Operating microscope-induced retinal phototoxicity: pathophysiology, clinical manifestations and prevention.

SURVEY OF OPHTHALMOLOGY

MAJOR

VOLUME

34 * NUMBER

4 -JANUARY-FEBRUARY

1990

REVIEW

Operating Microscope-induced Retinal Phototoxicity: Pathophysiology, Clinical Manifestations and Prevention MARK MICHELS, M.D., AND PAUL STERNBERG,

Department

JR., M.D.

qf OphthalmoloCg?r, Emory

University School of Medicine, Research Ceder, Atlanta, Georgia

and Yerkes Regional

Primate

Abstract.

Retinal light damage is a poorly understood phenomenon, due to its multifactorial It has been increasingly identified following etiology and relatively infrequent recognition. ocular surgery involving the intense light of the operating microscope. The authors describe the clinical entity, review salient features of its pathophysiology and provide guidelines for prevention of retinal phototoxicity. (Surv Ophthalmoi 34:237-252, 1990)

Key words.

blue light

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infrared

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light damage

The concept of light-induced retinal damage has been recognized since the time of Plato”‘” and was first clinically studied as early as 19 16 by Verhoeff et al.“‘” They described the nature of solar burns affecting primarily the retinal pigment epithelium and choroid. They attributed this damage to an increase in ocular temperature and not to an overstimulation of the retina with light. It was not until experimental work by Noel1 et al”’ in the mid- 1960s that nonthermal retinal light damage became recognized. The myth that such damage could be caused only by intense light sources, such as the sun and various photocoagulators, gave way to the reality that damage from lower intensity light was probable and that additivity of several exposures was possible. In the last ‘LO years, a burgeoning literature has described experimental light damage in several models caused by commonly used ophthalmic devices and nonophthalmic light sources. Hochheimer et al’” were the first to describe such damage in primates. In the last fifteen years, the use of intense light sources in ophthalmic surgery has increased. Since McDonald and Irvine in 1983 reported the first cases in patients undergoing uncomplicated extracapsular cataract ex-

l

retinal

phototoxicity

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ultraviolet

there have been numerous reports of traction,” iatrogenic phototoxicity following routine cataract extraction,. i.ll~.L’2.~7.Si.iX.jy.7R.100 epikeratophakia,” combined anterior segment procedures,“,“” and recently, following vitrectomy surgery.‘” While Kobertson and Erickson initially were unable to generate lesions in human eyes with the indirect Robertson and Feldman were ophthalmoscope,‘“” able to conclusively establish a cause and effect relationship between exposure of the operating microscope light and retinal lesions.“” Light has been suggested as a causative factor in cystoid macular edema,“:’ as well as in retinopathy of prematurity.“” Retinal damage following arc welding has also been reported.X”.“4 Concurrently, numerous reports implicate cumulative exposure to ambient light as contributing to retinal and retinal pigment epithelial degeneration, particularly to the process of agerelated macular degeneration.“” Light’s deleterious effect in retinal dystrophies has also been suggested.“,” Many authors have proposed methods by which the metabolic milieu or the light itself might be altered to effect the light damage process. This manuscript

attempts

to provide

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Fig. 1.

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MICHELS,

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Photo and fluorescein angiographic appearance of typical lesion in rhesus monkey at two weeks after expo-

sure.

view of this literature, specifically as it relates to operating microscope-induced retinal phototoxicity. Work in this controlled setting may have some application to the processes observed in chronic light exposure and age-related macular degeneration. However, it is essential to bear in mind that while many ophthalmic instruments generate high levels of irradiation,‘” total energy delivered to eyes under nonoperative conditions is much less than that delivered under operative conditions. The relationship between solar radiation and macular degeneration is discussed extensively in the review by Young.13’

I. Clinical Manifestations of Retinal Light Damage and Their Prevention The term “phototoxic lesion” is usually employed to describe the typical retinal lesion produced after a relatively short intense exposure to a light source such as the operating microscope. The lesion produced by tungsten filament illumination often assumes the horizontal, oval shape of the fiber bundle image, while the fiberoptic illumination system produces a round lesion. Tso divides photic injury into three phases: the acute, reparative and chronic degenerative. ’ ” Immediately after exposure, there is no evidence of clinical pathology. Within 24-48 hours, retinal edema may be demonstrated, although mild pigmentary disturbances alone are more characteristic. A subtle discrete margin is seen ophthalmoscopically, and fluorescein angiography more easily demonstrates early discrete hyperfluorescence with late staining (Fig 1). By the end of

the first week, lesions are characterized by alterations in pigmentation; a diffuse mottling in some cases with a target-like black clumping surrounded by clear halo in others. Little clinical change is noted during the reparative stage. After the first month, macular lesions become smaller; some are slightly elevated. Inner retinal surface wrinkling is sometimes noted. Pigmentation is variable, with some lesions demonstrating a yellowish white The reader is plaque at three to five months. I IYvL’?O,I?Z referred to works by Tso or Ham37 for details of light and electron micrographic findings. Longterm follow-up at live years reveals chronic decompensation of the blood-retinal barrier. Sub-RPE neovascularization with hemorrhage has been reported”2 in the phakic rhesus model after exposure to the indirect ophthalmoscope. Recently, a choroida1 neovascular membrane was noted 18 months after a well documented case of operating microscope induced-retinal phototoxicity in a pseudophakic human.” The similarity between late phototoxic lesions and AMD has been noted.“s~‘Oy~“”It has been suggested that this may result in poor recognition of the diagnosis in many patients.“’ Phototoxic lesions caused by the operating microscope are typically located superior or inferior to the fovea and are less intense in the fovea1 region. The latter is discussed under Energy Delivery-Absorption. The reason for the nonfoveal location is that most operating microscopes are not precisely coaxial, and, in fact, direct the “coaxial” beam just superior to the fovea. Brod et al” calculated that the fiber bundle image will project to 1.5 mm above

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the fovea in the emmetropic eye, 1.3 mm above in the myopic and 1.8 mm above in the hyperopic eye using their microscope.” The variability in location ofthese lesions is partly a function of this noncoaxiality which varies between different models of microscopes (6” for the Zeiss and 1.5” for the Wild) and the degree to which the eye or oculars are tilted by the surgeon for each case. Lesions occur most commonly on the inferior macula. The probable reason for this is that although the Zeiss operating microscope actually directs the noncoaxial illumination onto the superior macula, operating microscope tilt toward the surgeon, rotation of the eye inferiorly, and displacement of the microscope field of view toward the twelve o’clock meridian tends to move the fiber bundle image inferiorly on the retina. A small movement may direct the light into the fovea; however, a larger movement or a combination of those movements will safely direct the focal illumination below the fovea. ’ ’ .“I?.‘(‘:I Retinal phototoxicity as originally described in rats was thought to be permanent.!” Corn and Kuwabara demonstrated that this was not necessarily ~0.‘~ Tso et al later demonstrated both reappearance of photoreceptor elements”” and reasonably good vision in trained monkeys exposed to an hour of the indirect ophthalmoscope.“’ Naidoff and Slineyx” have reported visual recovery in a patient with welding arc-induced maculopathy, and Lindquist has reported marked recovery of phototoxic scotomas in two patients after cataract extraction.‘” Hupp has also made this observation in one patient.47 Moon et alsx have demonstrated visual recovery in rhesus monkeys exposed to an intermediate level ofenergy; animals exposed to 30 Jcm-’ less than the intermediate level were not affected while those exposed to 30 Jcm-’ more energy suffered permanent damage. It should be noted that recovery from solar retinitis and eclipse blindness is also well established in the literature.‘“.“‘” Age, nutritional status, pigmentation, and core temperature might also be expected to enter into the phototoxicity recovery picture. The likelihood of recovery is probably a function of many factors. While some eyes are likely to recover from retinal phototoxicity, few patients will manifest symptoms. Of Boldrey et al’s series, only a third were symptomatic”’ and none of the patients reported by Khwarg et al were symptomatic.“” One must realize that even though fewer than sixty cases of retinal phototoxicity have been published, the pathology is subtle. Ross suggested that the subtle pigmentary changes can easily be attributed to nonspecific atrophic macular changes often found in elderly patients

and these may be overlooked.“‘”

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RETINAL PHOTOTOXICITY

The find-

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Fig. 2. Graph depicts transmission percentage as a function of wavelength for the whole human eye. (Adapted from Roettner EA and Wolter JR” (ZnzlestigatingOphthalmolog?r94: 143-148, 1987) and reprinted from Michels M et al’” (Ophthalmology 94:143-148, 1987) with permission of Ophthalmology.

ing that such lesions may result in choroidal neovascularization, as described in the rhesus monkey study by Tso et al, IL”and the notion that this may occur in humans,79 while being attributed to the aging process, is disturbing.

II. Physical Factors Contributing to Retinal Phototoxicity A. LIGHT Light is a small portion of the broad electromagnetic spectrum to which the eye responds, giving sight. This visible light ranges from 400-700 nm.“” Infrared (IR) and ultraviolet (UV) light represent nonvisible irradiation adjacent to the long and short extremes of the visible spectrum respectively. Visible, UV, and IR represent that portion of the electromagnetic spectrum that interacts primarily with the eye. This irradiation comes from numerous sources, which vary in intensity and exposure duration; these include the sun, the operating microscope, ambient artificial lighting, and therapeutic as well as nontherapeutic monochromatic light sources. B. IRRADIATION

AND ENERGY

The manner in which light interacts with the eye is dependent on three factors: wavelength (nm), exposure time (set) and power level (Wcm-‘).“’ Wavelength is crucial because shorter wavelength light has more energy per photon than long wavelength light and is therefore “energy efftcient” for a

240 given

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Irradiance

(exposure

rate)

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MICHELS,

STERNBERG

is di-

radiance (brightness) and reflects power delivered to a target tissue.“4 The product of irradiance and exposure time expresses total energy delivered (Jcm-‘). These three factors in various combinations determine the primary mechanism for the various forms of ocular damage. rectly

related

to source

C. MECHANISM: PHOTOCHEMICAL, THERMAL OR COMBINED Mechanical damage is caused by high power ultrashort pulses; for example, the Nd-YAG (1064nm) laser produces local plasma and sonic transients that mechanically disrupt tissues such as the posterior lens capsule. Thermal damage is caused by high powered relatively short duration (< 10 set) exposures to light such as that emitted by the Argon, Krypton, or dye laser.J8 By raising the local temperature of the target tissue, denaturation of proteins, including vital enzymes, of the cell results. Photochemical damage is caused by low powered, relatively long-duration (> 10 set) exposures to visible light, resulting in damage to cellular constituents at temperatures too low to cause destruction as seen with thermal mechanisms. It is the photochemical mechanism by which most of what is described as retinal phototoxicity occurs.33 Noell’s finding of retinal damage at low temperatures was profoundly important because, by suggesting a nonthermal phototoxic mechanism, he introduced the concept that consecutive exposures might be additive. The implication that cumulative exposures to light might be toxic meant successive examinations with the indirect ophthalmoscope or that a lifetime of daily exposures to ambient light might be harmful. The precise contribution of the thermal and the photochemical process are difftcult to discern, especially since both are manifested as a disorder of retinal pigment epithelium and photoreceptor outer segments.’ However, certain characteristics have been thought diagnostic of each. Clinically, thermal burns appear almost immediately, while the phototoxic lesions require 24-48 hours.3’,“g.50 Because of the nature of thermal burns, more damage is seen in the hotter center of the lesion, while cooler borders of the lesion demonstrate decreasing degrees of damage. This effect may not be as evident in short duration, large diameter lesions when delivered with a fiberoptic photocoagulator. Photochemical lesions are uniform in appearance across the damage field. Clinical thermal lesions are typically smaller than clinical phototoxic lesions because a much smaller retinal area is exposed to damaging irradiances, and because of the nature of the thermal burns.“7~“y~“0

required to produce miniFig. 3. Radiant exposure mal lesion for eight wavelengths in the rhesus monkey. (Reprinted from Ham WT et al33 with permission of the authors and publishers of Photochemistry and Photobiology)

The work of Ham et al”” on determination of damage threshold using monochromatic light sources in the rhesus monkey provide some of the most useful information on the thermal and photochemical factors involved in light damage (Fig. 3). The data reveal a break in the damage threshold lines occurring at 10 seconds, after which the slope of the threshold curve is flatter for the shorter wavelengths - less than 514.5 nm. The longer wavelength light demonstrates a more uniform slope for short and longer exposures. The flatter slope for the short wavelength light demonstrates the effrciency of these wavelengths in producing pathology at comparatively lower power levels over time. The authors attribute the short wavelength curves to a primarily photochemical process after 10 seconds, and conclude the longer wavelength thresholds represent primarily thermal processes. Lawwill et al”’ studied threshold energies in dutch belted rabbits, comparing a broad-band light source to a monochromatic 514.5 nm light. They found that the short wavelength monochromatic

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Fig. 4. Retinal irradiance required to produce minimal lesion for broad-band sources. (Reprinted from Ham WT et al’” with permission of the authors and publishers of Photochemistry and Photobiology.)

light was chiefly responsible

for damage, since only 20% of energy required for a broad-band source produced a lesion using the short wavelength light. In later work, Lawwill et al’” compared two laser wavelengths, 457.9 and 590 nm. The difference in efficiency was eightfold, with the shorter wavelength light requiring less energy to produce a lesion.“’ These reports confirm the damage “efftciency” of short wavelength visible light. Polhamus,‘“” using rhesus monkeys and monochromatic light sources, measured threshold temperatures corresponding to both ophthalmoscopitally and microscopically visible lesions. Using the CW Krypton laser (647.1 nm), threshold temperatures in the macula were 12 to 17°C depending on exposure durations (9-1000 seconds). This temperature rise is high compared to the 0.7”C measured temperature rise produced by blue light at 120 seconds, suggesting a different, nonthermal mechanism for blue light damage.“‘” Friedman and Kuwabara found similar results.‘7 The relationship between retinal irradiance and time also has been elucidated by Ham et al.JJ They noted a nearly reciprocal relationship in thresholds between light ranging from 400 to 800 nm, whereas

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light ranging from 700 to 1400 nm did not display this reciprocity.“” The slope of this relationship is close to 45”, meaning that total threshold energy is constant and independent of exposure time and that the primary effect is linearly additive, a characteristic feature of all photochemical processes.‘,“’ (See Fig. 4.) The idea that the photochemical process might be enhanced by elevated temperature was first addressed in Noell’s work.“’ He found that hyperthermia greatly increased and intensified the damaging efffect of the light. For this reason most of his experiments were performed at controlled elevated temperatures. Friedman and Kuwabara altered core temperature between 35 and 40°C in their studies with rhesus monkeys.“‘They noted a significant decrease in threshold time to damage with an increase from 35 to 40°C core temperature. The authors measured local temperature using a microthermocouple and found a temperature increase of only 3°C required for lesion production. Because thermal retinal damage traditionally is thought to occur only if local temperatures are increased 10-20X,“” Friedman and Kuwabara concluded that phototoxic light damage was potentiated by heat.” Recently, Rinkoff et al”‘” came to the same conclusion in their studies with the New Zealand red rabbit. They found that intravitreal infusion of hypothermic fluid (22°C versus 39°C) extended the damage threshold from 25 to 60 minutes using an intraocular fiberoptic light probe. Zak et al”‘:’ presented their findings on the effects of retinal hypothermia in vitrectomized rabbit eyes in effecting argon blue laser lesion threshold. They noted that eyes treated with cool infusion fluid required S-16% more energy to produce threshold retinal lesions at 500 msec exposures. The difference was increased to 3040% more energy at 1000 msec exposures; there was no difference noted at 50 msec exposures. The authors concluded that cool retinal temperatures can protect against light toxicity in their model, particularly at lower powers with longer duration.“” One might argue that these data on heat potentiation of phototoxic retinal damage would obligate a reduction in the infrared or heated portion of light emitted from the operating microscope and other instruments, such as the fiberoptic endoilluminator.‘“.” Fuller et al” exposed the maculas of healthy owl monkeys to light from the intraocular fiberoptic probe. They documented flat transmission to the fiberoptic source between 540 and 1300 nm. A heat-reflecting mirror eliminating 700-I 100 nm was used in one phase of their work in which the contribution of IR irradiation was assessed. In the five IR-blocked eyes studied for one week, ophthal-

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moscopic lesions were produced which were similar to those produced in eyes treated for similar periods of time with the standard fiberoptic light spectrum. Likewise, no difference was noted histologically. The data suggest heat produced by the infrared portion of emitted irradiation plays a minimal role in potentiating retinal photic damage. Michels et alx” have demonstrated substantial IR output from the operating microscope. Recently, Michels et al”7 studied the utility of an efficient IR blocking filter in reducing the severity of operating microscope induced retinal phototoxicity. Clinical and fluorescein angiographic examination of rhesus eyes subjected to varying exposure durations from a Topcon OMS 300 microscope failed to demonstrate a consistent difference in appearance. However, serial sections showed cytoarchitectural disarray in nonblocked eyes at an electron microscopic level, as compared to the IR-blocked eyes (Fig. 5A and 5B). Using the Zeiss OPMI-6 microscope fitted with a IOOW bulb and fiberoptic cable delivery, we have not found a clinical difference in microscope burn, despite a greater than 75% reduction in total energy delivered when the IR (heat) filter is in use. Robertson and McLaren”” have most recently addressed this question in a blind phakic human eye; using both infrared and ultraviolet blocking filters, they learned that neither filter, alone or combined with the other, prevented retinal phototoxicity at exposures of sixty minutes.“” Several investigators have attempted to document a cumulative effect to repeated exposures. Irvine et al”O studied the effect of operating microscope retinal damage on pseudophakic rhesus monkeys. They found the threshold for damage to be between 4 and 7% minutes. They exposed one eye of a pair to 4 minutes of exposure with no lesion demonstrated. In the fellow eye a 4-minute exposure was followed by 5 minutes of no exposure and then 4 minutes of further exposure. The lesion produced in this eye after successive exposures for a total of eight minutes was described as similar to lesions produced by eight minutes of continuous exposure. The authors conclude that at least within this relatively short duration, sequential exposures have an additive effect.“” Lawwill et a17’ found that daily one-hour exposure of primate eyes for 4 days was equivalent to a single 4-hour exposure at the same retinal irradiance. Ham et al”” found a minimal photochemical lesion produced with 30Jcm-’ using monochromatic 441.6 nm. Two exposures of 15Jcm-’ separated by 48 hours also produced a minimal lesion. But, four exposures of 7.5Jcm-’ spaced 48 hours apart failed to produce a lesion.“” Sperling et al”” compared lesions from a single 120minute exposure with intermittent exposures and

MICHELS, STERNBERG

Fig. 5A. Rhesus retina exposed to IR filtered light (4.2K mag). RPE polarity is maintained with moderate intercellular vacuolization and myelin bodies demonstrated. Vacuolization is also seen between RPE and Bruch’s membrane. Bruch’s membrane and choriocapillaries are normal. Photoreceptor outer segment disarray is seen but is not as marked as in 5B.

found differences when studied histologically. Griess et al”’ studied additivity and repair of actinic damage in the rhesus monkey using a 458 nm monochromatic source to create funduscopically visible lesions. The authors concluded that repeated subthreshold exposures to blue light produce cumulative retinal changes which are countered by an exponential repair process.“” The mathematics of this interaction are detailed in the paper. The authors make no attempt, however, to characterize the damage or repair mechanisms. Colvard reviewed several reports and qualitatively came to a similar conclusion.‘” It is interesting to note that preexposure light adaptive state may also play a role. Birch and Jacobs demonstrated in albino rats that animals reared in cyclic illumination, compared to dark-reared animals, had much less severe

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be done in the primate model to carefully elucidate the potential for cumulative damage in exposure to visible light. D. ENERGY

DELIVERY

1. Transmission and Emission

Fig. 5B. Rhesus retina exposed to non-filtered light (3.OK mag). Loss of RPE polarity, vacuolization of intercellular junctions and between RPE and Bruch’s membrane are demonstrated. Intracellular vacuoles, pigment granular disturbances and lipofucsin inclusions are also seen. Bruch’s membranes and choriocapillaris are unaffected. Photoreceptor outer segment disarray is marked with demonstration of edematous and abnormally aligned outer segment discs.

reduction of scotopic sensitivity.’ To summarize, LJV, visible, and IR light play a role in retinal light toxicity. Little UV is generated by the operating microscope and very little is transmitted to the retina of the phakic eye, because of lenticular absorption in the adult. On the contrary, significant quantities of visible and IR light are transmitted to the retina of the phakic eye, induding high energy, damage efficient blue light at wavelengths less than 514.5 nm. The RPE seems to be the primary site of damage occurring in the primate model exposed under conditions of relatively high energy for short duration. There is good evidence for protection from damage by macular yellow pigment. That increased ocular pigmentation affords protection by any manner other than decreasing irradiance has not been well documented. Certainly under dilated conditions, this protection is lost. The process of retinal phototoxicity seems to be largely a photochemical process with some potentiation by heat. While altering the temperature of the experimental system affects the light damage threshold, eliminating heat from the light source itself has not proven to be of clinical benefit. This discrepancy with regard to additivity of phototoxic damage seems to lie in the work described by Griess.“’ It seems that the conflicting reports may be a function of a cumulative effect countered by an exponential repair process. Further work needs to

In order for light to cause retinal damage it must be transmitted to the retina through anterior ocular structures and it must be absorbed by tissue in or around the retina. Boettner and Wolter reported percent transmission of light through the whole human eyeY (Fig. 2). They found 80% transmission between 400 and 1400 nm with almost no ultraviolet transmission beyond the cornea, aqueous and lens. Similar work has been done on the rhesus monkey, demonstrating results very much like those of Boettner and Wolter.2”.77 The transmission data are valuable because they suggest that in the phakic system, UV light reaches the retina in negligible quantities. Conversely, UV light could cause damage to the retina in the aphakic eye or in the pseudophakic eye without a UV absorbing chromophore.:“‘l:i? In addition to ocular transmission of light, one must consider the light source. The operating microscope is fitted with a glass condensing lens which does not transmit any appreciable UV light..5.56 However, significant quantities of infrared are emitted even from operating scopes fitted with a standard heat filter.x” The KG-l heat filter on the Zeiss OPMI-6 microscope, for instance, attenuates the far infrared,‘” leaving a large window of nonuseful, nonvisible infrared amounting to 40-75% of total emitted irradiation. This serves only to add heat to the ocular milieu. This filter transmits 93% between 375-600 nm, 70% at 700 nm and is reduced to 10% at 900 nm.“’ 2. Absorption Site Once delivered to a target tissue, energy must be absorbed in order to effect change. Initial work by Noel1 on the rat model suggested that photochemical damage primarily affected the photoreceptor outer segments. ” He noted that dark-adapted animals exposed to diffuse fluorescent light at increased body temperatures demonstrated autolysis of all outer retinal nuclei with a secondary loss of pigment epithelial cells in areas of retinal cell death. In younger rats exposed to long periods of illumination under nonelevated temperature conditions, photoreceptor damage occurred while pigment epithelium survived and appeared normal. Kuwabara and Gorn reported similar findings using albino rats.‘j5 Sykes”” used fluorescent lamps and twelve-hour exposures in rhesus and pigtail monkeys; his studies also revealed that photoreceptor

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outer segments were the initial sight of damage. Hansson,” using a similar rat model, assessed histochemical function of cells exposed to light and found primary alterations in the pigment epithelial cells within a few hours. He concluded that changes seen in the photoreceptor layer were actually secondary.4’ Tso et al”’ studied photic maculopathy in the rhesus monkey and primarily found RPE damage dissimilar in appearance that described in rats. In rats, even though the photoreceptor cells were completely destroyed in severe cases, no plaque of RPE was described. In rats, visual cells were entirely destroyed before the pigment epithelium showed However, Tso used an indirect any damage.“’ ophthalmoscope light source for a shorter exposure period, and concluded that the differences between species were largely a function of different light sources and exposure parameters as well as different behavior of the animal’s tissues under study. Others using the indirect ophthalmoscope and the rhesus monkey have shown similar electron microscopic findings of primary RPE damage.” Sliney suggested that source and duration of exposure rather than species were largely responsible for the different histologic findings.“” In an attempt to make sense of the conflicting findings reported, Lawwill characterized three distinct pathophysiologic mechanisms of light damage that are combined in the various animal models.” The first, a rhodopsin specific mechanism, is responsible for damage in the rat and some other nocturnal animals, but is almost nonexistent in the primate. The second is cone pigment-specific and occurs in the most pure form in primates when longterm, repeated low intensity spectral exposures cause damage. It is also seen in combination with the third mechanism, short wavelength light effect.” The second mechanism, was first described by Harwerth and Sperling.” The third mechanism was suggested in early work by Lawwill et al. Damage near threshold was patchy and distributed in all retinal layers and fundus areas.” Lawwill hypothesized that the effect was due to direct action of light on mitochondrial respirating enzymes. Mitochondria of all layers of the retina were the organelles most sensitive to anatomic change in light damage. While Lawwill’s thesis seems well supported, Kremers and vanNorren have challenged Lawwill’s three mechanisms with regard to selective mitochondrial damage in their review of available data.63 They point out that others have not demonstrated a similar site of injury. Further, they conclude that the distinction between the rhodopsin and cone pigment-mediated damage as described by Lawwill cannot be justified except for the differences in animal model.

MICHELS, STERNBERG Kremers and vanNorren’s most valuable contribution, based on their review of the experimental literature, is their separation of factors involved in the primary site of damage: photoreceptor or retinal pigment epithelium. Class I damage is primarily manifested after prolonged exposure duration (12 hours or longer) at relatively low white light irradiances (below 1 mWcm_‘). This damage is seen mainly in photoreceptors. Class II damage is primarily manifested after shorter exposure durations (less than 4 hours) to higher white light irradiances (above 10 mWcm_‘). This damage is primarily located in the RPE. Noel1 et al” had described two types of damage in the rat model. Damage of the “first kind” was produced by light of 50 to 200 ft-C for 8 to 48 hours, enhanced by high body temperature, and resulted in loss of rod cells and pigment epithelium. Damage of the “second kind” was produced by long exposure durations and was seen in young rats. Selective a-wave reduction on ERG and widespread rod cell death with preservation of pigment epithelium was seen. Clinically, this second type of damage seems similar to the Class I damage described by Kremers and vanNorrens6” Noel1 et al”’ thought both kinds of damage were the result of damaging reactions initiated in the membranes of the outer segments activated by the light action on rhodopsin. For this reason, Kremers and vanNorren considered Noell’s classification as subtypes of their Class I. Whether this consolidation is useful has not yet been established. They indicate that in general the animal model is not likely a determining factor. They also found that while little direct data exist on small field thresholds at low irradiance and different species, the size of the exposed retinal field is not likely a key determinant of damage type. Most importantly, the authors point out a key weakness in the mechanism debate. Specifically, a complete sequence of experimental evidence in one single animal model, varying exposure time, power, and size of exposed retinal field, is lacking. They further suggest that the action spectrum of combined light toxic mechanisms is best fit by that of the absorption curve of photopigment bleach products like retinal.‘” The absorption of delivered energy within a given species varies according to the pigmentation in that species. Rapp and Williams studied the role of ocular pigmentation in protecting against retinal light damage using albino and pigmented rats.lo4 They found the pigmented rats to be very resistant to light damage when undilated, but once dilated the pigmented rats were subject to similar rates of light-induced retinal damage. The authors concluded that the animals’ inherent susceptibility to light damage was approximately equal, and that

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ocular pigmentation primarily functioned in their model by lowering retinal irradiance. Interestingly, when dilated, the albino rat required about 50% less total energy for damage than the pigmented rats. This is in contrast to work done by Cavonius et al” on the different damage thresholds between blue and dark eyed humans using a Xenon Arc lamp source. Blue-eyed subjects required about 50% more energy for threshold lesion than the subjects with dark irides. This discrepancy might be explained by the small number of blue-eyed patients in Cavonius’ group. It also might be explained by a genetic predisposition of certain strains of inbred mice to a low damage threshold described by LaVail et al.“’ The role of the RPE, independent of iris pigmentation barrier function, is debatable. Some see RPE as primarily a source of free radicals and heat absorption, while others cite its acute antioxidant function.“’ Macular xanthophyll pigment is known to absorb high energy blue light. It is thought that this is responsible in part for the protection of the fovea from phototoxic lesions. Indeed, Ham et al,“” using monochromatic light, demonstrated a twofold increase in energy required for a fovea1 compared to a parafoveal lesion. This may account in part for the earlier findings of Lawwill et al” that damage was more likely to be distributed around 7-15” from the fovea1 center. The protective effect of xanthophyll pigment was most recently described histologically by Jaffe and Wood.‘” III.

Prevention

of Retinal Phototoxicity

After initial reports of retinal phototoxicity by Noel1 et al using fluorescent light,“’ Friedman et al using the indirect ophthalmoscope,” and Fuller et al using the fiberoptic endoilluminator,“’ Hochheimer and colleagues reported their findings using the operating microscope and slit-lamp.“” In the same year Calkins et al” published their landmark article detailing calculations of light outputs from several operating microscopes at the Wilmer Institute. The paper was significant because it provided a rational, standard approach to measuring irradiation while emphasizing careful measurement of pupil size and focal lengths in accurately determining retinal irradiance. It is probably this difference in focal length coupled with pigmentation differences that explains different thresholds for damage in the human and nonhuman primate, though no studies have yet clarified the latter point. This also permits adjustment of thresholds from nonhuman study to approximate the human system. Most importantly, the authors noted that safe operating time as assessed by existing ANSI laser safety guidelines was very short, using the sources

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in the worst case scenario of constant exposure, emmetropia, and clear media.” Further calculations of safe exposure times for these and other devices were documented with confirmation in phakic monkeys one year later.‘” Others have reported similar maximum safe expposure times.“’ Irvine et al”” studied light damage in pseudophakic monkeys and found a threshold of 7.5 minutes at a high illumination setting, which correlated with the average of the power measurements reported by Calkins and Hochheimer.14 Even shorter threshold exposure times have been noted using microscopes equipped with halogenated light sources.“’ It is crucial to realize that thresholds measured by clinical or histologic change may be greater than those that might be assessed by psychophysical or electrophysiologic tests. Berler and Peyser” noted a statistically significant difference in final visual acuity six months after cataract extraction between patients matched for all factors except the operating microscope. Those operated on using the high power scope had poorer vision than those operated on using the lower power scope. No phototoxic lesions were noted clinically in any of these cases.’ Dawson and Herron” found that dark adaptation time was prolonged in patients exposed to the indirect ophthalmoscope for eight minutes. This subtle alteration was not associated with a documented fundus abnormality.” With this understanding that threshold damage varies according to measurement technique, specific factors in light toxicity prevention will be considered. A. HOST FACTORS Host factors, independent of light exposure, also contribute to the process of phototoxic retinal damage. Temperature and ocular pigmentation have been mentioned earlier in this manuscript. Increasing age and decreased antioxidative reserve of senescent cells for acute light toxic stress have not been examined in the primate, but have been studied in the rat model. Malik et al’” studied ERG response in rats exposed to light stress and found marked impairment of ERG response in older rats compared to young rats. Yew et al”” studied alkaline phosphatase and DNA-RNA reaction in rats of different ages exposed to photic stress. These histochemical indices of retinal metabolism revealed more activity in more retinal layers in young compared to older rats.‘“” Penn et al”” found similar results in a somewhat different experimental system. Lai et al”” demonstrated increased incidence and severity of peripheral retinal degeneration in older rats, as well as in rats subjected to prolonged exposure to high intensity light. Michels et al have demonstrated marked individual susceptibilities to

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identical light stress controlled for temperature, exposure time, and oxygenation (unpublished data). Variability of host factors in response to light stress is a real factor in the study of light and the eye. B. POWER AND ENERGY Despite careful descriptions of power and energy calculations by Calkins and Hochheimer,14 reported threshold irradiances and energy levels in different models using different light sources have varied by one-thousandfold, using similar devices to measure and emit irradiation. ‘I4 Likewise, experimental endpoints vary considerably from electron micrographic change to electrophysiologic change and from dark adaptation time to light microscopic change. A precise damage threshold energy can be calculated only for a given type of light source, using a specific type of measuring device with a specific endpoint in a given animal model. If one studies the data given for white light sources and rhesus monkeys compiled by Kremers and vanNorren, one sees remarkable similarity between threshold energies calculated from eight different laboratories.‘j3 Other laboratories have reported threshold energies several orders of magnitude different from those mentioned.45*R7*g6 Despite these differences, reduction of power and total energy delivered to a given system will clearly decrease the likelihood of generating retinal phototoxicity. C. EXPOSURE

TIME

To date, exposure time rather than power level or total energy is a quantity that has been better correlated with clinical phototoxicity. Khwarg5’ recently evaluated 135 consecutive cases of cataract extraction and found a 7.4% incidence of retinal phototoxicity. Of particular interest is that the incidence was 0.9% in cases requiring less than 100 minutes operating time, while the incidence increased to 39% for cases requiring greater than 100 minutes. The authors note a similar incidence between the two microscopes used in this series, one fitted with a 150W Halogen light source the other with a 30W Tungsten bulb. Other reports documenting operating times do not support the IOOminute cut-off and actually report times closer to 60 minutes. Khwarg et a15* had earlier reported a case of phototoxicity after 60 minutes in a patient who did not receive an intraocular lens nor a pupil constricting agent intraoperatively. Since pupillary diameter was shown to be of major significance in calculating delivered energy, the dilation probably accounted for this lower operating time association. In McDonald and Irvine’s cases, a tungsten filament was used as the illuminating source with oper-

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ative times of 75-90 minutes.“4 In the largest series of reported cases, operating times were between 55 and 175 minutes, with the mean of 103 minutes.” While the method of patient selection was not outlined in this study (making incidence calculation impossible), the paper is significant because a UV filter was used in 9 of 12 cases, suggesting its lack of effect. The specific band-pass parameters are not given, however. This is unfortunate since, of the six cases taking less than 100 minutes, all but one occurred using the tungsten bulb which produces more absolute short wavelength light than the external fiberoptics as documented by Berler and Peyser.5 D. WAVELENGTH Alteration of wavelength emitted from light sources in the clinical literature has been primarily accomplished with UV filters. Jampol et a154unsuccessfully attempted to demonstrate decreased pseudophakic cystoid macular edema (CME) when UV filtered operating microscope light was used. Others make mention of UV filtration without demonstrating a benefit to UV blockade.‘0~7”*‘07 Information regarding ocular transmission of UV light presented earlier in this manuscript should explain these equivocal results. While Yu et a113’ have most recently demonstrated UV as being most toxic in their aphakic monkey model, the appeal for removing high energy nonvisible light overshadowed the fact that little UV is involved in the processes of light toxicity in the phakic system. However, Ham’s demonstration of blue light efficiency in producing damage up to 5 15 nm provides other avenues of inquiry for selective wavelength attenuation since blue visible light is transmitted to the retina of phakic eyes, aphakic eyes and pseudophakic eyes.35 Hochheimer et a145 used a blue blocking (< 500 nm) filter which reduced total irradiation by 19% in their work using rhesus monkeys exposed to one hour of a tungsten filament-illuminated operating microscope. They noted the severity of damage was reduced in the blocked eye. Parver et alg6 exposed two cynomolgous monkeys to a similar light stress using a Zeiss SUV430 absorption filter as the experimental variable. The filter transmits almost no radiation ~420 nm and about 80% at 450 nm. The eyes were studied histologically at 48 hours and the filtered eyes revealed less severe damage. The authors concluded that, while the presence or absence of short wavelength light is of considerable importance in phototoxic damage, an alternative explanation might be that the protection offered by the blue filter was due to a general decrease in total irradiation, independent of selective short wave-

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length attenuation.gfi Both explanations seem plausible; the latter is useful and points out the need to mathematically correct for overall attenuation of irradiation when filters are used. Few reports detail this step.“.x” More definitive work on selective attenuation of blue visible light was reported by Buyukmihci in his study of photic retinopathy in the dog, using an indirect ophthalmoscope.” While this author’s prime objective was to study the different effects of light on the dog tapetal and nontapetal retina, interesting information emerges with regard to selective wavelength attenuation. The light was focused using a Volk 20 diopter condensing lens. Since the manufacturer suggested that the yellow tinted lens could prevent retinal damage, the author performed the experiment with the clear lens and again with the yellow lens. The yellow tinted lens blocks light up to 475 nm. The author found that no clinical or histologic lesion was produced in the tapetal nor nontapetal retina when the yellow lens was used during the hour’s exposure. With the clear lens, distinct pathology was noted in the tapetal retina and histological evidence of damage was seen in the non-tapetal retina.” We have recently completed a pilot study of eight rhesus monkeys exposed to the operating microscope fitted with a IOOW fiberoptic illumination systems (unpublished data). One eye of each pair was exposed to unattenuated light. The fellow eye was exposed to light filtered with a Schott Glass OG5 15, which effectively transmits < 1% at wavelengths < 500 nm, 63% at 520 nm and > 90% at wavelengths greater than 550 nm.“’ We learned that for exposure times between 14-18 minutes, five of six eyes exposed to filtered light had neither ophthalmoscopic nor fluorescein angiographic evidence of phototoxic lesions, while all unfiltered eyes demonstrated typical phototoxic lesions. While not yet statistically significant, these early findings are highly suggestive of protection from the yellow filter. Importantly, the filter only neglibly affects the surgeon’s view for either delicate anterior segment or posterior segment maneuvers. In fact, the reduction of some short wavelength light reduces chromatic aberration and light scattering, yielding a clearer view.“.“” In addition, we attempted to simultaneously study the effect of long wavelength attenuation (> 700 nm) using the same experimental apparatus and an efficient IR blocking filter. We attempted this because of the very high IR output from the operating microscope (25-75% of total irradiation). We could not demonstrate clinical benefit from the IR blocking filter alone or in combination with the benefit obtained using the OG515 filter. These findings are similar to those of Fuller et al.65

E. FOCUS The focusing power of the optical portion of an intraocular lens implant has been thought to play a major role in production of phototoxic lesions.‘” Irvine and Copenhagen point out in the rabbit eye that the irradiance is reduced by their defocusing in aphakia.“g Some have interpreted this to mean that the cataract provides ample dispersion of light and that one need not worry about the dose of light delivered early in a cataract extraction or during the period of intraoperative aphakia. We suggest that light reaches the retina, contributing to toxicity throughout the case, and should be minimized even before the pseudophakos is implanted. Indeed, three cases of phototoxicity have been reported without intraocular lens implantation.“~‘” The recent advice to cover the cornea while closing surgical wounds during vitrectomy is valuable, but fails to account for light delivered to the retina from the endoilluminator during the time of vitrectomy surgery.” F. MEDICATION 1. Free Radical

Formation,

02, Antioxidants

In recent years, the role of free radicals and the oxidative state of the retinal photoreceptors and retinal pigment epithelium has been under intensive study.” It is well known that rod outer segments contain the highest levels of long-chain polyunsaturated fatty acids of any tissue in the body. The fatty acid docosahexaenoic acid is especially susceptible to peroxidation reactions.” Wiegand et al”’ demonstrated that constant illumination was associated with reduction of docosahexanoic acid levels and an increase in lipid hydroperoxides in the albino rat model, suggesting that peroxidation of long-chain polyunsaturated fatty acids in rod outer segments may be a factor in light-induced retinal degeneration. This has been substantiated by Shvedova et al.‘12 Further, early work by Noel1 and Albrecht found a protective effect of vitamin A deficiency in preventing light toxicity in rats.YO These results were substantiated by Carter-Dawson et al.‘” Ham and colleagues demonstrated in their rhesus model that increased oxygenation from 75 to 271 torr resulted in a three fold drop in total threshold energy from 36 to 11 Jcm-’ using a 440 nm light source.“.“” Crockett and Lawwill noted light damage in their cultured bovine retinal pigment epithelium model was enhanced by a factor of 10 when exposures were conducted in an atmosphere of 95% oxygen instead of 20% oxygen.” Most recently Jaffe et a15’ studied the role of inspired oxygen in phakic rhesus monkeys exposed to light from a Zeiss operating microscope under condi-

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tions of 2 1% F 1OSand 99% F 10, and noted marked potentiation of phototoxic damage in lesions generated under increased oxygenation. Organisciak and others have provided some impressive evidence in the rat model for the protective effect of the antioxidant ascorbate.75.Y2.Y4.‘?”Ascorbate administration has been associated with increased intraretinal ascorbate and decreased loss of rhodopsin and photoreceptor cell nuclei after light exposure in both cyclic and dark-reared rats. In their work, ascorbate was found to be effective in preserving docosahexaenoic acid from isolated rod outer segments only when administered before light exposure.“4 In the baboon retina, ascorbate is noted in neural retina in reduced form while in oxidized form in the pigment epithelium. After light exposure, measures of reduced ascorbate are found to be decreased in both pigment epithelium and neural retina, suggesting an antioxidant effect.“” The role of other antioxidants such as Vitamin E has likewise been studied. Results from these studies have been equivocal.gR While the precise role of specific antioxidants in prevention of retina1 phototoxicity in humans remains to be determined, the concepts gleaned from this work have given us a better understanding of the process. Turkey farmers have learned that treatment with Promethazine prevents photoperoxidation of lipids in turkey eyes syndrome.“g8 suffering from “turkey blindness While such treatment may not be appropriate for humans, knowledge of this and other photoactivating drugs as described by Lerman may prevent overt phototoxicity. 2. Other Pharmacoiogic Factors In a small number of animals, Ham et al”‘j demonstrated a protective effect of injection of methylprednisolone one hour before light exposure as well as a protective effect in animals whose diet is supplemented with antioxidant B carotene. Parver et alq6 also have demonstrated a protective effect against phototoxicity in monkeys using dexamethasone.

IV. Other Retinal Pathology Attributed to Light of the Operating Microscope Cystoid macular edema following cataract extraction, although very different clinically from retinal phototoxicity, has been attributed to light from the operating microscope since 1977.49 Mannis and Becker reported a trend toward decreased postoperative cystoid macular edema in patients whose cataract operations were performed using an opaque contact lens.” Calkins and Hoccheimer alluded to the possibility of light’s role in postoperative cystoid macular edema.14 Jampol also suggest-

MICHELS, STERNBERG ed light’s role.“” But as operating room and microscope lights have become brighter, the incidence of postoperative CME has been noted to be decreased in extracapsular vs. intracapsular cases.“8 This is not a function of posterior capsule filtration, since Keates et al”’ noted 90% transmission between 200 and 400 nm in the lens capsule. Subsequently, Jampol et a1”4were unable to demonstrate a difference in rate of postoperative CME when UV blocking lenses were used on the operating microscope. Jampol’s result was substantiated by Iliff,4x who points out the paucity of experimental evidence for light-induced CME in animal models, and in his own study of humans. Bellhorn has indicated however, that no adequate model of CME, light-induced or otherwise, has been produced.” Kraff et a16’ did demonstrate marginal benefit in reducing postoperative CME when a UV blocking intraocular lens was used. Absolon has challenged the Kraff study as not adequately controlled.’ Accounting for all data available, the cause and effect relationship between light and CME appears unproven. However, since UV light has been the light variable studied and since we have already discussed the paucity of UV light emitted from most operating microscopes, further work on high energy blue light’s role is warranted.

V. Summary of Prevention Measures Since retinal damage is largely a function of power, exposure time, and wavelength, reduction of total energy delivered to the retina throughout an entire procedure can be accomplished by minimizing the power of the light source during noncrucial steps of the procedure. A better option is to use overhead surgical lights or side mounted oblique illumination during these phases of the surgery.15 For that light to which the eye is exposed, minimizing direct fovea1 exposure is also important. Microscope tilt and displacement of the globe toward 6 o’clock, if sufftcient to overcome the nonaxial displacement of the microscope as described by Brod et al,” may minimize subjective appreciation of scotoma (now in the superior visual held). Using miotits, when safe to do so, limits total energy by a function of the square of the power level. Likewise, use of an eclipse type filter, as described by McIntyre,H5 or an opaque plastic, as described by Yanoff et al,“” will minimize total energy by decreasing exposure time to the brightest light. An appreciation for potential phototoxicity prior to intraocular lens implantation in the case of cataract surgery is of obvious importance.. 58.76Use of an anterior chamber air bubble may help to defocus light from the retina depending on the type of intraocular lens im-

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Selective wavelength attenuation is another approach to minimize possible phototoxicity. The logical choice for filter band-pass seems to be 515 nm, nearly identical to the damage threshold efficiency curve described by Ham.“” While only minimal evidence exists to support simultaneous IR attenuation in prevention of retinal phototoxicity,x7 Robertson and Erickson’“” reported difficulty in their initial experiments because of cornea1 stromal edema and epitheliopathy caused by their light source in humans. They attribute this to high levels of infrared in the source. We have noted similar findings in an experiment exposing a well irrigated cornea to light from the operating microscope (unpublished data). Since Michels et al demonstrated high infrared output from the operating microof this invisible and useless porscope, “attenuation tion of the spectrum with appropriate filtration may help prevent cornea1 compromise in the postoperative period. While there have been no cases of intraoperative retinal phototoxicity reported with operating time less than 55 minutes, this does not take into account subtle or subclinical changes that might occur, as described by Berler and Peyser in final postoperative vision.” Selective attenuation should be considered in cases that one anticipates might last longer than one hour. Another option is currently under investigation in our laboratory in collaboration with Carl Zeiss, Inc. We are evaluating a patented device which measures light power and, given a preprogrammed total energy dose, displays remaining safe operating time. The device might be programmed to decrease illumination or insert a specific filter when a predetermined safe operating time has been reached, thus potentially “buying” the surgeon a longer safe operating time. Since animal studies have demonstrated benefit to altering core ocular temperature, irrigation solutions may possibly be cooled relative to room temperature. Specific recommendations cannot be made until physiologic effects of these cooled solutions have been assessed in diseased tissues. Removal of nonvisible IR has not been shown to be of clinical benefit, but a potential subclinical effect suggests it should be eliminated from illuminating systems when possible. The recent demonstration by Jaffe et al that increased inspired 0, significantly potentiates retinal phototoxicity makes selective use rather than routine use of oxygen seem prudent.“’ The authors specifically recommend elimination of 0, by nasal cannula in patients less than 40 yrs of age under local anesthesia unless medically contraindicated. For cases using general anesthetic, Jaffe et al suggest decreasing FlO, until after surgery is

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completed.“’ Postoperatively, protection of the retina from damaging short-wavelength light is important. The sun emits 4.86% of total irradiation in the UV range, 49.55% in the visible, and approximately 34% in the IR range to 1235 nm for air mass 1.5 and a 37” tilted surface, which represents average conditions and latitude for all solar applications in the 48 contiguous United States.‘17 More short-wavelength light is transmitted when the sun is directly overhead and the converse is true at sunset where little short-wavelength light is transmitted through the atmosphere. Mainster has shown that the clear PMMA lens transmits much more UV and blue light than the natural adult human lens.7x The danger of functional aphakia has been discussed.“” It seems logical to use a UV blocking chromophore in all IOLs. In fact, the idea of using IOLs that block some of the blue light up to 5 15 nm is also plausible and perhaps desirable. One study using pseudophakic monkeys and xenon arc lamp emitting large quantities of UV demonstrated protection from light damage in eyes fitted with UV blocking IOLs.“” This result is not surprising considering the light source. The result is of questionable value in the ambient environment, however. To date, there has been only one report examining visual performance in patients with UV blocking and non-UV blocking IOLs.‘“’ In the relative short term of this study (10 weeks), there was no difference in visual performance with either type of IOL.‘“’ Longterm studies are needed to demonstrate the prevalence of lightexacerbated decrease visual performance in the pseudophakic eye. In the meantime, we feel it is prudent to limit the exposure of pseudophakic eyes to excessive light. Finally, with regard to pharmacologic prevention of phototoxicity, the results vary. Conflicting data are at least partly the result of study in many species using different experimental conditions. At this point, no definitive recommendations can be made regarding pharmacologic prevention of retinal phototoxicity in humans. The problem of retinal phototoxicity is multifactorial. We have reviewed key factors that have been identified in the pathophysiology of the process. Individual host factors and different detection techniques result in varied prevalence rates. Despite this variance, experimental and clinical evidence suggest several means for the prevention of retinal phototoxicity. Acknowledgement The authors wish to thank W. Richard Green, M.D. for his advice and for preparation of the electron micrographs and Nancy Schwartz for editorial support.

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References 1. Absolon MJ: The effects of ultraviolet light on the eye. Trans Ophthulmol Sot Lily 1043522-523, 1985 2. Adrian W, Everson RW, Schmidt I: Protection against photic damage in retinitis pigmentosa. Adv Exfi Med Biol 77.233-247, 1971 3. Anderson RE, Rapp LM, Wiegand RD: Lipids peroxidation in retinal degeneration. Curr Eye Res J3:223-227, 1984 4. Bellhorn RW: Analysis ofanimal models ofcystoid macular edema. Sun, Ophthalmol 28 (suppl):520-524, 1984 5. Berler DA, Peyser R: Light intensity and visual acuity following cataract surgery. Ophthalmology 90:993-936, 1983 6. Berson EL: Experimental and therapeutic aspects of photic damage to the retina. Invest Ophthalmol 1235-44, 1973 7. Birch DC, Jacob GH: Light induced damage to photopic and scotopic mechanisms in the rat depends on rearing conditions. Experimental Neurology 68:269-283, 1980 8. Birngruber R, Gabel V-P: Thermal vs. photochemical damage in the retina - thermal calculation for exposure limits. Trans Ophthalmol Sot UK 103:422-427, 1983 9. Boettner EA, Wolter JR: Transmission of the ocular media. Invest Ophthalmol Vis Sci 1:776-783, 1962 10. Boldrey EE, Ho BT, Griffith RD: Retinal burns occurring at cataract extraction. Ophthalmology 91: 1287- 1302, 1984 10a. Brod RD, Olsen KR, Ball SF, Packer AJ: The site ofoperating microscope light-induced injury on the human retina. Am J Ophthalmol 107:390-397, 1989 11. Brod RD, Ball SF, Packer AJ: A model for predicting the site of paraxial retinal lesions secondary to “coaxial” operating microscope illumination system. Am J Ophthalmol 104:516-523, 1987 12. Brod RD, Barron BA, Suelflow JA, et al: Photic retinal damage during refractive surgery. Am J Ophthalmol 102: 121-23, 1986 13. Buyakmihci N: Photic retinopathy in the dog. Exp Eye Res jjr:95-109, 1981 14. Calkins JL, Hochheimer BF: Retinal light exposure from operating microscopes. Arch Ophthalmol 97:2363-2367, 1979 15. Calkins JL, Hochheimer BF, d’Anna SA: Potential hazards from specific ophthalmic devices. Vision Res 20: 1039-1053. 1980 16. Carter-Dawson L, Kuwabara T, Bieri JC: Effects of modern intensity light on vitamin A deficient rat retinas. fnuest Ophthalmol 20:569-574, 197 1 17. Cavonious CR, Elgin S, Robbins DO: Threshold for damage to the human retina by white light. Exp Eye Res 19:543-548, 1974 18. Cech JM, Choromokose EA, Sanitato JA: Light induced maculopathy following penetrating keratoplasty and intraocular lens implantation. Arch Ophthalmol 105:751, 1987 19. Colvard DM: Operating microscope light-induced retinal injury: Mechanisms clinical manifestations and preventive measures. Am Intra-Ocular Implant SocJ 10:4381143, 1984 20. Crockett RS, LawwillT: Oxygen dependence ofdamage by 435 nm light in cultured retinal epithelium. Curr Eye Res 3:209-215, 1984 2 1. Dawson WW, Herron WL: Retinal illumination during indirect ophthalmoscopy sunsequent dark adaptation. invest Ophthalmol 9:89-96, 1970 22. DeLaey JJ, DeWachter A, VanOye R, et al: Retinal phototrauma during intraocular lens implantation. Inl Ophthalmol 7:109-116, 1984 23. Fechner PV, Barth R: Effect on the retina ofan air cushion in the anterior chamber and coaxial illumination. Am J Ophthalmol 96:600-604, 1983 24. Feeney L, Berman ER: Oxygen toxicity: Membrane damage by free radicals. Invest Ophthalmol 15:789-792, 1976 25. Fine BS, Geeraets WJ: Observation on early pathologic efforts of photic injury to the rabbit retina. Acta Ophthalmol 43:684-691, 1965 26. Flynn HW, Brod RD: Protection from operating microscope-induced retinal phototoxicity during pars plana vitrectomy. Arch Ophthalmol 106: 1032, I988

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51. Jaffe GJ, Irvine AR, Wood IS, et al: Retinal phototoxicity from the operating microscope: The role of inspired oxygen. Ophthalmology 95:1130-1141, 1988 52. Jaffe GJ, Wood I: Retinal phototoxicity from the operating microscope: Protective effect by the fovea. Arch Ophthalmol 106:445-446, 1988 53. Jampol LM, Aphakic Cystoid Macular Edema: A Hypothesis. Arch Ophthalmol 103: 1134-l 135. 1984 54. Jampol LM, Kraff MC, Sanders DR, et al: Near UV radiation from the operating microscope and pseudophakic cystoid macular edema. Arch Ophthalmol 103:28-30, 1985 55. lohnson RN, Schatz H, McDonald HR: Photic maculopathy: Early angiographic and ophthalmoscopic findings and late develonment of chroidal folds. Arrh Ophthnlmol 105:1633-1634:1987 56. Keates RH, Genstler DE: UV Radiation. Ophthalmic Surg 13:327, 1982 57. Keates RH, Genstler DE, Tarabichi S: Ultraviolet light transmission of the lens capsule. Ophthalmic Surg 13:374376, 1982 58. Khwarg SG, Geoghegan M, Hanscom TA: Light induced maculopathy from the operating microscope. AmJ Ophthalmol 98:628-630, 1984 59. Khwarg SC, Linstone FA, Daniels SA et al: Incidence, risk factors and morphology in operating microscope light retinopathy. Am J Ophthalmol 103:255-263, 1987 60. Kirkness CM, Weale RA Does light pose a hazard to the macula in aphakia. Trans Ophthalmol Sot UK 104:699-702, 1985 61. Kossol J, Cole C: Spectral irradiances of and maximal permissible exposures to two indirect ophthalmoscopes. AmJ Optom Physiol Optics 60:616621, 1983 62. Kraff MC, Sanders DR. Jampol LM, et al: Effect of an ultraviolet filtering intraocular lens on cystoid macular edema. Ophthalmology 92:366-369, 1985 63. Kremers JJM, vanNooren D: Two classes ofphotochemical damage of the retina. Lasers Light Ophtkulmol2t4 l-52, 1988 64. Kuwabara T, Funahashi M: Light damage in the develon’ ing rat retina. Arch Ophthalmol-91: 1369--l 374, 1976 65. Kuwabara T, Corn RA: Retinal damage by visible light an electron microscopic study. Arch Ophthalmol 79:69-78, 1968 66. Lai Y-L, Jacoby RO, Jonas AM: Age-related and light-associated retinal changes in fischer rats. Invest Ophthalmol Vis Sri 17;634-638, 1978 67. Lanum J: The damaging effects of light on the retina. Empirical findings, theoretical and practical implications. Sun! Ophthalmol22:22 l-249, 1978 68. LaVail MM, Gorrin GM, Repaci MA, et al: Genetic regulation of light damage to photoreceptors. Invest Ohthnlmol Vir sci 28:1043-1048, 1987 69. Lawwill T: Effects ofprolonged exposure ofrabbit retina to low intensity light. Invest Ophthalmol Vis Sci 12:45-51, 1973 70. Lawwill ‘1‘: Three maior natholorric nrocesses caused bv light in the primate retna; A search fo; mechanisms. Tran> Am Ophthalmol Sot 80:517-579, 1982 71. Lawwill 1‘. Crockett S, Currier G: Retinal damage secondary to chronic light exposure thresholds and mechanisms Dot Ophthalmol 44:379, 1977 72. Lawwill T, Crockett RS, Currier G, et al: Review of the macaque model oflight damage with implantations for the use of ophthalmic instruction. Vision RPS 20: 1113-l 115, 1980 73. Leonardy NJ: Personal communication 74. Lerman S: Photosensitizing drugs and their possible role in enhancing ocular toxicity. Ophthalmology 93.304-318, 1986 75. Li Z-Y, Tso MOM, Wang H, Organisciak D7‘: Amelioration of photic injury in the rat retina by ascorbic acid. A histopathologic study. Invest Ophthalmol Vis Sci 2631589-98, 1985 76. Lindquist TD, Grutzmacher RD. Gofman JD: Light-induced maculopathy potential for recovery. Arch Ophthalmol 104:1641-1647, 1986 77. Maher EF: Transmission and asorption coefftcients for ocular media of the rhesus monkey. Report SAM-TR-78-32,

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Outline I. Clinical

manifestations of retinal light damage and their prevention to retinal phototoxII. Physical factors contributing icity A. Light B. Irradiation and energy C. Mechanism: photochemical, thermal or combined D. Energy delivery 1. Emission and transmission 2. Absorption site of retinal phototoxicity III. Prevention A. Host factors B. Power and energy C. Exposure time D. Wavelength E. Focus F. Medication 1. Free radical formation 02 and antioxidants 2. Other pharmacologic factors attributed to light from the IV Other retinal pathology operating microscope of prevention measures V. Summary

This work was supported in part by a departmental grant from Research to prevent Blindness, Inc., Southern Medical Association, American Medical Association Education and Research Foundation and Carl Zeiss, Inc. Dr. Michels is currently the Abe Meyer Fellow of Vitreoretinal Diseases and a Heed Foundation Fellow at the Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, CA. Reprint address: Paul Sternberg, Jr, M.D., Emory Eye Center, 1327 Clifton Road, N.E., Atlanta, GA 30322.

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