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Relationship of Senile Macular Degeneration to Ocular Pigmentation
Relationship of Senile Macular Degeneration to Ocular Pigmentation John J. Weiler, M.D., Francois C. Delori, Ph.D., Glenn L. Wing, M.D., and Karlotta A. Fitch, B.S.
We prospectively evaluated 650 consecutive white patients with senile macular degeneration and compared them to a control group of 363 patients. Ocular pigmentation (iris color and fundus pigmentation) was recorded for each patient, as was hair color (as a child and young adult) and age at evaluation. Patients were from the New England states and Florida. Our most significant finding was that 494 patients with senile macular degeneration (76%) had light-colored irides compared with 145 of the controls (40%). Fundus pigmentation closely corresponded to iris pigmentation (P<.Ol). Hair color was blond or light brown in 370 of the patients with senile macular degeneration (57%) and in 105 of the controls ~29%). Further, there was a tendency for individuals with lightly pigmented irides to have senile macular degeneration at an earlier age than those with dark irides (P<.Ol). Thus, increased ocular pigmentation tends to decrease the risk of developing senile macular degeneration. SENILE MACULAR DEGENERATION is a major cause of visual loss in the United States, and by far the leading cause of blindness in individuals 65 years old and older.' Unfortunately, its pathogenesis is poorly understood. We previously reported the inverse relation between retinal pigment epithelial melanin and lipofuscin concentranon.! Because lipofuscin accumulation increases with age and its topographic distribution shows an increase in the posterior pole," we speculated that lipofuscin accumulation could be
Accepted for publication Dec. 4, 1984. From the Eye Research Institute of Retina Foundation (Drs. Weiter and Delori and Ms. Fitch) and the Harvard Medical School (Drs. Weiter and Delori), Boston, Massachusetts; and Fort Myers, Florida (Dr. Wing). This study was supported in part by grant EY 03699 from the National Eye Institute (Dr. Weiter) and by the Massachusetts Lion Eye Research Fund (Dr. Weiter). Reprint requests to John J. Weiter, M.D., Retina Associates, 100 Charles River Plaza, Cambridge St., Boston, MA 02114.
associated with macular degeneration. This suggests that ocular pigmentation might have a protective role in the occurrence of senile macular degeneration.>' This is consistent with the observation that senile macular degeneration appears to be more prevalent among whites than among the more pigmented races.P" The purpose of this study was to test the hypothesis that there is a relationship between senile macular degeneration and the degree of ocular pigmentation.
Subjects
and Methods
We prospectively evaluated 650 white patients with senile macular degeneration and compared them to a control group of 363 patients. Each patient underwent biomicroscopic examination and indirect ophthalmoscopy. The patients with senile macular degeneration had stereoscopic fundus photography and fundus fluorescein angiography performed for documentation. The criterion for senile macular degeneration was the presence of macular drusen. The controls had no diagnosis of macular degeneration or macular drusen. Patients were drawn from large retina referral practices in New England (J.J.W.) and Florida (G.L.W.). A clinical co-ordinator, not aware of the ocular diagnosis, recorded the pigment characteristics. Ocular pigmentation (iris color and fundus pigmentation) was recorded for each patient, as was hair color (as a child and young adult), racial skin pigmentation, ease of sunburning, and age at evaluation. The fundus pigmentation was judged by having color fundus photographs of both control patients and senile macular degeneration patients randomized and placed in a slide tray. The slides were projected in this random order on a screen. An ophthalmologist (J.J.W.) estimated the fundus pigmentation. To facilitate analysis of the findings, all irides were classified as light (including blue, green, and gray) or dark (shades of brown) and hair as light (blond or
©AMERICAN JOURNAL OF OPHTHALMOLOGY 99:185-187, FEBRUARY, 1985
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light brown) or dark (brown or black). Fundus color was graded as light or dark. To relate the iris pigmentation to choroidal pigmentation more objectively, we evaluated autopsy eyes from 35 individuals with no known ocular abnormalities. We used microdensitometry techniques on pupil-optic nerve sections 6 urn thick to determine iris and choroidal melanin optical density. 4
Results Our most significant finding was that 494 of 650 patients with senile macular degeneration (76%) had light irides compared with 145 of 363 controls (40%) (P = .0001 by chi-square test for independent variables). Clinically, fundus pigmentation closely corresponded to iris pigmentation (Spearman's rank correlation coefficient = 0.88; (P<.OI). Because clinical fundus pigmentation was estimated from color photographs, variability could have been introduced by the photographic process. The histologic microdensitometric technique objectively verified the direct correlation between choroidal and iris pigmentation (P<.OI). Hair color was light in 370 of 650 patients with senile macular degeneration (57%) and in 105 of 363 controls (29%) (P = .0001). Initially, as part of the prospective study, race was included as a variable. Because there were no black or Oriental patients among the 650 individuals with senile macular degeneration, we excluded them from the controls also (only six non-white patients were in the original 363 control patients). Therefore, the study was limited to white patients. Furthermore, we believed that skin color and susceptibility to sunburning were too variable and subjective and excluded them from data analysis. The patients with senile macular degeneration and light irides were significantly (P = .0008) younger (mean age, 73.6 ± 7.3 years) than those with dark irides (mean age, 78.3 ± 5.8 years). These ages do not reflect age of onset of senile macular degeneration, but represent the age at the time of inclusion in the study. Because the patients were selected consecutively, there is no reason to expect, however, that this age difference would not be reflected in the age of onset of senile macular degeneration.
Discussion This prospective study verified our preliminary finding" that individuals with light irides and light
February, 1985
hair are at a higher risk of developing senile macular degeneration than more darkly pigmented individuals. This association of light irides with senile macular degeneration has been confirmed by a recent study." This observation is consistent with the clinical impression among ophthalmologists that the more pigmented races are less likely to develop senile macular degeneration than are whites. 6-8 (It should be noted, however, that the National Health and Nutrition Examination Survey" did not find an increase in the prevalence of senile macular degeneration in whites compared with blacks.) This association of an apparent protective effect of ocular pigmentation for senile macular degeneration may account for the familial tendency of senile macular degeneration," because the degree of pigmentation is a strongly inherited genetic factor. The protective effect of ocular pigmentation would also be consistent with the tendency that we noted for senile macular degeneration to occur at an earlier age in more lightly pigmented eyes. We do not believe that hair color is related to senile macular degeneration, except for the tendency for skin, hair, and uveal pigmentation to be correlated. Most probably, it is the degree of fundus pigmentation that is related to senile macular degeneration. The phenotypic characteristics of hair and eye color, however, allow obvious and readily identified markers that can be useful in identifying individuals at risk for senile macular degeneration at an early age. Although this study, showing an inverse association between the degree of ocular pigmentation and senile macular degeneration, did not prove whether increased pigment protects against senile macular degeneration or whether it is simply correlated with some other factor that is responsible for the observed association, it is worthwhile to speculate on possible mechanisms. We have previously shown an inverse relation between melanin and lipofuscin of the human retinal pigment epithelium, both topographically and with age. 2,4 Lipofuscin was significantly greater (P = .01) in the retinal pigment epithelium of whites compared to blacks. Lipofuscin increases with age. This rate of change is greatest in the first two decades of life and shows only a moderate increase in the third through fifth decades. 3,4,13 After age 50 years, a more rapid increase in lipofuscin was again noted, much more marked in whites than blacks. Because lipofuscin is thought to be related to photo-oxidative mechanisms, 14-17 it would be instructive to attempt to correlate this age-related accumulation of lipofuscin to light damage. We hypothesize that the rapid lipofuscin accumulation in the first two decades of life is related to the increased exposure of the retina to shorter ultraviolet wavelengths (295 to 400 nm), because the crystalline lens develops a
Vol. 99, No.2
Senile Macular Degeneration and Ocular Pigmentation
yellow pigment that blocks the shorter wavelengths on a time scale that matches the lipofuscin accumulation in the retinal pigment epithelium." The further accumulation of retinal pigment epithelium lipofuscin after age 50 years would be related to the trend towards decreasing retinal pigment epithelium melanin after age 50 years.v" Melanin could provide photoprotection not only by direct absorption of light but also by serving as a scavenger of lightinduced free radicals;" Although lipofuscin formation is a complex process, most probably involving lipid photooxidation.w'? many environmental factors such as nutrition ate likely to playa role and contribute to the marked variability noted. Despite the apparent protective role of melanin in the accumulation of lipofuscin and in the occurrence of senile macular degeneration, the link between lipofuscin accumulation and senile macular degeneration has not been firmly established. We have postulated that the gradual accumulation of lipofuscin in the cells of the retinal pigment epithelium over the course of a lifetime could result in cellular dysfunction and death." Indeed, large amounts of lipofuscin have been shown in several cases of regional atrophy of the retinal pigment epithelium, generally considered a variant of"atrophic" senile macular degeneration. 3,20,21 It awaits to be determined, however, whether lipofuscin accumulation represents causality in senile macular degeneration or just a nonspecific reaction of stressed retinal pigment epithelial cells. The strong association between ocular melanin and both senile macular degeneration and lipofuscin in the retinal pigment epithelium suggests a role for light damage in the eye and offers possibilities for research to prevent this important cause of blindness in our population.
References 1. Kahn, H. A., and Moorhead, H. B.: Statistics on blindness in the model reporting area 1969-1970. Department of Health, Education, and Welfare, publication No. (NIH) 73-427. 2. Wing, G. 1., Delori, F. C, Weiter, J. J., and Kurtis, K.: The relation between melanin and lipofuscin in human RPE. ARVO Abstracts. Supplement to Invest. Ophthalmol. Vis. Sci. St. Louis, C V. Mosby, 1982, p. 173. 3. Wing, G. 1., Blanchard, G. C, and Weiter, J. J.: The topography and age relationship of lipofuscin concentration
187
in the retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 17:600, 1978. 4. Weiter, J. J., Delori, F. C, and Fitch, K.: Pigments of the retinal pigment epithelium and choroid in human eyes. ARVO Abstracts. Supplement to Invest. Ophthalmol. Vis. Sci. Philadelphia, J. B. Lippincott, 1984, p. 247. 5. Gregor, 2., and Joffe, 1.: Senile macular changes in the black African. Br. J. Ophthalmol. 62:547, 1978. 6. Chumbley, L. C: Impressions of eye diseases among Rhodesian blacks in Mashonaland. S. Afr. Med. J. 52:316, 1977. 7. Green, W., and Key,S.: Senile macular degeneration. A histopathologic study. Trans. Am. Ophthalmol. Soc. 75:180,1977. 8. Schatz, H.: The senile maculopathies and the retinal pigment epithelium. Int. Ophthalmol. Clin. 15:169, 1975. 9. Mann, 1.: Culture, Race, Climate and Eye Disease. Springfield, Charles C Thomas, 1966, pp. 200-215, 239, and 242. 10. Wing, G. L., Weiter, J. J., Delori, F. C, Kurtis, K., and Walker, J. P.: Senile macular degeneration and its relation to ocular pigmentation. ARVO Abstracts. Supplement to Invest. Ophthalmol. Vis. Sci. Philadelphia, J. B. Lippincott, 1983, p. 244. 11. Hyman, L. A., Lilienfeld, A. M., Pirris, F. L., III, and Fine, S. L.: Senile macular degeneration. A case control study. Am. J. Epidemio!. 118:213, 1983. 12. Ganley, J., and Roberts, J.: Eye conditions and related need for medical care among persons 1-74 years of age, United States, 1971-72. Vital and Health Statistics, Series 11, No. 228. Department of Health and Human Services, publication No. (PHS) 83-1678, 1983. 13. Feeney-Burns, L., Hilderbrand, E. 5., and Eldridge, 5.: Aging human RPE. Morphometric analysis of macular, equatorial and peripheral cells. Invest. Ophthalmol. Vis. Sci. 25:195, 1984. 14. Sohol, R. 5.: Age Pigments. Amsterdam, Elsevier! North-Holland, 1981, pp. 102-155 and 317-334. 15. Noell, W. K., Walker, V. 5., Kang, B.S., and Berman, 5.: Retinal damage by light in rats. Invest. Ophthalmol. 5:450, 1966. 16. Feeney, L., and Berman, E. R.: Oxygen toxicity. Membrane damage by free radicals. Invest. Ophthalmol. 15:789, 1976. 17. Feeney-Burns, L., Berman, E. R, and Rothman, H.: Lipofuscin of human retinal pigment epithelium. Am. J. Ophthalmol. 90:783, 1980. 18. Lerman,S.: Radiant Energy and the Eye. New York, Macmillan Publishing Co., 1980, p. 153. 19. Barr, F. E., Saloma, J. 5., and Buchele, M. J.: Melanin. The organizing molecule. Med. Hypotheses 11:1,1983. 20. Weiter, J., and Fine, B.S.: A histologic study of regional choroidal dystrophy. Am. J. Ophthalmol. 83:741, 1977. 21. Eagle, R C., [r.: Mechanisms of maculopathy. Ophthalmology 91:613, 1984.
We prospectively evaluated 650 consecutive white patients with senile macular degeneration and compared them to a control group of 363 patients. Ocular pigmentation (iris color and fundus pigmentation) was recorded for each patient, as was hair color (as a child and young adult) and age at evaluation. Patients were from the New England states and Florida. Our most significant finding was that 494 patients with senile macular degeneration (76%) had light-colored irides compared with 145 of the controls (40%). Fundus pigmentation closely corresponded to iris pigmentation (P<.Ol). Hair color was blond or light brown in 370 of the patients with senile macular degeneration (57%) and in 105 of the controls ~29%). Further, there was a tendency for individuals with lightly pigmented irides to have senile macular degeneration at an earlier age than those with dark irides (P<.Ol). Thus, increased ocular pigmentation tends to decrease the risk of developing senile macular degeneration. SENILE MACULAR DEGENERATION is a major cause of visual loss in the United States, and by far the leading cause of blindness in individuals 65 years old and older.' Unfortunately, its pathogenesis is poorly understood. We previously reported the inverse relation between retinal pigment epithelial melanin and lipofuscin concentranon.! Because lipofuscin accumulation increases with age and its topographic distribution shows an increase in the posterior pole," we speculated that lipofuscin accumulation could be
Accepted for publication Dec. 4, 1984. From the Eye Research Institute of Retina Foundation (Drs. Weiter and Delori and Ms. Fitch) and the Harvard Medical School (Drs. Weiter and Delori), Boston, Massachusetts; and Fort Myers, Florida (Dr. Wing). This study was supported in part by grant EY 03699 from the National Eye Institute (Dr. Weiter) and by the Massachusetts Lion Eye Research Fund (Dr. Weiter). Reprint requests to John J. Weiter, M.D., Retina Associates, 100 Charles River Plaza, Cambridge St., Boston, MA 02114.
associated with macular degeneration. This suggests that ocular pigmentation might have a protective role in the occurrence of senile macular degeneration.>' This is consistent with the observation that senile macular degeneration appears to be more prevalent among whites than among the more pigmented races.P" The purpose of this study was to test the hypothesis that there is a relationship between senile macular degeneration and the degree of ocular pigmentation.
Subjects
and Methods
We prospectively evaluated 650 white patients with senile macular degeneration and compared them to a control group of 363 patients. Each patient underwent biomicroscopic examination and indirect ophthalmoscopy. The patients with senile macular degeneration had stereoscopic fundus photography and fundus fluorescein angiography performed for documentation. The criterion for senile macular degeneration was the presence of macular drusen. The controls had no diagnosis of macular degeneration or macular drusen. Patients were drawn from large retina referral practices in New England (J.J.W.) and Florida (G.L.W.). A clinical co-ordinator, not aware of the ocular diagnosis, recorded the pigment characteristics. Ocular pigmentation (iris color and fundus pigmentation) was recorded for each patient, as was hair color (as a child and young adult), racial skin pigmentation, ease of sunburning, and age at evaluation. The fundus pigmentation was judged by having color fundus photographs of both control patients and senile macular degeneration patients randomized and placed in a slide tray. The slides were projected in this random order on a screen. An ophthalmologist (J.J.W.) estimated the fundus pigmentation. To facilitate analysis of the findings, all irides were classified as light (including blue, green, and gray) or dark (shades of brown) and hair as light (blond or
©AMERICAN JOURNAL OF OPHTHALMOLOGY 99:185-187, FEBRUARY, 1985
185
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AMERICAN JOURNAL OF OPHTHALMOLOGY
light brown) or dark (brown or black). Fundus color was graded as light or dark. To relate the iris pigmentation to choroidal pigmentation more objectively, we evaluated autopsy eyes from 35 individuals with no known ocular abnormalities. We used microdensitometry techniques on pupil-optic nerve sections 6 urn thick to determine iris and choroidal melanin optical density. 4
Results Our most significant finding was that 494 of 650 patients with senile macular degeneration (76%) had light irides compared with 145 of 363 controls (40%) (P = .0001 by chi-square test for independent variables). Clinically, fundus pigmentation closely corresponded to iris pigmentation (Spearman's rank correlation coefficient = 0.88; (P<.OI). Because clinical fundus pigmentation was estimated from color photographs, variability could have been introduced by the photographic process. The histologic microdensitometric technique objectively verified the direct correlation between choroidal and iris pigmentation (P<.OI). Hair color was light in 370 of 650 patients with senile macular degeneration (57%) and in 105 of 363 controls (29%) (P = .0001). Initially, as part of the prospective study, race was included as a variable. Because there were no black or Oriental patients among the 650 individuals with senile macular degeneration, we excluded them from the controls also (only six non-white patients were in the original 363 control patients). Therefore, the study was limited to white patients. Furthermore, we believed that skin color and susceptibility to sunburning were too variable and subjective and excluded them from data analysis. The patients with senile macular degeneration and light irides were significantly (P = .0008) younger (mean age, 73.6 ± 7.3 years) than those with dark irides (mean age, 78.3 ± 5.8 years). These ages do not reflect age of onset of senile macular degeneration, but represent the age at the time of inclusion in the study. Because the patients were selected consecutively, there is no reason to expect, however, that this age difference would not be reflected in the age of onset of senile macular degeneration.
Discussion This prospective study verified our preliminary finding" that individuals with light irides and light
February, 1985
hair are at a higher risk of developing senile macular degeneration than more darkly pigmented individuals. This association of light irides with senile macular degeneration has been confirmed by a recent study." This observation is consistent with the clinical impression among ophthalmologists that the more pigmented races are less likely to develop senile macular degeneration than are whites. 6-8 (It should be noted, however, that the National Health and Nutrition Examination Survey" did not find an increase in the prevalence of senile macular degeneration in whites compared with blacks.) This association of an apparent protective effect of ocular pigmentation for senile macular degeneration may account for the familial tendency of senile macular degeneration," because the degree of pigmentation is a strongly inherited genetic factor. The protective effect of ocular pigmentation would also be consistent with the tendency that we noted for senile macular degeneration to occur at an earlier age in more lightly pigmented eyes. We do not believe that hair color is related to senile macular degeneration, except for the tendency for skin, hair, and uveal pigmentation to be correlated. Most probably, it is the degree of fundus pigmentation that is related to senile macular degeneration. The phenotypic characteristics of hair and eye color, however, allow obvious and readily identified markers that can be useful in identifying individuals at risk for senile macular degeneration at an early age. Although this study, showing an inverse association between the degree of ocular pigmentation and senile macular degeneration, did not prove whether increased pigment protects against senile macular degeneration or whether it is simply correlated with some other factor that is responsible for the observed association, it is worthwhile to speculate on possible mechanisms. We have previously shown an inverse relation between melanin and lipofuscin of the human retinal pigment epithelium, both topographically and with age. 2,4 Lipofuscin was significantly greater (P = .01) in the retinal pigment epithelium of whites compared to blacks. Lipofuscin increases with age. This rate of change is greatest in the first two decades of life and shows only a moderate increase in the third through fifth decades. 3,4,13 After age 50 years, a more rapid increase in lipofuscin was again noted, much more marked in whites than blacks. Because lipofuscin is thought to be related to photo-oxidative mechanisms, 14-17 it would be instructive to attempt to correlate this age-related accumulation of lipofuscin to light damage. We hypothesize that the rapid lipofuscin accumulation in the first two decades of life is related to the increased exposure of the retina to shorter ultraviolet wavelengths (295 to 400 nm), because the crystalline lens develops a
Vol. 99, No.2
Senile Macular Degeneration and Ocular Pigmentation
yellow pigment that blocks the shorter wavelengths on a time scale that matches the lipofuscin accumulation in the retinal pigment epithelium." The further accumulation of retinal pigment epithelium lipofuscin after age 50 years would be related to the trend towards decreasing retinal pigment epithelium melanin after age 50 years.v" Melanin could provide photoprotection not only by direct absorption of light but also by serving as a scavenger of lightinduced free radicals;" Although lipofuscin formation is a complex process, most probably involving lipid photooxidation.w'? many environmental factors such as nutrition ate likely to playa role and contribute to the marked variability noted. Despite the apparent protective role of melanin in the accumulation of lipofuscin and in the occurrence of senile macular degeneration, the link between lipofuscin accumulation and senile macular degeneration has not been firmly established. We have postulated that the gradual accumulation of lipofuscin in the cells of the retinal pigment epithelium over the course of a lifetime could result in cellular dysfunction and death." Indeed, large amounts of lipofuscin have been shown in several cases of regional atrophy of the retinal pigment epithelium, generally considered a variant of"atrophic" senile macular degeneration. 3,20,21 It awaits to be determined, however, whether lipofuscin accumulation represents causality in senile macular degeneration or just a nonspecific reaction of stressed retinal pigment epithelial cells. The strong association between ocular melanin and both senile macular degeneration and lipofuscin in the retinal pigment epithelium suggests a role for light damage in the eye and offers possibilities for research to prevent this important cause of blindness in our population.
References 1. Kahn, H. A., and Moorhead, H. B.: Statistics on blindness in the model reporting area 1969-1970. Department of Health, Education, and Welfare, publication No. (NIH) 73-427. 2. Wing, G. 1., Delori, F. C, Weiter, J. J., and Kurtis, K.: The relation between melanin and lipofuscin in human RPE. ARVO Abstracts. Supplement to Invest. Ophthalmol. Vis. Sci. St. Louis, C V. Mosby, 1982, p. 173. 3. Wing, G. 1., Blanchard, G. C, and Weiter, J. J.: The topography and age relationship of lipofuscin concentration
187
in the retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 17:600, 1978. 4. Weiter, J. J., Delori, F. C, and Fitch, K.: Pigments of the retinal pigment epithelium and choroid in human eyes. ARVO Abstracts. Supplement to Invest. Ophthalmol. Vis. Sci. Philadelphia, J. B. Lippincott, 1984, p. 247. 5. Gregor, 2., and Joffe, 1.: Senile macular changes in the black African. Br. J. Ophthalmol. 62:547, 1978. 6. Chumbley, L. C: Impressions of eye diseases among Rhodesian blacks in Mashonaland. S. Afr. Med. J. 52:316, 1977. 7. Green, W., and Key,S.: Senile macular degeneration. A histopathologic study. Trans. Am. Ophthalmol. Soc. 75:180,1977. 8. Schatz, H.: The senile maculopathies and the retinal pigment epithelium. Int. Ophthalmol. Clin. 15:169, 1975. 9. Mann, 1.: Culture, Race, Climate and Eye Disease. Springfield, Charles C Thomas, 1966, pp. 200-215, 239, and 242. 10. Wing, G. L., Weiter, J. J., Delori, F. C, Kurtis, K., and Walker, J. P.: Senile macular degeneration and its relation to ocular pigmentation. ARVO Abstracts. Supplement to Invest. Ophthalmol. Vis. Sci. Philadelphia, J. B. Lippincott, 1983, p. 244. 11. Hyman, L. A., Lilienfeld, A. M., Pirris, F. L., III, and Fine, S. L.: Senile macular degeneration. A case control study. Am. J. Epidemio!. 118:213, 1983. 12. Ganley, J., and Roberts, J.: Eye conditions and related need for medical care among persons 1-74 years of age, United States, 1971-72. Vital and Health Statistics, Series 11, No. 228. Department of Health and Human Services, publication No. (PHS) 83-1678, 1983. 13. Feeney-Burns, L., Hilderbrand, E. 5., and Eldridge, 5.: Aging human RPE. Morphometric analysis of macular, equatorial and peripheral cells. Invest. Ophthalmol. Vis. Sci. 25:195, 1984. 14. Sohol, R. 5.: Age Pigments. Amsterdam, Elsevier! North-Holland, 1981, pp. 102-155 and 317-334. 15. Noell, W. K., Walker, V. 5., Kang, B.S., and Berman, 5.: Retinal damage by light in rats. Invest. Ophthalmol. 5:450, 1966. 16. Feeney, L., and Berman, E. R.: Oxygen toxicity. Membrane damage by free radicals. Invest. Ophthalmol. 15:789, 1976. 17. Feeney-Burns, L., Berman, E. R, and Rothman, H.: Lipofuscin of human retinal pigment epithelium. Am. J. Ophthalmol. 90:783, 1980. 18. Lerman,S.: Radiant Energy and the Eye. New York, Macmillan Publishing Co., 1980, p. 153. 19. Barr, F. E., Saloma, J. 5., and Buchele, M. J.: Melanin. The organizing molecule. Med. Hypotheses 11:1,1983. 20. Weiter, J., and Fine, B.S.: A histologic study of regional choroidal dystrophy. Am. J. Ophthalmol. 83:741, 1977. 21. Eagle, R C., [r.: Mechanisms of maculopathy. Ophthalmology 91:613, 1984.