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In Vivo Diagnostics and Metrics in the Assessment of Laser-Induced Retinal Injury

Chapter 5

IN VIVO DIAGNOSTICS AND 

METRICS IN THE ASSESSMENT OF 

LASER-INDUCED RETINAL INJURY

HARRY ZWICK, PhD*; JAMES W. NESS, PhD†; MICHAEL BELKIN, MD‡; and BRUCE E. STUCK, MS§

INTRODUCTION

VISUAL FUNCTION: SHIFTING FOCUS BEYOND THE MACULA

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

*Formerly, Team Leader, Retinal Assessment Team, US Army Medical Research Detachment, Brooks City-Base, San Antonio, Texas 78235-5108; currently retired

†Colonel, Medical Service Corps, US Army; Program Director, Engineering Psychology, Department of Behavioral Sciences and Leadership, US Military 

Academy, West Point, New York 10996 ‡Goldschleger Eye Research Institute, Sheba Medical Center, Tel Aviv University, Tel Hashomer 52621, Israel 

§

Director, Ocular Trauma Research Division, US Army Institute of Surgical Research, 3400 Rawley East Chambers Avenue, San Antonio, Texas 78234-

6315; currently retired
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Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine

INTRODUCTION

in 1968 at the Frankford Arsenal in Philadelphia, 

Pennsylvania. The purpose of the Army’s laser safety 

program was to support development of military 

lasers by minimizing their potential risks to soldiers 

in the field. The laser safety research team was a 

group of highly dedicated investigators who worked 

at the forefront of all relevant scientific disciplines, 

including physics, histopathology, psychophysics, 

and medicine. The history of the research from its 

inception in 1968 to its discontinuation in 2011 is 

summarized in Exhibit 5-1. This chapter describes 

an approach to researching laser-induced changes to 

visual function, focusing on relating retinal structural 

changes, anomalies, and damage to changes in visual 

function based on the accumulated experience of the 

laser safety research team.

Worldwide today, military laser systems are 

known to be in use by 49 nations. Military lasers 

are used to support a wide variety of battlefield 

needs, including range-finding, communication, 

illumination, landmine and bomb detection and 

detonation, target designation, and detection of 

contamination. All are potentially hazardous to the 

human eye at tactical ranges. Although prophylactic and protective measures have been eminently 

successful in limiting the numbers of laser-induced 

injuries in the medical, laboratory, and industrial 

environments, these same measures are not easily 

applied in combat. In fact, the problem of protecting 

military combatants against laser-induced injury is 

exceedingly difficult. 

The field of laser–tissue interactions encompasses 

almost all branches of science, including 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 employed 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. 

The US military’s interest and involvement in laser 

bioeffects began soon after the laser was first invented 

in 1960. As the military began to investigate and use laser instruments at wavelengths potentially injurious to 

the human eye, it 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 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 

the United States and international standards for the 

safe use of all lasers.

The US Army established the US Army Medical 

Research and Development Command and the US 

Army Materiel Command Joint Laser Safety Team 

VISUAL FUNCTION: SHIFTING FOCUS BEYOND THE MACULA

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. In conventional 

classifications of laser-induced retinal damage, classification is based on acute laser-induced central retinal 

injury,1 with little attention given to the manifestation 

of secondary functional abnormalities as the effects 

of the acute damage diminishes. Together with the 

application of well-targeted functional assessment, 

advanced imaging techniques have enhanced the understanding of laser-induced retinal sequelae.2

 Exhibit 

5-2 provides a straightforward summary of military 

laser ocular hazards and protection, summarizing 

current knowledge for the soldier.

With the small, but increasing number of laser eye 

injuries associated with military target acquisition 

systems, the issue of suprathreshold laser-induced 

injury became increasingly important.3 These cases 

revealed that laser-induced retinal damage need not 

be restricted to the central retina to have significant 

consequences for visual function. These consequences 

involve the development of intraretinal scar formation 

(IRSF), retinal traction generally associated with IRSF, 

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 development, 

progression, and the long-term consequences to visual 

function to distinguish normal functioning retina from 

dysfunctional retina. These new techniques must 

cover the full spectrum of visual function to include 

measures of contrast required to resolve features that 

subtend a range of visual angles, the ability to detect 

fine differences in hue, and sensory/motor coordination of fixation eye movements. The ability to diagnose 

deficits in such visual qualities currently limits the 
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In Vivo Diagnostics and Metrics in the Assessment of Laser-Induced Retinal Injury

EXHIBIT 5-1

THE ARMY MEDICAL DEPARTMENT’S ROLE IN DEVELOPMENT, DEPLOYMENT, AND USE 

OF LASERS BY THE MILITARY

Shortly after the invention of the laser in 1960, the military began to develop ways to utilize the new technology to 

assist in its many complex missions. Science fiction and the popular press speculated on the laser’s potential and 

highlighted its use as a “ray gun” that could effectively engage both materiel and people rapidly (at the velocity of 

light) and with a “magazine” only limited by the power source. The laser was depicted as destructive to materiel at 

large distances, far exceeding those reached by most conventional munitions, albeit it did require line of sight. Concomitant with the desire to build high energy lasers to engage materiel was the development of low-power devices 

that could assist in the military’s fire control and training missions. The laser’s attributes included (a) monochromatic 

emission (one wavelength or color or emissions at multiple discreet wavelengths throughout the visible and infrared 

spectrums), (b) intense energy in a well-collimated beam (ie, a beam that does not spread much with distance), (c) 

emissions in extremely short duration pulses (ie, nanosecond exposure durations required for range finders), and (d) 

repetitive pulse or pulse-coded emissions. Laser range finders, laser target designators, and laser “live fire” training 

devices were under development to exploit the attributes offered by this emerging technology. 

The potential for laser energy to injure the eye was recognized early, and research groups who had studied the ocular 

hazards of nuclear fireballs shifted their attention to laser radiation. Technology programs began within the Department of Defense (DoD) to exploit the characteristics of the laser for military applications from training and fire control to weapons systems. Potential adversaries also had laser expertise. The technology was scientifically robust and 

emerging worldwide with new wavelengths, high emission energies, shorter duration pulses, and applications that 

continue to exploit these advances. 

Within a short period of time, a controversy arose surrounding the establishment of permissible exposure limits for 

the Q-switched ruby laser. The Army was developing the first ruby laser range finder at the Frankford Arsenal in 

Philadelphia, Pennsylvania. The Army Medical Department (AMEDD) recognized responsibility to ensure the health 

and safety of soldiers operating laser systems and understood that laser weapons would emerge on the modern 

battlefield and injure soldiers entrusted to care. Hence, the AMEDD established a joint research team at the Frankford 

Arsenal that combined the medical expertise of the AMEDD with the electronic, optics, optical fabrication, laser, and 

fire control systems expertise of the US Army Materiel Command. In 1968, the Joint US Army Materiel Command and 

the US Army Medical Research and Development Command Laser Safety Team (or the J AMC-AMRDC LST or simply 

the JLST) was established. The controversy on Q-switched ruby lasers was ultimately resolved, but many other laser 

issues continued to emerge. 

Argon lasers had already made their way to the ophthalmology clinic, but other lasers were relatively new or rare and 

could not be purchased commercially. To support the biomedical research, optical delivery systems were interfaced to 

fundus cameras, and laser systems were fabricated on site at the Frankford Arsenal. The group generated data from 

which exposure limits could be derived; both ocular and cutaneous injury thresholds were determined as a function 

of laser wavelength, exposure duration, irradiance diameter, and pulse repetition frequency. Biological effects of ruby, 

neodymium, argon, carbon dioxide, erbium, and gallium arsenide diode lasers were investigated and reported. 

In 1974 with the pending closure of the Frankford Arsenal, the AMEDD members of the JLST moved to the Letterman 

Army Institute of Research at the Presidio of San Francisco, California (Exhibit Figure E1-1). The research conducted 

in the 18 years at the Letterman Army Institute of Research (LAIR; 1974–1992) focused on medical issues surrounding 

the Army’s use of lasers in a wide range of systems. High-energy laser systems were developed by the DoD to engage 

targets at large ranges. Low-energy lasers were used in many fire control and mission assist applications. Laser weapons 

were prominent in the DoD threat statements. Medical applications of lasers emerged, and by the early 1990s, laser 

use in hospitals was quite common in most medical specialties. Ophthalmological applications emerged very rapidly. 

Industrial hygiene and occupational health guidance was established and continually updated to facilitate the safe 

use of lasers in the workplace. This guidance was based on the maximum permissible exposures or exposure limits for 

optical radiation that were predominately supported by the triservice DoD research. In 1979, LAIR organized the first 

Lasers on the Modern Battlefield (LMB) Conference. The LMB quickly became the annual forum for issues surrounding 

the development, deployment, and use of lasers by the military, and provides a classified forum for interaction across 

programs and corps, including international partners. 

(Exhibit 5-1 continues)
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Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine

A 1980 symposium on Combat Ocular Problems became the watershed event that resulted in the first development of military protective eyewear. The focus of the conference was broader than the laser threat issue and 

included eye trauma. Colonel Francis LaPiana, an accomplished ocular plastic surgeon, postulated that more 

than 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 3–4 mm thickness of polycarbonate (Lexan, a product of the General Electric Company, 

Fairfield, Conn). Lieutenant Colonel (Dr) Belkin, 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, made a similar 

argument. The human factor issues and limitations of protective solutions (absorptive dyes in glass or plastic) 

for laser protection were also discussed. The high attenuation of selected visible wavelengths for laser protection 

limited the overall visible light (luminous) transmission and distorted perception of the color space (inability to 

readily detect red warning lights with eye protection designed for ruby laser emissions at 694.3 nm). Although 

polycarbonate provided protection against fragments, there was no specification for fragment protection. Absorbing dyes introduced into the polycarbonate or surface preparations degraded the fragment protection properties, 

and polycarbonate was “soft” and difficult to edge if formed into corrective lenses. Polycarbonate was also very 

susceptible to scratches, and the lifetime of a spectacle or an aviator visor was estimated to be very short in a 

dusty/dirty combat environment. Although technology programs began to develop laser protection, there was 

no program addressing fragment protection. 

Exhibit 5-1 continued

Fig. E1-1. Key Laser Bioeffects Researchers at Letterman Army Institute of Research (LAIR), San Francisco, California. Pictured (left 

to right) are David Randolph, Bruce Stuck, Harry Zwick, Jack Lund, and Edwin Beatrice. 

(Exhibit 5-1 continues)
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In Vivo Diagnostics and Metrics in the Assessment of Laser-Induced Retinal Injury

Colonel Beatrice (Exhibit Figure E1-2), supported by his 

Commanding General, MG Rapmund, identified a clear 

Army need that was focused on protecting the soldier in 

development of laser and fragment protective eyewear. 

The team had a full research portfolio already, no budget 

for an eye protection program, and no official Army requirement, much less a complete picture of the acquisition 

process for materiel development. The soldier needed eye 

protection that he could function with day or night that 

protected against a few select laser wavelengths and ballistic fragments. Nevertheless, over the next 4–6 years, the 

Ballistic and Laser Protective Spectacles (BLPS) were developed. The laser protective clip-on was less than ideal, 

provided protection only against 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. The group developed saturation 

measurement methods, which have been adopted by 

the American National Standards Institute guidance for 

commercial laser protective eyewear. The BLPS program 

also produced visors for the HGU-56/P helmet (Gentex 

Corporation, Simpson, Pa) through active collaboration 

with the Army aviation materiel developer. Subsequently, 

the BLPS system was type classified, and some units in 

the first Gulf War were equipped. 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 

guide advancements in military protective eyewear development today. The Emerging Laser Threat Eye Protection 

Exhibit 5-1 continued

Fig. E1-2. Colonel Edwin S. Beatrice, leader of the Laser Bioeffects 

Research Team and later, Commander, Letterman Army Institute 

of Research (LAIR). 

(ELTEP) program was cancelled in 1991, with an understanding that protection outside the body (“skin out”) would 

be the mission of the PM (Project Manager) soldier, and the AMEDD would be responsible only for corrective lenses. 

Laser bioeffects research at LAIR was as diverse as the developmental laser systems and their applications (both 

military and civilian). The Multiple Integrated Laser Engagement Simulator (MILES) was a class of gallium arsenide 

laser-based systems designed to simulate live fire during training with conventional weapons. The M-16 rifle version 

of the MILES device had soldiers directing lasers at other soldiers in training for the first time. The AMEDD, as well 

as the developer, wanted to ensure that the system was safe prior to widespread use. The team conducted a series of 

biological effects studies that expanded the understanding of laser bioeffects through investigations of the additive 

effects of repetitive pulses, the dependence of the retinal injury threshold on retinal irradiance diameter, and an understanding of the retinal effects of near-infrared laser radiation. 

In October 1980, a Los Angeles Police Department helicopter was illuminated by an air-cooled argon ion laser that 

a technician had taken home to project Lissajous patterns on the wall for a Halloween party. Illumination of the Los 

Angeles Police Department helicopter crew resulted in evaluation of the pilot’s and co-pilot’s eyes and vision at LAIR, 

and an assessment of laser and exposure conditions. The laser obtained for inspection was operating at a wavelength 

of 448 nm; however, there was no retinal injury as would be anticipated by an overexposure at that wavelength. There 

was a corneal abrasion apparently due to rubbing the eye secondary to the startle when the bright intrabeam viewing 

experience occurred. The night illumination surprised the crew, and when they momentarily lost their visual cues, they 

were concerned about their safety and ability to safely fly the aircraft. Evaluation of the emission characteristics of the 

laser and the distance from the helicopter indicated that the exposure was well below levels required to produce retinal 

injury, but the laser glare at levels below the permissible exposure limit appeared extremely bright and compromised 

the crew’s ability to fly the aircraft. Suddenly, it was clear that laser glare, particularly under low luminance conditions 

(dawn, dusk, or night), could interfere with military operations and pose secondary hazards to soldiers or result in a 

(Exhibit 5-1 continues)
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Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine

“soft” mission defeat. Consequently, laser glare studies 

in a terrain board pursuit tracking simulator built at the 

LAIR were initiated. 

Emphasis was on threshold effects and research addressing the issue of potential long-term effects from laser 

exposure. Assessment of laser injury through enhanced 

ophthalmic imaging diagnostics (confocal scanning laser 

ophthalmoscopy, optical coherence tomography), novel 

visual function assessments, and emerging molecular 

biological assays complemented light and electron microscopy characterizations of laser-induced eye injury. 

The Aidman Vision Screener (AVS)—a 5 x 7 inch card with 

an acuity chart, Amsler grid, and evacuation criteria—was 

proposed to assist the combat medic in rapidly assessing laser-induced injury in an operational environment 

(Exhibit Figure E1-3). The AVS was accepted as a rapid 

screening tool and was type classified, and a new US 

Army Field Manual 8-50 titled “Prevention and Medical 

Management of Laser Injuries” was drafted. US Army 

Field Manual 8-50 was published in 1990 just before the 

first Gulf War. 

In September 1992, the Division of Ocular Hazards moved 

to Brooks City-Base, San Antonio, Texas, to be colocated 

with the Air Force Research Laboratory’s Directed Energy 

Bioeffects Research and the Navy’s nonionizing radiation programs that were being relocated from Pensacola, 

Florida. Fifty Rhesus monkeys were also moved from the 

Presidio of San Francisco to Brooks Air Force Base. The 

US Army Medical Research Detachment–Walter Reed 

Exhibit 5-1 continued

Fig. E1-3. The Aidman Vision Screener (AVS) 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 AVS is required to triage laserinduced 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.

a

b

(Exhibit 5-1 continues)
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In Vivo Diagnostics and Metrics in the Assessment of Laser-Induced Retinal Injury

Army Institute of Research (USAMRD–WRAIR) executed its mission at Brooks Air Force Base from 1992 through 

2010. The program continued to focus on acute laser bioeffects, addressing 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 emergence of the use of the oxygen iodine laser with emissions at 1.315 

mm, the emergence of the use of “particle cells switches” against pulse lasers operating the retinal hazard spectral region, and a relook at laser glare issues surrounding the use of green laser illuminators to deter unknown encroachers 

on valued assets. The team provided vital technical advice and expertise to the Department of State in discussions of 

the “Blinding Laser Weapon Protocol” negotiated in Vienna, Austria, in 1995. Accidental laser eye injuries continued 

to occur within the military, and the unit assisted in their assessment through the use of advanced imaging (scanning 

laser ophthalmoscopy and optical coherence tomography) and measurements of visual function. The Laser Accident 

and Incident Registry was developed to archive these and other laser exposure injuries and incidents. Although 

laser-induced eye injuries were infrequent and predominately involved the misuse of lasers in military settings, the 

information obtained from these and other laser-induced eye injuries that occurred in the private sector were important to enhance the understanding of cases and the collection of cases that occur in industry, medicine, and research 

laboratories. (This is the focus of Chapter 5.) 

Evaluation of corneal, lens, iris, and retinal injury threshold for laser wavelengths in the 1.1–1.4 mm region was driven 

by the DoD efforts to build high-energy lasers operating at the chemical oxygen-iodine laser (COIL) wavelength of 

1.315 mm. Colocation of directed energy bioeffects research program at Brooks Air Force Base allowed collaboration and 

design of complementary research on these issues. A complex series of experiments addressed both the wavelength 

dependence and locus of ocular injury for exposures in the near infrared and dependence of the retinal injury threshold on retinal irradiance diameter. These studies resulted in major changes to optical radiation exposure guidelines. 

High-powered laser diodes resulted in the proliferation of laser pointers, first red and now green, and the availability 

of high-power laser illuminators drew attention to laser glare and purposeful exposure issues. The team continued 

both laboratory and field studies of laser glare to assess the operation impact of noninjuring exposures. Investigations 

of natural protective mechanisms were conducted. The kinetics of the pupillary response and the aversion response 

(consisting of head or eye movement, squint, and blink), and a description of laser-induced after-images from the 

visible laser below the exposure limits were described. Eye movements were measured during deliberate fixations to 

more accurately assess the hazards of purposeful exposures. Data were used to develop the first retinal thermal injury 

model, wherein the source moved on the retina commensurate with the measured eye movements during deliberate fixation. With the emergence of wave front-corrected retinal imaging systems and to investigate the “worst” case 

viewing conditions, a series of experiments was conducted measuring the retinal injury threshold with the wave front 

correction for the optical aberrations in the eye that were exposed. This research, over a period of several years, was 

now critical to the adjustment of exposure limits for optical radiation. 

Treatment of laser-induced retinal injury was addressed with a comprehensive study of the efficacy of steroids and 

nonsteroidal antiinflammatory agents on thermal lesions and pulsed lesions. Treatment studies were conducted to 

investigate regimens that could be initiated by first responders, followed by therapies administered later at higher 

medical care echelons. Applications of photodynamic therapy in the treatment of laser-induced eye injury were examined, as well as the use of optical radiation in the treatment of laser-induced retinal injury. Multifocal electroretinogram 

was applied to the assessment of focal, laser-induced retinal injury. Most recently, a series of studies has investigated 

applications of stem cells in the treatment of retinal trauma. Final treatment approaches will ultimately be based on 

the taxonomy of the lesion or injury. This work, along with the diagnostic imaging and novel assessments of visual 

function, stands as the basis for future ocular trauma.

Exhibit 5-1 continued

ability to evaluate functional consequences of laser 

retinal injuries, particularly in differentiating between 

sequelae that is primarily retinal in origin from higher 

order sequelae. 

This chapter presents the clinical evaluation of five 

military laser accident cases representing a range of 

laser-induced retinal damage. The assessment of each 

case will highlight the complexity of the structure–

function relationship, as well as the importance of combining imaging techniques to more precisely identify 

structural damage with the application of well-targeted 

functional assessments. The evidence presented herein 

demonstrates that functional diagnostic tools cannot 

be limited to neural mechanisms at the retina. As the 

structural damage resolves, processing of visual neural 

code along the visual pathway often produces visual 

function outcomes not immediately evident from the 

structural damage at the retina. 
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Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine

EXHIBIT 5-2

SUMMARY OF MILITARY LASER OCULAR HAZARDS AND PROTECTION

Reproduced from: the Laser/Optical Radiation Program, US Army Center for Health Promotion and Preventive Medicine (USACHPPM). Aberdeen Proving Ground, Md: USACHPPM. Technical Bulletin 25-013-0498.
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In Vivo Diagnostics and Metrics in the Assessment of Laser-Induced Retinal Injury

The chapter begins with a discussion of imaging 

and visual techniques to assess retinal structure and 

visual function. This is followed by a brief discussion 

of the integration of these techniques to determine 

structure–function relationships used to assess visual 

function in each of the five presented cases. 

ASSESSING IN VIVO RETINAL MORPHOLOGY 

Confocal Scanning Laser Ophthalmoscopy

Confocal scanning laser ophthalmoscopy (CSLO)4

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.5–7 Figure 5-1 shows CSLO images 

for a nonhuman primate (NHP; Figure 5-1a) and a 

garter snake (Figure 5-1c). NHP eyes have relatively 

large focal lengths, and the graph reflects the current 

state of the art in axial domain resolution (18 mm) for 

eyes with relatively large focal lengths. The art of the 

possible 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 

(Figure 5-1a) to the retinal vasculature (Figure 5-1b). 

The optical properties of the garter snake eye permit, 

by comparison, a narrower range of axial separation, 

which is from the RNFL to the photoreceptor layer. 

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 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 utilizing adaptive 

optic algorithms to correct for optical aberrations of 

the imaged eye allow for diffraction-limited imaging 

in the “large” human eye. Confocal applications now 

allow observation of the photoreceptor and retinal 

pigmented epithelium (RPE) matrix 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. 

Fig. 5-1. Comparison of range of confocal slice between the Rhesus monkey (a, b) and the garter snake (c, d).

Photographs: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

a

b d

c
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Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine

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 5-2a shows 

the path of the OCT scan that rendered the image 

shown in Figure 5-2b. The figure shows the OCTrendered image taken through the macular region 

from the superior parafoveal retina into the foveal 

retina and ending in the inferior parafoveal retina. 

The thickness of the parafoveal retina is 250 mm and 

that of the foveal retina is 150 mm. These thicknesses 

correspond with histological retinal measurements 

and thus can be used to characterize the condition 

of the retina. 

Fig. 5-2. (a) Vertical scan through the fovea. (b) OCT image 

yields a full retinal thickness cross-section of the scanned 

retina. 

Photographs: Courtesy of the Laser Laboratory, with the 

technical assistance of André Akers.

a

b

FUNCTIONAL METRICS AND STRUCTURAL CORRELATES

Assessing Visual Function Along the Visual Pathway

High spatial resolution vision (ie, visual acuity) 

is mediated by the central foveal region.8 Visual acuity demands a higher order neural integration and 

augmentation, thus 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 a significant loss in visual acuity. Maximal visual 

spatial resolution, measured as visual acuity, is mediated at the center of the fovea. There, ganglion cells 

were originally thought to innervate the most central 

region of foveal photoreceptors in a ratio of 1 ganglion 

cell to 1 photoreceptor,9 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.10 However, more recent work by Curcio et al11,12 

has demonstrated that the central foveal cones have 

a 2:1 ratio with retinal ganglion cells. When the 2:1 

ratio is accounted for in the off-axis acuity function, 

a resulting small plateau of maximal acuity over 

the central foveal retinal space is revealed.12 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 mm) 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, visual acuity is often insensitive to 

associated visual function changes because there is 

significant neural plasticity/redundancy associated 

with visual acuity. 

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 (magnocellular/parvocellular ganglion cell 

systems) because higher order processing of spatial 

information tends not to compensate for anomalies 

at the retina.13 Furthermore, measurements of temporal contrast sensitivity indicate contrast sensitivity of the paramacular retina targeting the more 

transiently responding magnocellular system, which 

is involved in directing gaze to the more sustained 

responding, centrally dominated parvocellular system.14 Thus, the forms of the spatial and temporal 

contrast sensitivity functions provide a complete 

picture of threshold sensitivity across target size to 
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In Vivo Diagnostics and Metrics in the Assessment of Laser-Induced Retinal Injury

register detection and movement predominately at 

the level of the retina.

As with visual acuity, traditional clinical color 

vision metrics, such as the Farnsworth Munsell 100 

Hue (FM 100 Hue), are of limited utility due to their 

inability to accurately measure individual cone system damage. This is primarily because 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.15 Figure 5-3 shows 

the FM 100 Hue polar plots and their corresponding 

frequency density plots for a person whose vision is 

within normal limits (Figure 5-3a), a person with a 

congenital color deficiency (Figure 5-3b), and a laser 

accident case (Figure 5-3c).16 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 (Figure 5-3b), with weak 

F1 contributions suggestive of a primary color deficit. In laser cases (Figure 5-3c), significant F1 and F2 

contributions exist. The F1 contribution is suggestive 

of the extent of the retinal ablation of cone type, and 

F2 is suggestive of disruption of higher opponent 

processes. 

The FM 100 Hue presents a focal target of color 

and, as such, may be less sensitive to outer retinal 

photoreceptor assessment with regard to exposure 

effects that present with minimal ophthalmoscopic 

evidence of 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 visual acuity 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 

as well as the development of color contrast grating 

techniques19 and the application of equal luminance 

color acuity charts.20 The Rabin charts are especially 

notable in that they bring the capability to assess 

specific cone system functionality from the laboratory 

environment to that of the clinical environment. This 

capability is being applied to the current Aidman 

Vision Screener.21 The improvement to the screener 

uses spectral logMAR acuity targets with and without neural opponent chromatic backgrounds; this 

advancement promises the capability of diagnosing 

exposure effects that present with minimal ophthalmoscopic evidence.22

Fig. 5-3. 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 2nd-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 1st-order Fourier harmonic component. The axes of the FM 100 Hue test indicated in the center of the radial plots 

are as follows: B, blue; G, green; P, purple; R, red; and Y, yellow.

Illustrations: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

a b c
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Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine

Integrating Imaging With Visual Function

Two separate techniques have been developed by 

US Army Medical Research Detachment-Walter Reed 

Army Institute of Research 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 

5-4).23 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 that 

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, even though there is 

a visual complaint associated with suspected exposure. 

A second technique utilizes normal fixation eye 

movement pattern technology24 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 retinas based 

on the frequency of ocular motor visitation (Figure 

5-5). Figure 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 typically spanning 150 mm. Deviations from this 

pattern are strongly associated with disruptions in the 

sensory matrix, which impact governing of the motor 

system directing eye movements. 

Fig. 5-4. 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 acoustic-optic modulator, 

Det is detector, PC is personal computer, and C is a Landolt 

C projected directly on the retina.

Photographs/Illustration: Courtesy of the Laser Laboratory, 

with the technical assistance of André Akers.

Fig. 5-5. A normal eye movement map (c) acquired using an SRI Dual Purkinje Eye-tracker (SRI International, Washington, 

DC) (a) from a patient who had reacquired normal fixation. (b) The 1st and 4th Purkinje images that are used to determine 

fixation to within 1 minute of arc and to differentiate eye rotation from head translation. 

Photographs/Illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

a b c

LASER ACCIDENT CASES

The five military laser-retinal accident cases presented here were all associated with laser-induced 

macular retinal hemorrhage. All cases were evaluated 

using the techniques described previously. Four were 

induced by military laser range finders and one was 

induced by a laser designator. Despite similarities in 

dose for the first four cases, lesion location is revealed 

to be critical to outcome, but in ways not predicted by 

central/peripheral convention. Case 5 is comparable 

with case 4 in lesion placement and highlights the 
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In Vivo Diagnostics and Metrics in the Assessment of Laser-Induced Retinal Injury

importance of sensory and 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 [oculus dexter; pertains to the right 

eye]) from an AN/GVS-5 laser range finder with an 

operating wavelength of 1064 nm at an energy output 

at the aperture of 15 mJ/pulse. The range finder was 

held at arm’s length from the eye and delivered several 

pulses with an estimated total intraocular energy (TIE) 

of 2.0 mJ per pulse, which resulted in 4 retinal lesions, 

2 of which produced vitreous hemorrhages. (TIE is the 

total energy through the pupil that can be focused on 

the retina. If the total corneal radiant exposure is 10 mJ/

cm2 and the pupil diameter is 5 mm, then TIE = 10 mJ/

cm2 * 0.196 cm2 = 1.96 mJ. Pupil diameter is estimated 

based on light conditions at the time of exposure.) 

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.25,26

Figure 5-6 shows the resulting intraretinal scar at 18 

months postexposure.

Measurement of visual acuity in OD at 24 hours 

postexposure was 20/400 and at 3 months postexposure improved to 20/200. Measurements of visual 

Fig. 5-6. Case 1: multiple exposures about the fovea and 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.

Fig. 5-7. 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.

Illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

acuity 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 (OS [ocular 

sinister; pertains to the left eye]). Spatial and temporal 

contrast sensitivity functions measured at 6 months 

postexposure, using the CSLO technique described 

previously, showed both high- and low-spatial frequency deficits. Figure 5-7 shows the maximum difference in spatial (stationary) and temporal (dynamic) 

contrast sensitivity functions between OS and 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 having a larger contribution to the 

overall visual function deficit. 

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 (Figure 5-7, dynamic) shows that, for sinusoidal targets, luminance 

modulated at 1 Hz and maximal deficit is at 1 cycle/

degree. Under these measurement conditions, the 

typical temporal contrast sensitivity function peaks at 

4 cycles/degree.27 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 
142

Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine

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 (Figure 5-6) the extensive 

parafoveal traction, a secondary sequelae 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 5-8 

shows the resolving of the color deficit from a large 

average relatively undifferentiated deficit weighted 

toward the blue to an average deficit within normal 

limits, but nonetheless showing 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 

a 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.28 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. 

Furthermore, 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, and, 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. 

Case 2

Case 2 received bilateral accidental exposures from 

an AN/GVS-5 laser range finder with an operating 

Q-switched wavelength of 1,064 nm with an energy 

output at the aperture of 15 mJ/pulse. The range 

finder was held about 0.6 m from the eyes and delivered at least 2 pulses with an estimated TIE of 1.0 mJ 

per pulse, which resulted in bilateral retinal lesions 

Fig. 5-8. FM 100 Hue scores for the affected eye (OD) show a shift (a) from a large fundamental indicating a large average error with a strong 1st harmonic that is indicated in the graph as a strong blue deficit that diminishes (b), when 

fixation restrictions are relaxed, to an average error within normal limits although with significant 1st and 4th harmonic 

components. The axes of the FM 100 Hue test indicated in the center of the radial plots are as follows: B, blue; G, green; 

P, purple; R, red; and Y, yellow.

Illustrations: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

a b
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In Vivo Diagnostics and Metrics in the Assessment of Laser-Induced Retinal Injury

that produced macular holes. The focus of this case 

is the sequela observed in the right eye (OD) over a 

2-year period. 

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 required about 3 weeks 

of postexposure to resolve. The lesion itself eventually 

developed into a full-thickness paramacular hole. 

Immediately following exposure, visual acuity was 

25/50 (OD); at 3 weeks postexposure, visual acuity 

was 20/70 (OD); and by 13 months postexposure, visual acuity deteriorated to 20/800 (OD) postsurgery. 

At 13 months, contrast sensitivity was not measurable 

beyond 6 cycles per degree. 

Figure 5-9 shows the CSLO image of the paramacular hole, the CSLO image of the PMB-RNFL defect 

(Figure 5-9a), and an OCT scan through the center 

of the paramacular hole revealing complete loss of 

sensory retina (Figure 5-9b). The dotted outline shows 

the extent of RNFL pruning in the region of the PMB 

showing a wedge defect. This particular defect was 

first described by Frisch et al.29 Zwick et al30 later 

modeled the phenomenon in NHPs to investigate the 

functional implications of the laser-induced retinal 

neural pruning that was shown to progress with Wallarian degeneration. 

Figure 5-9c shows the fixation eye movement 

patterns at 18 months postsurgery, which removed 

epiretinal scar tissue that was producing traction 

that was 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 mm and that of the superior/

inferior axis ≈100 mm.31 Comparatively, the fixation 

eye movement pattern shown in Figure 5-9c 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 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 the communication between 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. 

Fig. 5-9. (a) CSLO image of OD paramacular hole taken after stabilization surgery at 18 months postexposure. Dashed outline

shows the RNFL defect. (b) OCT scan through this hole (arrow) showing loss of sensory retina leaving retinal pigmented 

epithelium and choroidal vasculature. (c) Fixation eye movement map obtained for OD postsurgery. Map shows a dysfunctional fixation pattern, with fixation at any one location minimal. The grid is ≈400 x 400 μm; 1 grid square is ≈9 μm. 

Photographs/Illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

a

b

c
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Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine

Figure 5-10 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 longterm absence of any significant harmonic frequency 

component indicates that the trichromatic receptor 

components have been equally affected (Figure 5-10c). 

This is most likely caused by the Wallerian neuronal 

degeneration observed in the PMB. These fibers 

transmit trichromatic cone output from the 3rd-order 

neuron to higher brain regions that require this input 

for color discrimination.

Fig. 5-10. (a) 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 as follows: B, blue; G, green; P, purple; R, red; and Y, yellow. 

BY: blue-yellow; RG: red-green; SQRT: square root error; wks: weeks

Illustrations: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

a

b c

Fig. 5-11. A full-thickness fundus photograph of the macular hole at 3 months postexposure (a), corresponding CSLO image 

showing evidence of traction (b), OCT 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.

a

b

d

c
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In Vivo Diagnostics and Metrics in the Assessment of Laser-Induced Retinal Injury

Case 3 

Case 3 received unilateral (OD) accidental exposure 

to a 1,064 nm beam emitted by a battery-operated 

Nd:YAG laser range finder. The exit port of the range 

finder was held approximately 0.6 m from the eye. The 

eye received an estimated TIE of 2.5–3.0 mJ per pulse, 

which produced vitreal hemorrhage.32 By 3 weeks postexposure, the vitreous hemorrhage had cleared. A fullthickness 100-mm diameter macular hole with evidence 

of traction was diagnosed at the 3-month postexposure 

fundus examination (Figure 5-11a,b). An OCT image 

taken through the center of the lesion site (Figure 5-11c) 

revealed total loss of sensory retina in the macula hole 

and a significant choroidal extension beneath the fovea. 

Reflectance in the CSLO indocyanine green (a clinical 

imaging technique using dye to evaluate blood flow in 

the retina) image indicated vascular blockage (Figure 

5-11d). At 12 months, CSLO images revealed a reduction in hole size, the disappearance of traction bands, 

and changes in the choroidal entity appeared weaker 

in reflectance but broader in extent (Figure 5-12a). OCT 

showed evidence of tissue bridging the gap of the macular hole consistent with spontaneous reduction of the 

macular hole size (Figure 5-12b). 

Visual acuity changed concomitantly with evidence 

of improvement in macular integrity. On presentation, visual acuity was 20/150 OD and 20/20 OS. At 3 

weeks, visual acuity improved to 20/60 OD, 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 5-13).

Fixation eye movement patterns at 3 months were 

dominated by a vertical search pattern (Figure 5-14a). 

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 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 mm 

extent. However, the persistence of the vertical component suggests that the signal attracting eye movement 

visitations is weak (Figure 5-14b). 

Case 4

Case 4 received bilateral accidental exposures from 

an AN/GVS-5 laser range finder with an operating 

Q-switched wavelength of 1,064 nm producing an 

Fig. 5-13. Contrast sensitivity measured using the CSLO 

technique showed a long-term OD deficit in sensitivity for 

high-spatial frequency visual stimuli. Note the significant 

suppression in OD sensitivity from 6 to 30 cycles/degree.

Illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Fig. 5-12. Macula hole diameter is reduced in size at about 12 

months postexposure compared with 3 months postexposure 

(see Fig. 5-11). (a) CSLO 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) OCT shows tissue bridging the gap of the macular hole. 

Photographs: Courtesy of the Laser Laboratory, with the 

technical assistance of André Akers.

a

b
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Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine

energy output at the aperture of 15 mJ/pulse. The 

range finder was held about 0.6 m from the eyes and 

delivered at least 2 pulses, with an estimated TIE of 

1.0 mJ per pulse, which resulted in bilateral retinal lesions that produced macular holes. The focus of this 

case is on the sequelae observed in the left eye (OS) 

over a 2-year period.

OS suffered an acute macular vitreous hemorrhage, 

with long-term damage restricted to the fovea. Figure 

5-15 shows a fundus (Figure 5-15a) and CSLO image 

(Figure 5-15b) demonstrating a discontinuity through 

the center of the fovea. Figure 15c shows an OCT image revealing the extent of a small flat macular hole 

through the center of the fovea. 

Visual acuity at 48 hours postexposure was 20/200; 

by 8 days postexposure, visual acuity improved to 

20/25; and, by 3 years postexposure, visual acuity 

improved to 20/15. Color discrimination measured 

with the FM 100 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 distinguishing 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 5-16). 

At 4 years postinjury, visual acuity was recorded at 

Fig. 5-14. Fixation eye movements changed significantly from 3 months (a) to 12 months (b) postexposure. At 3 months, an 

atypical vertical movement was observed that spanned over a 300-mm 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 mm; 

scale b: 1 box = 10 mm.)

Illustrations: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

a b

Fig. 5-15. The fundus photograph (a) shows a central 

anomaly in the macular area (light spot in center of the 

typical darker central macular area). The CSLO image shows 

a small foveal break in the retina and the track of the 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 André Akers.

a b

c

20/15. Figure 5-17 shows the fixation eye movement 

patterns at this time, the focus of which is consistent 

with that of the earlier CSLO observation (Figure 
147

In Vivo Diagnostics and Metrics in the Assessment of Laser-Induced Retinal Injury

5-16a). 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 pseudofovea.33 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 et al’s11,12 structural 

findings and suggests that the visual acuity function 

peak corresponding to the foveola (≈150 mm) is most 

likely a result of its visual cortex representation, which 

is magnified at a ratio of 7:1.10

Case 5

Case 5 received bilateral accidental exposures 

from a Q-switched Nd:YAG laser designator, which 

emitted 10 laser pulses per second at a wavelength of 

1,064 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 mJ per pulse. The exposure induced confined 

bilateral macular hemorrhages. The hemorrhage was 

slightly larger in 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.23 This case will 

describe sequelae in the OD. 

Figure 5-18 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 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, visual acuity, and contrast 

Fig. 5-16. The CSLO image shows contrast sensitivity test for the preferred retinal location for resolving fine-resolution targets 

(a). Placement of fine-resolution targets is superior and temporal to the fovea. Contrast sensitivity measured at 912 days 

postexposure shows a contrast sensitivity function within, although at the lower limit of normal (b). 

PRL: preferred retinal location 

Photograph/Illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

Fig. 5-17. Fixation eye movements recorded at 4 years postexposure for fine-resolution targets. The pattern confirms 

the earlier finding with CSLO 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.
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Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine

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.16

Visual acuity at 3 hours postexposure was 20/50 

OD and diminished to 20/200 OD by 2 days postexposure. Visual acuity 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.16 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 midspatial 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 5-19a). 

Figure 5-19b shows that fixation eye movements at 9 

months are consistent with typical human fixation eye 

movement patterns.24 The map shows no functional 

disruption within the foveal region. 

Fig. 5-18. The large exit port of the designator makes it possible for bilateral exposure at ocular distances of a few centimeters 

(a). OCT images (b) show the progression of OD wound healing from 4 days through 4 months, and CSLO images (c) from 

2 days through 12 months postexposure.

Photographs: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

a b c

Fig. 5-19. The CSLO 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/Illustration: Courtesy of the Laser Laboratory, with the technical assistance of André Akers.

a b
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In Vivo Diagnostics and Metrics in the Assessment of Laser-Induced Retinal Injury

REVIEW

major neural pathway carrying foveal neural retinal 

code to higher order brain mechanism. 

In the absence of secondary damage mechanisms 

described previously, spatial and chromatic vision 

may recover, but still require about 3 to 6 months to 

demonstrate such recovery, 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 visual acuity were unexpected, 

but documented by the capability of CSLO imaging 

to capture anterior retinal pathology. Nevertheless, 

whereas 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, which is indicative of this metric’s strong 

association with lower order retinal ganglion cell 

systems.36,37 On the other hand, the rapid recovery of 

color discrimination at 12 months to normal levels 

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. 

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 

.25 diopters, sufficient to produce a baseline acceptable 

point spread function.31

Case 5 initially showed a PRL superior and slightly 

temporal to the fovea, identical to that of case 4. However, during this time, other visual functions—including 

visual acuity and sine wave contrast sensitivity—were 

still recovering through the 3 to 6 months postexposure 

period. 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 recovFive laser injury cases, which involved retinal hemorrhage, were evaluated with ophthalmic techniques, 

which related structural insult to visual function. The 

results from these cases indicate the complexity of 

the structure–function relationship and the scope of 

resilience of the visual system (Table 5-1). Thus, 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 visual acuity 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. 

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 

of retinal traction demonstrated that retinal traction 

exists above the RNFL and may often extend into 

the vitreous, possibly altering normal photoreceptor 

orientation, which has been demonstrated to cause 

reduction in visual sensitivity.34

Spatial visual function metrics of visual acuity 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. The failure of acuity to recovery 

over the 2-year period is also significant, because 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.35 

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. Although this lesion was parafoveal, and ordinarily such 

lesions are given less importance than more central 

retinal lesions, this particular lesion interrupted the 
150

Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine TABLE 5-1 SUMMARY OF CASE FINDINGS Visual Visual Contrast Color Case Dose Acuity Acuity Sensitivity Discrimination Ocular Secondary No. TIE (mJ) Injury Initial Hemorrhage Initial Resultant Resultant Resultant Motor Sequelae 1 1.96 4 Paramacular 2 Paramacular 20/400 20/400 Significant overall Overall Some functional Retinal scar retinal lesions, holes suppression peak disruption, central retinal between 2 producing produced shift to 10 blue axis in vicinity of scar paramacular macular holes vitreous cycles/degree prominence holes bridging hemorrhage the macular and associated traction 2 1.0 Full-thickness Vitreous 20/50 20/800 Not measurable Uniform Atypical vertical Considerable paramacular hemorrhage beyond 6 suppression scan pattern with nerve fiber hole, temporal cycles/degree with no no dominant retinal degeneration in to optic disc, dominant axis site attracting eye PMB with evidence nasal to movement of Wallerian macular in degeneration to PMB the optic nerve 3 2.5–3.0 Full-thickness Vitreous 20/150 20/40 Significant WNL Significant typical Reduction in hole 100-mm hemorrhage suppression in OD horizontal scan size and diameter sensitivity from 6 to with persistence of disappearance of central 30 cycles/degree atypical vertical traction bands macular hole component 4 1.0 Small flat Vitreous 20/200 20/15 Contrast sensitivity WNL PRL superior/ No change from macular hole hemorrhage function within temporal to fovea initial injury

through the normal limits, with typical fixationcenter of the although at the movement patternfovea lower normal limit

5 0.315 Break in RPE Confined 20/50 20/15 OU at Recovered from WNL PRL shift from Treated with steroid,

beneath the macular OD at 10 months uniform suppression superior/temporal significant nervefovea hemorrhage 3 hours, and 20/25 with peak sensitivity to fovea back to fiber thickening

centered in 20/200 OU at 14 shifted to 1 cycle/ the fovea close to normal,fovea at 2 days months (OD degree to a function foveal thickness

postexposure only was not within normal limits

recorded)

OD: oculus dexter (pertains to the right eye); OU: oculus uterque (pertains to both eyes); PMB: papillomacular bundle; PRL: preferred retinal location; RPE: retinal pigmented epithelium; TIE: total intraocular energy; WNL: within normal limits.
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EXHIBIT 5-3

THE FUTURE AND FUTURE RESEARCH

The emergence of the use of military systems that emit hazardous levels of electromagnetic radiation continues. Few 

eye injuries in Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) current operations have been 

attributed to laser radiation. However, laser range finders, designators, illuminators, training devices, retinal scanned 

displays, high-energy laser systems for both tactical and theater ballistic missile defense, secure infrared communication systems, laser battlefield contaminant detection systems, and laser “dazzlers” all present new threats to soldier 

health and performance. 

Optical denial systems use radiation in the optical region of the electromagnetic spectrum. Laser dazzlers, such as 

HELIOS and GHOST (developed by the US Army’s Rapid Equipping Force), emerged in 2006 for rapid insertion into 

OIF and OEF operations. The emergence of a solid-state fiber laser with emission powers in the 25–100 kW range in a 

relatively small package has reenergized the military system developers in refining application specifications. Tactical 

high-energy lasers are emerging with potential injury to personnel a likely scenario in both training and operational 

scenarios. The maturing of access denial systems that operate in the infrared and millimeter wavelength regions requires enhanced awareness of the medical effects by the Army Medical Department. Issues with respect to their testing, 

training, and fielding will require judgment from the Army Medical Department in the protection of soldiers. New 

military radar systems, individual soldier communications systems with body-worn antennas for local situational 

awareness, electronic countermeasures, guidance and jamming systems, satellite communications, and rail guns all 

use or generate radiofrequency radiation. A robust biomedical database of radiation effects pertinent to the wide range 

of military systems is required to protect the soldier and to sustain military operations.

Treatment of laser-induced retina injury must continue to be a focal area of research to minimize the loss of vision 

induced by laser radiation for a wide range of exposure conditions inherent to the multiplicity of military uses of directed energy. Whereas the relative efficacy of some drugs has been demonstrated for specific forms of laser-induced 

injury, combined therapies and possible stem cell applications will offer better treatment efficacy. Eye injuries from blast 

and fragments are a problem in current operations. Pharmacological and surgical interventions under investigation 

for laser-induced retinal trauma certainly have applicability to eye trauma from blast. Local as opposed to systemic 

administration of drugs to the eye requires testing of innovative approaches. Ocular pharmacokinetics and optical 

techniques to make both qualitative and quantitative assessments are required for treatment of ocular trauma.

The medical aspects of laser exposure from glare to laser-induced hemorrhage must be better 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 

from repeated exposure (several focal “full bleach” exposures with no ophthalmoscopically observable changes) in a 

single, multiple exposure engagement or cumulative effects over a period of days or months are not well characterized 

or understood. Developments of advanced rapid assessments of visual function are needed to ensure the soldiers’ visual 

health in operational scenarios and to have early assessment of potential functional changes from repeated or chronic 

exposure. Advanced diagnostic imaging of the retina (optical coherence tomography, scanning laser ophthalmoscopy, 

wave front-corrected retinal imaging) have great potential in assisting far-forward ocular evaluations, particularly 

when coupled to telemedicine implementations. 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. 

Exploration of the efficacy of new drugs and the combination of drugs are based on the mechanism of injury at the 

molecular level, and the subsequent time course and manifestation of the injury pathway.

The biological database that supports development of exposure guidelines for lasers must continue to be expanded 

to meet the challenges posed by new military systems. With the emergence of nonlethal-directed energy systems, 

soldier protection must be ensured by the availability of “results-based” directed energy exposure guidelines. This 

database must also assist in the specification of the level of protection required for laser eye protection systems. 

A closer cooperation with military laser developers is needed to ensure that the system technology does not exceed 

the understanding of the biomedical implications of soldier exposure. The emergence of nonlethal-directed energy 

will require updates to testing and training policies for soldier exposure to nonionizing radiation. New technology 

must be used to assess radiation bioeffects, to understand injury mechanisms, and to determine the efficacy of treatment regimens. As the research in the use of these technologies matures, the results must be integrated in military 

medical doctrine and practice.
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ered or were sufficiently active to minimize possible 

residual selective cone dysfunction. This is most likely 

due to a greater inherent redundancy of the cone-toganglion 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 visual acuity and not on contrast sensitivity.18 However, when accidental exposure is repeated 

by malfunction19 or by intentional exposure,36 functional loss in spatial retinal-based metrics may become 

permanent, although high-contrast achromatic visual 

acuity may still be compensated by static or dynamic 

visual cortex plasticity. Of special note is the color contrast examination developed by Arden et al19 that uses 

both color opponency and color contrast. These metrics 

interrogate both retinal ganglion cells, as well as higher 

order visual processing that render contrast, color opponency, and color contrast information. Although this test 

represents a major advance in utilizing various levels of 

neural code arising from the retina, it could be improved 

to track the neural code arising from the fovea as well, 

by utilizing a broader range of spatial frequencies in 

evaluation of retinal systems associated with central 

fovea visual function. This is the current effort for the 

enhancement of the Aidman Vision Screener.22

Finally, the animal behavioral and morphological 

evaluations of outer retinal cone function require some 

discussion. Sperling et al38 demonstrated the photic 

toxicity of short wavelength light to S cone photoreceptors and that such exposures occurred in the range of 

5 log trolands. This brightness level is slightly higher 

than comfortable brightness, but is 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 that either the S cone or some other 

component in the retina sensitive to such visible radiation was vulnerable.39 The experiments of Zwick2

 and 

Schmeisser40 bring another aspect to this discussion, 

which is the possibility that the unique interference 

patterns induced by visible laser light when irradiating a surface (speckle) may have peak powers high 

enough to produce significant retinal dysfunction or 

photoreceptor loss. Although 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 prolonged viewing of speckle with moderate peak powers above average power may induce 

neural reorganization in ways that may degrade visual 

function. Notwithstanding, 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.41 These 

changes may have been responsible for detuning receptor systems associated with high acuity criteria and 

sensitizing receptor systems at lower acuity criteria; 

but, 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,2 suggesting 

that such effects may be triggered by a wide range of 

laser energy exposure levels.

The ability to address the diagnostic issues reviewed 

herein with an animal model capable of providing an 

in vivo view of such processes in “action” is unique. 

The authors have shown, in imaging damage and repair processes in the small eye, changes in the internal 

reflection of the photoreceptor indicative of changes 

in mode structure.42 Changes in mode structure suggest a change in photoreceptor orientation and thus 

in sensitivity to particular spectral frequencies.43 Such 

reflectivity is not the same as a lesion observed in a 

large eye (eg, NHP) due to the full thickness and low 

resolution with respect to cellular structure in the large 

eye. The in vivo small eye model is different from 

histological preparations, as well, because it exists in 

its natural state within the retina and its behavior can 

be documented, such as 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 damaged photoreceptors.44 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. Therefore, replacement receptors from peripheral retina, if migration is a 

relevant explanation of visual function recovery, must 

have characteristics that provide trichromatic cone 

characteristics. Such characteristics may simply be the 

greater redundancy that worked in case 5 for return of 

color discrimination. However, long wavelength cone 

emergence was also demonstrated over very different 

spectral and energy levels, suggesting that the reemergence of long wavelength cone systems may involve 

unique photoreceptor spectral tuning requiring an 

active rootlet system within the photoreceptor, as well 

as one within the RPE to provide a range of movement 

parameters that might be necessary for such spectral 

tuning of the waveguide (Exhibit 5-3).45
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SUMMARY

sual centers. This investigative functionality will allow 

for the identification of vision loss without easily identifiable retinal damage, because a dysfunctional state 

may exist within the retinal/brain physiology itself.

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. 

Acknowledgment

The authors thank Dr Victoria Tepe for her invaluable assistance in preparing this manuscript and an extract 

of a previous work on Biomedical Implications of Military Laser Exposure (SURVIAC [Survivability/Vulnerability Information Analysis Center] Technical Report for the US Army Medical Research Detachment, 

Medical Research and Materiel Command, 2007).

REFERENCES

1. Wolfe JA. Laser retinal injury. Mil Med. 1985;150:177–185.

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

3. Barkana Y, Belkin M. Laser eye injuries. Surv Ophthalmol. 2000;44:459–478.

4. Masters B, Boenke M. Three-dimensional confocal microscopy of the living human eye. Ann Rev Biomed Eng. 2002;4:69–91.

5. Zwick H, Elliot R, Schuschereba S, et al. In-vivo confocal scanning laser ophthalmoscopic characterization of retinal 

pathology in a small-eye-animal model. Proc SPIE. 1997;2974:44–50. 

6. Zwick H, Elliot R, Li G, et al. In-vivo imaging of photoreceptor structure and laser injury pathophysiology in the snake 

eye. Proc SPIE. 1999;359:368–374. 

7. Li G, Zwick H, Tribble J, et al. On-off-axis confocal double pass measurements of the point spread function in the 

human eye. Proc SPIE. 1999;3591:351–358. 

8. McIlwain J. An Introduction to the Biology of Vision. New York, NY: Cambridge University Press; 1996.

9. Brodal P. The Central Nervous System: Structure and Function. 3rd ed. New York, NY: Oxford University Press, Inc.; 2004.

10. Langus A, Zwick H, Stuck B, Belkin M. Foveal photoreceptor explanation of short-term visual acuity recovery associated with laser-induced foveal damage. Proc SPIE. 2003;4953:39–50.

11. Curcio CA, Kimberly AA, Sloan KR, et al. Distribution and morphology of human cone photoreceptors stained with 

anti-blue opsin. J Comp Neurol. 1991;312:610–624.

12. Curcio C, Allen K. Topography of ganglion cells in human retina. J Comp Neurol. 1990;300:5–25. 

The wide variety of damage and recovery processes 

was revealed through metrics that combine structural 

and functional diagnostic techniques. The techniques 

are needed for reliable, rapid, and valid measures of 

visual function deficits associated with laser retinal 

injury and will require further development as lasers 

become smaller, more spectrally agile, and more 

widespread. 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 higher order vi-
154

Military Quantitative Physiology: Problems and Concepts in Military Operational Medicine

13. Zwick H, Stuck B, Dunlap W, et al. Accidental bilateral Q-switched neodymium laser exposure: treatment and recovery 

of visual function. SPIE. 1998;3254;80–89.

14. Breitmeyer B, Valberg A. Local foveal inhibitory effects of global peripheral excitation. Science. 1979;203:463–464. 

15. Allen D. Fourier analysis and the Farnsworth-Munsell 100-Hue test. Ophthalmic Physiol Opt. 1985;5:337–342.

16. Zwick H, Lund B, Brown J, et al. Human color vision deficits induced by accidental laser exposure and potential for 

long-term recovery. Proc SPIE. 2003;4953:27–39. 

17. Zwick H, Bedell RB, Bloom KR. Spectral and visual deficits associated with laser irradiation. Mod Probl Ophthalmol.

1974;13:299–306.

18. Zwick H, Bloom KR, Beatrice ES. Permanent Visual Change Associated with Punctate Foveal Lesions. Presidio of San Francisco, Calif: Letterman Army Institute of Research; 1986. Institute Report No. 86-59. 

19. Arden GB, Grundez K, Perry S. Colour vision testing with a computer graphics system. Clin Vis Sci. 1988;2:303–320.

20. Rabin J. Cone specific measures of human color vision. Invest Opthalmol Vis Sci. 1996;37:2771–2774.

21. Gunzenhauser J. Issues in the Development of the Aidman Vison Screener. Laboratory Report. Presidio of San Francisco, 

Calif: Letterman Army Institute of Research; 1990.

22. Boye M, Zwick H, Stuck B, et al. Development of an Advanced Aidman Vision Screener (AVS) for selective assessment 

of outer and inner laser-induced retinal injury. Proc SPIE. 2007;6426:2–10. 

23. Zwick H, Stuck B, Brown J, et al. Long term evaluation of two bilateral laser eye accident cases. Proc Intl Laser Safety 

Conf. 1999;83–92. 

24. Ness J, Zwick H, Stuck B, et al. Retinal image motion during deliberate fixation: implications to laser safety for long 

duration viewing. Health Phys. 2000;78:131–142. 

25. Zwick H, Stuck B, Gagliano D, et al. Two Informative Cases of q-Switched Laser Eye-Injury. Presidio of San Francisco, 

Calif: Letterman Army Institute of Research; 1991. Institute Report No. 463. 

26. Stuck B, Zwick H, Molchany J, et al. Accidental human laser retinal injuries from military laser systems. SPIE. 

1996;2674:7–20. 

27. Robson JG. Spatial and temporal contrast sensitivity functions of the human visual system. J Opt Soc Am A Opt Image 

Sci Vis. 1996;56:1141–1142. 

28. Chatterjee S, Callaway E. S cone contributions to the magnocellular visual pathway in the macaque monkey. Neuron. 

2002;35:1135–1146.

29. Frisch G, Shawaluk P, Adams D. Remote nerve fibre bundle alterations in the retina caused by argon laser photocoagulation. Nature. 1974;248:433–435.

30. Zwick H, Belkin M, Zuclicih J, et al. Laser-induced retinal nerve fiber layer injury in the nonhuman primate. Proc SPIE. 

1996;2674:89–96. 

31. Ness J, Zwick H, Lund B, et al. Fixational eye movement patterns reflect macular pathology induced by accidental 

laser exposure. Invest Ophthalmol Vis Sci. 2000;41(4). Abstract 4323-B270.

32. Zwick H, Stuck B, Scales D, et al. Longitudinal evaluation of selected human laser eye accident cases. Laser and noncoherent light ocular effects: epidemiology, prevention and treatment. Proc SPIE. 1999;3591:386–393.
155

In Vivo Diagnostics and Metrics in the Assessment of Laser-Induced Retinal Injury

33. Zwick H, Ness J, Molchany J, et al. 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.

34. Enoch J, Van Loo J, Okun E. Realignment of photoreceptors disturbed in orientation secondary to retinal detachment. 

Invest Opthalmol Vis Sci. 1973;12:849–853.

35. Gilbert C, Wiesel T. Receptive field dynamics in adult primary visual cortex. Nature. 1992;356:150–152.

36. Jenkin M, Harris L. Seeing Spatial Form. New York, NY: Oxford University Press; 2006.

37. 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. 

38. Sperling HG, Johnson C, Harwerth RS. Differential spectral photic damage to primate cones. Vision Res. 1980;20:1117–

1125.

39. Ham WT Jr, Mueller HA, Sliney DH. Retinal sensitivity to damage from short wavelength light. Nature. 1976;11:153–155.

40. Schmeisser E. Laser flash effects on laser speckle shift VEP. Am J Optom Physiol Opt. 1985;62:709–714.

41. Schuschereba S, Zwick H, Stuck B, Beatrice E. Basal Body and Striated Rootlet Changes in Primate Macular Retinal Pigmented 

Epithelium After Low Level Diffuse Argon Laser Radiation. Fort Belvoir, Va: Defense Technical Information Center; 1982.

42. Zwick H, Edsall P, Stuck B, et al. Laser-induced photoreceptor damage and recovery in the high numerical aperture 

eye of the garter snake. Vision Res. 2008;48:486–493. 

43. Li G, Zwick H, Stuck B, Lund D. On the use of schematic eye models to estimate image quality. J Biomed Opt. 2000;5:307–

314.

44. Tso MO, Robbins DO, Zimmerman LE. Photic maculopathy. A study of functional and pathologic correlation. Mod 

Probl Ophthalmol. 1974;4:220–228.

45. Westheimer G. Directional sensitivity of the retina: 75 years of Stiles-Crawford effect. Proc R Soc Biol Sci. 2008;275:2777–

2786.
156

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