their contribution to visual function are often interested in the detailed description of the eye movements. This will often take the form of a Fourier analysis of one or more components of the motion (see, eg, Eizenman et al[6]). However, such a detailed description is not necessary to gain an understanding of eye movement effects during long-duration laser exposure. Here, a simpler measure, the fixation ellipse, will be used to characterize the extent of the eye movement pattern.

EYE MOVEMENT PATTERN DURING FIXATION ON A LASER SOURCE

Measurements at the US Army Medical Research Detachment

Two experiments were performed at USAMRD to gather data needed to assess the effect of eye movements on retinal radiant exposure distributions and heating patterns during laser exposure.3,7 A dual Purkinje image (DPI) eye tracker[8] was used to record high spatial and temporal resolution measurements of eye movements during fixation. In both experiments, the extent of the fixation target in the visual field was kept much smaller than the minimum angular subtense, αmin = 1.5 mrad, defined in the current safety guidelines.4,5 The fixation targets in both studies could therefore be treated as small (vs extended) sources.

The experiment of Ness et al[3] used light-emitting diodes to produce the fixation targets. Diodes of various peak wavelengths (420, 527, and 662 nm) were used, ad-justed to have similar luminance values. These sources were very dim, producing corneal irradiance values <1 pW cm–2. The trials lasted 100 s, and measurements were made with the subjects’ heads held steady using a head and chin rest combination. Data were also collected without the use of the head and chin rest, allowing subjects some limited range of movement. The result from this experiment was a key factor in the decision to increase the MPE for long-duration exposures to CW laser sources by an order of magnitude (see Figure 11-1).

Lasers easily available to the public are capable of producing much more intense beams than the LEDs (light-emitting diodes) used by Ness et al.[3] Lund et al[7] extended the study to higher irradiance values by using a helium-neon (HeNe; λ = 632.8 nm) CW laser to produce the fixation target. Fixation sources covering eight orders of magnitude were used, producing corneal irradiance values from 0.6 pW cm–2 (very dim) to 6 µm cm–2 (very bright). Trials lasted 50 s, and a head and chin rest combination was used in all cases.

It should be noted that a subject deliberately staring into a laser beam while his or her head is held steady represents the worst-case scenario from a laser safety perspective. Although head-held steady viewing is unlikely to occur during any individual’s normal daily routine, it is a scenario that occurs commonly in experimental and clinical environments, where control over the exposure site or a steady view of the eye is needed.

Eye Movement Plots

Eye movement data were analyzed and interpreted in terms of the location of the image of the fixation target on the retina and the pattern “painted” by the image as it moves about the retina due to eye movements. The relative position of the image on the retina was derived from the orientation of the eye (as recorded by the DPI eye tracker) using an effective focal length for the optics of the human eye of fe = 17 mm. (Using this value, 1 degree in the field of view corresponds to 297 µm on the retina.) Because it was not possible to view the interior of the eye during these experiments, the absolute location of the image of the fixation target on the retina could not be precisely determined. However, studies using a scanning laser ophthalmoscope have shown that the image will be located within the fovea during a fixation task.[9] Therefore, it is assumed that the eye movement patterns recorded in the fixation studies are centered in the middle of the fovea at the onset of the trial.

Figure 11-2. Eye movement visitation plots, illustrating the extent of eye movements during the fixation task. Color indicates visitation time at each point; scales are to the right of each plot. The fixation ellipses derived from the data are noted in white on each figure. Minimum contour in these plots = 0.001 s. Note that the time scales are different for each plot. 300 mm on the retina corresponds to ~1° in the field of view. (Top) Subject 1: fixate for 50 s on the helium-neon source producing a corneal irradiance of 0.6 pW cm–2. (Middle) Subject 4: 50 s, 60 pW cm–2. (Bottom) Subject 6: 45 s, 6 µW cm–2.
Data source: Adapted from Lund BJ, Zwick H, Lund DJ, Stuck BE. Effect of source intensity on ability to fixate: im-plications for laser safety. Health Phys. 2003;85(5):567–577.

Eye movement patterns are conveniently visualized using visitation time contour plots.[1] These plots show the cumulative time the location of the image was centered, for example, on a particular 10 µm × 10 µm area of the retina. The exact details of the eye movements are lost in this representation, but the overall extent and tightness of the fixation pattern are readily apparent.

A few samples of the eye movement patterns recorded in the fixation studies are shown in Figure 11-2. These data are from the study by Lund et al,[7] in which a HeNe laser was used to produce the fixation target. The corneal irradiance experienced by the subjects for each of these movement plots is listed in Table 11-1. For a stationary eye, the visitation time plot is a delta function (ie, a dot in the center of the plots). The maximum value of the visitation time plot for each of the moving eyes is a small fraction of the total duration of the trial.

The overall extent of the movement patterns clearly varies across individual subjects. The narrowest pattern covered 150 to 200 µm on the retina (one-half to two-thirds of a degree in the visual field). The broader patterns extended across 500 to 600 µm (nearly two degrees in the visual field). All of the movement patterns were concentrated in a limited region about the center of the pattern, although subject 6 (see Figure 11-2) exhibited an unusually pronounced nasal/temporal extent to the central peak. As expected, the narrower pattern had a higher peak visitation time value compared to the broader patterns (see Table 11-1). Theses peak values were far less than the duration of the fixation trials.

TABLE 11-1
PARAMETERS FOR THE EYE-MOVEMENT PATTERNS OF FIGURE 11-2

Fixation Ellipse

Movement Data

Trial Duration (s)

Corneal Irradiance

Peak Visitation Time (s)

σH (μm)

σV (μm)

Area (μm^2)

Stationary

50

—

50

0

0

0

Subject 1

50

0.6 pW cm–2

1.581 (0.03)[*]

43.5

47.9

6,546

Subject 4

50

60 pW cm–2

2.871 (0.06)[*]

21.5

12.4

838

Subject 6

45

6 μW cm–2

1.071 (0.02)*,†

59.0

21.7

4,022

*Value in parentheses is ratio to value for the stationary eye.

†Stationary eye data scaled to a 45-s trial for comparison with subject 6.

This brief examination of the eye movement patterns indicates that, during a long-duration laser exposure, the beam spot will move about an extended region of the retina. However, it is confined to a limited area most of the time. A primary goal of this research is to assess how much difference this makes in the retinal heating pattern and thus in the risk of thermal damage from a long-duration exposure.

Fixation Ellipse: Measure of the Extent of the Eye Movement Pattern

Although the detailed nature of eye movements can be quite complex, it is the physical extent of the movement pattern that is of primary interest to understanding long-duration exposure damage mechanisms. The pattern of eye movements during fixation is characterized by an ellipse centered at the means and of the recorded nasal/temporal and superior/inferior retinal position measurements. The axes of the “fixation ellipse” are determined by the standard deviations and of the data. (This is a variation of the bivariate contour ellipse concept introduced by Nachmias.[10]) The ellipse, therefore, represents an area containing roughly 68% of the data (ie, the center of the image of the fixation target was located within this area of the retina for 68% of the trial duration). The area of the ellipse, A = πσH σV, is used as a measure of the “tightness of fixation” of the eye movements. Alternatively, it gives a measure of how large an area on the retina receives significant direct irradiation from a laser beam during a long-duration exposure.

The fixation ellipse is not a perfect representation of the eye movement pattern in all cases. However, it is easy to calculate from the data and has a readily understood geometrical interpretation that is directly pertinent to laser bioeffects issues of interest. (Certainly more so than, for example, a Fourier analysis of the movement data, or a breakdown of saccade frequency.)

Fixation ellipses are included on the eye move-ment patterns plotted in Figure 11-2. The dimensions and areas of the ellipses are listed in Table 11-1. Note that the extent of the ellipses ( or ) are all larger than 25 µm, which is the diameter of a beam spot corresponding to the minimal angular subtense αmin. This indicates that the eye movement will indeed be an important consideration for direct viewing of a laser beam, where retinal spot size is expected to be minimal.

Diode Study: Growth of Fixation Ellipse, Effect of Wavelength

Ness et al[3] measured the growth in the area of the fixation ellipse during a fixation trial. The area of the fixation ellipse as a function of time during the trial is illustrated in Figure 11-3. The fixation target for this experiment was a light-emitting diode (LED) producing a corneal irradiance <1 pW cm–2, a very dim target. Figure 11-3 is the average for six subjects performing the fixation task. This figure includes data from measurements in which the subjects’ heads were constrained using a head and chin rest combination. Measurements taken without the head and chin rest are also included. This unconstrained experimental condition allowed the subject some range of head and body movement; however, the individual had to remain fairly steady in order to allow the DPI eye tracker to maintain a lock on the subject’s eye. Not surprisingly, the ellipse area was larger when the head was allowed some freedom of movement. However, the ratio of the area of the ellipse in the constrained and unconstrained conditions stayed within a relatively narrow range.

Figure 11-3. Growth in the area of the fixation ellipse during a fixation trial. The fixation target is a light-emitting diode producing a corneal irradiance of <1 pW cm–2. Data set is the average of six subjects.
Data source: Adapted from Lund BJ, Zwick H, Lund DJ, Stuck BE. Effect of source intensity on ability to fixate: implications for laser safety. Health Phys. 2003;85(5):567–577.

Diodes of various peak wavelengths were used (420 nm, blue; 527 nm, green; and 662 nm, red). However, the area of the fixation ellipse showed no dependence on wavelength. The color of the stimulus had no apparent effect on the nature of the eye movement pattern.

Laser Study: Intensity Effect

The diode study indicated that the eye movement patterns were large enough to warrant a significant increase in the long-duration exposure MPE levels for CW lasers (see Figure 11-1). Additional data were needed to investigate whether the eye movement patterns would be different in response to a brighter stimulus more representative of visible laser light.

Lund et al[7] extended the study to higher irradiance values by using a HeNe laser to produce the fixation target. Fixation sources with corneal irradiance values from 0.6 pW cm–2 to 6 µW cm–2 (covering eight orders of magnitude) were used. The results of this study are summarized in Figure 11-4, in which the area of the fixation ellipse after a 50-s trial is plotted against the source corneal irradiance. Data represent the average of two or three trials at each source strength. There is clearly a variation across individual subjects. However, over the eight orders of magnitude in stimulus intensity used in this study, none of the subjects exhibited a variation in the area of the fixation ellipse as large as one order of magnitude. In fact, data indicate no statistically significant trend in the area of the fixation ellipse as a function of the source intensity. Although the brightest source used herein was uncomfortable to view, none of the subjects refused to perform the fixation task, nor was there any breakdown in their ability to fixate on the source.

Figure 11-4. Areas of the fixation ellipse after staring at the sources for 50 s as a function of the source corneal irradiance for each of the seven volunteers used in the study by Lund et al. Examples of the fixation ellipse are shown in Figure 11-2. Each data point is the average of two or three trial runs at the irradiance level, except for subject 6 at 6 nW cm^2, for which only one measurement was available. The average of the data from all subjects is also plotted.
Data source: Adapted from Lund BJ, Zwick H, Lund DJ, Stuck BE. Effect of source intensity on ability to fixate: implications for laser safety. Health Phys. 2003;85(5):567–577.

The average fixation ellipse area for all of the data included in Figure 11-4 is 3,654 µm^2 or a typical diameter of about 68 µm. The fovea of the human eye has a diameter of about 200 µm, corresponding to a circle with an area >30,000 µm^2.

The maximum corneal irradiance value used was limited by the current safety guidelines in effect at the time this experiment was proposed.[11] In the current standards,4,5 the MPE for a long-duration exposure to visible wavelengths is 1 mW cm–2 for a small-beam spot. This is more than two orders of magnitude greater than the most intense source used in the laser fixation study (corneal irradiance of 6 µW cm–2). It is possible that more intense sources would produce a high enough level of discomfort that an individual would be unable to maintain a steady fixation on the source. An increase in the extent of the movement pattern, as measured by the fixation ellipse, could occur as the individual fights against the desire to look away from the source of discomfort. Perhaps the more likely response would be a dramatic increase in the frequency of blinking or an outright refusal to perform the fixation task.

Figure 11-5. Small-beam spot retinal radiant exposure distribution calculated from the eye movement data shown in Figure 11-2. Color indicates radiant exposure at each point; scales are to the right of each plot. Minimal contours represent 1% of the peak value. Calculations are for an exposure to a helium-neon laser (λ = 632.8 nm) producing a corneal irradiance of 1 mW cm–2. The power of the beam at the retina is P = 250 µW (see text). The beam is assumed to have a Gaussian irradiance profile with a 1/e diameter of 25 µm. This diameter is smaller than the size of the fixation ellipses (see Table 11-1). In this case, there is a significant reduction in the peak radiant exposure in the moving eyes compared to a stationary eye.
Data source: Adapted from Lund BJ, Zwick H, Lund DJ, Stuck BE. Effect of source intensity on ability to fixate: implications for laser safety. Health Phys. 2003;85(5):567–577.

DISTRIBUTION OF ENERGY AT THE RETINA: RETINAL RADIANT EXPOSURE PATTERN

During exposures to shorter-wavelength light (λ < 540 nm), damage is induced predominantly through a photochemical process.[12] In such a process, a constant energy dose (retinal radiant exposure) is required to elicit a damage response. The radiant exposure pattern received at the retina can be calculated from the eye movement plots. If is the cumulative visitation time at the point on the retina, and is the irradiance profile of the beam incident on the retina, then the radiant exposure experienced at the point is given by the two-dimensional convolution integral:

For a Gaussian beam, the irradiance distribution has the form

where P is the total power in the beam at the retina, and a is the radius at which the intensity of the beam falls to 1/e of the central value. Inserting equation (2) into equation (1) leads to the following expression for the retinal radiant exposure from Gaussian beam:

In a stationary eye, is a delta function, and the radiant exposure distribution (equation (1)) reduces to the beam irradiance distribution multiplied by the duration of the exposure.

Figure 11-6. Large-beam spot retinal radiant exposure distribution calculated from the eye movement data shown in Figure 11-2. Color indicates radiant exposure at each point; scales are to the left of each plot. Minimal contour represents 1% of the peak value. Calculation is for an exposure to a helium-neon laser (λ = 632.8 nm) producing a corneal irradiance of 1 mW cm-2. The power of the beam at the retina is P = 250 µW (see text). The beam is assumed to have a Gaussian irradiance profile with a 1/e diameter of 150 µm. This diameter is larger than the size of the fixation ellipses (see Table 11-1). The radiant exposure distributions in the moving eyes are very similar to the distribution in the stationary eye.
Data source: Adapted from Lund BJ, Zwick H, Lund DJ, Stuck BE. Effect of source intensity on ability to fixate: implications for laser safety. Health Phys. 2003;85(5):567–577.

Examples of the retinal radiant exposure patterns calculated from eye movement plots are shown in Figures 11-5 and 11-6. These figures were calculated for an MPE-level exposure to light from a HeNe laser. The current MPE for a long-duration exposure to visible laser light is an irradiance of 1 mW cm–2 at the cornea for small spot sizes.4,5 In laser safety calculations, a 7-mm diameter pupil is used as the limiting aperture, which admits a total intraocular power of 385 µW from a beam producing 1 mW cm–2 at the cornea. At a wavelength of λ = 633 nm (eg, from a HeNe laser), direct transmittance through the ocular medium to the retina is approximately 65%[13] (see Figure 11-7). When the beam reaches the retina, it will, therefore, have a total power that is approximately P = (385 µW)(0.65) = 250 µW. This value was used in equation (3) to produce the retinal radiant exposure patterns shown in Figures 11-5 and 11-6.

Figure 11-5 shows the retinal radiant exposure patterns resulting from a 25-µm diameter beam spot, ie, a = 12.5 µm in equation (2). This diameter is smaller than the size of the fixation ellipses (see Table 11-1). Therefore, it is expected that the eye movements will have a significant effect on the radiant exposure distribution because the source will be moved a distance on the retina that is comparable to or larger than the beam diameter. The peak values of these distributions, listed in Table 11-2, are reduced to ¹⁄₅ or ¹⁄10 the value that would be experienced in a completely stationary eye for a long-duration exposure.This suggests that for small-beam spots, the threshold for photochemical damage in an awake, alert person will be five to ten times greater than the damage threshold measured or simulated in a stationary eye. Alternatively, for a given exposure level, the exposure duration may be five to ten times longer than the allowable duration determined for a stationary eye.

Figure 11-7. Retinal pigment epithelium (RPE) absorption coefficient, ARPE, and direct ocular transmission coefficient, Tocular, as a function of wavelength for visible light. The product of these two coefficients gives the percentage of the total intraocular power that is absorbed in the RPE. (ARPE is from Gabel et al. Tocular is from Boettner and Wolter.)
Data sources: Boettner EA, Wolter JR. Transmission of the ocular media. Invest Ophthalmol. 1962;1:776–783. Gabel V-P, Birngruber R, Hillenkamp F. Visible and new infrared light absorption in pigment epithelium and choroids. In: International Congress Series, No. 450: XXIII Concilium Ophthalmologicum, Kyoto, Japan, 14–20 May 1978. Amsterdam, The Netherlands: Excerpta Medica; 658–662.

The retinal radiant exposure distribution resulting for a 150-µm diameter beam spot is shown in Figure 11-6. In this case, the beam diameter is larger than the size of the fixation ellipses. Most eye movements will shift the source a distance that is small compared to the spot size; therefore, the shape of the radiant exposure distributions is expected to be similar to what would be experienced by a stationary eye. Furthermore, the peak value of these distributions should be similar in the moving and stationary eyes. This is indeed observed—the peaks of the radiant exposure distributions in the moving eyes are within a factor of two of the peak value in the stationary eye (see Table 11-2).

Eye movements occurring during a fixation task are likely to have a significant impact on the onset of retinal damage occurring from exposure to a small spot-size source, as expected from a laser exposure. For sources producing beam spots of a few hundred micrometers or larger in diameter, eye movements are unlikely to play a significant role in determining retinal damage thresholds.

TABLE 11-2
COMPARISON OF RETINAL EXPOSURE FROM SMALL AND LARGE-BEAM SPOTS

Peak Retinal Radiant Exposure (J cm–2)

Movement Data

25-μm spot[*]

150-μm spot[†]

Stationary

2,546

70.7

Subject 1

234 (0.09)[‡]

41.4 (0.59)[‡]

Subject 4

489 (0.19)[‡]

63.2 (0.89)[‡]

Subject 6

195 (0.08)‡,§

40.3 (0.63)‡,§

*See Figure 11-5.

†See Figure 11-6.

‡Value in parentheses is ratio to value for the stationary eye.

§Stationary eye data scaled to a 45-s trial for comparison with subject 6.

RETINAL HEATING DURING FIXATION ON A LASER SOURCE

At wavelengths greater than about 540 nm, the predominant damage mechanism is the thermal denaturization of proteins.[12] The rate of this denaturization reaction is strongly temperature dependent[14]; therefore, a detailed examination of the thermal history of the retina during an exposure is needed to predict the onset of injury.

Absorption of visible and near-infrared light occurs primarily in the dense layer of melanin granules of the retinal pigment epithelium[12] (RPE); thus, the greatest temperature rise will occur within this layer. Energy absorbed by a melanin granule is rapidly converted to heat, causing the temperature of the granule to increase. The thermal confinement time for melanin granules (ie, how long it takes a heated granule to reach thermal equilibrium with its immediate environment) is on the order of 10 µs. Thus, heat energy generated within the melanin rapidly diffuses into the surrounding (cooler) cellular media. Because of this, for exposure durations on the order of a few hundred microseconds or longer, it is reasonable to treat the tissue of the retina as an isotropic, homogeneous absorbing medium, and neglect that absorption actually takes place at well-localized sites (ie, the melanin granules). Certainly, this is true for the long-duration, CW exposures being examined herein.

From the study of thermodynamics, we know that heat flows from regions of higher temperature to regions of lower temperature.[15] This flow will be greatest in regions where the temperature gradient is large (ie, large local temperature differences). The conduction of heat is also dependent on the physical properties of the conducting media. Because water is the largest constituent of biological material, most models of retinal heating treat ocular structure as being an isotropic, homogeneous medium having the thermal properties of water.

Damage to the retina or to other ocular tissue will change the thermal properties of the medium. This will alter the flow of heat in the eye and therefore affect the heating pattern observed in the retina. However, until the damage point is reached, we can build the following conceptual model to understand the heating pattern observed in the retina during a laser exposure.

Energy absorbed by the retina rapidly causes heating of the region directly exposed to the laser beam. At first, temperature difference between the absorbing volume and the surrounding ocular tissue is small, and there will be very little heat flow into the surrounding tissue. Initially, a rapid increase in the temperature of the absorbing volume will occur. Because most absorption occurs in the RPE, the highest temperature is expected within this layer.

As the temperature in the absorbing volume increases, so will the temperature difference between the absorbing volume and the surrounding tissue. The rate of heat flowing from the absorbing volume will become significant, causing a temperature increase in the tissue immediately surrounding the absorbing volume. Note that this process is three-dimensional—heat will flow not only along the plane of the retina, but will also diffuse into the interior of the eye (vitreous) and toward the exterior of the eye (sclera). This diffusive process can be a very efficient method of moving energy if the absorbing volume is very small, as would be expected for a laser beam focused onto the retina.

With further energy absorption, the temperature of the absorbing volume will increase, and the temperature difference with the surrounding media will increase further. The rate of heat flow into the surrounding media will increase until it nearly balances the rate at which energy is absorbed from the laser beam. At this point, the rate at which the temperature of the irradiated area increases becomes very slow.

When the heat source is removed (eg, an eye movement changes the location of the laser beam spot on the retina), the previously directly irradiated portion of the retina no longer directly receives energy from the beam. However, it will still have a relatively high temperature relative to the surrounding portion of the retina. The flow of heat from this hot region will be large, causing the previously irradiated spot to cool rapidly to a temperature near that of the surrounding retina.

Any particular location on the retina can be expected to have a complicated thermal history during a long-duration exposure. There will be periods of increased temperature when the location is directly irradiated by the laser beam and cooler periods when the beam spot is moved elsewhere by eye movements. This is especially true for a small-beam spot diameter because a smaller eye movement is adequate to shift the particular location of the retina completely beyond exposure to the beam. At some exposure duration, the heating pattern in the retina will differ significantly from the pattern expected in a stationary eye.

Direct measurements have been taken of temperature change in the retina during a laser exposure. Birngruber[16] recorded the thermal response of rabbit retinas by inserting a probe into the globe of the eye. Such an invasive procedure obviously changes the nature of the subject’s eye movement patterns. Therefore, we turn to a computer simulation to model the retinal thermal response in a moving eye.

Modeling the Retinal Heating Pattern: The RHME (Retinal Heating, Moving Eye) Program

Modeling the heat pattern in the retina involves solving the standard heat conduction equation for an isotropic, homogeneous medium[15]:

Here,

ΔT

=

the temperature increase in Celsius above the ambient body temperature (generally taken to be 37°C),

Ρ

=

the density of the ocular media in g cm–3

C

=

the specific heat in J g–1 °C–1, and

k

=

the thermal conductivity in J cm–1 s–1 °C–1

The heat source term Q is given in J cm–3 s–1 and rep-resents heat deposited in the retina by the laser beam.

A number of analytical and computational models have been developed to study heating in the retina during laser exposure. (For some examples, see Birn-gruber,[16] Birngruber et al,[17] Mainster et al,[18] and Takata et al.[19]) These models have treated the eye as stationary and generally assume a cylindrically symmetric beam. This reduces the problem to two spatial dimensions: (1) the distance along the beam direction, z (or equiva-lently, the depth into the retina), and (2) the radial distance from the beam axis, r. Eye movements break this cylindrical symmetry; thus, the laser-induced heating of the retina in a moving eye must be treated as a fully three-dimensional problem.

A computer program called RHME was developed at USAMRD to simulate the heating of the retina dur-ing long-duration laser exposure.[20] This program is designed to provide insight into how the heating pat-tern in a moving eye differs from that in a completely stationary eye. Primary emphasis is placed on handling a moving source (Q(x,y,z,t) of equation (4)).

The RHME program uses a number of simplifying assumptions to reduce the computational effort needed to simulate an exposure. The geometry of the model is illustrated in Figure 11-8. The RPE is modeled as a flat slab 10 µm thick. The volume above the RPE slab represents the interior media of the eye, whereas the volume below the RPE slab represents post-RPE tis-sue, such as the choroid, sclera, etc. All absorption is assumed to take place only in the RPE layer—heating due to absorption in pre- and post-RPE tissue is con-sidered to be negligible. RPE absorption is taken from Gabel et al[21] and is plotted as a function of wavelength in Figure 11-7. Light absorption is taken to be uniform throughout the depth of the RPE layer; there is no Beer’s law attenuation calculation. This means that the highest temperature occurs in the plane at the center of the model RPE.

In the following sections, RHME simulation re-sults are shown for a MPE-level exposure to a HeNe laser (λ = 632.8 nm). The physical parameters used for these simulations are listed in Table 11-3. A beam spot diameter of 25 µm was used in these calculations, corresponding to the small spot size expected from exposure to a laser beam. The retina radiant exposure pattern resulting from such an exposure was discussed previously in reference to Figure 11-5.

Simulation Results: A Look at Retinal Heating During a Long-Duration Exposure

Figure 11-9 shows the results of a simulation for a stationary source (no eye movements) in which the beam is turned on for 1 s. This particular plot shows the temperature rise ΔT as a function of time at the point (x = 0, y = 0, and z = 0) (see Figure 11-8). This point is located on the beam axis and at the center of the model’s RPE layer—the largest temperature increase will occur at this location. The thermal response to the application of the laser is very rapid; within 10 ms, the temperature increase is >90% of the value it will attain at 1 s (ΔT (0.01 s) = 1.03°C, ΔT (1.0 s) = 1.12°C). Were the beam to be left on after this time, the temperature would continue to rise, but at a very slow rate: ΔT (50 s)= 1.14°C. Once the laser is removed, cooling occurs as rapidly as heating: (ΔT (1.01 s) = 0.10°C).

Figure 11-8. Geometry of the RHME (Retinal Heating, Mov-ing Eye) model. (a) Side view: the z = 0 plane bisects the retinal pigment epithelium (RPE) slab. (b) Top view: position of the cylinder, representing the volume of the RPE in which energy is absorbed, moves about in accordance with measured eye movement data. Energy is assumed to be deposited uni-formly throughout the cylindrical volume.

TABLE 11-3
PARAMETERS USED IN THE THERMAL SIMULATIONS

Properties of Ocular Media

Thermal conductivity

k = 0.0063 J cm–1 s–1 °C–1

Specific heat

C = 4.184 J g–1 °C–1

Density

ρ = 1.0 g cm–3

Thermal diffusivity

α = k/Cρ = 0.0015 cm^2 s–1

RPE thickness

h = 10 μm

Beam Properties

Irradiance at cornea*,†

1.0 mW cm–2

Ocular transmittance at λ = 632.8 nm

0.65[‡]

Absorption in RPE at λ = 632.8 nm

0.29[§]

Power absorbed in RPE

72.5 μW

Beam radius at RPE¥

a = 12.5 μm (d = 25 μm)

*Averaged over a 7-mm diameter pupil.

†This is the current maximum permissible exposure for a longduration exposure to visible light.

‡Boettner EA, Wolter JR. Transmission of the ocular media. Invest Ophthalmol. 1962;1:776–783.

§Gabel V-P, Birngruber R, Hillenkamp F. Visible and new infrared light absorption in pigment epithelium and choroids. In: International Congress Series, No. 450: XXIII Concilium Ophthalmologicum, Kyoto, Japan, 14–20 May 1978. Amsterdam, The Netherlands: Excerpta Medica; 658–662.

¥Corresponds to the minimal angular subtense, αmin. (American National Standards Institute [ANSI]). Safe Use of Lasers, Standard Z136.1. Orlando, FL: Laser Institute of America; 2000.)

RPE: retinal pigment epithelium

One consequence of this rapid thermal response is illustrated in Figure 11-10, which shows the results of running the RHME simulation using the eye movement data of subject 6 from the study performed by Lund et al[7] (see Figure 11-2). The nine frames show the temperature rise in the z = 0 plane during a flick that moved the laser spot a distance of about 230 µm on the retina in <50 ms. Due to the rapid thermal response time illustrated in Figure 11-9, only the region of the retina directly irradiated by the beam undergoes a significant temperature rise. When the beam moves away from this region, that region cools rapidly. The location of the beam can be readily identified in each of the frames of Figure 11-10.

Figure 11-9. RHME (Retinal Heating, Moving Eye) simulation for a stationary source that is turned on at t = 0 s and turned off at t = 1.0 s. Plot shows temperature increase versus time at the retinal location (x = 0, y = 0, z = 0). Note the rapid thermal response time for the small beam spot.

Any point of the retina that becomes directly exposed to the laser beam, even if only briefly due to eye movements, will be quickly heated to a temperature near the maximum temperature reached for a stationary source. Therefore, we might expect that a plot of the maximum temperature rise distribution, defined as

for, say, the z = 0 plane (the central plane of the model RPE layer), will be a plateau having the same shape as the overall eye movement pattern. This is indeed the case, as illustrated in Figure 11-11. The region of higher temperature increase fills the area defined by the contours of the eye movement pattern.

The peak value of the ΔTmax distributions is listed in Table 11-4. This temperature is fairly insensitive to the nature of the eye movement pattern. Once again, this is a consequence of the rapid thermal response of the retina. Note that the peak temperature increases calculated by the RHME simulation for an MPE-level exposure at λ = 632.8 nm are small. From Table 11-4, we note that ΔTmax is about 1.2°C. A temperature increase of 10° to 20°C is generally needed to induce thermal injury.12,14,16–19 On this basis, the large increase in the small-source exposure limits (see Figure 11-1) was certainly reasonable.

Another consequence of the rapid thermal response is that the time-averaged temperature rise distribution, defined as

should reflect the eye movements. This is clearly demonstrated in Figure 11-12, where the average temperature rise distribution for the small-diameter source reflects the peaks in the visitation time plots. Table 11-4 lists the peak values of the ΔTavg distributions. As expected, the peak ΔTavg value is seen to have an inverse relation with the fixation ellipse area. However, even for the tightest eye movement pattern (subject 4), the ΔTavg peak value is significantly less than the peak value expected to occur in a stationary eye.

Figure 11-10. Response of the temperature in the retina (z = 0 plane) to source movement. Eye movement data are from subject 6 of Lund et al (see, also, Figure 11-2, bottom) during a microsaccade (flick). Scales along each plot indicate an increase in temperature, ΔT (°C).
Data source: Lund BJ, Zwick H, Lund DJ, Stuck BE. Effect of source intensity on ability to fixate: implications for laser safety. Health Phys. 2003;85(5):567–577.

The time-averaged temperature rise distribution of Figure 11-12 is more relevant to understanding the probability of injury than the peak temperature rise distribution of Figure 11-11. A location with a higher value for ΔTavg has spent more time during exposure at an elevated temperature. However, the smoothness of the ΔTavg distribution (an artifact of the averaging process) hides the complex thermal history of a given point of the retina. Figure 11-13 demonstrates the heating and cooling that a particular retinal location may undergo during a long-duration exposure. These graphs show the temperature rise as a function of time at the location of the peak of the ΔTavg distributions (see Figure 11-12) for a stationary eye and for the sample eye movement patterns of Figure 11-2. The periods of higher temperature occur when the particular retinal location is nearly or directly exposed to the laser. The cooler temperatures indicate periods when eye movements have shifted the laser beam spot to a point on the retina some distance away.

Figure 11-11. Maximum temperature increase in the z = 0 plane. Color indicates peak temperature increase at each point; scales are to the right of each plot. Calculations are for a maximum permissible exposure level.

ESTIMATING THERMAL DAMAGE THRESHOLDS FROM SIMULATION RESULTS

Results from the RHME simulation show that the intrinsic eye movements can have a large impact on the temperature history of the retina during a long-duration laser exposure. The goal of the research outlined in this chapter is to determine if the eye movements also have an impact on the likelihood of retinal damage from a laser exposure. This assessment will be made quantitative by comparing the thermal damage thresholds predicted for moving and stationary eyes.

TABLE 11-4
COMPARISON OF RESULTS FOR SMALLSOURCE EXPOSURE

Fixation Ellipse Area (μm^2)

Peak ΔTmax (°C)[*]

Peak ΔTavg (°C)[†]

Stationary

0.0

1.14

1.14

Subject 1

6,552

1.23

0.24 (0.21)[‡]

Subject 4

951

1.21

0.42 (0.37)[‡]

Subject 6

4,033

1.15

0.25 (0.22)[‡]

*See Figure 11-11.

†See Figure 11-12.

‡Value in parentheses is ratio to value for the stationary eye.

Thermal damage thresholds are estimated using an activated rate process model.[14] The onset of damage is assessed by evaluating an Arrhenius integral:

Where,

t

=

the total exposure time,

T(t)

=

the absolute temperature (in Kelvin) as a function of time, and

R

=

the universal gas constant (8.314 J K–1 mole–1).

Figure 11-12. Time-averaged temperature increase in the z = 0 plane. Color indicates average temperature increase at each point; scales are to the right of each plot. Calculations are for a maximum permissible exposure level.

Figure 11-13. Temperature increase versus time at the location of the peak of the time-averaged temperature rise distribution (see Figure 11-12). Stationary eye: 50 s, ΔTmax = 1.14°C, ΔTavg = 1.14°C. Subject 1: 50 s, ΔTmax = 1.14°C, ΔTavg = 0.24°C. Subject 4: 50 s, ΔTmax = 1.13°C, ΔTavg = 0.42°C. Subject 6: 45 s, ΔTmax = 1.13°C, ΔTavg = 0.25°C.

The frequency factor A (s–1) and the activation barrier Ea (J mole–1) are, in principle, related to the underlying chemical or physical processes leading to tissue damage. However, for practical use, the parameters A and Ea are obtained from fits to experimental damage threshold data. They are adjusted so that Ω = 1 is an indicator of the onset of permanent, irreversible damage. Here, the values A = 1.3 × 10^99 s–1 and Ea = 6.28 × 105 J mole–1 from Welch and Polhamus[22] are used.

To do a systematic search for thermal damage thresholds, it is possible to use equation (7) in conjunction with the full, three-dimensional, time-dependent temperature distributions calculated by RHME. Such a procedure quickly becomes extremely labor-intensive if multiple sets of eye movement data are considered (to avoid statistical anomalies). Furthermore, we would like to systematically investigate exposure durations from 50 or 100 ms to 50 s. The rest of this section will outline a procedure to estimate damage thresholds from temperature increase versus time traces of Figure 11-13. Recall that these plots represent temperature history at the location of the time-averaged temperature rise distributions of Figure 11-12. This simplified analysis still provides useful physical insight into the retinal thermal damage process.[23]

To estimate the thermal damage threshold using the RHME simulation results, first note that the diffusion equation (5) is linear in the temperature increase, ΔT(x, y, z, t), and the source term, Q(x, y, z, t). If the source term is multiplied by some numerical factor β, then the resulting temperature increase is multiplied by the same factor: if Q → Q′ = β . Q, then ΔT → ΔT′ = β . ΔT. Temporal and spatial dependence are unchanged, but the magnitude of the thermal response scales with the magnitude of the source term. For example, the temperature increases shown in Figure 11-13 were calculated for a source producing a corneal irradiance of 1 mW cm–2. To obtain the temperature increase for a 2 mW cm–2 source having the same beam profile or spot size, multiply the results for 1 mW cm–2 by 2: ΔT2mW(x,y,z,t) = 2 . ΔT1mW (x,y,z,t). Conversely, if it is known that the temperature increase of Figure 11-13 must be multiplied by some factor β to produce damage, then the required source must be β mW cm–2 at the cornea.

The temperature in equation (7) can be expressed as

where the normal body temperature T_0 is taken to be 310 K, and ΔT(t) is the temperature increase obtained from the RHME thermal model for a 1 mW cm–2 source (see Figure 11-13). The damage threshold is then found by searching for the value of β such that Ω = 1. This is most easily done by writing a computer program to calculate the temperature (equation (8)) for a given value of β, then using the resulting temperature trace to evaluate the integral of equation (7). The value of β is then iteratively adjusted until Ω = 1 within a desired tolerance. Because of the simplifying assumptions that have been incorporated into the temperature calculation and damage models, the absolute value of β can only be considered a rough estimate of the actual damage threshold. The ratio βmoving/βstationary will be less sensitive to these assumptions.

The thresholds obtained by this procedure for 50-s exposures are listed in Table 11-5. The ratio βmoving/βstationary may be interpreted as the “protection factor” eye movements provide in preventing thermal damage from a laser exposure. This ratio, about 1.37 for each of the three eye movement data sets, may seem surprisingly small given that the peak time-averaged temperature increase for a stationary eye is 1/0.37 = 2.7 to 1/0.21 = 4.8 times larger than for the moving eyes (see Table 11-4). A look at the temperature rise traces for damage-level exposures (Figure 11-14, top) shows that the peak temperature in the moving eye is about 5.4°C higher than the temperature reached by a stationary eye. Although this particular retinal location is at a constantly elevated temperature in the stationary eye, the corresponding location in the moving eye spends only a small fraction of the time at the elevated temperature. However, the thermal damage rate process is extremely sensitive to temperature—an increase in temperature of 5.4°C causes the rate of the thermal damage reactions to increase by over an order of magnitude (see Figure 11-14, bottom: dΩ/dt = 0.02 at 325.4°C, dΩ/dt = 0.87 at 330.8°C).

TABLE 11-5
FACTOR β (EQUATION 8) MULTIPLYING THE TEMPERATURE INCREASE TRACE OF FIGURE 11-13 TO PRODUCE THERMAL DAMAGE FOR A 50-S EXPOSURE)*

β

β/βstationary

Stationary

13.6

1.00

Subject 1

18.3

1.35

Subject 4

17.2

1.36

Subject 6

18.7

1.38

*Because the traces of Figure 11-13 were calculated for a 1 mW cm–2 corneal irradiance, the thermal damage threshold is given by β mW cm–2.

Figure 11-14. (Top) Temperature increase versus time for a damage-level exposure of 50-s duration. Green line is the temperature trace in Figure 11-13 for subject 1, scaled by the factor β listed in Table 11-5, whereas the red line is for the stationary source (see Figure 11-13 for stationary eye). (Bottom) Integrand of the Arrhenius damage integral, dΩ/dt = A exp(–Ea/RT), in the region of the maximum temperatures attained during a damage-level exposure. Values for A and Ea are listed in the text. Peak temperatures attained in the moving and stationary eyes are indicated (stationary eye: Tpeak = 325.4 K, dΩ/dt = 0.02 s–1; moving eye: Tpeak = 330.8 K, dΩ/dt = 0.87 s–1).

SUMMARY

This chapter looks at the impact of the intrinsic motion of the eye on the likelihood of retinal damage occurring during a long-duration laser exposure. This is done by using simple models to estimate the retinal thermal damage thresholds, including and excluding eye movements. Eye movements affect the pattern of energy deposition in the retina very significantly (see Figure 11-5 and Table 11-2). However, because of the rapidity of the thermal response and the high sensitivity of the rate of the thermal damage process to temperature, eye movements have a less dramatic (but still significant) effect on the damage threshold. Thresholds calculated from the eye movement samples for a 50-s exposure are a factor of 1.35 to 1.40 larger than the threshold obtained if eye motion is ignored.

The moving/stationary eye threshold ratio quoted previously is for a 25-μm diameter beam spot and a 50-s exposure. Figure 11-15 shows a plot of the protection factor βmoving/βstationary for exposure durations from 0.1 to 50 s obtained from simulations using eye movement data sets from seven subjects.[23] If the exposure duration is reduced to a few milliseconds or shorter (ie, shorter than the time scale of the eye movements), then the threshold ratio falls to a value very close to 1.0. This ratio initially increases rapidly as the exposure duration extends beyond 10 to 20 ms, a time scale on which eye motion becomes significant compared to the size of the beam spot. The threshold ratio reaches a value of 1.1 for an exposure duration of around 600 ms. After a few seconds, the full extent of the eye movement pattern will be sampled. At this point, the threshold ratio increases slowly as the exposure duration is increased. The threshold ratio reaches the value of 1.2 at an exposure duration of about 8 s and only increases to 1.3 for exposure durations nearing 50 s.

The moving/stationary eye threshold ratio is also expected to reach its maximum value for the small-beam spot size. Beam spots of a few hundred micrometers in diameter are large compared to the extent of the eye movement pattern. The eye movement will cause only a small perturbation in the retinal heating pattern. The threshold ratio will therefore fall to 1.0 as the beam spot diameter is increased. A detailed investigation of the threshold ratio as a function of the beam spot size is another area for further investigation.

Figure 11-15. Thermal retinal injury protection factor βmoving/ βstationary due to small-scale eye movements for exposure durations from 0.1 to 50 s obtained from RHME (Retinal Heating, Moving Eye) simulations. Line indicates the average of all data sets.

The eye movement data used in this study represent the worst-case scenario from a laser safety perspective: a subject whose head motion is arrested deliberately fixates on the beam from a laser. In “real-world” scenarios, head motions will add to the movement of the beam spot on the retina. The moving/stationary damage threshold ratio in such cases will be larger than the value reported here for a fixed-head position. The ratio presented here, therefore, represents a lower limit for the impact of eye movements on the likelihood of incurring damage from a laser exposure.

REFERENCES

1. Ditchburn RW. Eye-Movements and Visual Perception. Oxford, UK: Clarendon Press; 1973.

2. Kowler E. The stability of gaze and its implications. In: Carpenter RHS, ed. Visual and Visual Dysfunction. Vol 8. Eye Movements. Boca Raton, LA: CRC Press, Inc; 1991: 71–92.

3. Ness JW, Zwick H, Stuck BE, et al. Retinal image motion during deliberate fixation: implications to laser safety for long duration viewing. Health Phys. 2000;78(2):131–142.

4. American National Standards Institute (ANSI). Safe Use of Lasers, Standard Z136.1. Orlando, FL: Laser Institute of America; 2000.

5. International Commission on Non-Ionizing Radiation Protections (ICNIRP). Revision of guidelines on limits of exposure to laser radiation of wavelengths between 400 nm and 1.4 mm. Health Phys. 2000;79(4):431–440.

6. Eizenman M, Hallett PE, Frecker RC. Power spectra for ocular drift and tremor. Vision Res. 1985;25(11):1625–1640.

7. Lund BJ, Zwick H, Lund DJ, Stuck BE. Effect of source intensity on ability to fixate: implications for laser safety. Health Phys. 2003;85(5):567–577.

8. Crane HD. The Purkinje image eyetracker, image stabilization, and related forms of stimulus manipulation. In: Kelly DH, ed. Visual Science and Engineering: Models and Applications. New York, NY: Marcel Dekker, Inc; 1994.

9. Zwick H, Lund DJ, Gagliano DA, Stuck BE. Function and ophthalmoscopic observations in human laser accident cases using scanning laser ophthalmoscopy. SPIE. 1994;2126:144–153.

10. Nachmias J. Two-dimensional motion of the retinal image during monocular fixation. J Opt Soc Am. 1959;49(9):901–908.

11. American National Standards Institute (ANSI). Safe Use of Lasers, Standard Z136.1. Orlando, FL: Laser Institute of America; 1993.

12. Sliney D, Wolbarsht M. Safety With Lasers and Other Optical Sources. New York, NY: Plenum Press; 1980.

13. Boettner EA, Wolter JR. Transmission of the ocular media. Invest Ophthalmol. 1962;1:776–783.

14. Pearce J, Thomsen S. Rate process analysis of thermal damage. In: Welch AJ, van Gemert MJC, eds. Optical-Thermal Response of Laser-Irradiated Tissue. New York, NY: Plenum Press; 1995: Chap 17.

15. Carslaw HS, Jaeger JC. Conduction of Heat in Solids. Oxford, UK: Clarendon Press; 1959.

16. Birngruber R. Choroidal circulation and heat convection at the fundus of the eye: implications for laser coagulation and the stabilization of retinal temperature. In: Wolbarsht ML, ed. Laser Applications in Medicine and Biology. Vol 5. New York, NY: Plenum Press; 1991: 271–361: Chap 6.

17. Birngruber R, Hillenkamp F, Gabel V-P. Theoretical investigations of laser thermal retinal injury. Health Phys. 1985;8(6):781–796.

18. Mainster MA, White TJ, Tips JH, Wilson PW. Retinal-temperature increases produced by intense light sources. J Opt Soc Am. 1970;60(2):264–270.

19. Takata AN, Goldfinch L, Hinds JK, Kuan LP, Thomopouolis N, Weigandt A. Thermal Model of Laser-Induced Eye Damage. Chicago, IL: IIT Research Institute, Engineering Mechanics Division; 1974. Final Technical Report IITRI J-TR 74-6324.

20. Lund BJ. Computer model to investigate the effect of eye movements on retinal heating during long-duration fixation on a laser source. J Biomed Opt. 2004;9(5):1092–1102.

21. Gabel V-P, Birngruber R, Hillenkamp F. Visible and new infrared light absorption in pigment epithelium and choroids. In: International Congress Series, No. 450: XXIII Concilium Ophthalmologicum, Kyoto, Japan, 14–20 May 1978. Amsterdam, The Netherlands: Excerpta Medica; 658–662.

22. Welch AJ, Polhamus GD. Measurement and prediction of thermal injury in the retina of the Rhesus monkey. IEEE Trans Biomed Eng. 1984;BME-31(10):633–644.

23. Lund BJ. Laser retinal thermal damage threshold: impact of small-scale ocular motion. J Biomed Opt. 2006;11(6):064033.

Chapter 12

ULTRASHORT LASERS AND THEIR BIOEFFECTS

BENJAMIN A. ROCKWELL, PhD, * Principal Research Physicist, Air Force Research Laboratory, 711th Human Performance Wing, Human Effectiveness Directorate, Bioeffects Division, Optical Radiation Bioeffects Branch, 4141 Petroleum Road, Joint Base San Antonio, Fort Sam Houston, Texas 78234-2644 and WILLIAM P. ROACH, PhD † Chief, Physical and Biological Sciences Branch, Air Force Research Laboratory, Air Force Office of Scientific Research, 875 North Randolph Street, Arlington, Virginia 22203-1768

INTRODUCTION

WHAT MAKES ULTRASHORT LASER PULSES DIFFERENT?

Spectral Content of Laser Pulse

Peak Power

Generation With Chirped Pulse Amplification

MEASUREMENT OF ULTRASHORT LASER PULSES

Traditional Measurement Techniques

Interferometric Measurements: Autocorrelation

ULTRASHORT LASER EFFECTS ON THE RETINA

Nanosecond to Femtosecond Minimum Visible Lesion Thresholds

Damage Mechanisms

ULTRASHORT LASER EFFECTS ON THE SKIN

ULTRAFAST, ULTRAINTENSE LASERS

SUMMARY

INTRODUCTION

Previous chapters in this volume present basic information related to the biomedical implications of military lasers. Traditional laser applications involve possible exposures to laser light with pulse durations ranging from as long as several seconds of continuous exposure to as short as several billionths of a second. Novel applications are emerging for lasers with much shorter pulse durations within the “ultrashort regime,” pulses with duration in the range of trillionths to quadrillionths of a second. (This chapter refers to quadrillion in the American English context, that is, the number 1 divided by 1 followed by 15 zeros.)

The traditional terminology of ultrashort lasers uses scientific notation to describe the pulse duration in seconds. One such term is femtosecond (also abbreviated as “fs”), which is equal to one-quadrillionth (1/1,000,000,000,000,000) of a second, expressed in scientific notation as 1 x 10-15 s. In Britain and in Germany, quadrillion refers to the number 1 followed by 24 zeros. In the British vernacular, the number 1 followed by 15 zeros is referred to as one septillion. Another relevant term is picosecond (also abbreviated as “ps”), which is one-trillionth (1/1,000,000,000,000) of a second, expressed in scientific notation as 1 x 10-12 s. Ultrashort pulses generally have durations between 10 fs and 500 ps. In this regime, novel phenomena occur that produce never-before-possible results. Several basic properties of ultrashort laser pulse systems set them apart from longer pulse systems. This chapter considers the most relevant differences related to laser–tissue interaction—which includes spectral content of the pulse, peak power, and the special techniques—that are required to produce and measure ultrashort pulses.

The field of ultrashort-pulse laser technology is now an established field, and femtosecond lasers offer revolutionary solutions to many of today’s toughest problems. Associated novel nonlinear optical phenomena support multiphoton biomedical imaging and treatment1-3 and precise alteration of cells.4-6 Femtosecond lasers have also been used to alter the refractive index of glass at a depth to inscribe light pipes.7,8 Some spectroscopic techniques may benefit from the application of ultrashort laser pulse technology, the unique attributes of which include their ability to generate coherent white light.[9]

Military applications are not yet in use, but the introduction of military ultrashort laser systems is inevitable. The current military arsenal includes laser systems that are continuous wave (CW) or pulsed, some of which could be adapted to the use of femtosecond laser technology. Because the spatial extent of an ultrashort laser is several microns, application of this technology could be used to support high-precision laser ranging and LIDAR (LIght Detection And Ranging). Ultrashort lasers have already been applied in science and medicine, and will eventually be used by the military. Therefore, it is essential that ultrashort laser–tissue interaction effects be understood.

WHAT MAKES ULTRASHORT LASER PULSES DIFFERENT?

Spectral Content of Laser Pulse

Sunlight dispersed through a prism (or dispersed in the form of a rainbow) provides an example of how a beam of light can be made up of a broad spectrum of light. In fact, sunlight includes components of much of the ultraviolet, visible, and infrared ranges of the electromagnetic spectrum. Some portions of the spectrum are absorbed by the Earth’s atmosphere, but most of the visible and near-infrared components reach the Earth’s surface. The sun’s spectral output is very large. The extent of its output is expressed in terms of the bandwidth of the spectral emission and its spread in wavelength (Δλ). The sun’s spectral bandwidth is hundreds of nanometers (1 nm = 0.001 μm = 10-9 m).

In contrast to the sun, traditional laser output is typically characterized by a very well-defined wavelength bandwidth less than 1/10 of 1 nm. Put through a prism, an ordinary laser beam (eg, HeNe [helium-neon] or laser diode) would produce no discernable wavelength spread. Although some lasers can simultaneously produce output at several distinct wavelengths, each laser line itself has a very narrow bandwidth. An exception to this is the ultrashort laser.

A fundamental law of quantum physics known as the “uncertainty principle” asserts that as pulse duration is decreased, bandwidth must increase. This is not an easily measurable effect until pulse durations decrease well below 50 ps. For laser pulses below 50 fs, this property dramatically affects every aspect of pulse propagation, even through air. To capture the relative values of the bandwidth for ultrashort pulses, one must evaluate the following relationship between minimum pulse duration and minimum wavelength bandwidth:

where

∆τFWHM = pulse width,
∆λFWHM = bandwidth,
c = speed of light, and
λ = center wavelength.

Table 12-1 lists a range of minimum bandwidths required for femtosecond pulses as a function of pulse width and wavelength.

As can be seen in Table 12-1, wavelength bandwidths for pulses in the shorter femtosecond regime are significant, much different than traditional laser output. There are several consequences of this spectral content. First, generation of femtosecond pulses cannot be done using traditional lasing materials such as Nd:YAG (neodymium-doped yttrium aluminum garnet), which supports output wavelength on the order of nanometers and thus cannot be used to generate pulses shorter than a few picoseconds. Second, the broad bandwidth of the ultrashort laser affects propagation. Every optical material has a refractive index, which is dependent on wavelength. For example, water has a refractive index[10] of 1.337 at 500 nm and 1.328 at 1,000 nm. This means that the longer wavelength portion of a femtosecond pulse travels through water at a higher speed than the shorter wavelength portion. Because of this, the pulse lengthens as it travels through water. The term for this effect is group velocity dispersion (GVD). The extent of GVD for a given distance will depend directly on the refractive index and how it changes with wavelength. Therefore, even the simple propagation of femtosecond pulses can be a complex phenomenon.

TABLE 12-1
MINIMUM BANDWIDTH IN NANOMETERS OF ULTRASHORT LASER PULSE REQUIRED TO GENERATE A PULSE OF THE GIVEN DURATION

Pulse
Duration (fs)

Center Wavelength

450 nm

800 nm

1,060 nm

1,300 nm

10,000 (10 ps)

0.03

0.009

0.17

0.25

1,000 (1 ps)

0.3

0.9

1.7

2.5

100

3.0

9.4

17

25

50

6.0

19

33

50

20

15

47

83

124

10

30

94

165

249

Peak Power

For a given pulse energy, peak power is directly related to pulse duration. For example, a 10 ns pulse with a pulse energy of 100 mJ has a peak power of 10 MW. If this same pulse energy is applied as a 1 ps pulse, its peak power is 100 GW (1 GW = 1 x 10^9 W) or one-tenth of a terawatt (1 TW = 1 x 10^12 W). At peak powers of even a few gigawatts, significant nonlinear optical processes can occur in either propagation or interaction. For example, if a 1 mJ pulse is focused with a pulse duration of 10 ns into a square block of glass, a laser-induced breakdown (LIB) occurs and the material is permanently damaged. If the same pulse is delivered at a pulse duration of 50 fs, it can produce a broad spectrum of light known as a supercontinuum.[11]

Generation With Chirped Pulse Amplification

Materials have been created to support lasing action across a broad bandwidth range. The most common material used today is a sapphire crystal doped with a small percentage of titanium, known as Ti:Sapph (titanium-sapphire). Figure 12-1 illustrates typical optical schematics for a femtosecond oscillator (top) and a femtosecond amplifier (bottom). The distinction between these two types of systems is important to consider for applications and the possibility of tissue effects.

Figure 12-1. The typical setup for a femtosecond laser oscillator (top) and femtosecond amplifier (bottom).
CW: continuous wave; fs: femtosecond; Rep: repetition;
Ti:Sapph: titanium-sapphire

There are several differences between the femtosecond oscillator and the femtosecond amplifier. The femtosecond oscillator generates laser pulses at an extremely high-pulse repetition frequency, typically near 100 MHz. The average power is typically several hundred milliwatts. This combines to produce approximately 10 nJ of energy per pulse. With such a large repetition frequency, exposed tissue reacts with the same damage mechanism to pure CW exposures. Although this thermal damage occurs at the same exposure level for CW and femtosecond oscillator laser exposures, some differences in pathological and cellular responses have been reported.[12]

The femtosecond amplifier illustrated in the bottom half of Figure 12-1 uses the output pulse train from a femtosecond oscillator. These pulses are first stretched, which means that the pulse duration is significantly lengthened. This is done because, as pulses are amplified, short femtosecond pulses would exceed the damage irradiance threshold for the mirrors and optics of the system. Stretched pulses allow the amplifier peak irradiances to remain below damage thresholds for internal optics. The amount of stretching necessary depends on input pulse characteristics, but any input pulse is typically stretched from one to several hundred picoseconds. A pulse selector is used to inject very few of the hundreds of millions of femtosecond pulses into the amplifier section of the laser system. A very high-energy pulsed pump laser intersects the Ti:Sapph crystal simultaneously with the injected femtosecond pulse. This pulsed pump laser runs at the same rate as the injected pulses, typically at 10 to 1,000 Hz. As noted in Figure 12-1, the pump light (typically green for Ti:Sapph amplifiers) is injected into the system through one of the near-infrared laser amplifier “pump-through” mirrors. The resulting low-repetition rate pulses circulate in the amplifier cavity for several round trips until the pulse energy has been increased through successive passes through the Ti:Sapph crystal. When pulse energy is sufficiently high, the pulse is ejected from the amplifier section into the compressor. In the compressor, the pulse lengthening that was achieved by stretching is reversed. The pulse is compressed to a significantly shorter pulse. The eventual shortest pulse duration is limited by the input pulse bandwidth due to the bandwidth-limiting process discussed earlier in this chapter. Pulse energy is limited by the amount of available pump energy, and by the size and saturation of the Ti:Sapph crystal because of thermal loading from optical pumping.

As shown, femtosecond oscillators produce lowenergy pulses at very high repetition frequencies, and femtosecond laser amplifiers produce high-energy pulses with extreme peak powers at relatively lowpulse repetition frequencies. The eventual output of the femtosecond amplifier is typically several millijoules of energy in approximately 100 fs pulses. This produces several gigawatts of peak power, making possible many nonlinear optical mechanisms. As will be discussed later, these same nonlinear mechanisms may occur in many laser–tissue interaction scenarios.

MEASUREMENT OF ULTRASHORT LASER PULSES

Because ultrashort lasers have special properties, special care must be taken to characterize femtosecond laser pulses that have

- extremely short pulse duration,

- large peak irradiances, and

- large bandwidths.

Some techniques of measurement apply equally well to femtosecond, nanosecond, and microsecond laser pulses. However, it is often the case that special techniques must be used to characterize femtosecond pulse duration.

Traditional Measurement Techniques

Pulse energy and wavelength measurements of femtosecond pulses can be taken in much the same way as longer wavelength pulses. The same energy detectors that are used to measure typical Q-switched nanosecond pulse energy can also be used to measure femtosecond laser energy. Usually, this requires no change in setup or detector, although higher detector sensitivity may be required to adjust for the fact that typical femtosecond laser pulses have less energy than do their Q-switched counterparts. Laser wavelength can be measured easily thanks to the development of integrating spectrometer units (eg, those that fit on a PC [personal computer] board). A fiberoptic can be used to collect light and deliver it to the time-integrating spectrometer. The wavelength bandwidth will be greater for femtosecond laser pulses and, therefore, the resolution requirements are somewhat relaxed for measurement of laser bandwidth. The measurement of femtosecond pulse width is usually much more challenging, however. These challenges (the photodiode and oscilloscope and streak camera) are outlined in the next section.

Figure 12-2. Typical setup for measuring pulse duration using an oscilloscope and photodiode.

Photodiode and Oscilloscope

The most commonly used method for measuring pulse duration is with a photosensitive element (eg, a photodiode) and an oscilloscope to detect its response. This method is illustrated in Figure 12-2. However, because the typical high-speed photodiode has a limiting rise time of 1 ns, this technique is not sufficient to precisely characterize a femtosecond laser pulse. The most carefully crafted photodiode with an extremely small detector surface coupled to a fiber achieves a 10 ps response time at best. Therefore, novel techniques have been devised to measure femtosecond laser pulse duration.

Streak Camera

A second method used for measuring laser pulses is a streak camera. A streak camera works in a manner similar to how a television tube electron gun diverts its beam. The streak camera first converts optical pulses into a package of electrons with similar duration and then sweeps the electrons with a pair of plates that diverts their position on a phosphorous screen. Unfortunately, this technique is also limited by minimum measurable pulse duration. The shortest pulse duration measurable by the streak camera is several hundred femtoseconds. The streak camera also requires a large capital investment on the order of several hundred thousand dollars.

Interferometric Measurements: Autocorrelation

Due to the limitations of traditional measurement techniques, more novel means have been devised to measure the pulse duration of femtosecond lasers. These techniques usually involve splitting a pulse and optically interfering the pulse on itself. The first such technique is the second harmonic autocorrelator (illustrated in Figure 12-3) that requires multiple pulses. A femtosecond laser pulse is split into two equivalent beams. These beams are then intersected in a frequency-doubling crystal. One of the beam paths has a variable length that is swept from a longer path through an equivalent path to a shorter path. This produces increasing second harmonic generation radiation as a function of the multiplicative pulse energies. The result is a unique pattern in second harmonic intensity as a function of beam path difference.

Figure 12-3. Measurement of femtosecond laser pulse using second harmonic autocorrelation.
fs: femtosecond

The result of this measurement has been uniquely correlated with pulse duration. The output is a plot of second harmonic intensity versus the relative positions of the pulses (ie, time between peaks arriving at center of the crystal). This measurement correlates realspatial coordinates with time, allowing for resolutions equivalent to several femtoseconds if the accuracy of the stage is on the order of several micrometers. This autocorrelation technique has been adapted for both low-repetition and high-repetition rate systems (eg, mode-locked lasers).

A number of other techniques have also been developed for pulse width measurement, primarily for lasers shorter than 50 fs. Examples include the following:

- frequency-resolved optical gating (FROG),

- spectral-phase interferometry for direct electric field reconstruction (SPIDER),

- temporal analysis by dispersing a pair of light E-fields (TADPOLE), and

- grating-eliminated no-nonsense observation of ultrafast incident laser light E-fields (GRENOUILLE).

These advanced measurement techniques are used to determine the relative phase of the laser pulse in addition to its pulse duration. The phase of an ultrashort pulse is the relationship between the differing spectral content in spatial position and extent. Phase is relevant for pulse durations shorter than 100 fs and for propagation of pulses in biologically significant distances.

ULTRASHORT LASER EFFECTS ON THE RETINA

Nanosecond to Femtosecond Minimum Visible Lesion Thresholds

The first scientific reports on injury to the retina from subnanosecond laser pulses were published13,14 in 1974 and 1975, using 25 to 35 ps pulses, and reported a threshold of 13 ± 3 μJ at 1,064 nm. Experiments during this period used rhesus monkey eyes in vivo as the model of choice to determine retinal injury thresholds. The injuries observed in these studies were recognized as different from retinal thermal injuries previously noted by researchers who employed longer duration exposures15,16 using the same model. It was speculated that the unusual retinal injuries may be due to nonlinear effects. Researchers theorized that melanin granules were responsible for retinal light absorption in a way that differed from simple thermal denaturation of retinal tissue. Immediate subretinal hemorrhages were reported at 150 μJ, and comparison to previous work showed a dramatic departure of threshold values using Nd:YAG Q-switched sources as seen in Table 12-2.

These experimental findings reinforced the hypothesis that the effects of subnanosecond pulses occurred by a mechanism other than thermal denaturation. Histological evaluation led many of the earlier investigators to speculate that retinal damage originated from photomechanical shock waves originating in melanin granules. They found that a change in radiant exposure was not linearly dependent on exposure beam diameter, as would be the case in a thermal damage model. Therefore, a new nonthermal mechanism for damage was found to be necessary for ultrashort laser exposures.

TABLE 12-2
PRELIMINARY INDICATION OF DEPARTURE FROM THERMAL DAMAGE MECHANISMS WHEN SUBNANOSECOND LASER PULSES ARE USED TO DETERMINE RETINAL THRESHOLDS

Pulse Duration

Retinal Threshold (μJ)

Wavelength (nm)

Reference

30 ns

280

1,064

15

15 ns

68 ± 12

1,064

13

10 ns

164

1,064

16

30 ps

8.7 ± 4.8

1,064

17

30 ps

18.2 ± 8.3

532

17

Data sources: see References

In 1978, Taboada and Gibbons [17] applied probit analysis[18] and reported an ED_50 (estimated dose for 50% probability of laser-induced damage) at 95% confidence level as 2.2 μJ (fiducial limits: 1.9 and 2.5 μJ) at 24-h postexposure for 5.9 ps using a wavelength of 1,060 nm. Based on this work, the minimum visible lesion (MVL) criterion was defined as the smallest ophthalmoscopicobservable grayish opacification differing from the retinal background viewed by an observer at 1- and 24-h postlaser exposure. The investigators provided both 1- and 24-h ED_50s for 1,064 nm 5.9 ps pulses (3.5 and 2.2 μJ, respectively). At the time, these pulses were the shortest investigated in vivo, and the authors discussed possible nonlinear effects, such as the four-photon process, dielectric breakdown, and increases in short-wavelength radiation (superbroadening).

In 1982, Bruckner and Taboada[19] reported on the effects of laser pulses of 6 ps in duration operating at 530 nm and delivered to the retina in vivo. The 24-hour ED_50 was again determined by probit analysis and found to be 0.24 μJ (0.17–0.35 μJ) corresponding to a retinal irradiance of 4.4 × 10-3 J cm-2, with a correction of 0.88 for ocular transmission and a spot size at the retina reported as 78 μm. When compared with earlier work by Goldman et al20, who determined a threshold of 18.2 μJ with a retinal spot size of 25 μm, an irradiance of 6.5 J cm-2 for 30 ps is easily calculated. The results immediately suggest nonlinear effects scaling with pulse power (Bruckner and Taboada[19] measured 0.73 GW cm-2, and Goldman et al[20] measured 220 GW cm-2). Bruckner and Taboada[19] argued that the integrated irradiance of 4.4 × 10-3 J cm-2 at 6 ps could only create a small temperature rise, calculated as an increase of 4.0° C above ambient. Because this thermal rise would decay rapidly within microseconds, it would not be sufficient to cause phase change such as that typically associated with thermal retinal damage induced by longer duration laser exposures. This work sparked more than a decade of controversy concerning the validity of the data by Bruckner and Taboada.

The first femtosecond pulse retinal damage was reported in 1987 by Birngruber et al,[21] who worked with the Chinchilla grey rabbit model. The ED_50s measured ophthalmoscopically and angiographically were reported as 4.45 μJ and 0.75 μJ, respectively. Visible lesions were created using a 632 nm laser with 80 fs single pulses delivered directly to the retina and a controlling external optic to achieve an 80-μm diameter spot consistently on the retina. Albino rabbits were also used to compare and consider the role of melanin. Interestingly, the albino rabbit retinas were not injured by the 80 fs pulses. In the Chinchilla grey rabbits, the type of damage observed at threshold energies appeared no different, even at pulse energies 100 times that of the ED50. In fact, researchers were unable to produce a subretinal hemorrhage at any energy. This provided clear experimental evidence that the injuries caused by 80 fs pulses were due to nonlinear rather than thermal effects. Investigators also noted that melanin was central to the mechanism of retinal damage even at femtosecond laser exposures. Nonlinear mechanisms appeared to be a reasonable explanation as to why the extent of retinal damage was limited at energies well above threshold.

In 1995, Cain et al[22] reported the first comprehensive subnanosecond retinal damage study using rhesus monkeys (Table 12-3). They were able to compare their data to previous work and found that Bruckner and Taboada’s data fit within the experimental error of their own. This brought an end to the long controversy. But with the new data came new questions concerning the departure from a thermal damage model, the absence of a trend in the data as a function of wavelength,[23] and issues surrounding the role of nonlinear phenomena, such as thermal acoustic transients, LIB, self-focusing, and continuum generation.

TABLE 12-3
MINIMUM VISIBLE LESION THRESHOLD AT THE 95% CONFIDENCE LEVEL (SHOWN IN PARENTHESES)

Pulse Duration

ED_50 (μJ) @24 Hours

Wavelength (nm)

Reference

4 ns

0.9 (0.60–1.35)

532

22

80 ps

4.2 (3.0–5.8)

1,064

23

60 ps

0.43 (0.32–0.54)

532

22

20 ps

4.6 (3.8–5.5)

1,064

23

6 ps

0.24 (0.17–0.35)

530

20

3 ps

0.58 (0.31–0.83)

580

22

1 ps

2.0 (1.4–2.5)

1,060

23

600 fs

0.26 (0.21–0.31)

580

22

150 fs

1.0 (0.8–1.2)

1,060

23

100 fs

0.16 (0.11–0.23)

530

23

90 fs

0.43 (0.27–0.60)

580

22

44 fs

0.17 (0.13–0.22)

810

24

Data sources: see References

Damage Mechanisms

As questions persisted concerning the basis of retinal damage from subnanosecond laser pulses, simultaneous work in the 1980s and 1990s found scientists exploring the impact of nonlinear laser-induced phenomena on the human eye.[24] In particular, it was interesting that such nonlinear phenomena might be put to use as ophthalmological treatments for eye diseases.25-35 Of particular interest were the nonlinear phenomena of

- self-focusing,

- stimulated Brillouin scattering (SBS),

- supercontinuum generation, and

- laser-induced breakdown.

These phenomena had been well characterized experimentally and theoretically for homogeneous nonbiological materials. Their potential influence on the human retina would yet have to be considered in terms of laser beam spot size, wavelength, and pulse duration. These are the characteristics essential to determining the resultant peak power (critical power) at which phenomena of interest become viable as a pulse of laser light makes its way from the cornea to the retina.[36]

Self-Focusing

Self-focusing is an induced lensing effect that results from wavefront distortion inflicted on the beam by itself. Consider a laser beam with a Gaussian profile propagating into a medium with a refractive index, n, given by

where,

n_0

=

the linear refractive index of the medium,

n_2

=

the nonlinear refractive index of the medium,

E

=

the electric field of the laser pulse, and

|E^2|

=

directly proportional to the power of the laser pulse.

If Δn(|E^2|) is positive and the beam has achieved a critical power sufficient to overcome n_0, then the central part of the beam (having a higher intensity) will experience a larger refractive index than the beam edge. The central part of the beam will undergo a distortion similar to that imposed on the beam by a positive lens. Thus, it will appear to focus by itself. Self-focusing leads to an increase in irradiance, which can in turn contribute to other nonlinear optical effects. Two self-focusing effects have been described in detail37,38 as having potential impact on subnanosecond retinal damage. Weak self-focusing has a threshold of occurrence below 10 ps. Critical beam collapse has a threshold below 100 fs when compared to MVL data. Note that the critical power for beam collapse in water has been reported as near 500 kW peak power.[38]

Stimulated Brillouin Scattering

SBS is laser light scattering from refractive index variations associated with sound waves generated in a medium by a laser pulse. The most common mechanism for the creation of such sound waves is electrostriction, where there is a tendency of the medium to become compressed in an area of high intensity. In general, when the thresholds for SBS are compared to MVL data from the visible spectrum, the conclusion is that SBS would not be a factor in the resultant retinal damage for visible wavelengths. Further, if one considered nearinfrared pulses around 1,064 nm with a pulse duration of 1 ns and a damage threshold of 1 mJ cm-2, a critical power of 385 kW could be achieved within the threshold for SBS. However, this would lead to an increase in the retinal damage threshold because a percentage of the laser light would be backscattered away from the retina.

Supercontinuum Generation

Supercontinuum generation occurs when a pulse of laser light reaches a critical power within a medium and the nonlinear refractive index changes during propagation, thus leading to the production of a wide spectral bandwidth. When required critical peak power is compared to MVL data below 1 ns, the conclusion is that supercontinuum generation is not a contributing factor to subnanosecond MVLs in the visible spectral region. In general, when compared to actual retinal threshold data, the regime in which supercontinuum generation is calculated to change the characteristics of the forward propagating beam is near 1 fs. With the multiphoton excitation increases in the 2014 release of the ANSI (American National Standards Institute) Z136.1[39] standard (Safe Use of Lasers) for the 1.2 to 1.4 μm range, the possibility of supercontinuum generation needs to be evaluated where incident peak powers at the cornea approach the critical power for self-focusing after propagation with absorption into the eye. Further research is warranted.

Laser-Induced Breakdown

LIB offers the most plausible explanation for observed anomalies in the trends away from thermalinduced lesions above the 1 ns exposure time domain. LIB is a catastrophic dielectric breakdown due to extremely large electric fields associated with high peak powers when laser pulses are focused into a medium (solid, liquid, or gas). This effect can be coupled with self-focusing. Dielectric breakdown through optical absorption of laser radiation is the partial or complete ionization of the medium. This ionization results in a gas of charged particles called plasma, which absorbs optical radiation much more strongly than ordinary matter. Associated with the plasma is rapid heating by the laser pulse, expansion of the plasma, an audible acoustic signature, and a visible emission.

LIB may occur from either of two distinct mechanisms: (1) indirect ionization (avalanche ionization) of the medium and (2) direct ionization (multiphoton absorption) of the medium. By using indirect ionization, one or more “free” electrons must be in the focal volume of the pulse to initiate the process whereby free or “seed” electrons can absorb light through collisions with atoms or molecules. Avalanche ionization occurs when an energy greater than the ionization potential is reached by a free electron, which in turn transfers energy through collision with another atom or molecule to produce a second free electron, and the process continues geometrically until breakdown is achieved. With direct ionization, each electron is independently ionized, thus requiring no free electrons or collision processes to drive it. Multiphoton ionization is a process that becomes significant only at high irradiances and wavelengths in the near-infrared or shorter regime.

To consider LIB in terms of MVL production in the eye, the mechanisms described previously require an understanding of focused beam wavelength, pulse duration, and spot size that lead to the critical power needed for the event to occur. Kennedy[40] identifies three laser pulse exposure time domains of concern:

1. a long pulse regime (>100 ns) dominated by avalanche ionization;

2. a short pulse regime (100 ns–200 fs), where both types of ionization can be significant; and

3. an ultrashort pulse regime (<200 fs) dominated by multiphoton ionization.

In the 100 ns to 200 fs time domain, the laser pulse may be so short that avalanche ionization cannot occur unless a multiphoton ionization process “jump starts” the avalanche process. Note that below the thresholds necessary for the previously described processes, a fourth process can occur that is initiated by any one of the three processes. Specifically, very hot gas bubbles can form in the focal region of the laser pulse. This process does not quite reach a full-blown LIB as described by the formation of a visible event or acoustic signature.41,42

Table 12-4 summarizes our laboratory’s predicted nonlinear threshold phenomena as it compares to experimental ED50 thresholds at 24 hours postretinal exposure. Here, the two LIB processes (avalanche and multiphoton ionization) are not comparable with the much lower ED50 thresholds down to 90 fs. However, the self-focusing threshold does become comparable between 600 fs and 90 fs, respectively. In fact, there is an increase in the avalanche threshold from 600 fs to 90 fs, respectively, whereas the multiphoton threshold process continues to diminish.

TABLE 12-4
THRESHOLD ENERGIES FOR SEVERAL NONLINEAR PHENOMENA COMPARED TO THE RETINAL DAMAGE THRESHOLD

Pulse Duration

ED_50 at 24 Hours (μJ)

Retinal Image Diameter (μm)

Self-Focusing Threshold (μJ)

Avalanche Threshold (μJ)

Multiphoton Threshold (μJ)

4 ns: 532 nm

0.9

30

2,400

181.0

9,536

60 ps: 532 nm

0.43

39

36

33.6

580

6 ps: 530 nm

0.24

39

3.6

13.6

99

3 ps: 580 nm

0.58

30

2.1

15.4

156

600 fs: 580 nm

0.26

30

0.43

13.3

83

90 fs: 580 nm

0.43

30

0.06

32.7

20

Studies are currently underway to determine the response of the retina to exposure to laser pulses shorter than 100 fs. Current laser safety standards do not provide maximum permissible exposure levels for these shortest pulses. Cain et al[43] showed that retinal threshold damage for exposures <90 fs is the result of LIB in the retina. Another study by Cain et al[24] reported the retinal damage threshold for a 40 fs laser exposure, which is the shortest-duration laser pulse to create a retinal lesion ever recorded. Also, the damage energies for retinal lesions described in that report were made with the smallest single-pulse energy (0.17 μJ) of any study ever published. The authors found that, depending on how the pulse was preconditioned, retinal damage threshold could be reduced from 0.25 μJ per pulse to 0.17 μJ per pulse, respectively. Beam preconditioning was achieved by adjusting the phase of the pulse, which is the relative position in time of the longer wavelength portion to the shorter wavelength portion. This effect was shown to be more pronounced as pulse duration decreased below 20 to 50 fs for wavelengths of 450 to 800 nm, respectively (see Table 12-1). The effects on propagation for these shortest pulse durations are defined by GVD (Figure 12-4). It is believed that the modeling done by Cain et al[24] can be extended to determine the expected retinal damage thresholds for all retinal hazard wavelengths for pulse durations below 100 fs. If so, this will allow future safety standards to establish maximum permissible exposure levels for sub-100 fs laser exposures. Figure 12-4 summarizes our discussion on retinal damage mechanisms.

Figure 12-4. Damage mechanisms are listed as labels on this plot of single-pulse laser exposure threshold versus duration (data points). The lines are the current maximum permissible exposure levels from the ANSI Z136-2014 standard.
MPE: maximum permissible exposure; MVL: minimal visible lesions

Thermal and photochemical damage are delineated in Figure 12-4 for pulses longer than approximately 20 μs. These are long-term exposures whereby heat can produce protein denaturation or photochemical damage can occur for long-term, blue-to-green exposures. For pulse durations between 100 fs and 20 μs, respectively, Lin et al[44] have shown that microcavitation around melanosomes of the retina can induce cell injury. This is delineated in Figure 12-4 as melanin microcavitation. For pulse durations on the order of 1 ps, Rockwell et al[36] have shown that self-focusing can occur, thus reducing the retinal spot size and thereby reducing the corneal irradiance required for minimal damage.

ULTRASHORT LASER EFFECTS ON THE SKIN

There have been three studies documenting damage to the skin from femtosecond exposures.45-47 These studies result in different conclusions, possibly because their parameters are slightly different. Watanabe et al[45] used an amplified 65 fs laser pulse at 630 nm to study the damage threshold for producing immediate whitening (and ultrastructural changes in melanosomes) utilizing the black guinea pig skin model. Using a 50 μm spot size, they found that, at 0.31 J cm-2, there was melanosome disruption. No other damage was seen up to 0.58 J cm-2. At 0.92 J cm-2, the investigators noted increased electron density of the cytoplasm in electron microscopy of the area. They further observed that when gross and ultrastructural damage thresholds of melanin were plotted versus pulse width, there was a near-constant fluence damage threshold for 65 fs to 10 ns, and an increase in threshold for 40 ns to 0.4 ms exposure durations.

Frederickson et al[46] employed 800 nm, 120 fs laser exposures using 1 mm spot size exposures to measure the ablation threshold for skin. They used shaved, Sprague-Dawley female rats as their skin model. The threshold energy for tissue ablation was 2 mJ, which translates to 2.5 TW cm-2 peak power or a radiant exposure of 0.26 J cm-2. Very little tissue was removed with these threshold exposures because it took 100 pulses to ablate the epidermis.[46] Using 9 mJ per pulse, 10 pulses would remove the epidermis.

Kumru et al[47] used 810 nm, 44 fs laser exposures with sufficient propagation distance to allow the beam to collapse to a filament (or set of filaments) before impinging the skin of Yucatan mini-pigs. Using this setup, they determined that a pulse energy of 8.2 mJ produced a minimally visible ED_50 lesion 1 hour after exposure. This damage threshold corresponds to the energy required to produce a femtosecond filament, implying that this phenomenon was required for these low-pulse energies to produce skin damage.

Examination of these three studies highlights the importance of relative biophysical thresholds in determining the damage from lasers. The ablation threshold for femtosecond laser exposure is near the threshold for melanosome disruption; but, if the peak power in the beam is sufficient for a filament to be created, a lower threshold for skin damage may be possible. Both of these phenomena will lead to skin damage, but the threshold for damage will depend on which phenomenon leads to a lower threshold for any given combination of pulse width, wavelength, propagation distance, and spot size.

ULTRAFAST, ULTRAINTENSE LASERS

It is necessary to consider the effects produced by ionizing radiation as a byproduct and therefore a safety challenge for femtosecond lasers operating at ultra-intense power densities. Technological advances have led to the development of lasers with extreme powers and intensities, where the current record set by the HERCULES laser in 2008 achieved a focal intensity of 2 × 10^22 W cm-2.[48] This was achieved at the University of Michigan in 2008 through the use of adaptive optics that provided an ideal focusing of the laser pulse, thus achieving a peak power of 300 TW. Several facilities in the world can now provide laser pulses of 1 PW (where TW is the terawatt unit or 10^12 W and PW is petawatt unit or 10^15 W).

Intensities on the order of 10^12 W cm-2 correspond to field strengths that are capable of perturbing electrons at the highest energy levels strong enough to cause a nonlinear response. At intensities of the order of 10^14 W cm-2, laser fields start to compete with intraatomic fields, causing rapid ionization and complex dynamics of electrons. As available laser intensity has reached a level of the order of 10^16 W cm-2, laser fields begin to surpass the intraatomic fields that bind electrons, thus providing the mechanism for rapid ionization of various targets and for studies considering nonlinear processes. Between 10^16 and 10^22 W cm-2, competing matter interaction mechanisms are operative that account for the induced relativistic motion of electrons, relativistic self-induced transparency, and the ability to overcome the ponderomotive force that is responsible for excitation of Langmuir waves by a laser pulse propagating in undersense media.49,50

It is important to consider the interaction of ultrashort, ultraintense laser light with matter where ionizing radiation may be produced in terms of the potential hazard and how in the process this hazard can be mitigated. In one such reported study, Qiu et al[51] note that a very limited number of studies have considered the issue of laser-induced ionizing radiation protection. In their work, they focused on the physics and characteristics of laser-induced X-ray hazards. Their concern centered on the possible X-ray dose rate associated with 4 TW and a peak intensity of 2.4 × 10^18 W cm-2. Their conclusion called for a graded approach to mitigate the laser-induced X-ray hazard with a combination of engineered and administrative controls being proposed.

SUMMARY

Femtosecond lasers are finding application in a host of novel applications. Here, we have described the novel damage that is seen with femtosecond laser exposure to the retina and skin. Femtosecond laser pulses create tissue damage with the reduction of photoacoustic effects, resulting in more precise damage zones.3,52,53 With damage mechanisms found to occur, treatment and injury response are possible. Multiphoton absorption in microscopy and DNA dissection techniques have made possible several new fields of study related to the use of femtosecond laser pulses with no photomechanical effect. Although battlefield applications may be years away, ultrashort lasers will inevitably be militarized, and their eventual utility will likely be determined by their initial application in nonmilitary settings.

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13. Ham WT, Mueller HA, Goldman AJ, Newman BE, Holland LM, Kuwabara T. Ocular hazard from picosecond pulses of Nd:YAG laser radiation. Science. 1974;185:362–363.

14. Goldman AI, Ham WT, Mueller HA. Mechanisms of retinal damage resulting from the exposure of rhesus monkeys to ultrashort laser pulses. Exp Eye Res. 1975;21:457–469.

15. Vassiliadis A. Thresholds of laser eye hazards. Arch Environ Health. 1970;20:161–170.

16. Ebbers RW, Dunsky IL. Retinal damage thresholds for multiple-pulse lasers. J Aerospace Med. 1973;44:317–318.

17. Taboada J, Gibbons WD. Retinal tissue damage induced by single ultrashort 1060 nm laser light pulses. Appl Opt. 1978;17:2871–2873.

18. Finney DJ. Probit Analysis. 3rd ed. New York, NY: Cambridge University Press; 1971.

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22. Cain CP, Toth CM, DiCarlo CA, et al. Visible retinal lesions from ultrashort laser pulses in the primate eye. Invest Ophthalmol Vis Sci. 1995;36(5):879–888.

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24. Cain CP, Thomas RJ, Noojin GD, et al. Sub-50-fs laser retinal damage thresholds in primate eyes with group velocity dispersion, self-focusing and low-density plasmas. Graefe’s Arch Clin Exp Ophthalmol. 2005;243(2):101–112.

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Chapter 13

CORNEAL EFFECTS OF LASER RADIATION

RUSSELL L. McCALLY, PhD, * Principal Staff Physicist (Retired), Johns Hopkins University Applied Physics Laboratory, Laurel, Maryland, and Johns Hopkins University Wilmer Eye Institute, 4940 Eastern Avenue, Baltimore, Maryland 21224 and BRUCE E. STUCK, MS, ScD † Formerly, Detachment Director, US Army Medical Research Detachment–Walter Reed Army Institute of Research, 7965 Dave Erwin Drive, Brooks City-Base, Texas 78235

INTRODUCTION

Anatomy of the Cornea

Wavelength Dependence of Infrared Absorption

Response Criteria

Animal Models

CORNEAL INJURY THRESHOLDS AND PERMISSIBLE EXPOSURE LIMITS FOR CARBON DIOXIDE LASERS

Epithelial Injury Thresholds

Endothelial Injury Thresholds

Corneal Stromal Effects

THERMAL MODELS AND TEMPERATURE MEASUREMENTS

CORNEAL EFFECTS AT OTHER LASER WAVELENGTHS

Epithelial Injury Thresholds for Erbium Glass Laser Radiation

Epithelial Injury Thresholds for Holmium Laser Radiation

SUMMARY

INTRODUCTION

Infrared radiation at wavelengths longer than 1.4 μm is absorbed to varying degrees by water in body tissue. Due to their relatively high water content and accessibility, the cornea and skin are particularly susceptible. Because corneal absorption of infrared radiation blocks retinal exposure, the infrared spectral region is typically regarded as “eyesafe”; however, this term is misleading. In fact, overexposure to infrared radiation can cause painful and visually disabling corneal injuries.

Anatomy of the Cornea

In addition to the tear layer, which is about 7 μm thick,[1] the human cornea is comprised of five distinct layers of tissue. From anterior to posterior, these are the epithelium, Bowman layer, stroma, Descemet membrane, and endothelium. The epithelium is about 50 μm thick and composed of several layers of cells. It is attached to a basement membrane that separates it from the Bowman layer. The Bowman layer is approximately 10 μm thick; it is acellular, composed of thin collagen fibrils aligned randomly in a ground substance. The stromal layer accounts for 90% of the human corneal thickness, which averages 520 μm. The stroma is com¬posed of layers of parallel collagen fibrils embedded in a ground substance. Interspersed between the collagen fibril layers are keratocytes; these cells account for 3% to 5% of the stromal volume. The Descemet membrane is a highly ordered network of very thin collagen fila¬ments; in adults, this membrane is about 10 μm thick. The Descemet membrane is the basement membrane of the endothelium, which is a single cell layer about 3 μm thick. The endothelium actively pumps fluids into the anterior chamber to maintain corneal hydration at its normal physiologic value. Maintenance of proper hydration is essential for corneal transparency. Because human endothelium does not regenerate readily after injury, it is important that its health be maintained. The human cornea is 78% water by weight; the remaining 22% is composed of collagen, other proteins, glycos¬aminoglycans, and salts.[2]

Figure 13-1. Absorption spectrum of water in the infrared range.

α: absorption coefficient; λ: wavelength

Data source: Maher EF. Transmission and Absorption Coefficients for Ocular Media of the Rhesus Monkey . Brooks Air Force Base, TX: US Air Force School of Aerospace Medicine; 1978. Report SAM-TR-78-32.

Cells in all corneal layers are subject to thermal damage from absorbed infrared radiation. Further, temperatures above about 57 °C will cause the corneal collagen matrix to shrink.[3] This effect is the basis for laser thermokeraplasty as a treatment for hyperopia.

Wavelength Dependence of Infrared Absorption

The absorption of radiation in a material is described by Beer’s law, which is expressed as

where I(z) is the irradiance at a distance z into the material, I_0 is the incident irradiance, and α is the absorption coefficient. The value of the absorption coefficient depends upon material type and radiation wavelength. Figures 13-1 shows the absorption spectrum of water in the infrared range from 1.4 μm to 11 μm.4 Table 13-1 presents the values of α for water, physiological saline, and cornea at several infrared laser wavelengths of interest.[4] Due to the thickness of the cornea (520 μm), its absorption spectrum cannot be measured for wavelengths greater than ~2.5 μm. Table 13-2 shows plots of I(z)/I_0 as a function of distance into the cornea for laser wavelengths of 1.54 μm (erbiumdoped [Er] fiber), 2.02 μm (thulium yttrium aluminum garnet [Tm:YAG]), and 10.6 μm (carbon dioxide [CO_2]). A schematic representation of the human cornea is also shown for reference. Note that CO_2 radiation is absorbed almost entirely in the epithelial layer, and Tm:YAG radiation is absorbed almost entirely in the cornea. By contrast, only ~40% of Er fiber laser radiation is absorbed in the entire depth of the cornea.

TABLE 13-1
ABSORPTION COEFFICIENTS FOR SEVERAL INFRARED LASERS

Laser

Distilled Water α (cm–1)

Physiological Saline α (cm–1)

Cornea α (cm–1)

Er Fiber (1.54 μm)

12.3

12.0

9.03

Tm:YAG (2.02 μm)

55.0

57.5

38.1

Ho:YAG (2.10 μm)

28.6

28.6

20.9

HF (2.7 μm)

610

423

[*]

Er:YAG (2.94 μm)

17,700

7,260

[*]

CO_2 (10.6 μm)

920

>2,000

[*]

*Due to the thickness of the cornea, its absorption spectrum cannot be measured for wavelengths greater than ~2.5 μm.

α: absorption coefficient

CO_2: carbon dioxide

Er: erbium-doped

HF: hydrogen fluoride

Ho: holmium

Tm: thulium

YAG: yttrium aluminum garnet

Response Criteria

Once absorbed, infrared energy is rapidly converted to heat. This raises the temperature of the absorption volume. Heat is then conducted to deeper layers, whereupon temperature rises throughout the exposed tissue. Increased temperature is thus the combined result of direct radiation and heat conduction. Sufficiently high temperatures will cause thermal damage to exposed tissue. At very high irradiance or radiant exposure levels, this damage can be severe and may even cause tissue charring or ablation.5–8 This chapter, however, is primarily concerned with threshold damage.

In general, threshold injury involves only the corneal epithelium; deeper layers of the stroma and endothelium are typically unaffected. (Injury thresholds for keratocytes and corneal endothelium will be discussed later in this chapter.) Threshold injury to the epithelium is usually repaired within 24 to 48 hours of exposure and causes no lasting effects.6,9–11 The injury first appears as a superficial gray-white spot that is barely visible in the slit-lamp microscope.9,12 This damage develops immediately after exposure, although some investigators have applied the criterion of its appearance within 10 minutes,[11] 30 minutes,12-16 or 60 minutes following exposure.17,18 In general, if a minimal lesion has not appeared within this initial period of time, none will develop in the subsequent 24 to 48 hours.6,11 (However, one study found the contrary: Ham and Mueller reported the development of corneal lesions 24 hours following 100-second exposures to 1.55 μm radiation at very low irradiance levels.[19] This puzzling result will be discussed in more detail later in this chapter.)

Figure 13-2.(a) Absorption of infrared radiation in cornea as described by Beer’s law for wavelengths of 1.54 μm, 2.02 μm, and 10.6 μm. (b) A schematic of the cornea on the same scale. Reproduced with permission from: McCally RL, Bargeron CB, Bonney-Ray JA, Green WR. Laser eye safety research at APL. Johns Hopkins APL Tech Digest. 2005;26:48. © The Johns Hopkins University Applied Physics Laboratory.

Threshold exposure levels are determined by delivering a series of exposures with fixed irradiance and varying exposure durations, or with fixed exposure duration and varying irradiance levels. Observations can then be made to determine which exposures produce a lesion and which do not. Many investigators have used the probit method to analyze such data10,12,14,17,20; this method assumes that a dose-response function will describe the probability that an exposure will produce a lesion.21,22 The probit analysis can thus be used to determine ED_50, which is that dose for which there exists a 50% probability of injury in the form of a visible lesion. A bracketing procedure is used to broadly bracket exposures above and below threshold. The bracket is then narrowed until only about a 10% difference remains in either the irradiance or radiant exposure for exposures that produce minimal lesions and those that produce none. The threshold is taken to be at the center of the bracket.11,13,15,16,23 Some experiments of this type have yielded very well-defined thresholds involving little or no overlap between exposures that produce minimal lesions and those that do not.

Animal Models

Many investigations of corneal injury thresholds have used New Zealand white or Dutch belted rabbits. 6,11,13-16,19,23-25 Rhesus and owl monkeys also have been used.9,12,14,17,18 One purpose of the latter studies was to determine if damage thresholds differ between species. No such difference has been found, thus increasing confidence that thresholds measured in animal subjects likely also apply to human subjects.[14]

CORNEAL INJURY THRESHOLDS AND PERMISSIBLE EXPOSURE LIMITS FOR CARBON DIOXIDE LASERS

Most laser biological threshold studies have focused on understanding biological thresholds and thermal injury mechanisms at the ubiquitous CO_2 laser wavelength of 10.6 μm. As explained above, radiation at this wavelength is strongly absorbed at a depth of just ~10 μm. Thus, CO_2 radiation would be almost entirely absorbed within the corneal epithelium. Limited studies of corneal injury thresholds have also been done using a hydrogen fluoride laser at wavelengths of 2.7 and 2.8 μm, with corresponding absorption depths of 16 and 2 μm, and a deuterium-fluoride laser at a wavelength of 3.73 μm with an absorption depth of 76 μm.

Wavelengths in the mid-infrared spectral region between 1.3 and 3 μm do not penetrate to the retina, but overexposure to these wavelengths can, in fact, cause painful and visually disabling corneal injuries. Moreover, optical aids such as binoculars and telescopes readily transmit these spectral wavelengths and greatly increase corneal irradiance at the eyepiece. For example, a 10× sighting telescope would increase corneal irradiance by more than 50-fold. Thus, irradiances that may be relatively “safe” to the unaided eye can be amplified to very dangerous levels by optical aids.

With the large number of fire-control telescopes and binoculars now on the battlefield, service members can be exposed to dangerous infrared wavelengths from anti-sensor lasers. Depending on the magnifying power and entrance aperture of telescopic optics, the cornea could be exposed to a range of laser spot sizes. Certain laser wavelengths, particularly those in the 1.4 to 1.7 μm range, are much more likely to damage the corneal endothelium, and thus are more likely to involve delayed effects and corneal healing.

Before about 1990, only a few studies had been done on corneal injury thresholds at laser wavelengths in the mid-infrared spectrum. Stuck et al[17] investigated thresholds for short pulses of holmium laser radiation at 2.06 μm (absorption depth ~250 μm) and Er glass laser radiation at 1.54 μm (absorption depth > 1,000 μm). Other studies of Er glass radiation using Q-switched pulses were performed by Lund et al[18] and Avdeev et al.[26] Ham and Mueller also reported damage thresholds for continuous wave exposures from a laser diode operating at 1.54 μm.19,27

Since 1990, there have been several extensive investigations at penetrating wavelengths. McCally et al[15] and McCally and Bargeron16,28 determined thresholds for single- and multiple-pulse exposures from Tm:YAG laser radiation at 2.02 μm (absorption depth 174 μm). McCally and Bargeron also determined the diameter dependence of thresholds for single-pulse exposures from Er fiber laser radiation at 1.54 μm.29-31 Finally, Zuclich et al determined injury thresholds for cornea, lens, and retina from highly penetrating neodymiumdoped yttrium aluminum garnet (Nd:YAG) laser radiation at 1.318 and 1.356 μm.32,33 The results and implications of these investigations of corneal injury thresholds for infrared radiation are discussed in the following sections.

Epithelial Injury Thresholds

Dependence on Exposure Duration

Many early studies of the ocular effects of CO_2 lasers were concerned primarily with damage from relatively high exposure levels.5,6,8,25 Researchers then turned their attention to determining the minimum radiant exposure or irradiance levels that produce minimal (threshold) corneal damage. Because CO_2 radiation is almost entirely absorbed in the corneal epithelium, threshold damage is confined to this cellular layer. Information about damage threshold exposures provides a rational basis for setting laser safety standards.

TABLE 13-2
EPITHELIAL DAMAGE THRESHOLDS FOR CARBON DIOXIDE LASER RADIATION (EXPOSURE DURATIONS > 1 MILLISECOND)

τ (s)

Hth (J/cm^2)

I th (W/cm^2)

Beam diameter[*] (cm)

ΔTmax [†] (°C)

Reference

0.00096

0.599

624

0.102

53.9

1

0.001

0.800

800

0.250

NC

2

0.002

0.970

485

0.250

NC

2

0.0035

0.550

157

0.400

NC

3

0.0039

0.690

177

0.180

47.0

1

0.0092

0.793

86.2

0.252

41.4

1

0.010

0.725

72.5

0.250

NC

2

0.010

0.770

77.0

0.400

NC

2

0.015

0.964

64.3

0.178

42.2

1

0.018

0.945

51.1

0.180

38.1

1

0.019

1.092

57.2

0.254

43.6

3

0.031

1.20

38.8

0.260

39.5

1

0.055

1.20

21.8

0.400

NC

3

0.100

2.46

24.6[‡]

0.250

NC

4

0.101

2.07

20.4

0.158

39.5

1

0.498

4.48

8.99

0.182

37.9

1

0.500

4.69

9.39

0.224

41.0

1

0.977

6.31

6.46

0.244

38.3

1

1.00

7.70

7.70

0.250

NC

2

5.00

15.0

3.00

0.250

NC

2

9.73

28.1

2.89

0.248

34.7

1

900

220

0.244

1.04[§]

NC

5

1,800

360

0.200

1.04[§]

NC

5

*Gaussian beam (1/e diameter) unless noted otherwise.

†Calculated on the beam axis 10 μm beneath tear surface.

‡Average value of thresholds for Dutch belted rabbit, rhesus monkey, and owl monkey.

§Uniform beam distribution.

τ: exposure duration

Hth: threshold radiant exposure per pulse

Ith: irradiance threshold

ΔTmax: maximum temperature increase

NC: not calculated for this exposure condition

(1) Bargeron CB, Deters OJ, Farrell RA, McCally RL. Epithelial damage in rabbit corneas exposed to CO_2 laser radiation. Health Phys. 1989;56:85–95. (2) Beatrice ES, Stuck BE. Ocular effects of laser radiation: Cornea and anterior chamber. In: NATO-AGARD Publication No. LS-79. Neully sur Seine, France: NATO-AGARD: 1975: 5-1–5-5. (3) Peppers NA, Vassiliadis A, Dedrick LG, et al. Cornea damage thresholds for CO2 laser radiation. Appl Opt. 1969;8:377–381. (4) Byer HH, Carpino E, Stuck BE. Determination of the Thresholds of CO_2 Laser Corneal Damage to Owl Monkeys, Rhesus Monkeys, and Dutch Belted Rabbits. Philadelphia, PA: Frankford Arsenal; 1972. Report M72-3-1; DTIC AD9010862. (5) Fine BS, Fine S, Feigen MS, MacKeen D. Corneal injury threshold to carbon dioxide laser radiation. Am J Ophthalmol. 1968;1–14.

Most threshold determinations have been made using lasers operating in the fundamental transverse electromagnetic (TEM_00) Gaussian mode, which has a Gaussian irradiance profile given by

Here the peak irradiance, I_0, is related to the total laser power, P, by I_0 = P/A1/e, where A1/e is the area within the 1/e radius, r1/e. Note that some investigators have used the 1/e^2 radius to characterize the beam. In this case, I_0 = 2P/A1/e^2, where A1/e^2 is the area within the 1/e^2 radius. Obviously, a similar relationship holds for radiant exposure. Use of either the fundamental TEM_00 mode or a beam with a uniform irradiance profile (see Fine et al[24]) allows for easy comparisons between experimental results. Moreover, as will be discussed later in this chapter, use of such beam profiles facilitates comparisons with thermal models.

TABLE 13-3
EPITHELIAL DAMAGE THRESHOLDS FOR CARBON DIOXIDE LASER RADIATION (EXPOSURE DURATIONS < 1 MILLISECOND)

τ (ns)

Hth (mJ/cm^2)

Beam diameter[*] (cm)

ΔTmax [†] (°C)

Reference

1.4

6.1[‡]

0.90[§]

1.80

1

1.4

14.7¥

0.90[§]

4.33

1

1.7

660[¶]

0.424

65.0

2

25.0

1,080[¶]

0.424

106

2

80.0

307

0.372

30.2

3

120

350

0.320

34.4

4

250

360¶

0.424

35.5

2

*Gaussian beam (1/e diameter) unless noted otherwise.

†Calculated on the beam axis 10 μm beneath tear surface.

‡Slight stippling at 48 hours postexposure.

§Uniform beam distribution.

¥Lowest exposure for which immediate damage was reported.

¶Values are twice those reported by Zuclich et al[2] to correct for the fact that they divided the total incident energy by the 1/e^2 area to obtain the radiant exposure.

τ: exposure duration

Hth: threshold radiant exposure per pulse

ΔTmax: maximum temperature increase

(1) Mueller HA, Ham WJ. The Ocular Effects of Single Pulses of 10.6 μm and 2.5–3.0 μm Q-Switched Laser Radiation. Los Alamos, NM: Los Alamos National Laboratory; 1976. L-Division Report. (2) Zuclich JA, Blankenstein MF, Thomas SJ, Harrison RF. Corneal damage induced by pulsed CO_2 laser radiation. Health Phys. 1984;47:829–835. (3) Mc- Cally RL, Bargeron CB. Epithelial damage thresholds for multiplepulse exposures to 80 ns pulses of CO2 laser radiation. Health Phys. 2001;80:41–46. (4) Lee ST, Anderson T, Zhang H, Flotte TJ, Doukas AG. Alteration of cell membrane by stress waves in-vitro. Ultrasound Med Biol. 1996;22:1285–1293.

Epithelial injury thresholds for single pulses of CO_2 radiation have been determined for exposure durations ranging from nanoseconds to 30 minutes. Table 13-2 lists the available threshold data for CO_2 exposures from ~1 ms to 30 minutes, and Table 13-3 lists thresholds for exposures from 1.4 to 250 ns. These threshold radiant exposures and irradiances are the peak values (see Equation 13-2). Also listed are the calculated peak temperature increases that would result in each case. These will be discussed in the section on thermal models later in this chapter. Excepting the 1.4-ns exposures used by Mueller and Ham (see Table 13-3)[34] and the very long exposures investigated by Fine et al (see Table 13-2),[24] which were done using a uniform beam profile, all other exposures were done with Gaussian beam profile lasers. Data for exposure durations shorter than 10 seconds are plotted in Figure 13-3. The following section will begin with discussion of threshold data for exposures with durations greater than or equal to 1 ms, and then consider thresholds for shorter duration exposures.

Although the various investigators found some minor differences in the thresholds obtained for exposure durations over 1 ms—especially for durations between 1 and 4 ms—there is remarkable agreement overall. There are several possible reasons for the minor differences observed, including different laser beam diameters, the use of anesthetized versus nonanesthetized animals, different types of anesthesia, variability in tear film thickness, different threshold determination methods, and possible experimental dosimetry errors. Threshold dependency on laser beam diameter will be discussed later in this chapter, but for present purposes, it should simply be noted that for exposure durations greater than ~0.2 second, thresholds are sensitive to beam diameter for diameters less than 0.3 cm.

In the investigations performed by Bargeron et al,[13] Beatrice and Stuck,[35] and Byer et al,[14] experimental animals were anesthetized. In the studies conducted by Peppers et al[20] and Fine et al,[24] experimental animals were not anesthetized. Bargeron et al used a mixture of ketamine hydrochloride and xylazine as well as topical proparacaine hydrochloride,[13] whereas Beatrice and Stuck[35] used either sodium pentobarbitol or halothane gas (this information was inferred from the paper by Brownell and Stuck,[12] which discussed these experiments). Byer et al used sodium pentobarbital.[14] Because the absorption depth of CO_2 radiation is only ~10 μm, threshold exposures are extremely sensitive to tear film thickness. The thickness of normal tear film is about 7 μm.[1] If irrigation is not carefully controlled, absorption differences in the resulting thicker or thinner tear layer can be substantial and may exert a significant influence on resulting temperature increase in the epithelium. Finally, Bargeron et al applied a bracketing procedure to determine thresholds, whereas the other investigators used probit methods.

Figure 13-3. Epithelial injury threshold radiant exposures for single pulses of carbon dioxide (CO_2) laser radiation as a function of exposure duration.

Hth: radiant exposure per pulse; τ: duration

Data sources: (1) Bargeron CB, Deters OJ, Farrell RA, McCally RL. Epithelial damage in rabbit corneas exposed to CO2 laser radiation. Health Phys. 1989;56:85–95. (2) Brownell AS, Stuck BE. Ocular and skin hazards from CO_2 laser radiation. In: Proceedings of the 1974 Army Science Conference, US Military Academy, West Point, NY, June 18–21, 1974, Vol 1 . Washington, DC: Office of the Chief of Research and Development, Department of the Army; 1974;1: 123–137. DTIC AD0785609. (3) Peppers NA, Vassiliadis A, Dedrick LG, et al. Cornea damage thresholds for CO_2 laser radiation. Appl Opt. 1969;8:377–381. (4) Byer HH, Carpino E, Stuck BE. Determination of the Thresholds of CO_2 Laser Corneal Damage to Owl Monkeys, Rhesus Monkeys, and Dutch Belted Rabbits . Philadelphia, PA: Frankford Arsenal; 1972. Report M72-3-1; DTIC AD9010862. (5) Zuclich JA, Blankenstein MF, Thomas SJ, Harrison RF. Corneal damage induced by pulsed CO_2 laser radiation. Health Phys. 1984;47:829–835. (6) McCally RL, Bargeron CB. Epithelial damage thresholds for multiplepulse exposures to 80 ns pulses of CO_2 laser radiation. Health Phys. 2001;80:41–46.

In a lesion produced by an exposure slightly above the damage threshold, there was a central area of epithelial edema that extended through all cell layers.[31] Within this area the cells were moderately disrupted, with edematous spaces between the cells as well. This is typical of thermal lesions. Indeed, damage for exposure durations over 1 ms is thermal, and thresholds can be correlated either by a modified critical temperature model or by a damage integral model (these models and their predictions are discussed later in this chapter). 12,13,20,36

There are fewer data points for exposure durations shorter than 1 ms (see Table 13-3), and more variability occurs among these data than is seen for longer-duration exposures. In particular, the thresholds at 1.4 ns and 1.7 ns differ by nearly two orders of magnitude. Unlike other thresholds, damage from the lowest threshold reported by Ham and Mueller had a latency period of 48 hours, but even the exposure that produced immediate damage was 45 times lower than the (similar) 1.7-ns threshold obtained by Zuclich et al.37,38 Other differences between experiments were considered unlikely causes of the discrepancy. Zuclich et al attributed threshold damage for their exposures (1.7 ns to 250 ns) to a thermal mechanism, whereas Ham and Mueller attributed damage to mechanical rupture or stress caused by sonic transients.11,34,37,38 Both groups reported hearing an audible report from the cornea at exposure levels that produced lesions. Thus, acoustic damage mechanisms should be considered.

Some studies found that large temperature gradients at the anterior surface of the cornea may produce pressure transients via a thermoelastic process.39-43 Indeed, Farrell et al[41] presented histology of nearthreshold lesions resulting from 80-ns pulses that had features consistent with tensile stress and thermal damage; resulting disruptions of the superficial epithelial cells were consistent with the type of structural alteration that might be produced by a tensile stress wave. In this regard, it is noteworthy that the thermoelastic stress wave generated by laser absorption at free surfaces consisted of a compression wave followed by a tensile wave.40,42,43 However, vacuolation and loss of well-defined organelles in the anterior epithelial cells are characteristic of thermal damage.

The temperature increases calculated as those that would result from thresholds obtained by Mueller and Ham are too low (see Table 13-3) to be consistent with any known thermal mechanism.34,41 However, temperature increases that would result from the 1.7-ns and 25-ns thresholds obtained by Zuclich et al are in reasonable agreement with the empirical modified critical temperature model originally proposed by Egbert and Maher.[36] According to this model, threshold damage occurs when the tissue reaches a critical damage temperature, which is a weak function of exposure duration. To produce damage, short pulses should require greater temperature increases than do longer pulses. Thus, the thresholds for 80-ns,[23] 120-ns, and 250-ns[11] pulses are not in good agreement with the empirical modified critical temperature model. Nevertheless, McCally and Bargeron[23] showed that threshold damage from 80-ns pulses involves a substantial thermal component. Because stress waves can decrease cell viability and increase permeability,43,44 McCally and Bargeron suggested that although thermoelastic stress waves may not be the primary mechanism of damage, they may serve to potentiate thermal damage and thus cause damage to occur at a lower temperature.

Dependence on Beam Diameter

If the modified critical temperature damage model provides a valid description of threshold epithelial damage, damage thresholds should have the same dependence on beam diameter.7,13 For laser beams that have a Gaussian irradiance profile (see Equation 13-2), theory predicts that the irradiance (or radiant exposure) required to produce a given temperature rise depends on the diameter of the laser beam. This dependence is due to radial heat conduction. Exposures from small-diameter beams produce larger temperature gradients in the radial direction than do exposures from large-diameter beams. Consequently, more heat is conducted away in the radial direction from small-diameter beams, and larger irradiances are required to produce a given temperature increase on the beam axis.

Damage threshold dependence on beam diameter has been tested experimentally.7,13 As predicted by the modified critical temperature damage model, the irradiance required to produce threshold damage indeed increases as the beam diameter decreases. Furthermore, as expected from theory, the threshold dependence beam diameter also depends on exposure duration. The effect of beam diameter on threshold irradiance manifests itself at increasingly large beam diameters as exposure duration is increased.

Repetitive Pulse Exposures

Many laser systems emit sequences of pulses. Although there have been several studies of retinal damage from such systems,18,45-47 Farrell et al[7] and Bargeron et al[13] were the first to study threshold corneal damage from sequences of subthreshold pulses. As these investigators observed, it is a more complex task to specify exposure conditions for pulse sequences than to describe single pulse exposures. In addition to peak irradiance (or peak radiant exposure), 1/e beam radius, and pulse duration, it is also necessary to specify the number of pulses (N) and pulse repetition frequency (PRF).7,13 In one set of experiments, irradiance and beam diameter were held (approximately) constant and individual pulse duration was varied to determine the threshold for several values of N and two values of PRF. The results of these experiments are listed in Table 13-4.7,13 In subsequent experiments, pulse durations and beam radius were held (approximately) constant and the radiant exposure per pulse was varied to determine the thresholds for a variety of values of N and PRF. Table 13-5 lists results for exposures with individual pulse durations of ~10 ms and ~1 ms,7,13 and Table 13-6 lists results for exposures with individual pulse durations of 80 ns.[23] Included in these three tables are the maximum temperatures attained at the conclusion of the respective pulse sequences. Temperatures were calculated on the beam axis, 10 μm beneath the tear surface. Figure 13-4 shows results of these temperature calculations for three of the conditions in Table 13-5.

TABLE 13-4
MULTIPLE-PULSE INJURY THRESHOLDS

PRF (Hz)

N

Ith[*] (W/cm^2)

τ (s)

Hth[*] (J/cm^2/pulse)

Beam diameter[†] (cm)

ΔTmax [‡] (°C)

1

1

9.39

0.500

4.69

0.224

41.0

1

2

9.82

0.370

3.63

0.222

44.6

1

4

9.73

0.270

2.63

0.220

42.3

1

8

11.2

0.240

2.69

0.206

48.3

10

8

10.6

0.080

0.848

0.210

47.3

*Threshold irradiances and radiant exposures are peak values.

†Gaussian beam (1/e diameter).

‡Calculated on the beam axis 10 μm beneath the anterior tear surface.

§PRF: pulse repetition frequency

¥τ: duration

Hth: threshold radiant exposure per pulse

Ith: irradiance threshold

ΔTmax: maximum temperature increase

Adapted with permission from: Farrell RA, McCally RL, Bargeron CB, Green WR. Structural Alterations in the Cornea From Exposure to Infrared Radiation. Laurel , MD: Applied Physics Laboratory, Johns Hopkins University; 1985: 31. Report TG 1364.

TABLE 13-5
MULTIPLE-PULSE INJURY THRESHOLDS FOR ~10- AND ~1-MILLISECOND PULSES

PRF (Hz)

N

τ (s × 10-3)

Ith[*] (W/cm^2)

Hth[*] (J/cm^2/pulse)

Beam diameter[†] (cm)

ΔTmax [‡] (°C)

1

1[‡]

9.2

86.2

0.79

0.252

41.4

1

4

10.1

79.6

0.804

0.172

43.4

1

32

9.3

66.8

0.621

0.250

38.4

10

4

9.7

60.0

0.582

0.256

43.3

10

32

10.9

32.7

0.356

0.244

44.6

10

128

9.2

25.3

0.233

0.270

39.8

20

4

10.0

55.3

0.553

0.252

46.8

20

32

9.9

27.8

0.275

0.240

47.7

20

128

8.9

16.4

0.146

0.276

38.8

1

1[§]

0.96

624

0.599

0.102

53.9

20

10

0.94

239

0.225

0.186

34.7

20

100

0.95

171

0.162

0.174

39.0

20

500

0.92

122

0.112

0.174

33.0

100

10

0.96

153

0.147

0.202

36.0

100

100

0.95

59.6

0.057

0.196

35.2

100

999

0.96

42.0

0.040

0.174

40.1

*Threshold irradiances and radiant exposures are peak values.

†Gaussian beam (1/e diameter).

‡Calculated on the beam axis 10 μm beneath the anterior tear surface.

§Data are from Table 13-2.

τ: exposure duration

Hth: threshold radiant exposure per pulse

Ith: irradiance threshold

PRF: pulse repetition frequency

ΔTmax: maximum temperature increase

Adapted with permission from: Farrell RA, McCally RL, Bargeron CB, Green WR. Structural Alterations in the Cornea From Exposure to Infrared Radiation. Laurel, MD: Applied Physics Laboratory, Johns Hopkins University; 1985: 33. Report TG 1364.

Figure 13-4 shows wide variability among the temperature histories for the different exposures. Owing to the complexity of the temperature histories, it is more difficult to deduce a general injury correlation for sequenced pulses than for single-pulse exposure conditions, in which temperatures increase monotonically during exposure. Bargeron et al[13] calculated the damage integral using parameters appropriate for cornea[12] (see discussion on damage models later in this chapter) for the threshold conditions listed in Table 13-4, and found that it varied by a factor of about 40 for the different conditions. They noted that this variability was substantially greater than has been found in other systems, including single-pulse exposures in cornea,12,36,48,49 and concluded that the damage integral model is inappropriate for multiple-pulse exposures in cornea. For exposures having individual pulse widths greater than ~10 ms, peak temperature increases for the exposures in Tables 13-4 and 13-5 average 41.3 ± 4.76°C (mean ± standard deviation). Thus, they are constant to within about ± 11%. Bargeron et al noted that there was some systematic max temperature variation with individual pulse widths. In particular, for pulse widths near 1 ms, ΔTmax = 36.5 ± 3.6°C, for pulse widths near 10 ms, ΔTmax = 43 ± 4.7°C, and for pulse widths near 300 ms (from Table 13-3), ΔTmax =45.3 ± 3°C, where ± denotes the full range of values.[13] These ranges are consistent with the experimental uncertainties of ±10%, which arise primarily from the bracketing procedure used to determine thresholds. The authors therefore concluded that injury thresh-olds for multiple-pulse exposures (with individual pulse widths > ~1 ms) are consistent with a critical temperature damage model.

TABLE 13-6
MULTIPLE-PULSE INJURY THRESHOLDS FOR 80-NANOSECOND PULSES

PRF (Hz)

N

Hth[*] (J/cm^2/pulse)

Beam diameter[†] (cm)

ΔTmax [‡] (°C)

–

1

307

0.372

30.2

10

2

235

0.348

25.7

10

8

228

0.380

32.0

10

32

154

0.378

29.2

10

128

136

0.341

32.4

10

1,024

95

0.321

26.6

16

2

265

0.362

29.7

16

8

205

0.375

31.3

16

32

150

0.373

32.9

16

128

105

0.382

32.8

16

1,024

85

0.358

35.1

*Peak radiant exposure.

†Gaussian beam (1/e diameter).

‡Calculated on the beam axis 10 μm beneath the anterior tear layer.

Hth: threshold radiant exposure per pulse

PRF: pulse repetition frequency

Ith: irradiance threshold

PRF: pulse repetition frequency

ΔTmax: maximum temperature increase

Adapted with permission from: McCally RL, Bargeron CB. Epithelial damage thresholds for multiple-pulse exposures to 80 ns pulses of CO_2 laser radiation. Health Phys. 2001;80:43.

The calculated maximum temperature increases listed in Table 13-6 for exposures to 80-ns pulse se-quences are lower than those for longer individual pulse widths. Nevertheless, they are constant to within ±10% of their mean values, and they are independent of the number of pulses in sequence. For the exposures at 10 Hz, ΔTmax = 29.4 ± 2.8°C (mean ± standard deviation), and for the exposures at 16 Hz, ΔTmax = 32 ± 2°C. These results suggest that the damage mechanism has a substantial thermal component and can be described by a critical temperature damage model.[23] McCally and Bargeron tested this further by measuring damage thresholds in enucleated eyes that had been cooled to room temperature. They noted that if a critical temperature model is valid, damage should occur at the same final critical temperature (not temperature increase).[23] For a cooled cornea, sufficient energy would have to be supplied to raise the temperature, first to the in vivo temperature (assumed to be 35°C^50) and then to the damage temperature. They tested this hypothesis by measuring thresholds in corneas cooled to 21°C for exposures to sequences of 8 and 32 pulses at 16 Hz. Their results confirmed that the energy needed to produce threshold damage raised the temperature to a level greater than that associated with damage in the in vivo corneas. This result provides additional strong evidence that the damage from sequences of 80-ns pulses has a substantial thermal component. As noted previously with regard to thresholds for single-pulse exposures, McCally and Bargeron suggested that the lower damage temperatures for the 80-ns pulses might be a result of thermal damage potentiated by thermoelastic stress waves.[23]

Figure 13-4. Calculated temperature-time histories at a depth of 10 μm below the anterior tear surface for three of the exposures listed in Table 13-5: (a) Four 0.0097 sec pulses at 10 Hz. (b) Four 0.010 sec pulses at 20 Hz. (c) Thirty-two 0.0099 sec pulses at 20 Hz.

Data sources: (1) Farrell RA, McCally RL, Bargeron CB, Green WR. Structural Alterations in the Cornea From Exposure to Infrared Radiation. Laural, MD: Applied Physics Laboratory, Johns Hopkins University; 1985. Report TG 1364. (2) Bargeron CB, Deters OJ, Farrell RA, McCally RL. Epithelial damage in rabbit corneas exposed to CO_2 laser radiation. Health Phys. 1989;56:85–95.

Early investigations of retinal damage from multiple-pulse exposures45,51 showed that thresholds were correlated by an empirical relationship of the form

In this equation, Hth is the radiant exposure per pulse and N is the number of pulses. Ideally, the constant C would be the threshold radiant exposure for a single pulse, and would therefore depend on pulse duration. Bargeron et al[13] found that their data (see Table 13-5) were consistent with this type of relationship. This question can be considered in more detail, specifically, whether multiple-pulse thresholds can be described by an empirical power law of the form

where the exponent α may differ from 0.25. Figure 13-5 shows threshold radiant exposure per pulse as a function of the number of pulses for exposures with individual pulse widths of ~10 ms and ~1 ms, respectively. The lines are least-squares fits to Equation 13-4 for N > 1. The plots show that Equation 13-4 indeed describes multiple-pulse threshold data, but that the exponent α appears to increase with pulse repetition frequency. For pulse widths near 10 ms, the values of C are somewhat above the 10-ms single-pulse threshold (21% in the worst case); however, for pulse widths near 1 ms, the values of C are substantially below the 1-ms singlepulse threshold. In the latter case, if the measured single-pulse threshold was used for the constant C, the power law relationship would overestimate thresholds for larger numbers of pulses, and the resultant margin of safety would be reduced. A similar result was reported for multiple-pulse thresholds for 2.02 μm radiation from a Tm:YAG laser.[16] These results will be discussed later in this chapter. McCally and Bargeron found that the relationship in Equation 13-4 accurately described the data in Table 13-6 for sequences of 80-ns pulses.[23] For the 10-Hz thresholds, C = 0.29 J/cm^2/pulse and α = 0.16, and for the 16 Hz thresholds, C = 0.30 J/cm^2/pulse and α = 0.19. These values of the constant C are very close to the threshold for a single 80-ns pulse (0.307 J/cm^2/ pulse), and the exponent α again appears to increase with pulse repetition frequency, just as it did for the 1-ms and 10-ms pulses.

Figure 13-5. The dependence of the threshold radiant exposure per pulse as a function of the number of pulses from a CO_2 laser (data are from Table 13-5). Individual pulse durations are ~10 ms in (a) and ~1 ms in (b). The lines are leastsquares fits to a power law of the form Hth = CN–α

Hth: threshold radiant exposure per pulse; C and α: constants that are determined from the fit of the line to the data; N: number of pulses in the repetitive pulse train

Data sources: (1) Farrell RA, McCally RL, Bargeron CB, Green WR. Structural Alterations in the Cornea From Exposure to Infrared Radiation. Laural, MD: Applied Physics Laboratory, Johns Hopkins University; 1985. Report TG 1364. (2) Bargeron CB, Deters OJ, Farrell RA, McCally RL. Epithelial damage in rabbit corneas exposed to CO_2 laser radiation. Health Phys. 1989;56:85–95.

Endothelial Injury Thresholds

An early report by Beatrice and Stuck suggested the possibility of endothelial cell damage near the threshold exposure level for epithelial cell injury.[35] At exposure levels near the epithelial injury threshold, they reported staining of endothelial cells with the vital stain trypan blue. They noted that such staining is indicative of altered biochemical cell processes and called for further evaluation of the significance of these suggested cellular alterations. Unlike the epithelium, in which threshold lesions are repaired by regenerating cells, the human endothelium is repaired primarily by undamaged cells enlarging and sliding to cover the wound.[52] Thus, the effect of repeated exposures could be cumulative.

Motivated by the Beatrice and Stuck report, Bargeron et al undertook an investigation to determine endothelial damage thresholds for exposures to CO_2 laser radiation.[53] In their experiments, corneas of anesthetized rabbits were exposed to radiation from a CO_2 laser operating in the TEM_00 mode, which has a Gaussian irradiance profile given by Equation 13-2. Thresholds were determined for peak irradiances, I^0, of 24.5, 10.0, and 3.6 W/cm^2, with a beam radius, r1/e = 0.10 cm. In determining the damage thresholds, exposure durations were increased above those for the corresponding epithelial injury thresholds at their respective irradiance levels to determine the minimum time to produce endothelial damage. Rabbits were sacrificed 2 hours postexposure, and damage was detected by staining the endothelium with alizarin red S and trypan blue (or indocyanine green).[54] In a few instances, rabbits receiving the 10 W/cm_2 exposure were sacrificed at 24 and 48 hours postexposure. The same threshold was obtained.

Table 13-7 lists the exposure times required to produce minimal endothelial damage at the three irradiance levels. These times are approximately five to ten times larger than the epithelial damage thresholds for corresponding irradiances (see Table 13-2). Also listed in Table 13-7 are peak temperature increases on the beam axis at the position of the endothelium (the average thickness of the corneas in the study was 400 μm). These temperature increases are similar to those found for threshold epithelial damage (see Table 13-2), suggesting that both cell types have a similar critical damage temperature. This result is especially significant with exposures to more penetrating infrared radiation. Such radiation causes much more uniform heating of the entire depth of the cornea; consequently, there is a risk of endothelial damage at exposures close to the epithelial injury threshold. This issue will be discussed in more depth later, relative to 1.54 μm radiation exposures.

TABLE 13-7
ENDOTHELIAL DAMAGE THRESHOLDS

Ith[*] (W/cm^2)

τ (s)

Beam diameter[†] (cm)

ΔTmax [‡] (°C)

24.5

1.0

0.200

50

10.0

5.2

0.200

50

3.6

240

0.200

32

*Peak irradiance.

†Gaussian beam (1/e diameter).

‡Calculated at depth of 400 μm, which was the average position of the endothelium in these experiments.

τ: exposure duration

Ith: irradiance threshold

ΔTmax: maximum temperature increase

Ith: irradiance threshold

Data source: Bargeron CB, Farrell RA, Green WR, McCally RL. Corneal damage from exposure to IR radiation: Rabbit endothelial damage thresholds. Health Phys. 1981;40:855–862.

According to Bargeron et al, 2 hours after an exposure at the endothelial damage threshold, a slit-lamp examination showed severe corneal edema at the lesion site and intense stromal light scattering to a depth of ¾ to full corneal thickness.[53] They noted that the severity of anterior damage depends strongly on irradiance level. In particular, the 1-second, 24.5 W/cm^2 exposure destroyed the epithelium and severely cratered the stroma. By contrast, the 240-second, 3.5 W/cm^2 exposure damaged but did not destroy the epithelium and did not cause stromal cratering. Bargeron et al noted further that threshold damage was characterized by distorted cells and uneven staining of cell borders.[53] The boundary between damaged and undamaged regions was quite sharp. The staining characteristics of alizarin red S appeared to be more indicative of thermal damage than trypan blue. Trypan blue (or indocyanine green) staining was more sporadic and was often associated with preparation artifacts such as folds.53,55

Corneal Stromal Effects

Keratocyte Injury Thresholds

McCally et al[55] have observed that when exposed at levels between the epithelial and endothelial damage thresholds, corneas developed characteristic saucershaped stromal lesions. At 48 hours postexposure, lesion edges were extremely well defined when viewed in the slit-lamp; histology revealed that the injured area was essentially devoid of cells. Moreover, keratocytes lying just beneath the cell-free region were found to be normal. These observations suggest comparable epithelial and endothelial thresholds. Likewise, stromal keratocyte injury threshold is sensitive to a comparable laser-induced thermal insult.

To investigate this hypothesis, McCally et al[55] exposed rabbit corneas at two levels: 9.7 W/cm^2 (peak irradiance) for 2.5 seconds, and 26 W/cm^2 for 0.4 seconds. The 1/e beam diameters were 0.188 cm and 0.240 cm, respectively. The durations of these exposures are about four times longer than those required to produce threshold epithelial lesions. The investigators noted that each exposure produced similar damage. One hour after an exposure of 26 W/ cm^2 for 0.4 seconds, there was an interior circular area about 0.2 cm in diameter surrounded by a raised ring of epithelium. Histology revealed that the epithelium was destroyed in the interior circular area. By 48 hours postexposure, such lesions were covered by a smooth layer of epithelial cells and the cornea had recovered its normal thickness.

Slit-lamp photographs were made with geometry that enabled accurate measurements of the depth of the lesion border beneath the corneal surface.[55] The lesion borders (stromal and epithelial) resulting from the 9.7 W/cm^2, 2.5-second exposure had a 47°C temperature rise. The lesion borders resulting from the 26 W/cm^2, 0.4-second exposure had a 52°C temperature rise. These maximum temperature rises, calculated at the center of the beam in the stroma, corresponded closely to those calculated at the edge of the lesion at the epithelial surface. These results suggest that epithelial cells, stromal keratocytes, and endothelial cells have essentially the same thermal damage mechanism.

Healing Response to Deep Stromal Burns

As part of their research supported by what was then the Army Medical Research and Development Command, Farrell et al investigated long-term healing response to deep stromal wounds of the type discussed in the previous section.[7] In their study, two groups of rabbits were exposed at 25 W/cm^2 for 0.4 seconds. All exposures were made to the central cornea with a 1/e beam diameter of 0.28 cm. Rabbits in the first group were examined by slit-lamp at 1, 24, and 48 hours, and at 1, 2, 4, and 8 weeks postexposure. Two rabbits were sacrificed at each of these time points, and their corneas were prepared for light and electron microscopy. In the second group, slit-lamp observations were made at 3, 4, and 5 days postexposure, and one rabbit was sacrificed at each of these time points for light and electron micros microscopy. The remaining three rabbits in this group received slit-lamp examinations up to 11 months postexposure.

The characteristics of the wounds at 1 and 48 hours postexposure were described in the previous section. At 24 hours, the completely opaque epithelium remained and covered the wound in some corneas. In other corneas, the opaque covering had sloughed, revealing the bright, light-scattering stromal wound. At this time, a ~30-μm-thick immature epithelial layer covered the wound. Basal cells had not yet attained their usual columnar form, and there was just a single layer of wing cells.[7]

At 1 week, the appearance of the wound in the slitlamp resembled its appearance at 48 hours. However, by 2 weeks, the anterior surface of the cornea was slightly flattened and the cornea appeared thinner in the lesion area. Histology revealed that the epithelium was completely normal at 1 week and the stroma was still acellular, although some debris of necrotic keratocytes remained. By 2 weeks postexposure, the stroma was repopulated by keratocytes.[7]

Stromal thinning and flattening persisted at 4 weeks and 8 weeks postexposure. At 4 weeks, the lesion was still clearly visible in a narrow-slit view, but it was only faintly visible in wide-slit views. Stromal scattering was confined to the anterior-most region. At 8 weeks, the anterior scattering was diminished and, although it remained visible in narrow-slit views, the hazy lesion area was very faint in wide-slit views.[7]

No involvement of vascular components (eg, monocytes or polymorphonuclear leukocytes) or vascularization of the cornea was observed during the 8-week period. Moreover, the endothelium and Descemet membrane were observed as normal throughout this period.7 It should be noted, however, that the wounds in this study had small diameters compared to the cornea and were located in the central cornea, well away from the limbus. It is possible that a wound of this type could present more serious complications if it were located near the limbus, or if limbal area involvement elicited a vascular response.

Observations of the second series of rabbits were unremarkable at 8 months and 11 months postexposure. By 8 months, the lesion was undetectable using wide-slit illumination, but a very slight increase of anterior scattering was still visible with a narrow slit. The stroma remained thin in the wound area. Lesion appearance was essentially the same at 11 months postexposure.[7]

THERMAL MODELS AND TEMPERATURE MEASUREMENTS

The literature describes several thermal models for calculating the temperature-time history of corneas that have been exposed to laser radiation.13,20,36,49,56-58

T(r,t), is obtained from the solution of the heat diffusion equation,

with appropriate boundary conditions.[59] The absorbing medium (tear layer and cornea) occupies the halfspace, z ≥ 0. In this equation, ρ is the density, C is the heat capacity, ∂ is the partial derivative of temperature T with respect to time t, K is the thermal conductivity, A is the volume production of heat that results from absorption of the incident laser radiation, and the position vector, r, is usually expressed in cylindrical polar coordinates (r, θ, z). The density, heat capacity, and thermal conductivity of the cornea are assumed to be the same as water.13,20,36,48,56-5813,20,36,48,56–58 The models also assume that there is no scattering and that absorption is described by Beer’s law (see Equation 13-1). In the case of uniform incident illumination as treated by Peppers et al,[20] the heat production term is given by

where u(t) describes the time-dependence of the incident radiation, α is the absorption coefficient, and I_0 is the irradiance. In the more general case of an incident Gaussian beam (see Equation 13-2), the heat production term is given by

where, in this case, I_0 is the peak irradiance.56,57 The form of u(t) is usually taken to be that of a Heaviside unit step function, that is, u(t) = 1 for t > 0 and u(t) = 0 for t ≤ 0.

Mainster et al[57] provided numerical solutions to Equation 13-5 for a Gaussian beam incident on the cornea. They ignored convective heat transfer at the cornea-air interface, but did account for the possibility of heat conduction into the air. The initial temperature, T(r,0), was assumed to be zero; thus, the solution described the temperature rise. Takata et al[48] extended this model, and it was also used extensively by Egbert and Maher.[36] Peppers et al[20] provided an analytic solution to Equation 5 for the case of uniform incident irradiation, again assuming that there was no heat transfer at the corneaair interface (ie, ∂T(z,t)/∂zz=0 = 0), and also that T(z,0) = 0. Peppers et al noted that the 1-dimensional model would be adequate to predict epithelial temperature increases for short exposures (even with a Gaussian beam), but that it would not be accurate for longer exposures, when the effects of radial heat transfer become important. Subsequently, Chang and Dedrick[56] developed a Green’s function solution to Equation 13-5 for an incident Gaussian beam, accounting for radial heat transfer. Their solution assumes the same boundary conditions as those used by Peppers et al. The solution is given by a definite integral

where

In Equation 9, erfc(x) is the complementary error function given by

Equations 8 and 9 can be integrated numerically to provide the temperature at any position within the cornea.13,23,53,55,58,60 Rectangular pulses of duration τ can be represented as the difference of two Heaviside unit step functions. Thus, according to the principle of superposition, the temperature history resulting from exposure to a rectangular pulse of duration τ is given by

Bargeron et al[58] conducted a series of experiments to test the efficacy of Chang and Dedrick’s model. The epithelial surface of a freshly excised rabbit cornea was irradiated with a CO_2 laser (Gaussian beam profile). The cornea was mounted in a special holder, and its endothelial surface was bathed with Ringer solution pressurized hydrostatically to maintain the natural curvature of the cornea. A 25-μm diameter chromel-alumel thermocouple was inserted through the back of the holder, and its junction was positioned at the endothelial surface with the aid of a slit-lamp microscope. The small thermal inertia associated with this thermocouple gave it a sufficiently rapid response time (conductive heat loss from the junction via the small-diameter wires was negligible). It was essential to align the probe accurately on the axis of the invisible incident Gaussian beam. This was accomplished by moving the entire corneal holder/thermocouple assembly with an x-y micropositioner until a maximum temperature rise was recorded from a very low exposure (~25 W/cm^2 for 0.05 seconds; this is about half the epithelial damage threshold at this irradiance; see Table 13-3). By this method, Bargeron et al were able to locate the probe to within about 0.01 cm of the center of the beam (d1/e = 0.20 cm).

Temperature-time histories were measured with the thermocouple in a 380-μm-thick cornea. The exposures corresponded respectively to the epithelial and endothelial injury thresholds for the given peak irradiance. Temperature was calculated from Chang and Dedrick’s model. Although calculated temperatures were higher than measured temperatures, their agreement is quite reasonable. Small discrepancies can be understood in terms of the assumptions of the model and potential sources of error in the measurements. In addition to the assumptions noted above (eg, no heat transfer at the cornea-air interface), the model also ignores effects of water vaporization and collagen melting, as well as the fact that temperature rise at the endothelium can induce connective currents in the fluid bathing the endothelial surface. Because these effects, which would act to reduce the temperature, are not accounted for in the model calculations, the calculated temperature rise would exceed the actual temperature rise. In addition, possible measurement errors (eg, imperfect thermal contact between the probe and endothelial surface, heat loss in thermocouple leads, and finite thermocouple response time), though assumed to be small, also would act to reduce measured temperature. Thus, reasonable agreement between measured and calculated endothelial temperature- time histories indicates that together with the use of thermal properties of water in the calculations, the assumptions of the model are justified, at least for CO_2 radiation. (Bargeron et al also used a liquid crystal technique to measure the spatial and temporal variations of temperature at the endothelial surface.[58] Although it is not discussed here, that method led to similar reasonable agreement with the calculations, both on- and off-axis.)

There are two classes of thermal models generally used to predict threshold corneal damage: damage integral models12,36,48 and critical temperature (or critical peak temperature) models.13,15,16,20,36,53,55,57 A third model has also been proposed[13]13 based on the occurrence of an endothermic phase transition at the anterior surface. All three models require temperature calculations such as those discussed in the preceding section.

The damage integral model formulation is based on the idea that thermal damage is due to heat denaturation of constituent tissue molecules (eg, proteins).12,61 Damage models usually assume that denaturation can be described by a first-order reaction. The reaction rate is then given by

where k is Boltzmann’s constant, T is the absolute temperature, h is Plank’s constant, and k* is the equilibrium constant between the normal and activated states of the molecules undergoing the reaction. The equilibrium constant is related to the free energy, ∆G = ΔH – TΔS, by

where ΔS is the entropy of activation and ∆H is the enthalpy of activation. These relationships are usually expressed in the form of an Arrhenius rate process, k’ = A exp(–E/RT), where the frequency factor, A, is given by

where R is the universal molar gas constant and E is an activation energy associated with the reaction.

These concepts are discussed in detail by Dawes.[62] Henriques used these ideas to characterize burn injuries in skin.[63] He formulated a damage integral given by

and chose values of A and E such that Ω(r,z) = 1 corresponded to irreversible damage. The upper limit of the integral is usually taken to be the time at which the tissue returns to its initial temperature. This formulation has been used successfully to predict threshold injuries in the cornea, particularly for single-pulse exposures. However, as noted previously, it does not provide a good estimate of epithelial injury thresholds from multiple-pulse exposures.

Brownell and Stuck determined values of A and E/R by fitting Equation 13-13 to their experimentally determined epithelial and skin injury thresholds for exposure to CO_2 laser radiation.[12] For cornea, they found A = 3.13 × 10^61 sec–1 and E/R = 48,400 K, whereas for skin (white pigs) they found A = 4.21 × 10^63 sec–1 and E/R = 49,000 K. These skin values differ substantially from those found by Henriques (A = 3.1 × 10^98 sec–1 and E/R = 75,000 K)63 and later by Takata (A = 4.3 × 10^64 sec–1 and E/R = 50,000 K for 317 K < T< 323 K and A = 9.4 × 10^104 sec–1 and E/R = 80,000 K for T ≥ 323 K).48 Such differences are likely due to the exposure of different areas and types of skin and to the definition of damage endpoints. Obviously, because both A and E are very large numbers, model predictions are highly sensitive to chosen values.

The idea that thermal damage occurs at a critical temperature has long been cited in the biological literature. 20,36,64 Peppers et al noted that their epithelial damage thresholds for CO_2 laser exposure durations between 3.5 ms and 55 ms were associated with a temperature increase of about 35°C.[20] Bargeron et al found that peak temperature rises were essentially constant for CO_2 laser threshold exposure durations between 0.01 and 1 second, where they averaged 40 ± 2°C. However, there was a slight variation over this entire range. This type of variation, in which the predicted damage temperature increased as the exposure durations decreased, had been noted earlier by Egbert and Maher.[36] They analyzed threshold data from several groups and several laser types in terms of critical temperature damage and damage integral models. To account for slight variation in damage temperature, Egbert and Maher proposed an empirical critical peak temperature damage model as

In this equation, the temperature is calculated on the beam axis at a depth of 6 μm beneath the anterior tear surface, τ is the exposure duration, and the critical peak temperature, CPTEM, is the sum of the peak temperature increase and the ambient temperature of the cornea surface (assumed to be 35°C^50). Bargeron et al found that their data were described by a similar empirical relationship,

where peak temperatures were calculated on the beam axis at a depth of 10 μm beneath the anterior tear surface. Empirical relationships such as these depend on damage endpoints and the location where the temperature is calculated. Thus, as was noted by Egbert and Maher, the CPT does not represent an actual damage temperature; rather, it is a convenient parameter that relates the peak temperature at a chosen location on the beam axis to the experimental threshold exposure.

Bargeron et al postulated that threshold damage might be due to the occurrence of an endothermic phase transition in the lipids of proteins in the epithelium. [60] They based this idea on the observation that the measured threshold radiant exposure appeared to be approaching an asymptotic value as the exposure duration decreased (for durations 0.001–10 seconds; see Figure 13-3). They also noted that because heat losses due to conduction would be minimal, very-shortduration exposures would approximate the behavior of a thermally isolated epithelium. Moreover, if damage were associated with an endothermic phase transition, a thermally isolated epithelium would sustain damage when it absorbed enough energy to transition its temperature and to supply the latent heat needed to cause the transition. In the case where the epithelium is not thermally isolated (ie, for longer-duration exposures), additional energy would be necessary to compensate through conduction.

To examine this hypothesis, Bargeron et al developed a simple two-part, one-dimensional model based on a surface absorber. The first part of the model corresponds to the classic problem of a uniform flux of heat, F0, incident on a semi-infinite slab.[59] The surface temperature rises as the square root of time until the transition temperature, Tc, is reached at time tc (Tc and tc are parameters to be determined from the data). At times greater than tc, the surface temperature remains constant (this is analogous to a water-ice mixture that remains at 0°C during melting). For times greater than tc, the model corresponds to a second classical problem in which a semi-infinite slab has an initial temperature distribution given by the solution to the first part at tc, and its surface is maintained at Tc.[59] The amount of heat per unit surface area that goes into the transition, Qc, was calculated as the difference between the incoming flux and the quantity of heat per unit area per unit time conducted into the cornea (Qc is a parameter to be determined from the data). Because the data were obtained with a Gaussian beam, the flux was chosen such that, in the absence of a phase transition, calculated peak temperature at the end of the exposure would be the same as for the actual Gaussian beam. The model provided excellent fits to the data for Tc = 33°C and Qc = 0.84 J/cm^2. This value of Tc is in the range found for protein dena-turation or for phase transitions of certain lipids.65-67 Bargeron et al[13] noted that if approximately 5% of the epithelial material in the wound area underwent the phase transition, the value of Qc would correspond to a latent heat of ~80 calories per gram.[13] They observed that although this value is about three times greater than values reported for proteins and lipids,65-67 the result was encouraging given the model’s simplicity and assumptions.

CORNEAL EFFECTS AT OTHER LASER WAVELENGTHS

Epithelial Injury Thresholds for Erbium Glass Laser Radiation

Corneal injury thresholds have been determined for 1.54 µm radiation from Er glass lasers operating in either the free oscillation (long pulse) or Q-switched modes.17,18,26 When operating in the long-pulse mode, an Er glass laser emits an envelope of closely spaced short pulses, each having a duration of ~1.5 µs. The total duration of the envelope is ~1 ms. In the Q-switched mode, the Er glass laser emits a single pulse of duration 40 to 50 ns. The beams of the lasers used in the investigations discussed below were approximately Gaussian.

Lund et al[18] determined the damage threshold in owl monkey cornea for Q-switched radiation. The ED_50 was 21 J/cm^2 (Table 13-8). They investigated exposures up to ~70 J/cm^2 and found that damage was limited to the cornea even at the highest exposures. All exposures greater than 30 J/cm^2 produced damage; no damage was observed for exposures below 17 J/cm^2. Lesions just above threshold were characterized by a shallow depression in the epithelial surface with localized epithelial edema. Grayish opacities were evident in the Bowman layer and anterior stroma. The lesions stained mildly with fluorescein. The more severe lesions had a whiter opacification that penetrated to deeper stromal layers, and wrinkling of the Descemet membrane occurred in some cases. The stromal opacification in these lesions was unchanged for up to 3 weeks postexposure. Histology of the fresh lesions revealed coagulation of the epithelium, Bowman layer, and anterior stroma. Healed lesions showed epithelial proliferation and collagenous scar tissue in the anterior stroma.

TABLE 13-8
EPITHELIAL DAMAGE THRESHOLDS FOR ERBIUM GLASS, HOLMIUM, HYDROGEN FLUORIDE, AND DEUTERIUM-FLUORIDE LASERS

Laser

Wavelength (μm)

τ(sec)

Beam diameter (cm)

ED_50 (J/cm^2)

Ref

Er

1.54

0.93 × 10–3

0.1[*]

9.6

1

Er

1.54

1.0 × 10–3

0.1–0.2

7.2

2

Er

1.54

40 × 10–9

0.1–0.2

4.7

2

Er

1.54

50 × 10–9

0.1*

21.0

3

Ho

2.06

42 × 10–9

0.032

5.2

1

Ho

2.06

100 × 10–6

0.18

2.9

1

HF

2.6–2.9

45 × 10–9

0.082

0.156

4

DF

3.6–3.9

100 × 10–9

0.096

0.377

4

*Gaussian beam (1/e diameter).

τ: exposure duration

DF: deuterium-fluorid

Er: erbium glass

HF: hydrogen fluoride

Ho: holmium

Ref: reference

(1) Stuck BE, Lund DJ, Beatrice ES. Ocular effects of holmium (2.06 μm) and erbium (1.54 μm) laser radiation. Health Phys. 1981;40;835– 846. (2) Avdeev PS, Gudakovskii YP, Muratov VR, Murzin AG, Fromzel VA. Experimental determination of maximum permissible exposure to laser radiation at 1.54 μm wavelength. Sov J Quantum Elec. 1978;8:137–139. (3) Lund DJ, Landers MB, Bresnick GJ, Powell JO, Chester JE, Carver C. Ocular hazards of the Q-switched erbium laser. Invest Ophthalmol. 1970;9:463–470. (4) Dunsky IL, Egbert DE. Corneal Damage Thresholds for Hydrogen and Deuterium Fluoride Chemical Lasers. Brooks Air Force Base, TX: US Air Force School of Aerospace Medicine; 1973. Report SAM-TR-73-51.

Stuck et al[17] used a slightly modified version of the laser used by Lund et al to determine injury thresholds in rhesus monkeys for the long-pulse mode. With this laser, the duration of the envelope was 0.93 ms at the half-power points and 1.6 ms overall. The ED_50 was 9.6 J/cm^2 (see Table 13-8). The diameter of the lesions was dose dependent; higher doses produced largerdiameter lesions. Doses of 15 J/cm^2 produced strongly light-scattering conical-shaped lesions in the stroma. The lesions produced in the long-pulse mode were visible immediately after exposure and persisted for up to 10 months with little change of appearance in the scar. No lenticular effects were observed.

One monkey was administered nine closely spaced exposures of 15 to 18 J/cm^2 in one eye. The eye was observed using specular microscopy for 10 months. After 10 months, the monkey was sacrificed, and the endothelium of the exposed cornea was stained with trypan blue and alizarin red dye. Specular microscopy showed essentially no change in the endothelial cell density in the regions immediately adjacent to the wounds (the region immediately under the wounds could not be observed because of the dense scar). Endothelial cell density determined from the stained cornea was substantially reduced from the preexposed value (2,140 ± 190 cells/mm^2 vs 3,260 ± 180 cells/mm^2), and the cells under the wounds were irregular in shape. Histology of these lesions showed disruption and undulation of the Bowman layer, and the keratocytes were enlarged and irregular in shape throughout the entire depth of the cornea.

Avdeev et al[26] determined injury thresholds in chinchilla corneas for both Q-switched and longpulse modes. Their exposure conditions are listed in Table 13-8. Their ED_50 value of 4.7 ± 1.2 J/cm^2 for the Q-switched mode was nearly four times less than that obtained by Lund et al,[18] and their ED_50 value of 7.2 ± 0.6 J/cm^2 for the long-pulse mode also was somewhat less than that obtained by Stuck et al.[17] The reasons for these differences are not readily apparent. It is unlikely that they are due to the species differences. Moreover, the differences in the reported durations of the Q-switched pulses in the two studies (40 ns vs 50 ns) are unlikely to account for the four-fold difference in thresholds.

Epithelial Injury Thresholds for Holmium Laser Radiation

Stuck et al determined corneal injury thresholds in rhesus monkeys for exposures to 2.06 μm radiation from a Holmium laser operating in either free oscillation (long-pulse) or Q-switched modes.[17] In long-pulse mode, the beam profile was not Gaussian and was neither uniform nor circular; laser output consisted of a series of pulses in an envelope whose duration at the half-power points was 100 μs. The envelope decayed to 0 in 260 μs. In the Q-switched mode, irradiance profile was approximately Gaussian; the laser emitted a single pulse having a duration of 42 ns at the half-power points. The ED_50 for the long-pulse mode was 2.9 J/cm^2, with an effective beam diameter of 0.018 cm, and increased to ~4.1 J/cm2 when the effective beam diameter was reduced to 0.011 cm (see Table 13-8). In the Q-switched mode the 50 was 5 J/cm^2, with a beam having a 1/e diameter of 0.032 cm (see Table 13-8). The diameter of the lesions was dose dependent, and their depth extended to the anterior ⅛ to ¼ of the cornea. Long-pulse lesions near ED50 were not visible after 24 hours, but resulted in a mild stromal scar. Lesions produced near ED50 in the Q-switched mode were difficult to see at 1 week postexposure, but lesions resulting from exposures greater than 8 J/cm^2 produced a stromal scar that remained visible at 8 months. Histology obtained 3 months after a Q-switched exposure of 19 J/cm^2 showed alterations in the Bowman layer and a scar in the superficial stroma. For exposures that involved the anterior ¼ of the stroma, scars were observed 10 months postexposure.

SUMMARY

Dose-response relationships for corneal effects of infrared laser exposure have been characterized in animal models. Computational models that calculate temperature-time histories within the cornea have complemented the experimental threshold determinations to assist in development of permissible exposure limits for a wide range of exposure conditions. Accidental or purposeful military exposures from infrared lasers will not be limited to the cornea, but will also involve exposure or injury to the ocular adnexa and surrounding skin. With the development and deployment of small, high-energy lasers that emit 50 to 100 kW for ship or area defense, the likelihood increases that military personnel will be exposed. Methods to manage the medical consequences of such exposures must be investigated, and new treatment regimes developed.

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ABBREVIATIONS and ACRONYMS

A

AA: air-to-air

ABL: airborne laser

ACGIH: American Conference of Governmental Industrial Hygienists

ACP: air commander’s pointer

AD: air defense

ALL: airborne laser laboratory

AMC: Army Materiel Command

AMEDD: Army Medical Department

AMEDDC&S: Army Medical Department Center and School

AMRDC: Army Medical Research and Development Command

ANSI: American National Standards Institute

APC: armored personnel carrier

AR: Army regulation

ArF: argon fluoride

ARPA: Advanced Research Projects Agency (US Department of Defense)

AT: antitank

ATGM: antitank guided missile

AVS: Aidman Vision Screener

B

BLPS: Ballistic and Laser Protective Spectacles

BMP: Boyevaya Mashina Pekhoty (Russian for “infantry fighting vehicle”)

BOLT: bomb, laser, target

BRAC: Base Realignment and Closure

C

C-CLAW: close-combat laser assault weapon

CIE: International Commission on Illumination (Commission Internationale de l’Éclairage)

CLGP: cannon-launched guided projectile

COIL: chemical oxygen-iodine laser

C-RAM: counter rockets, artillery, and mortar rounds

C-RAMD: counter rockets, artillery, mortar rounds, and drones

CSLO: confocal scanning laser ophthalmoscopy

CW: continuous wave

D

DARPA: Defense Advanced Research Projects Agency (successor to ARPA)

DF: deuterium-fluoride

DoD: Department of Defense

DoDI: DoD Instruction

DPI: dual Purkinje image

E

ED_50: median effective dose

EDL: electrical discharge laser

ELRF: eyesafe laser rangefinder

ELTEP: Emerging Laser Threat Eye Protection (program)

Er: erbium-doped

F

FIST-V: fire support team vehicle

FM: Farnsworth Munsell

FM: field manual

G

GA: General Atomics

GaAlAs: gallium-aluminum-arsenide

GaAs: gallium arsenide

G-BAD: ground-based air defense

GBU: guided bomb unit

GCP: ground commander’s pointer

GDL: gas dynamic laser

GLATGM: gun-launched antitank guided missile

G/VLLD: ground/vehicular laser locator designator

H

He-Cd: helium-cadmium

HEL: high-energy laser

HELLADS: high-energy liquid laser area defense system

He-Ne: helium-neon

HF: hydrogen fluoride

HMMWV: high-mobility multipurpose wheeled vehicle

Ho: holmium

I

ICG: indocyanine green

ICNIRP: International Commission on Non-Ionizing Radiation Protection

ICRC: International Committee of the Red Cross

IEC: International Electrotechnical Commission

IFV: infantry fighting vehicle

IRSF: intraretinal scar formation

ISMT: indoor simulated marksmanship trainer

J

JLST: Joint Laser Safety Team

JLTV: joint light tactical vehicle

K

KrF: krypton fluoride

L

LADS: laser area defense system

LAIR: Letterman Army Institute of Research

LAMC: Letterman Army Medical Center

LAPD: Los Angeles Police Department

LAV: light-armored vehicle

LaWS: Laser Weapon System

LCMS: laser countermeasures system

LED: light-emitting diode

LEL: low-energy laser

LEP: Laser Eye Protection

LGM: laser-guided munitions

LLDR: lightweight laser designator rangefinder

LMB: Lasers on the Modern Battlefield (conference)

LOSAT: line-of-sight antitank

M

MAD: mobile Army demonstrator

MD: mobile demonstrator

MELIOS: mini-eyesafe laser infrared observation set

MILES: Multiple Integrated Laser Engagement System

MIRACL: midinfrared advanced chemical laser

MLRF: miniature laser range finder

MPE: maximum permissible exposure

MRT: military ruggedized tablet

MTHEL: mobile tactical high-energy laser

MTU: mobile test unit

MULE: modular universal laser equipment

MVL: minimum visible lesion

N

NATO: North Atlantic Treaty Organization

Nd:YAG: neodymium-doped yttrium aluminum garnet

NFL: nerve fiber layer

NHP: nonhuman primate

NIR: near-infrared

NOHD: nominal ocular hazard distance

O

OCT: optical coherence tomography

OD: right eye (ocular dexter)

OPA: optical phased array

OS: left eye (ocular sinister)

P

PEO: Program Executive Office

PLC: pocket laser communicator

PMB: papillo-macular bundle

PRF: pulse repetition frequency

PRL: preferred retinal location

R

RBS: Robotsystem

R&D: research and development

RDT&E: research, development, test, and evaluation

RHME: retinal heating, moving eye (model)

RNFL: retinal nerve fiber layer

ROBS: rapid optical beam steering

RPE: retinal pigment epithelium

S

SAM: surface-to-air missile

SDI: strategic defense initiative

SLO: scanning laser ophthalmoscopy

SRI: Stanford Research Institute

SSL: solid-state laser

T

TD: technology demonstrator

TEM: transverse electromagnetic

THEL: tactical high-energy laser

TIE: total intraocular energy

TLOS: target location and observation system

Tm:YAG: thulium yttrium aluminum garnet

TOW: tube-launched, optically tracked, wire-guided

TSL: tri-service laser

U

UAV: unmanned aerial vehicle

UNFT: unified Navy field test

USACHPPM: US Army Center for Health Promotion and Preventive

Medicine (now the US Army Public Health Center)

USAMRD: US Army Medical Research Detachment

UV: ultraviolet

V

VA: visual acuity

VEP: visual-evoked potential

W

WRAIR: Walter Reed Army Institute of Research

INDEX

A

AABB, 51, 52, 57, 59–60, 106, 132, 170, 201–202

Abbott Laboratories, 55, 56, 108, 187

ABCC. See Armed Services Blood Program Blood Coordinating Committee

Aberdeen Proving Ground, Maryland, 77

ABP. See Army Blood Program

ABPO. See Army Blood Program Office

Accreditation, 57, 59–62

ACD. See Acid-citrate-dextrose anticoagulant

Acid-citrate-dextrose anticoagulant, 5, 62

ACP215, 145, 146, 168, 170

Acquired immune deficiency syndrome, 85–87, 106, 216

Adamian, Wendy, 176

Additive solutions, 82, 176

Adsol, 82, 84

Adviento, Jocelyn, 192

Agiliu, Louis, 34

AIDS. See Acquired immune deficiency syndrome

Air Force Blood Transshipment Center, 159

Akeroyd, Joseph H., 5, 6, 201, 211–212

Alanine aminotransferase liver test, 84, 107

Albert, Specialist 4th Class, 40

Class, 40

Allen, Turman, 60

Alley, Jack, 192

Alsever’s solution, 2, 5

ALT. See Alanine aminotransferase liver test

AMEDD. See Army Medical Department

AMEDDC&S. See Army Medical Department Center and School

American Association of Blood Banks, 52, 57, 59–60, 106, 132, 170, 201–202

B

Ballistic and Laser Protective Spectacles, 12

Base Realignment and Closure, 6

Beam riders, 30

Beatrice, Lieutenant Colonel Edwin S., 7, 8, 9, 10

Bedel, Major R. Bruce, 7

Bigler, First Lieutenant Duane, 7

Biomedical research team, 5, 6

Blaser tracking simulator, 9–10, 123, 124, 126–127

Blinding Weapons, 143

Blink reflex, 99–100, 117–119

Bloch’s law, 105

Bloom, Kenneth, 7

BLPS. See Ballistic and Laser Protective Spectacles

BOLT-117, 28

Bombs, laser-guided, 28

BRAC. See Base Realignment and Closure

Brightness enhancement, 100

Broas, Reynaldo, 16

Broca-Sulzer effect, 100

Brooks Air Force Base, 14

Brown, Major Jeremiah, Jr., 16

Brownell, Arnold S., 7

Bunsen-Roscoe law of reciprocity, 105

Butts, Calvin, 7

C

C-CLAW. See Close-combat laser assault weapon

C-RAMD, 41

Cameo Bluejay, 36

Cannon-launched guided projectiles, 29

Carbon dioxide lasers

cornea endothelial injury thresholds, 264

cornea epithelial injury thresholds, 256–265

corneal stromal effects, 264–265

Carpino, Eugene D., 7

Carver, Charles T., 7

Cataracts, 156–157

Chemical oxygen-iodine laser, 15

Chirped pulse amplification, 241–242

CIE. See International Commission on Illumination

CLGPs. See Cannon-launched guided projectiles

Close-combat laser assault weapon, 35

Coastal Riverine Squadron THREE, 69

Cobra, 36

COIL. See Chemical oxygen-iodine laser

Color discrimination, 52, 62

Complementary afterimage, 104

Confocal scanning laser ophthalmoscopy, 50–53, 56–60

Continuous-wave lasers, 220, 221

Contrast sensitivity, 52, 54–55, 58, 62

Copperhead antitank round, 29

Corneal injuries

action spectra for laser effects, 152–153

anatomy of the cornea, 254

animal models, 256

beam diameter and, 260

carbon dioxide lasers, 256–265

comparison of thresholds from helium-cadmium and kryptonion lasers, 162

corneal clouding, 152

corneal stromal effects, 264–265

cumulative effects of laser radiation, 155–156

endothelial injury thresholds, 264

epithelial injury thresholds, 256–263, 268–270

erbium glass laser radiation, 268–269

exposure duration and, 256–260

healing response to deep stromal burns, 265

Holmium laser radiation, 269–270

injury thresholds, 256–265, 268–270

keratocyte injury thresholds, 264–265

permissible exposure limits, 256–265

photoablation, 153–154

photokeratitis, 152

pulsewidth dependence of laser effects, 154–155

repetitive pulse exposures, 260–263

response criteria, 255–256

temperature measurements, 265–268

thermal models, 265–268

thresholds for transient opacities, 156

wavelength dependence of infrared absorption, 254

Coronet Prince, 36

Cross, Michael, 16

CSLO. See Confocal scanning laser ophthalmoscopy

Cunningham, Roosevelt, 16

D

Dallas, Alvin, 7

DARPA. See Defense Advanced Research Projects Agency

Dazer, 36

Dazzling glare, 101

Debility syndrome, 135

Defense Advanced Research Projects Agency, 39

Dembrowski, Specialist John, 16

Deuterium-fluoride lasers, 269

DiCarlo, Lieutenant Colonel Cheryl, 16

Diode study, 223–224

Disability glare, 101

Discomfort glare, 101

Division of Non-Ionizing Radiation, 7–8

Dixon, Captain Steven, 7

DPI. See Dual Purkinje image eye tracker

Dual Purkinje image eye tracker, 221, 224

Dye lasers, 200–201, 204–205

E

Edsall, Peter R., 16

Elliott, Roe, 16

ELRF. See Eyesafe laser rangefinder

ELTEP. See Emerging Laser Threat Eye Protection

Embarked Security Team, 69

Emerging Laser Threat Eye Protection, 12

Entoptic light-limiting responses, 117–120

Entoptic scatter model, 126–127

Equivalent background luminance, 101

Equivalent veiling luminance, 101

Erbium glass laser radiation, 268–269

Excalibur, 40

Exercise Iron Sword, 1

Experimental Psychology Group, 7

Exposure limit guidelines, 15–16

Extraocular scatter, 102–103

Eye injuries. See also Laser injuries; Visual performance changes

absorption properties of ocular tissues, 150–151

assessing in-vivo retinal morphology, 50–51

assessing visual function along the visual pathway, 51–53

confocal scanning laser ophthalmoscopy, 50–53, 56–60

corneal effects, 152–156, 254–270

diagnosis and treatment research for battlefield laser-induced injury, 16

estimating thermal damage thresholds, 232–235

exposure duration, 178–179

functional metrics and structural correlates, 51–53

injury evaluation guidelines, 12–14

integrating imaging with visual function, 53

Laser Accident and Incident Registry, 14

laser accident cases, 54–65

laser glare, 9–10, 102–107, 120–123

laser radiation safety standards, 12–14

lens effects, 156–161

optical coherence tomography, 51

protective eyewear, 10–12

repetitive pulses, 179–182

research on effects of laser energy exposure, 8–9

retinal effects, 161–166, 172–182, 188–214, 225–235, 244–248

wavelength dependence, 174–178

Eye movements

diode study, 223–224

estimating thermal damage thresholds and, 232–235

eye movement maps, 53, 56, 58–60

eye movement plots, 221–223

fixation ellipse, 223–224

during fixation on a laser source, 221–227

intensity effect, 224–225

laser study, 224–225

measurements at the US Army Medical Research Detachment, 221

Retinal Heating, Moving Eye program, 229–235

retinal heating during fixation on a laser source, 228–232

retinal heating during long-duration exposure, 229–232

during steady gaze, 220–221

Eyesafe laser rangefinder, 27–28

F

Farnsworth Munsell 100 Hue, 52–53, 55, 57

Femtosecond amplifier/oscillator, 241–242

Femtoseconds, 240

Fixation ellipses, 223–224

Flash blindness, 104

Flash parameters, 105–107

Fort Knox Armored Medical Research Laboratory, 4, 6

Frankford Arsenal, 6–7

Frisch, Georg D., 7

Fuller, Staff Sergeant Dan, 16

Functional somatic syndrome, 138–140

G

G-BAD. See Ground-based air defense directed energy on-themove

G/VLLD. See Ground/vehicular laser locator designator

Gallium arsenide radiation, 9

Gas dynamic lasers, 33

Gaze, 220–221

GBU. See Guided Bomb Unit

GDLs. See Gas dynamic lasers

Glare

dazzling glare, 101

description of, 100–101

disability glare, 101

discomfort glare, 101

equivalent background luminance concept, 101

glare recovery, 104–105

laser glare, 9–10, 102–107, 120–123

GLD. See Ground/vehicular laser locator designator

GLIS. See Green Laser Interdiction System

Green Laser Interdiction System, 116

Ground-based air defense directed energy on-the-move, 41–43

Ground/vehicular laser locator designator, 29

Group velocity dispersion, 241

Guided Bomb Unit, 28–29

Gurley, SPC Jameson, 147

GVD. See Group velocity dispersion

H

Handheld laser markers, 29–30

Haze, 103

Health Hazard Assessment Program, 14

Heathkit H8 computer, 9

Helfrich, James, 7

Helicopter-launched, antitank munitions, 29

Helium-cadmium lasers

ocular thresholds, 162

retinal injury thresholds as function of retinal irradiance diameter, 195

Helium-neon lasers, 199, 204–205

HELLADS. See High-energy liquid laser area defense system

HELs. See High-energy lasers

Henrichs, Sergeant Connie, 16

Hersch, Katheryn, 7

High-energy laser technology demonstrator and mobile demonstrator, 40

High-energy lasers

advanced tactical laser, 39

aero-optic beam controller, 39

airborne laser, 39

Airborne Laser Laboratory, 33

comparison of laser testbeds, 34

criteria for, 32–33

Excalibur, 40

ground-based air defense directed energy on-the-move, 41–43

high-energy laser technology demonstrator and mobile demonstrator, 40

high-energy liquid laser area defense system, 40–41

high-mobility multipurpose wheeled vehicle laser ordnance

neutralization system, 40

Laser Weapon System, 41

Maritime Laser Demonstration, 41

midinfrared advanced chemical laser, 34

mobile Army demonstrator, 33–34

mobile tactical high-energy laser, 39

mobile test unit, 33

multipurpose chemical laser, 33–34

Nautilus, 38–39

shipboard lasers, 41

Solid-State Laser Technology Maturation program, 41

tactical high-energy laser, 38–39

tactical laser system, 41

Tri-Service laser, 33

Unified Navy Field Test Program, 34

High-energy liquid laser area defense system, 40–41

High-mobility multipurpose wheeled vehicle laser ordnance neutralization system, 40, 42

HMMWV. See High-mobility multipurpose wheeled vehicle laser ordnance neutralization system

Holmium laser radiation, 269–270

Homochromatic afterimage, 104

Hoxie, Sergeant First Class Stephen, 16

Hydrogen fluoride lasers, 269

I

ICNIRP. See International Commission on Non-Ionizing Radiation Protection

ICRC. See International Committee of the Red Cross

IEC. See International Electrotechnical Commission

Indoor simulated marksmanship trainer, 32

Injury evaluation guidelines, 12–14

Interferometric measurements, 243

International Commission on Illumination, 98, 102–103, 164–166

International Commission on Non-Ionizing Radiation Protection, 178–179, 191, 214

International Committee of the Red Cross, 134–135, 143–144

International Electrotechnical Commission, 191–192, 211, 214

Intraocular scatter, 102, 120–123

Intraretinal scar formation, 50, 54

Intrinsically photoreceptive retinal ganglion cells, 117

ipRGCs. See Intrinsically photoreceptive retinal ganglion cells

IRSF. See Intraretinal scar formation

ISMT. See Indoor simulated marksmanship trainer

J

Jaguar, 36

Jensen, Ruthanne, 16

Jensen, Specialist, 16

JLST. See Joint Laser Safety Team

JLTV. See Joint light tactical vehicle

Joint Laser Safety Team

creation of, 6–7

Frankford Arsenal location, 6–7

keys to success, 7

Letterman Army Institute of Research move, 7

mission of, 50

Joint light tactical vehicle, 42

K

Keller, Jack B., Jr., 16

Keratocyte injury thresholds, 264–265

Kerensky, Charles, 7

Krypton-ion lasers

ocular thresholds, 162

retinal injury thresholds as function of retinal irradiance diameter, 199

L

LADS. See Laser area defense system

LAIR. See Letterman Army Institute of Research

Landers, Captain Maurice B., MD, 7

Landolt rings, 74–82, 85–89, 92

Laser Accident and Incident Registry, 14

Laser accident cases, 54–65

Laser area defense system, 43

Laser countermeasures system, 37

Laser glare

extraocular scatter, 102–103

factors affecting laser glare effects, 102–104

factors affecting visual recovery time, 105–107

flash intensity and duration, 105–106

flash source size and location, 106–107

flash spectral content, 107

glare recovery, 104–105

intraocular scatter, 102, 120–123

military performance and, 9–10

retinal light distribution, 102–103

task luminance, 103–104

transient effects of laser exposure, 107–108

visual task parameters, 103–104

Laser-guided bombs, 28

Laser-guided Maverick, 29

Laser-guided munitions, 29

Laser-induced breakdown, 241, 246–248

Laser injuries. See also Eye injuries

effective response to, 140

immediate an appropriate care for, 141

importance of accurate information, 141–142

issues of scale, 142–143

media reports and, 143, 144

planning for future laser casualties, 140–141

politics of, 143–144

positive therapeutic relationship and, 142

psychological effects, 135–140

skin damage from ultrashort lasers, 248

surveillance program, 144

training and, 144

treatment challenges of, 142–144

Laser markers, 29–30

Laser navigation systems, 38

Laser ordnance neutralization system, 40

Laser radiation

absorption properties of ocular tissues, 150–151

action spectra, 152–153

corneal effects, 152–156

cumulative effects of, 155–156

lens effects, 156–161

military relevance, 150

overview, 150

photoablation, 153–154

photokeratitis, 152

pulsewidth dependence, 154–155

retinal effects, 161–166

Laser research

animal models, 72–93, 150–166, 173–182, 204–213, 244–245, 256

bioeffects research team accomplishments, 5

BRAC moves, 6

civilian research, 26

directions for the future, 17

exposure limit guidelines for laser radiation, 15–16

Frankford Arsenal, 1968–1974, 6–7

high-energy laser weapons, 32–34, 38–43

inventing the laser, 26–27

laser bioeffects research team accomplishments, 5

Letterman Army Institute of Research, 1974–1992, 7–14

low-energy laser weapons, 35–38

militarizing the laser, 27–32

military research, 27

radiation safety standards, 12–14

reinvention and mission reset, 6

safety and performance limits, 4–6

USAMRD-WRAIR, 1992–2010, 14–16

Laser safety

guidelines, 191–193

historical empirical basis for laser safety guidelines, 193–195

issues of, 188–189

safety and performance limits, 4–6

safety standards, 12–14

Laser Safety Program, 73

Laser spot tracker, 38

Laser training devices, 31–32, 33

Laser Weapon System, 41

Lasers, military. See Military lasers

Lasers on the Modern Battlefield conference, 10, 11

LAV-AD, 27–28

LaWS. See Laser Weapon System

LCMS. See Laser countermeasures system

LED. See Light-emitting diode

LELs. See Low-energy lasers

Lens injuries

cataracts, 156–157

fluorescence, 158–161

thresholds for transient opacities, 156

transient clouding of, 156–157

Letterman Army Institute of Research

BRAC moves, 6

Division of Non-Ionizing Radiation, 7–8

injury evaluation guidelines, 12–14

Laser Accident and Incident Registry, 14

laser glare, vision disruption, and military performance, 9–10

laser radiation safety standards, 12–14

Lasers on the Modern Battlefield conference, 10, 11

Multiple Integrated Laser Engagement System, 9

protective eyewear, 10–12

research officer talent and leadership, 8–9

Levine, Major Rick, 9

LGM. See Laser-guided munitions

Li, Guo, 16

LIB. See Laser-induced breakdown

Light Armored Vehicle-Air Defense, 27–28

Light-emitting diode, 224

Lightweight laser designator rangefinder, 30–31

Line-of-sight antitank, 30

LLDR. See Lightweight laser designator rangefinder

LMav. See Laser-guided Maverick

LMB. See Lasers on the Modern Battlefield conference

LOSAT. See Line-of-sight antitank

Loveday, Staff Sergeant Janis, 16

Low-energy lasers

Cameo Bluejay, 36

close-combat laser assault weapon, 35

Cobra, 36

Coronet Prince, 36

Dazer, 36

Jaguar, 36

laser countermeasures system, 37

laser navigation systems, 38

laser spot tracker, 38

LX-5 Laser Diode Illuminator, 37

nonweapon lasers for the modern battlefield, 37–38

Outrider, 36

pocket laser communicator, 37

rapid optical beam steering, 37–38

Saber 203 Laser Illuminator, 37

Stingray, 35–36

target location and observation system, 37

weapons-mounted lasers, 36–37

Lund, D. Jack, 7, 8, 9, 15, 16

Lund, Dr. Brian J., 15

LX-5 Laser Diode Illuminator, 37

M

Macula, 174

MAD. See Mobile Army demonstrator

Maritime Laser Demonstration, 41

Martin, Specialist Freddie A., 7

Mastroianni, Lieutenant Colonel George, 9, 10, 16

Maximum permissible exposure, 86, 91–93, 156, 177–179, 191–192, 212–214, 220

Maxwellian view, 189

Media reports, 143, 144

Memes, 141

Midinfrared advanced chemical laser, 34

MILES. See Multiple Integrated Laser Engagement System

Military lasers. See also Laser injuries; Laser research; Laser safety

case studies of psychological effects, 137–140

challenges of psychological effects, 142–144

immediate psychological effects, 135–136

media relations and, 144

preparing for future psychological effects, 140–142

surveillance of psychological effects, 144

training for exposure to lasers, 134, 144

Minimum visible lesion, 172–173, 179, 193, 209, 244–246

MIRACL. See Midinfrared advanced chemical laser

Mobile Army demonstrator, 33–34

Mobile tactical high-energy laser, 39

Mobile test unit, 33

Modular universal laser equipment, 29

Molchany, Jerome W., 15, 16

MPE. See Maximum permissible exposure

MTHEL. See Mobile tactical high-energy laser

MTU. See Mobile test unit

MULE. See Modular universal laser equipment

Multiple Integrated Laser Engagement System, 1, 9, 31–32

Multiple-pulse injury thresholds, 260–263

Multipurpose chemical laser, 33–34

Multiuse lasers, 30–31

MVL. See Minimum visible lesion

N

Nautilus, 38–39

Naval Health Research Center Detachment, 6

Nawim, Sergeant Maqsood, 16

Nd:YAG. See Neodymium-doped yttrium aluminum garnet laser

Negative afterimage, 104

Nemeth, Thomas, 16

Neodymium-doped yttrium aluminum garnet laser, 76, 80–84, 86–89, 197–198, 202–203, 207–208

Nerve fiber layer, 73

Ness, Colonel James W., 15, 16, 116

Ness, Jonathan M., 116

Neuropsychiatric syndrome, 135

NFL. See Nerve fiber layer

NOHD. See Nominal ocular hazard distance

Nominal ocular hazard distance, 116

Nonionizing radiation

Division of Non-Ionizing Radiation, 7–8

International Commission on Non-Ionizing Radiation Protection, 178–179, 191, 214

research officer talent and leadership, 8–9

Nonweapon lasers, 37–38

O

OCT. See Optical coherence tomography

O’Mara, Major Peter, 9

OPA. See Optical phased array

Optical coherence tomography, 13–15, 51, 58–59, 61, 121

Optical phased array, 40

Oscilloscopes, 243

Outrider, 36

P

Papillomacular bundle, 56–57

Penetar, Major Dave, 9

PEO-Soldier. See Program Executive Office

Performance limits, 4–6

Photic blink reflex, 117–119

Photoablation, 153–154

Photochemical effects, 161–163

Photodiodes, 243

Photokeratitis, 152

Photometric system, 98

Photopic spectral luminosity, 98

Photoreceptor bleaching, 123–124

Photostress recovery test, 105

Picoseconds, 240

PLC. See Pocket laser communicator

PMB. See Papillomacular bundle

Pocket laser communicator, 37

Portable laser markers, 29–30

Positive afterimage, 104

Posttraumatic stress disorder, 135

Preferred retinal location, 61

Prevention and Medical Management of Laser Injuries, 13

PRF. See Pulse repetition frequency

PRL. See Preferred retinal location

Program Executive Office (Soldier), 12

Protective eyewear, 10–12

Psychological effects

beliefs and, 138–139

case studies, 137–140

challenges of scale, 142–143

effective response to laser injury, 140

functional somatic syndromes, 138–140

immediate and appropriate care for injuries, 141

immediate effects, 135–136

importance of information about laser injury and recovery, 141–142

importance of preexisting knowledge about lasers, 137

laser exposure and, 136

media reports and, 143, 144

planning for future laser casualties, 140–142

politics of laser injuries, 143–144

positive therapeutic relationship and, 142

psychosomatic responses to laser exposure, 137–138

role of suggestion, 139

sick role, 139

stress and, 139–140

suppressive effects of laser use, 135–136

surveillance program, 144

training and, 144

treatment challenges, 142–144

Psychosomatic responses, 137–138

Pulse repetition frequency, 260

Pupillary constriction, 99

Pupillary responses, 119, 125–126

Q

Q-switched pulse lasers, 72, 74–93

Q-switched ruby laser, 27

R

Radiometric system, 98

Randolph, David, 8

Rangefinders, 27–28

Rapid optical beam steering, 37–38

Raulston, George, 7

Repetitive pulse exposure, 179–182, 260–263

Research. See Laser research

Research and development laboratories, 27

Retinal Heating, Moving Eye program, 229–235

Retinal injuries. See also Eye injuries; Visual performance changes

assessing in-vivo retinal morphology, 50–51

assessing visual function along the visual pathway, 51–53

comparison of thresholds from helium-cadmium and kryptonion lasers, 162

computer models, 200–204

confocal scanning laser ophthalmoscopy, 50–53, 56–60

damage mechanisms, 245–248

distribution of energy, 225–227

estimating thermal damage thresholds, 232–235

exposure duration, 178–179

historical empirical basis for laser safety guidelines, 193–195

image diameter, 190–191

image size, 189

images with complex profiles, 211

integrating imaging with visual function, 53

laser accident cases, 54–65

laser glare, 9–10, 102–107, 120–123

laser-induced breakdown, 246–248

laser safety guidelines, 191–193

laser safety issues, 188–189

model results, 204–208

nanosecond to femtosecond minimum visible lesion thresholds, 244–245

overview, 172–174

photochemical effects of lasers, 161–163

physical models and calculations, 195–211

proposed time dependence of the maximum angular subtense, 212

refractive errors impact on image size, 189–190

repetitive pulses, 179–182

Retinal Heating, Moving Eye program, 229–235

retinal heating during fixation on a laser source, 228–232

retinal heating during long-duration exposure, 229–232

retinal hemorrhage, 175

retinal injury thresholds, 195–208

retinal irradiance diameter, 195–208

retinal laceration, 116

retinal radiant exposure pattern, 225–227

self-focusing damage, 245

simple models, 195–200

stimulated Brillouin scattering, 245–246

supercontinuum generation, 246

thresholds for ultraviolet exposures, 162

ultrashort lasers, 244–248

variations to fit the small spots, 208–211

veiling glare, 163–166

wavelength dependence, 174–178

Retinal nerve fiber layer, 50, 56

Retinal pigment epithelium, 173–178, 200, 208–209, 227–230

Retinal scar formation, 73

Rhesus monkeys, 74–93

RHME. See Retinal Heating, Moving Eye program

Rim of the Pacific, 69

RIMPAC. See Rim of the Pacific

RNFL. See Retinal nerve fiber layer

“Roadrunner,” 35

ROBS. See Rapid optical beam steering

Rodgers, Specialist, 7

RPE. See Retinal pigment epithelium

Ruby lasers, 200–201, 204–205, 207

Ruiz, Sergeant First Class Sally, 16

S

Saber 203 Laser Illuminator, 37

Saccades, 221

Safety. See Laser safety

SBS. See Stimulated Brillouin scattering

Scales, Lieutenant Colonel David, 16

Scanning laser ophthalmoscopy, 13, 14, 15

Scatter model, 123–127

Schawlow, Arthur L., 26

Schmeisser, Major Elmar, 9

Schuschereba, Dr. Steven T., 16

Second harmonic autocorrelator, 243

Self-focusing damage, 245

Shipboard lasers, 41

Sick role, 139

Skin injuries, 248

Sliney, Dr. David H., 14, 16

SLO. See Scanning laser ophthalmoscopy

Small Angle Disability Glare Equation, 102

Snellen acuity, 78, 80

Soft kills, 35

Solid-State Laser Technology Maturation program, 41

Solid-state lasers, 41

Somatic syndrome, 135

Spatial induction, 100

Spatial summation, 100

Special Operation Forces, 29–30

SSLs. See Solid-state lasers

Stamper, David, 9, 15

Stanislau, Helen, 7

Stimulated Brillouin scattering, 245–246

Stingray, 35–36

Streak cameras, 243

Stuck, Bruce E., 7, 8, 16

Supercontinuum, 241

Supercontinuum generation, 246

T

Tactical high-energy laser, 38–39

Tactical laser system, 41

Target designators, 28–30

Target location and observation system, 37

Task luminance, 103–104

Temporal induction, 100

Temporal summation, 100

THEL. See Tactical high-energy laser

TIE. See Total intraocular energy

Titanium:sapphire lasers, 207

TLOS. See Target location and observation system

Total intraocular energy, 54, 56, 60, 62, 116, 191–194

TOW missiles, 10

Townes, Charles H., 26

Tracking simulator, 9–10

Training devices and systems, 31–32, 33

Transient localized visual desensitization, 104

Transillumination, 102

Traumatic brain injury, 135

Travis, Major General Thomas, 12

Tri-Service laser, 33

TSL. See Tri-Service laser

U

Ujimora, Sergeant Veronica, 16

Ultrafast, ultraintense lasers, 248–249

Ultrashort lasers

damage mechanisms, 245–248

generation with chirped pulse amplification, 241–242

interferometric measurements, 243

laser-induced breakdown, 246–248

measurement of, 242–243

nanosecond to femtosecond minimum visible lesion thresholds, 244–245

peak power, 241

retinal injuries, 244–248

self-focusing damage, 245

skin injuries, 248

spectral content of, 240–241

stimulated Brillouin scattering, 245–246

supercontinuum generation, 246

traditional measurement techniques, 242–243

ultrafast, ultraintense lasers, 248–249

Ultrashort-pulse laser technology, 240

Ultraviolet laser radiation. See Laser radiation

Uncertainty principle, 240

Unified Navy Field Test Program, 34

US Army Center for Health Promotion and Preventive Medicine, 14

US Army Institute of Surgical Research, Joint Base San Antonio, Fort Sam Houston, 6

US Army Materiel Command, 6

US Army Medical Department

BRAC moves, 6

eye protection programs, 12

Joint Laser Safety Team, 6

role in laser development and use, 4

US Army Medical Research and Development Command, 6

US Army Medical Research and Materiel Command, 14–15

US Army Medical Research Detachment

BRAC moves, 6

diagnosis and treatment research for battlefield laser-induced

eye injury, 16

exposure guidelines for laser radiation, 15–16

eye movement measurements, 221

laser research, 14–15

USACHPPM. See US Army Center for Health Promotion and Preventive Medicine

USAMRD. See US Army Medical Research Detachment

USAMRMC. See US Army Medical Research and Materiel Command

USNS Rainier, 69

V

Van Sice, Charles W., 16

Vehicle-mounted laser markers, 29–30

Veiling glare, 163–166

VEPs. See Visual-evoked potentials

Visual acuity, 51–54, 58–59, 62, 74–92

Visual disruption. See Laser glare

Visual-evoked potentials, 107, 163–164

Visual Function Laboratory, 14

Visual performance

assessing performance, 125–127

Blaser visual pursuit system, 9–10, 123, 124, 126–127

blink reflex, 99–100

entoptic light-limiting responses, 117–120

entoptic scatter model, 126–127

eye movement, 119

glare and, 100–101

light-limiting strategies, 124–125

mechanical mechanisms, 99–100

modeling intraocular scatter, 120–123

monocular lid closure, 119

neurophysiological processes, 100

normal visual adaptation, 98–100

partial lid closure, 119

photic blink reflex, 117–118

photochemical mechanisms, 100

photometric quantities, 98

photoreceptor bleaching and performance, 123–124

pupillary constriction, 99

pupillary responses, 119, 125–126

radiometric quantities, 98

resolving power of the eye, 119–120

scatter model validation, 123–127

spot size to intensity relationship, 118–119

temporary changes in visual sensitivity, 100–108

units of measurement, 98

Visual performance changes. See also Eye injuries

animal models, 72–93

data analysis, 76

discrimination task, 74–75

laser exposures, 75–76

laser glare, 9–10, 102–107, 120–123

test results, 76–89

testing apparatus, 74

visual performance test system, 9–10

W

Walter Reed Army Institute of Research

BRAC moves, 6

diagnosis and treatment research for battlefield laser-induced

eye injury, 16

exposure guidelines for laser radiation, 15–16

laser research, 14–15

Wang, Dr. Heuy-Ching Hetty, 16

Weapons-mounted lasers, 36–37

Whitmer, Lieutenant Colonel Deborah, 16

Wire-guided TOW missiles, 10

Wood, Claudia, 16

Wood, Fremont E., 16

WRAIR. See Walter Reed Army Institute of Research

X

Xenon arc lamp, 205–207

Z

Zeus, 40

Zuclich, Dr. Joseph A., 15, 16

Zwick, Dr. Harry, 7, 8, 14, 16

Zwicker, William, 7