Eye (1987) 1,304-310
Light and Macular Degeneration: A Biophysical and Clinical Perspective
MARTIN A. MAINSTER Kansas City, Kansas
Summary The evidence linking photic retinopathy to ageing macular degeneration (AMD) is compelling but circumstantial. The biophysical foundations of ageing theory are presented, in addition to an analysis of retinal senescence ",ndthe potential contribu tory role of photochemical retinal damage. Although there is pressure to implement clinical therapy for AMD based on laboratory studies of photic retinopathy, there is no evidence at this time that any such therapy is effective. Nonetheless, until the relationship between photic retinopathy and AMD is better understood, it is appro priate for individuals to use ultraviolet and deep blue protective sunglasses in bright environments, particularly if they have reduced ocular pigmentation or if they are aphakes or pseudophakes without an ultraviolet-protective intraocular lens.
Time and ageing moving backwards in time, when we deal with Notions of time are implicit in all studies of phenomena involving large numbers of parti ageing. In contemporary physics, time is cles, entropy offers a direction for time's merely another dimension, and there are no arrow. Entropy is a measure of a system's dis privileged moments such as 'now'. Confusion order, and it either remains constant or arises because relativity theory offers con increases in any closed system. Entropy pro vincing evidence that the magnitude of a time vides only temporal asymmetry. It does not tell interval depends on the velocity and location how rapidly 'now' moves into the future, only (local space-time curvature) of the observer. that the universe appears differently when Thus, the 'now' of two different observers may viewed forward or backward in time. proceed at different rates, and the 'nows' of a All living systems are open systems that can group of humans are readily desynchronised exchange matter and energy with their sur by differences in their velocities and locations. roundings. Since living systems are open, In other words, 'now' may not extend beyond entropy can decrease temporarily during life, 'here'. as manifested by the highly improbable Physics does not provide an explanation for ordered structure of living systems. The the subjective concepts of 'now' and the 'flow dynamic order of living systems probably of time', but it does address the issue of the arises because of self-organising fluctuationsin direction of time's arrow.! Although useful these open, far-from-equilibrium systems theories have been developed to explain sub ('dissipative' systems).2 .3 The laser is a familiar microscopic phenomena in terms of electrons example of a dissipative system in which there
This research was supported in part by Research to Prevent Blindness, Inc and Kansas Lions Sight Foundation, Inc.
Correspondence to: Martin A. Mainster, M.D., Ph.D., Department of Ophthalmology, Kansas University Medical Center, 39th and Rainbow Boulevard, Kansas City, Kansas 66103. LIGHT AND MACULAR DEGENERATION 305
is self-organisation of coherent emitters. The tor-RPE juncture).6,7 Constant light blocks photoreceptor and retinal pigment epithelium disc shedding but maximises disc production, (RPE) cell are further examples of dynamic, resulting in longer rod outer segments. Short self-organising, open, non-equilibrium, ened light periods and reduced temperature space-time structures that arise, and after a reduce disc production, resulting in shorter variable period of time, decay. The openness rod outer segments. Rod and cone disc shed of cellular systems is the basis of life and death. ding occurs after light onset and offset, respec It is also the basis for our hopes to findmethods tively. Disc shedding and replacement provide for increasing the time interval in which an effective method of eliminating outer seg humans and their retinae function properly. ment damage caused by light or other detri mental influences, but place a metabolic load Retinal Senescence on adjacent RPE cells responsible for pha After development, organisms and their com gocytosis and degradation of the phagosomes. ponents deteriorate structurally and func In the aged retina, lengthy, convoluted rod tionally. There is a remarkable similarity in the outer segments are observed, suggesting rate at which organ systems decline, however, impaired disc shedding, possibly because of prompting numerous vain attempts to find a diminished RPE function. 8 single unified 'cause' for ageing. Over the The RPE is also a delicate balance, between years, causes proposed for ageing have paral ingestion of outer segment tips apically and leled areas of contemporary research interest, apoptosis of RPE cytoplasm basally.9 Since the including toxic products of intestinal bacteria, RPE is subject to the damaging effects of lipid hormone deficiencies, dehydration of body oxidation in an oxygen-rich environment, it colloids, latent viruses or lethal genes, and free has evolved a variety of defense mechanisms radical toxicity. Adding to the complexity of including anti-oxidants such as superoxide dis the problem are recent statistical studies show mutase, peroxidase, catalase andvitaminE. In ing that psychiatric factors influence rates of addition, light absorption by melanin helps ageing and death.4 Bell's interconnectedness defend against high light levels, and melanin theorem adds further complexity, establishing acts as an electron transfer agent. The RPE and non-local reality at an even more fundamental sensory retina are also protected by macular level, and forcing us to choose either objec xanthophyll.10 In senescence, there is an tivity (i.e. a world that exists in a definitestate increase of RPE melanolipofuscin, apart from measurement) or local causality melanolysosomes and lipofuscin,l1 and a (i.e. systems can be influenced only by medi decrease in RPE melanin11 and probably other ated interactions travelling no faster than the defense mechanisms. Surprisingly, the great speed of light). 5 est increase in lipofuscin occurs between the While we have far to go in our search for a firstand second decades of life (rather than in unified theory of ageing, the retina does not old age), with the melanin to lipofuscin ratio exist independently of its host body, and it is reversing from 2: 1 to 1: 2 by the end of the unlikely that the problem of retinal ageing will second decade.11 One may speculate that the be solved by studies limited to the retina. continuing increase of lipofuscin and other Nonetheless, the retina does have unique debris leads to a decrease in functional characteristics, and the identification and cytoplasmic space and progressive failure of modification of deleterious influences may transport, phagocytic and other metabolic permit prolongation of retinal function. Light functions of the ageing RPE cell. is one such influence.Its effects are manifested Ageing of Bruch's membrane is due in part primarily at the level of the photoreceptor, to deposition of RPE cytoplasmic debris, RPE and Bruch's membrane. resulting in basal laminar deposits above the Photoreceptor outer segment structure is a RPE basement membrane, and drusen on or delicate balance between disc production at within the inner collagenous layer.9,12 In addi the proximal end of the outer segment and tion, there is mineralisation of the inner col periodic shedding of packets of discs at the dis lagenous and elastic layers. It is probable tal end of the outer segment (the photorecep- though not currently proven that most RPE 306 MARTIN A. MAINSTER cytoplasmic debris passes through Bruch's radiation which varies periodically in intensity membrane to the choroid. This is consistent as the earth spins on its axis and orbits the sun. with the observation that cytoplasmic debris is Complex systems operate by periodic transfor often absent from the inner collagenous layer mation of energy into work, and many biolog underlying drusen, suggesting that drusen may ical systems exhibit a circadian rhythm that is result from blockage of the transport of debris largely independent of temperature and through the inner collagenous layer to the environmental influences. choroid. 9 The photoreceptor and RPE cell are com As the retina ages, retinal thickness plex open systems, incorporating autocatalytic decreases, probably in part from a loss of reti chemical reactions, undergoing auto-oscilla nal neurons and photoreceptors. Drusen are tions in structure and function, dependent on the earliest ophthalmoscopic sign of ageing the provision of essential raw materials and the macular degeneration (AMD). They can removal of cellular debris, and existing in a remain stationary, coalesce, or lead to large dynamic order subject to numerous local geographic areas of atrophic RPE. Serous catastrophes. This complex, dynamic order drusen are often harbingers of exudative eventually collapses in senescence. While we AMD, which is present in only 10 per cent of readily appreciate changes at individual points patients with AMD, but responsible for 90 per in time (such as lipofuscin accumulation), or cent of all serious visual loss due to AMD. 13 In those occurring during short intervals of our exudative AMD, choroidal neovascularisa life (such as choroidal neovascularisation), we tion may cause haemorrhagic detachment of may fail to observe very slowly evolving the RPE and/or sensory retina, producing a dynamic changes equally fundamental to our disciform macular scar and concomitant understanding of senescence. scotoma. Exudative AMD is rare in Blacks and Photic Retinopathy Japanese,14 consistent with the observation In 1900, Max Plank deduced the continuous that increased ocular pigmentation decreases spectrum of light emitted by a perfect absorber the risk of AMD in white patients. 15 In addition ('blackbody') by assuming that the light is pro to decreased pigmentation, dermal elastotic duced in discrete packets, now known as degeneration in sun-exposed or sun-protected photons, and that the energy of each photon is tissues is another risk factor for AMD, possibly inversely proportional to its wavelength. Thus, because elastic fibresin these patients have an the energy of an ultraviolet Jight photon is increased susceptibility to photic or other greater than that of blue light photon, and a degenerative stimuli, and the elastic layer of photon of blue light has greater energy than a Bruch's membrane would be a less effective green light photon. If a photon has sufficient barrier to choroidal neovascularisation . 16 energy, it can produce a change in the energy Choroidal neovascularisation in areas of state of an atom or molecule, inducing con angioid streaks is common in conditions invol formational changes, or even promoting ving elastic tissue abnormalities, such as chemical reactions known as photochemical pseudoxanthoma elasticum and Ehlers reactions. The yellowing of transparent poly Danlos syndrome. On the other hand, choroi methylmethacrylate in sunlight and photic dal neovascularisation is uncommon in retinopathy are both photochemical effects. patients with diabetic retinopathy or macular Photochemical retinal damage was first holes. Choroidal neovascularisation may also demonstrated in rats, and subsequently in pri play a role in geographic AMD, with some mates and humans. 17-21 Photic retinopathy RPE atrophy caused by cumulative, abortive, occurs at temperature increases far below the primarily subclinical leakage. 10 to 20 degrees C temperature rise needed for During evolution, stable systems equilibrate photocoagulation. Solar retinitis (eclipse reti and become one with the environment; unsta nopathy) is an example of photic retinopathy, ble systems degrade and perish; and only since unaided solar observation produces a systems of a oscillatory nature survive. 2 Evolu temperature increase ofless than 4 degrees C. 22 tion has been fuelled by solar electromagnetic Photochemical damage can affect the photo- LIGHT AND MACULAR DEGENERATION 307 receptors, the RPE, or both the neurosensory mined by the exposure history and the effec retina and RPE.17-20 tiveness of individual retinal defence Photochemical damage may be divided into mechanisms. two categories.17 At the lowest light levels There has been a marked increase in (class 1), photic retinopathy appears to be reported cases of photic retinopathy from mediated by visual photopigments, as in rat operating microscopes in the past few years, experiments17 and later primate cone damage complementing previous reports of photo studies.20 At higher light levels (class 2) that are chemical retinal damage from solar and weld still below photocoagulation irradiances, pho ing arc observation, and emphasising the tic retinopathy is probably an actinic process, clinical significance of photic retinopathy. 26 but the identity of target molecules in the RPE Unfortunately, experimental studies show and neurosensory retina is currently unknown. that mild photochemical retinal damage may Solar retinitis and welder's maculopathy most not be visible ophthalmoscopically, so clinical likely are class 2 effects, not primarily of photo reports probably represent only the most pigment origin. A striking feature of class 2 severe injuries. It is also possible that intense photic retinopathy is that damage suscep erythropsia leaves permanent effects that are tibility increases with decreasing wavelength, not initially apparent, at least ophthalmo so that ultraviolet radiation and blue light pose scopically, and that this condition may be the the greatest risk.18 --20 This latter findingis con clinical analog of blue-sensitive cone photo sistent with the fact that photon energy chemical damage observed in primates at very increases with decreasing wavelength, so there low light levels. is a higher probability that a shorter wave The electromagnetic spectrum spans a con length photon will have sufficient energy to tinuous range of wavelengths, including visible induce a critical reaction. Class 2 photic reti light between 400 and 700 nm, and ultraviolet nopathy appears to be additive, and is radiation at shorter wavelengths. In a normal enhanced by increased oxygen tension.2 3,24 It human eye, the cornea is opaque to ultraviolet depends on the species, and the location and light below 300 nm, so the cornea shields inter extent of the exposed retina. It also depends on nal ocular components from potential harm the duration, intensity and spectrum of the from light below 300 nm.27 In the near-ultra light source. violet region between 300 and 400 nm, how Photic retinopathy in primates may occur ever, the cornea is transparent. Fortunately, because the retina's defence mechanisms the crystalline lens absorbs near-ultraviolet against toxic free radicals from light and oxy radiation between 300 and 400 nm,27 thereby gen are overwhelmed by light levels exceeding shielding the retina from potential harm. those normally encountered in our environ When the crystalline lens is removed in catar ment. While a free radical mechanism gains act surgery, however, the retina's near-ultra considerable support from studies showing violet light protection is also removed. that susceptibility to photic retinopathy Replacing the crystalline lens with a clear increases with increased blood oxygen ten PMMA intraocular lens provides little protec sion,23,24 other damage mechanisms may be tion, because clear PMMA allows most of the involved. For example, light could damage near-ultraviolet light to get through to the ret critical intracellular biochemical systems, ina.28,29 Use of a UV-absorbing IOL increases responsible for controlling ionic homeostasis, this protection, but there is considerable vari calcium storage, transport functions, cell res ability in the protection afforded by commer piration, or RPE phagocytosis. In addition, cially available lenses, and none provides the maintenance of photoreceptor discs in a blue light protection offered by the native crys bleached state for a prolonged interval of time talline lens. could lead to thermal instabilities that ultimately disrupt the dynamic structure of the Photic Retinopathy and Macular outer segment.25 Photic retinopathy probably Degeneration comprises a continuum of related hazards, the The evidence linking photic retinopathy to nature of biochemical events being deter- macular degeneration is circumstantial but 308 MARTIN A. MAINSTER compelling, and cumulative photochemical plementation of antioxidant vitamins E and C, retinal damage from environmental light and cofactors selenium (for glutathione perox exposure has been proposed as a cause for idase) and zinc (for catalase). While deficien AMD.29 Indeed, ultraviolet radiation was cies of antioxidants and cofactors may increase implicated in macular degeneration over sixty susceptibility to AMD and photic retinopathy, years ago, long before solar retinitis was there is no evidence that supplements help known to be photochemical in origin.3D The individuals already receiving a balanced diet. primary reason initially for linking UV radia Although laboratory studies show that vitamin tion to macular degeneration was the clinical C supplementation protects rats against photic observation in a large series of patients that retinopathy,35 clinical studies show no correla macular degeneration was less common in tion between exudative macular degeneration patients with cataractformation. 30 This inverse and blood levels of vitamins A, C or E.!6 In relationship is supported by recent statistical fairness, however, since the largest increase in studies showing a reduced incidence of macu lipofuscin occurs between the firstand second lar degeneration in patients with nuclear (but decade,l1 it may be necessary to correlate not cortical) cataract formation,3! and a three blood levels in youth to identify individuals at fold increase in the incidence of drusen forma subsequent risk to AMD. tion in the non-phakic eye (aphakic or clear Bright, warm environments are conducive PMMA IOL) of patients who have undergone to foveomacular retinitis, at least in the mili unilateral cataract extraction.32 tary, but the aetiology of this disorder remains In addition to these statistical studies, and puzzling, along with why it is sporadic and the similarity of retinal findingsin photic reti apparently absent in civilian populations nopathy and macular degeneration, further exposed to similar climates. Solar retinopathy evidence linking these two disorders arose in is a potential contributing factor, but there is 1941-4 and 1966--9.33 Aside from pilots, anti no firm evidence for this association, and the aircraft observers and others who might be many other possible explanations include exposed to solar retinitis in their line of duty, a immunisations, chorioretinal infections, liver similar condition known as foveomacular reti diseases, drug photosensitisation, and vitamin nitis arose in personnel without a history of sun deficiencies. In any event, malnutrition gazing who were stationed generally in bright hastens macular degenerative changes in white environments. Macular disorders were even people in bright, hot environments, suggesting more prevalent among prisoners of war in the the need for a better understanding of the role south Pacific, where malnutrition was com of light and ambient temperature in premature bined with high environmental illuminances macular ageing, and the value of light protec and temperatures. 34 tion in patients with malabsorption syndromes. Clinical Implications One effective form of light protection is sun While we are only beginning to understand the glasses which screen out UV-radiation and nature of photic retinopathy and its relation to blue light below 450 nm. These sunglasses macular degeneration, AMD is a widespread should be used in bright environments by problem, and there is pressure to translate aphakes or clear PMMA (i.e. PMMA without experimental results from photic retinopathy UV -absorbing chromophores) pseudophakes studies into clinical therapies. There is no whose retinae are no longer protected by the proof at this time that any therapy reduces the crystalline lens.28,36 Whether such sunglasses risk of AMD, and patients should not be misled provide any significant protection for phakic by speculative extrapolation oflaboratory data individuals with normal nutrition in temperate on photic maculopathy. climates remains to be determined. In any Since humans and experimental animals event, just as it is important to wear protective develop retinal abnormalities similar to macu ear plugs around intense sound sources such as lar degeneration when deprived of key jet aircraft, and use sunscreen lotion in high vitamins and cofactors, one therapy proposed ultraviolet radiation environments, it also for macular degeneration is dietary sup- makes sense to wear appropriate protective LIGHT AND MACULAR DEGENERATION 309 sunglasses in bright environments, at least red light for routine photocoagulation since until the role of photic retinopathy in macular these have a lower potential for producing degeneration is better understood. It must be photic retinopathy in the operator or patient. emphasised that most sunglasses are poorly Light is the source of life and the origin of labelled, however, and that poor sunglasses decay. It is responsible for retinal development are potentially more harmful than none at all. and involution. The photoreceptor, RPE and For example, a sunglass that filtersout most of Bruch's membrane are all complex, open the visible spectrum but transmits UV-radia systems in dynamic order. Excessive light dis tion and deep blue light would relax the eye's rupts that order, but some light is undoubtedly squint and pupillary constriction defence needed to stimulate retinal defences against mechanisms, thereby placing the user at light damage, and cyclic light is required to greater risk to lenticular or retinal damageY entrain the rhythm of structure and function of Clinical light sources must provide adequate light levels for both clear and hazy media, and the outer segment, RPE and Bruch's mem levels needed for patients with hazy media may brane. Light surely plays a role in retinal senes be uncomfortable or dangerous for patients cence, just as usage is related to the longevity of with clear media. Several methods are avail any implement. It is not known, however, if able for improving the safety of clinical exam light exposure history is any more or less sig inations. (1) Filtering out light with nificantover a lifetime than a myriad of other wavelengths below 450 nm would reduce the factors such as climactic temperature, basal risk of photic retinopathy without significantly body temperature, childhood febrile illnesses, impairing visualisation of necessary clinical and variations or interruptions in the light/dark detail. Filtering out wavelengths greater than cycle (e. g. by leaving room lights on constantly 700 nm would eliminate needless infrared radi in premature infant nurseries, or by time zone ation which could thermally-enhance photo changes in transcontinental travel). chemical ciamage.36 (2) Examinations should The patient with advanced glaucoma has a always be performed with a minimum amount narrow perspective of space, but we have a nar of light exposure for both patient comfort and row perspective of time, viewing events with a safety. This fact should be understood by resi patience proportional to the longevity of our dents mastering diagnostic and surgical skills. 36 species. Contemporary scientificmethods are (3) Occlusion devices should be used whenever not well-suited to studying events, such as fundus visualisation is unnecessary, whether 'human ageing, whose duration is comparable by occluding part of the illuminating beam or to an investigator's lifespan. Indeed, the 'pro placing an opaque shield on the cornea. In this gress' to be demonstrated in a contemporary latter case, highly absorbing ( vs. absorbing and research grant limits techniques to those which scattering) occluders such as those made from show 'results' within a 2 or 3 year cycle of black PMMA should be avoided since they can research funding. Just as we fail to discern attain temperatures high enough to cause ther motion in the subtle unfolding of a rose, we mal keratitis. may fail to appreciate the dynamics of slowly Ophthalmologists themselves are at risk to developing intraretinal changes, or detect photic retinopathy from incandescent or laser improbable events such as electron tunnelling light scattered back at them off optical inter whose repetitive effects could be significant faces such as contact examination lens surfaces over a lifetime. Unfortunately, the vital math and mirrors. A primary area of concern is ematical methods needed to understand these photocoagulation with visible light. The scat long-term processes, such as non-equilibrium tered light viewed when observing a photo thermodynamics and catastrophe theory, are coagulator aiming beam usually is not abstruse disciplines in the early stages of their attenuated by protective filters.Clinicians are development. Light undoubtedly affects reti subject to periodic dazzling reflexes that are nal senescence, but intraretinal dynamics and safe in the short term, but have an unknown, ageing in a healthy human are too complex to cumulative, long-term effect. Thus, it is prob expect serendipitous cures, and the solution of ably safer to use dye or krypton laser yellow or retinal ageing awaits better comprehension of 310 MARTIN A. MAINSTER human ageing and relevant interactions in by light in the primate retina: a search for mecha nisms. Trans. Am. Ophthalmol. Soc. 1982; 80: nature. 517-79. 20 Sperling HG, Johnson C, Harwerth RS: Differential References spectral photic damage to primate cones. Vision 1 Morris R: Time's arrows: scientific attitudes toward Res. 1980;20: 1117-25. time. New York: Simon and Schuster, 1985;7-27. 21 Tso MOM, LaPiana FG: The human fovea after 2 Volkenshtein MV: Biophysics. Moscow: Mir, 1983; sungazing. Trans. Am. Acad. Ophthalmol. 339-45. Otolaryngol. 1975;79: 788-95. 3 Prigogine I, Stengers I: Order out of chaos. New 22 White TJ, Mainster MA, Wilson PW, Tips JH: York: Bantam, 1984;189-209. Chorioretinal temperature increases from solar 4 Dossey L: Space, time and medicine. Boston: New observation. Bull. Math. Biophys. 1971;33: 1-17 Science Library, 1982;59-71. 23 Crockett RS, Lawwill T: Invest. Ophthalmol. Vis. 5 Herbert N: Quantum reality. Garden City NY: Sci. Supp 1983;24: 253. Anchor, 1985;211-31. 24 Ruffolo JJ, Ham WT, Mueller HA, Millen JE: Photo 6 Young RW: Biological renewal. Applications to the chemical lesions in the primate retina under con eye. Trans. Opthalmol. Soc. UK. 1982; 102: ditions of elevated blood oxygen. Invest. 42-75. Ophthalomol. Vis. Sci. 1984;25: 893-8. 7 Besharse JC: Photosensitive membrane turnover: 25 Mainster MA: Destructive light adaptation. Ann. differentiated membrane domains and cell-cell Ophthalomol. 1970; 2: 44-8. interaction. In: Adler R, Farber D, eds. The ret 26 Fishman GA: Light-induced maculopathy from sur ina: a model for cell biology studies, Part I. gical microscopes during cataract surgery. In: Orlando: Academic Press, 1986;297-352. Ernest JT, ed. 1985 Year Book of Ophthalmology. 8 Marshall J, Grindle J, Ansell PL, Borwein B: Con Chicago, Year Book Medical Publishers, 1985; volution in human rods: an ageing process. Br. l. 177-80. Ophthalmol. 1979;63: 181-7. 27 Boettner EA, Wolter JR: Transmission of the ocular 9 Feeney-Burns L, Ellersieck MR: Age-related media. Invest. Ophthalmol. Vis. Sci. 1962;1: 776- changes in the ultrastructure of Bruch's mem 83. 8 brane. Am. l. Ophthalmol. 1985; 100: 686-97. 2 Mainster MA: Spectral transmittance of intraocular 10 Snodderly DM, Auran JD, Delori FC: The macular lenses and retinal damage from intense light pigment. II. Spatial distribution in primate reti sources. Am. l. Ophthalmol. 1978;85: 167-70. nas. Invest. Ophthalmol. Vis. Sci. 1984; 25: 674- 29 Mainster MA: Solar retinitis, photic maculopathy 85. and the pseudophakic eye. Am. Intra-Ocular 11 Feeney-Burns L, Hilderbrand ES, Eldridge S: Age Implant. Soc. l. 1978;4: 84-6. ing human RPE: morphometric analysis of macu 30 van der Hoeve J: Eye lesions produced by light rich in lar, equatorial and peripheral cells. Invest. ultraviolet rays. Senile cataract senile degenera Ophthalmol. Vis. Sci. 1984;25: 195-200. tion of the macula. Am. l. Ophthalmol. 1920; 3: 12 Sarks SH: Drusen and their relationship to senile 178-94. macular degeneration. Austr(d. 1. Ophthalmol. 31 Sperduto RD, Hiller R, Seigel D: Lens opacities and 1980;8: 117-30. senile maculopathy. Arch. Ophthalmol. 1981;99: 13 Ferris FL, Fine SL, Hyman L: Age related macular 1004-8. degeneration and blindness due to neovascular 32 Guyer DR, Alexander MF, Auer CL, Hamill MB, maculopathy. Arch. Ophthalmol. 1984; 102: Chamberlin JA, Fine SL: A comparison of the 1640-2. frequency and severity of macular drusen in pha 14 Hoshino M, Mizuno K, Ichikawa H: Aging altera kic and non-phakic eyes. Invest. Ophthalmol. Vis. tions of retina and choroid of Japanese: light Sci. Supp 1986;27: 20. microscopic study of macular region of 176 eyes. 33 Marlor RL, Blais BR, Preston FR, Boyden DG: lpn. l. Ophthalmol. 1984;28: 89-102. Foveomacular retinitis, an important problem in 15 Weiter JJ, Delori FC, Wing GL, Fitch KA: Relation military medicine: epidemiology. Invest. ship of senile macular degeneration to ocular pig Ophthalmol. 1973; 12: 5-16. mentation. Am. l. Ophthalmol. 1985; 99: 185-7. 34 Clarke CA, Sneddon IB: Nutritional neuropathy in 16 Blumenkranz MS, Russell SR, Robey MG, Kott prisoners-of-war and internees from Hong-Kong. Blumenkranz R, Penneys N: Risk factors in age Lancet. 1946; 1: 734-7. related maculopathy complicated by chloroidal 35 Li ZY, Tso MOM, Wang H, Organisciak DT: Ame neovascularisation. Ophthalmol. 1986;93: 552-7. lioration of photic injury in rat retina by ascorbic 17 Noell WK: Possible mechanisms of photoreceptor acid: a histopathologic study. Invest. Ophthalmol. damage by light in mammalian eyes. Vision Res. Vis. Sci. 1985;26: 1589-98. 1980;20: 1163-71. 36 Mainster MA, Ham WT, Delori FC: Potential retinal 8 1 Ham WT, Mueller HA, Sliney DH: Retinal sen hazards. Instrument and environmental light sitivity to damage from short wavelength light. sources. Ophthalmol. 1983;90: 927-31. Nature. 1976; 260: 153-5. 37 Sliney DH: Eye protective techniques for bright light. 19 Lawwill T: Three major pathologic processes caused Ophthalmol. 1983;90: 937-44.