The Relationship of Age-Related Maculopathy, Cataract, and Glaucoma to Visual Acuity

Ronald Klein, Qin Wang, Barbara E. K. Klein, Scot E. Moss, and Stacy M. Meuer

Purpose. To investigate the relationship of age-related maculopathy, cataract, and glaucoma to visual acuity in the population-based Beaver Dam Eye Study. Methods. A cross-sectional, population-based study was performed in people 43 through 86 years of age residing in Beaver Dam, Wisconsin, who were identified between 1987 and 1988 and examined (n = 4926) between 1988 and 1990. Of those who participated, 99.4% were white. Visual acuity was measured (n = 4886) using a modification of the Early Treatment Diabetic Retinopathy Study protocol. Stereoscopic color fundus photographs and slit lamp and retroillumination photographs of the lens were graded in a masked fashion using standardized protocols to determine the presence of age-related maculopathy and central cataract. Results. Fifty-seven percent of those who were legally blind had late age-related maculopathy in both eyes. The frequency of visual acuity of 20/200 or worse was not significantly different in eyes with exudative maciilar degeneration (48%) than in eyes with pure geographic atrophy (42%). While controlling for other factors (age, central cataract, and glaucoma) in participants with both gradable age-related maculopathy and visual acuity measurable in at least one eye (n = 4716), investigators found that each of the early age-related maculopathy lesions was associated with a decrease in visual acuity of approximately two letters or fewer when compared to eyes without these lesions. Late age-related maculopathy was associated with a decrease of approximately seven lines of letters read correctly. Conclusion. These data demonstrate that exudative macular degeneration and pure geographic atrophy are the most important causes of legal blindness in this population and that early age-related maculopathy, central cataract, and glaucoma had a small effect on visual acuity. Invest Ophthalmol Vis Sci. 1995;36:182-191.

.Late age-related maculopathy (exudative macular de- tion) is associated widi less severe loss of vision.8'9 Cata- generation and geographic atrophy) and cataract are ract, especially in rural areas5 or among black Americans important causes of decreased vision as people grow living in urban areas,4 is another important cause of age- older. '~5 Data from the Macular Photocoagulation Study related loss of vision. There are few population-based show that eyes with untreated exudative macular degen- data describing the relationship of age-related eye dis- eration with extrafoveal choroidal neovascularization eases to blindness and visual acuity.2"589 The purposes have approximately a 50% increased risk of losing six of this report are to examine the relationship of age- or more lines of vision in a 5-year period compared to related maculopathy, central cataract, and glaucoma to eyes that were treated.6'7 Data from other studies suggest monocular severe vision impairment (visual acuity of that "dry" macular degeneration (geographic atrophy 20/200 or worse) and legal blindness (20/200 or worse or nonatrophic retinal pigment epithelial depigmenta- in the better eye) in the entire Beaver Dam population and to examine the relationships of these three age- related eye diseases to visual acuity after excluding other From the Department of Ophthalmology and Visual Sciences, University of causes of decreased vision. Wisconsin Medical School, Madison, Wisconsin. Supported by the National Institutes of Health/National Eye Institute grant U10- EYO6594 (RK, BEKK) and, in part, by Research to Prevent Blindness (RK). RK i METHODS AND MATERIALS a Research to Prevent Blindness Senior Scientific. Investigator. Submitted for publication March 22, 1994; revised August 15, 1994; accepted The Population August 17, 1994. The Beaver Dam Eye Study population has been de- Proprietary interest category: N. 10 No reprints available. scribed in detail in previous reports. " In brief, a

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private census of the population of Beaver Dam, Wis- 4,926 Participants consin was performed from September 15, 1987 to Examined May 4, 1988. All residents (n = 5924) 43 to 84 years of age at the time of the census were invited to partici-

pate. Of these, 4926 (83.2%) were seen for the study 40 participants visual examination. Two hundred twenty-six (3.8%) people acuity unmeasurable or 20/200 or worse and died before the examination, 100 (1.7%) moved out unreliable in both eyes. of the area, and 18 (0.3%) could not be located. Two hundred seventy-six (4.6%) permitted an interview only, and 378 (6.4%) refused to participate. Compari- Included* sons between participants and nonparticipants have 4,886 participants with been presented elsewhere" Of those who partici- reliable visual acuity in pated, 99.4% were white. at least one eye. To examine late age-related maculopathy, cataract, and glaucoma as causes of blindness in the population, we excluded 29 people in whom visual acuity 11 participants visual acuity 20/40 to 20/160 could not be determined in both eyes and 11 people and unreliable in both eyes in whom visual acuity was less than 20/200 and unreli- 138 participants age-related maculopathy able because of organic mental syndrome, stroke, or ungradable in both eyes. Excluded some other condition. This left us with 4886 partici- 8 participants with age-related maculopathy pants in whom visual acuity was measurable (Fig. 1). availalble in one eye, visual To evaluate the relationships of early and late age- acuity available in the other. 13 participants related maculopathy, cataract, and glaucoma to visual with other ocular conditions in acuity, we excluded an additional 11 people in whom both eyes.

visual acuity was better than 20/200 and worse than Included! 20/40 and was judged to be unreliable in both eyes, 4,716 eligible people 138 people in whom the location and the severity of 4262 people with both age- related maculopathy age-related maculopathy lesions were not gradable in and visual acuity both eyes, 8 people in whom visual acuity could not be both eyes. determined in one eye and age-related maculopathy 220 people with both age-related maculopathy could not be graded in the other, and 13 people who and visual acuity had bilateral conditions other than cataract, age-re- right eye only. lated maculopathy, or glaucoma that significantly af- 234 people with both age- related maculopathy fected visual acuity. This resulted in 4262 persons in and visual acuity measurable in left whom the relationships between the age-related macu- eye only. lopathy and visual acuity could be determined in both eyes, 220 in whom these relationships could be exam- FIGURE 1. Description of population. ined only in the right eye, and 234 in whom these relationships could only be examined in the left eye the Early Treatment Diabetic Retinopathy Study (Fig. 1). Exclusions were based on a review of exami- (ETDRS) protocol with a modified chart R at a 2- nation findings, history, and fundus photographs. Per- meter distance.12 If the best corrected visual acuity was sons who were excluded (n = 210) were older (72.3 20/40 or worse, an ETDRS refraction was performed versus 61.6 years of age, P < .0001) and had higher and the visual acuity was remeasured. For each eye, serum glucose levels (118.6 mg/dl versus 106.2 mg/ the visual acuity was recorded as the number of letters dl, P= .001). (range, 0 [<20/200] to 70 [20/10]) correctly identified. Impaired vision was defined as best corrected Procedures and Definitions visual acuity of 20/40 or worse and included eyes that Tenets of the Declaration of Helsinki were followed. were blind (a visual acuity of 20/200 or worse). Legal Informed consent was signed, and institutional human blindness was defined as best corrected visual acuity experimentation committee approval was granted. of 20/200 or worse in the better eye. Monocular severe The parts of the examination pertinent to this vision impairment was defined as best corrected visual article consisted of a standardized refraction and mea- acuity of 20/200 or worse in one eye, with visual acuity surement of the visual acuity using the Humphrey 530 better than 20/200 in the other. refractor (Allegan Humphrey, San Leandro, CA)." During the examination, the pupils were dilated. The refraction was placed in a trial lens frame, and Stereoscopic 30° color fundus photographs centered the best-corrected visual acuity was remeasured using on the disk (Diabetic Retinopathy Study Standard

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early or late age-related maculopathy had to be present in the specific subfield involved. For example, early age-related maculopathy in the central circle subfield of the grid was defined as present when either soft indistinct drusen were found in the central subfield or when increased retinal pigment or retinal pigment epithelial degeneration and hard or soft drusen were present in the central subfield in the absence of signs of late age-related macular degeneration. For purposes of analyses, two categories were used—absent (includes questionable) and present in that specific area. The procedures for grading of both slit-lamp and retroilluminated photographs of the lens are detailed elsewhere.16"18 For the purposes of this article, nuclear sclerotic cataract was defined as present if the photo- graph of the lens was graded as more opaque than standard 3 (levels 4 or 5 in a five-step scale of severity). Grading of the Neitz photographs was designed to FIGURE 2. The grid used in the study. determine the area of the lens involved with cortical and posterior subcapsular opacities. A measuring grid was used that divided the red reflex photographs into Field 1) and macula (Diabetic Retinopathy Study Stan- a central circular area and eight sectors of equal size, dard Field 2) and a nonstereoscopic color fundus pho- which were defined by clock hours. The grader esti- tograph, temporal to but. including the fovea, were mated the area involved with cortical and posterior taken of each eye. subcapsular opacity in each of the fields, including Grading was performed in a masked fashion using information from both anterior and posterior photo- a standardized protocol, The Wisconsin Age-Related graphs for cortical opacity. For purposes of this investi- Maculopathy Grading scheme.ls Procedures have gation, central cataract was defined as the presence of been described in detail elsewhere.13"15 In brief, before grading, a grid consisting of three circles concen- a nuclear sclerotic cataract or a posterior subcapsular tric with the center of the macula and four radial lines cataract or cortical cataract involving 25% or more of were superimposed over one member of the stereo- the central circle. scopic pair of field 2 (Fig. 2). The procedures in detecting and defining glau- 19 20 Assessment of the presence and severity of lesions coma have been presented elsewhere. ' A visual field associated with age-related maculopathy was made in screening test of each eye using a Henson CFS 2000 each subneld and in the entire macular area (any perimeter (Keeler Instruments, Broomall, PA) was subfield of the grid). More detailed descriptions of performed. In those eyes that failed the screening test, these lesions appear elsewhere.13"15 For purposes of full perimetric testing was performed. Intraocular this article, overall early age-related maculopathy was pressure was measured according to a standard proto- defined as the presence in any subfield of the grid of col using a Goldmann applanation tonometer (Haig- either soft, indistinct drusen or hard or soft drusen Streit, A.G., Switzerland). Stereoscopic fundus photo- plus pigmentary abnormalities (increased retinal pig- graphs of field 1 were used for grading of optic disks ment or retinal pigment epithelial degeneration) in and cups according to a detailed standardized proto- the absence of signs of late age-related maculopathy. col. A standardized history was obtained. Subjects were Late age-related maculopathy was defined as the pres- queried about whether they had ever been told that ence of signs of exudative age-related macular degen- they had glaucoma, were taking medicines for glau- eration or pure geographic atrophy. Exudative macu- coma, or had surgery for glaucoma. lar degeneration was defined as the presence of a reti- At least two of the following three characteristics nal pigment epithelial detachment or a serous were required for a designation of definite glaucoma: detachment of the sensory retina, subretinal or sub- abnormal visual field; large (>0.8) or asymmetric RPE-hemorrhage, and/or subretinal fibrous scars. (>0.2) cup-to-disk ratio; or a high (>22 mm Hg) in- Pure geographic atrophy was defined by the presence traocular pressure. If a subject had a history of taking of geographic atrophy and the absence of exudative drops or had undergone surgery for glaucoma (ex- macular degeneration. cluding glaucoma secondary to rubeosis irides or For specific subfield analyses, lesions defining trauma), it was considered indicative of probable glau-

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coma. Both these groups were included in analyses The analyses (Tables 2 to 6) describing the rela- considering glaucoma.1' tionships of age-related maculopathy, central cataract, and glaucoma to visual acuity were performed in eyes Statistical Methods (4482 right eyes and 4496 left eyes) in which other SAS was used for calculating prevalence proportions, causes of impaired vision were excluded and both vi- means, chi-square statistics, and Kests.21 Age-adjusted sual acuity and age-related maculopathy data were prevalences were calculated by the direct method us- available for at least one eye (Fig. 1). Twenty-four per- ing the Beaver Dam Eye Study population as the stan- cent of the 138 participants, excluded because age- dard population.22 Significance of trend in propor- related maculopathy was ungradable in both eyes, had tions was tested by the Mantel-Haenszel procedure.23 central cataract. For these analyses, we examined the Multiple linear regression and multivariate logistic re- relation of specific age-related maculopathy lesions gression analyses were performed.24 The method of and their specific locations to visual acuity. Liang and Zeger was used to assess multivariate rela- The frequencies of specific age-related maculopa- tionships with data regarding age-related maculopathy thy lesions by location are presented in Table 2, and status from both eyes.25 the frequencies of central cataract, glaucoma, and impaired vision are presented in Table 3. The prevalence of maculopathy, cataract, glaucoma, and impaired vi- RESULTS sion all increased with increasing age. Age-adjusted Monocular severe vision impairment was present in frequencies of involvement of the central subfield of 2.6% (128/4886) of the population. Late age-related the macula (as defined by the grid) varied from 0.9% maculopathy was present in 21.1% (27/128) of these for soft indistinct drusen to 4.2% for increased retinal eyes (Table 1). Other causes of monocular severe vi- pigment (Table 2). sion impairment are listed in Table 1. In subjects with Visual acuity decreased with increasing age (Table monocular severe vision impairment who were 4). The mean visual acuity in the presence or absence younger than 65 years of age, late age-related maculo- of late age-related maculopathy, central cataract, or pathy was present in 2.3% of severely vision impaired glaucoma are presented in Table 4. When the other eyes (1 eye with exudative macular degeneration of two ocular conditions were absent, the age-adjusted 44 eyes with visual acuity of 20/200 or worse); in those mean visual acuity was 47.6 letters (20/25) in die pres- 65 to 74 years of age, it was present in 16.2% of severely ence of central cataract, 52.9 letters (20/20) in the vision impaired eyes (6 eyes, 5 with exudative macular presence of glaucoma, and 23.5 letters (20/80) in degeneration and 1 with pure geographic atrophy of those with late age-related maculopathy (right eye). 37 eyes with visual acuity of 20/200 or worse); and in Eyes with exudative macular degeneration or pure those 75 years of age or older, it was present in 42.6% geographic atrophy had higher frequencies of visual of severely vision impaired eyes (20 eyes, 15 with exu- acuity of 20/200 or worse (48.0% and 41.9%, respec- dative macular degeneration and 5 with pure geo- tively) than eyes with early age-related maculopathy graphic atrophy of 47 eyes with visual acuity of 20/ (0.3%). The difference in the frequency of 20/200 200 or worse). The proportion of eyes widi monocular or worse visual acuity in eyes with exudative macular severe vision impairment, in which late age-related degeneration, compared to eyes with pure geographic maculopathy was present, increased with increasing atrophy, was not statistically significant (P > .05). age (P < .001). Twenty-five percent of monocular se- Using multiple linear regression analyses, we ex- verely vision impaired eyes was due to ocular trauma. amined the relation of each of the age-related maculo- The third most frequent cause of monocular severe pathy lesions to visual acuity (expressed as the number vision impairment in the population was amblyopia of letters read correcdy), controlling for age, central (Table 1). In subjects with monocular severe vision cataract, and glaucoma (Table 5). For right eyes, le- impairment, age-related central cataract in the ab- sions of early age-related maculopathy in any subfield sence of late age-related maculopathy was present in within the grid were associated with decreases in mag- 8.6% of eyes. nitude of fewer than two letters read correcdy. There Legal blindness was present in 0.43% (21/4886) were significant but small changes in the number of of the total population (Table 1). Late age-related letters read correctly in eyes widi any central involve- maculopathy was present in both eyes in 57.1% (12/ ment of the macula by lesions associated widi early 21) of these subjects. Of these, 66.7% (8/12) had exu- age-related maculopathy (Table 5). The magnitude of dative macular degeneration in both eyes, none had the decreases varied from 0.4 to 2.0 letters. Odierwise, pure geographic atrophy in both eyes, and 33.3% (4/ there were few consistent or significant relationships 12) had exudative macular degeneration in one eye of either location (lesions involving the central point and pure geographic atrophy in the other. Other or confined to either the inner or outer subfields) or causes of legal blindness are presented in Table 1. severity of early age-related maculopathy to decreased

Downloaded from iovs.arvojournals.org on 09/29/2021 186 Investigative Ophthalmology & Visual Science, January 1995, Vol. 36, No. 1 TABLE l. Causes of Monocular Severe Vision Impairment or Legal Blindness in the Beaver Dam Eye Study, 1988-1990 Causes of Blindness Number % of Total

Monocular Blindness Late age-related maculopathy 27 21.8 Early age-related maculopathy 1 0.8 Ocular trauma Enucleation 11 8.6 Corneal opacity 11 8.6 Lens opacity 2 1.6 Retinal scar 5 3.9 Optic nerve atrophy 3 2.3 Amblyopia 12 9.4 Age-related cataract 10 7.8 Amblyopia and age-related cataract 1 0.8 Retinal detachment 10 7.8 Retinal vascular occlusion 8 6.3 Optic nerve atrophy (not glaucoma or trauma-related) 6 4.7 Macular hole 4 3.1 Diabetic retinopathy 2 1.6 Congenital retinal anomaly 2 1.6 Open angle glaucoma 1 0.8 Epiretinal membrane 1 0.8 Fuch's dystrophy 1 0.8 Bullous keratopathy status-post cataract surgery 1 0.8 Choroidal melanoma (enucleation) 1 0.8 Myopic degeneration 1 0.8 Presumed ocular histoplasmosis syndrome 1 0.8 Toxoplasmosis chorioretinal scar 1 0.8 Non-age-related maculopathy, ? etiology 2 1.6 Unknown etiology 3 2.3 Total 128 Legal Blindness Late age-related macular degeneration 12 57.1 Diabetic retinopathy 2 9.5 Late-stage cataract 1 4.8 Ocular trauma with sympathetic uveitis 1 4.8 Retinopathy or prematurity 1 4.8 Optic atrophy associated with hydrocephaly 1 4.8 Interstitial keratitis secondary to syphilis 1 4.8 Congenital coloboma of the fundus 1 4.8 Herpes zoster retinitis one eye, central retinal vein occlusion odier eye 1 4.8 Total 21

For monocular severe vision impairment, visual acuity is 20/200 or worse in the worse eye and better _k. than 20/200 in the other eye. For legal blindness, visual acuity is 20/200 or worse in the better eye.

visual acuity (data not shown). Relations of age-related There was an interaction between central cataract maculopathy to decreased vision were similar in left and late age-related maculopathy. In right eyes with eyes (data not shown). There were no interactions late age-related maculopathy without central cataract, between central cataract and lesions associated with there was a decrease in visual acuity of 27.3 letters; for early age-related maculopathy. right eyes with central cataract without late age-related While controlling for age, age-related maculopa- maculopathy, there was a decrease in visual acuity of thy, and glaucoma, we found that the presence of 4.3 letters. If both late age-related maculopathy and central cataract was associated with a significant de- central cataract were present, there was an additional < crease in visual acuity (approximately four to five let- decrease in visual acuity of 16.1 letters. The relations ters). While controlling for age, age-related maculopa- were similar in left eyes (data not shown). We reran thy, and cataract, we found that the presence of glau- the regression analyses for right eyes in which central T coma was associated with a more modest decrease in cataract was present and right eyes in which central acuity (one to two letters) (Table 5). cataract was absent (Table 6). In the presence of cen-

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TABLE 2. Frequency of Specific Lesions Associated With Age-Related Maculopathy by Location* in Macular Area in Right Eye by Age in the Beaver Dam Eye Study, 1988-1990 Age (years)

Age-Adjusted 43-54 55-64 65-74 75+ Rate

Number Number Number Number Number at Risk % at Risk % at Risk % at Risk % at Risk %

Soft indistinct drusen Any central subfield involvement only 1461 0.0 1240 0.4 1151 1.0 622 3.1 4474 0.9 Any subfield involvement 1461 0.9 1240 3.3 1151 5.1 622 13.8 4474 4.7 Retinal pigment epithelial degeneration Any central subfield involvement only 1460 1.2 1240 1.9 1151 2.6 622 8.4 4473 2.9 Any subfield involvement 1460 1.8 1240 2.6 1151 4.8 622 11.6 4473 4.4 Increased retinal pigment Any central subfield involvement only 1461 1.9 1240 2.7 1152 4.9 624 10.1 4477 4.2 Any subfield involvement 1461 3.1 1240 4.9 1152 6.9 624 15.1 4477 6.5 Early age-related maculopathy Any central subfield involvement only 1460 2.1 1235 3.3 1139 5.1 589 12.4 4423 4.9 Any subfield involvement 1460 4.2 1235 8.1 1139 10.9 589 25.6 4423 10.5 Late age-related maculopathy Any central subfield involvement only 1461 0.0 1240 0.3 1152 0.9 629 5.4 4482 1.2 Any subfield involvement 1461 01 1240 04 1152 1.1 629 64 4482 1 5

* Location defined as follows: any central subfield involvement = involvement by lesion in central only, central + inner subfield(s), central + outer subfield(s); central + inner subfield(s) + outer subfield(s); denominators vary due to missing data.

tral cataract, while controlling for age and glaucoma, age-related maculopathy to impaired vision, control- we found that late age-related macular degeneration ling for age and the presence of central cataract, were was associated with a significant decrease of approxi- examined (Table 7). The risk of impaired vision was mately 8 lines of vision read correctly; in the absence 2.1 times greater for eyes with early age-related macu- of central cataract, late age-related macular degenera- lopathy than for eyes without early age-related maculo- tion was associated with a significant decrease of ap- pathy (95% confidence interval [CI], 0.89 to 4.78). proximately 6 lines of vision read correctly. This de- This relation was not statistically significant. Involve- crease in acuity was significant only when signs of late ment of the central subfield by retinal pigment epithe- age-related maculopathy involved the foveal area (cen- lial degeneration ([odds ratio] 1.27, 95% CI, 0.23 to tral subfield) as well as the inner subfields of the grid 6.95) or increased retinal pigment (OR 2.18, 95% CI, (data not shown). 0.71 to 6.70) was not significantly (P> .05) associated Using logistic regression analyses, the relations of with an increased odds ratio of impaired vision. For

TABLE 3. Frequencies of Central Cataract, Open-Angle Glaucoma, and Impaired Vision by Age in the Beaver Dam Eye Study, 1988-1990 Age (years)

Age-Adjusted 43-54 55-64 65-74 75+ Rate

Number Number Number Number Number at Risk % at Risk % at Risk % at Risk % at Risk %

Central cataract* OD 1441 0.3 1196 4.8 1087 20.1 536 47.6 4260 12.6 OS 1442 0.6 1210 5.1 1100 20.8 518 47.3 4270 12.7 Open angle glaucomaf OD 1460 0.8 1236 2.2 1141 3.9 613 8.5 4450 4.8 OS 1462 0.6 1240 1.8 1157 3.8 611 7.4 4470 2.7 Impaired vision (20/40 OD 1461 0.7 1240 1.3 1152 5.7 629 19.9 4482 4.8 or worse) OS 1462 0.4 1248 0.9 1164 4.5 621 20.1 4495 4.3 * Central cataract status was not available in 222 right eyes and 255 left eyes. | Glaucoma status was missing in 32 right eyes and 25 left eyes.

Downloaded from iovs.arvojournals.org on 09/29/2021 188 Investigative Ophthalmology 8c Visual Science, January 1995, Vol. 36, No. 1 TABLE 4. Relation of Visual Acuity to Age-Related Maculopathy, Cataract, and Glaucoma by Age and Eye in the Beaver Dam Eye Study (1988-1990) Age (years)

Age-adjusted 43-54 55-64 65-74 75+ Rate

n Mean* n Mean* n Mean* n Mean* n Mean* Pt Eyes without late maculopathy, cataract, OD 1430 57.0 1122 55.4 837 53.5 249 50.2 3638 55.2 — glaucoma OS 1430 58.1 1126 56.5 840 54.3 246 49.5 3642 56.1 — Whole study population]; OD 1461 57.0 1240 55.1 1152 52.0 629 44.8 4482 53.5 <:ooi OS 1462 58.1 1248 56.2 1164 53.1 622 44.8 4496 54.4 <.001 Eyes with central cataract OD 5 55.8 56 52.4 213 48.9 234 45.0 508 47.6 <.001 without late maculopathy OS 8 55.0 62 53.7 227 49.8 228 45.3 525 48.4 <.D01 Eyes with glaucoma without central cataract and late OD 12 55.7 21 55.7 23 51.0 14 49.2 70 52.9 <.001 maculopathy OS 9 55.7 19 55.1 26 53.7 17 48.9 71 53.2 <.001 Eyes with late maculopathy, without central cataract OD 1 — 4 49.5 6 0.2 12 23.8 23 23.5 <.001 and glaucoma OS 0 — 5 25.2 3 50.7 11 21.0 19 26.8 <.001 * Number of letters read correctly: 20 = 20/100; 25 = 20/80; 30 = 20/60; 35 = 20/50; 40 = 20/40; 45 = 20/32; 50 = 20/25; 55 = 20/20; and 60 = 20/15. f P value for the difference of age-adjusted mean visual acuity from that in eyes without late age-related maculopathy, cataract, and glaucoma. X Eyes in which other causes of impaired vision were excluded and both visual acuity and age-related maculopathy data were available in at least one eye.

late age-related maculopathy, the odds ratio of visual Eye Study, 57% of those who were legally blind had impairment was 19.8 (95% CI, 5.9 to 66.2) compared late age-related maculopathy. In the Baltimore Eye to eyes without age-related maculopathy. Study,4 late age-related macular degeneration was the cause of blindness in 3(3% of white people who were legally blind, whereas it was not the cause of blindness DISCUSSION in black people who were legally blind. Ferris et al8 These data demonstrate the significant relation of late showed that the neovascular exudative form of macu- age-related maculopathy to severe visual loss and are lar degenerationvwas present in 79% of legally blind consistent with earlier studies.'~5'8i9 In the Beaver Dam eyes in the Framingham Eye Study and 90% of those

TABLE 5. Relation in Right Eyes of Age-Related Maculopathy and Its Specific Lesions by Location to Visual Acuity While Controlling for Central Cataract and Glaucoma in the Beaver Dam Eye Study, 1988-1990 Retinal Pigment Soft Indistinct Epithelial Increased Retinal Early Age-Related Drusen Degeneration Pigment Maculopathy

Coefficient P Coefficient P Coefficient Coefficient P

3990 3967 4047 4205 Any subfield involvement -1.95 <0.001 -1.09 0.02 -0.28 0.46 -0.54 0.08 Age (years) -0.21 <0.001 -0.21 <0.001 -0.21 <0.001 -0.21 <0.001 Central cataract, present -4.39 <0.001 -4.42 <0.001 -4.49 <0.001 -4.46 <0.001 Glaucoma, present -1.12 0.05 -1.32 0.02 -1.21 0.03 -1.07 0.06 n 3840 3916 3968 3988 Any central subfield involvement -2.08 0.04 -1.80 0.001 -0.88 0.05 -0.41 0.34 Age (years) -0.20 <0.001 -0.21 <0.001 -0.21 <0.001 -0.21 <0.001 Central cataract, present -4.20 <0.001 -4.35 <0.001 -4.34 <0.001 -4.20 <0.00l Glaucoma, present -1.20 0.04 -1.32 0.02 -1.21 0.03 -1.06 0.06

1 Denominators vary because of missing data and exclusion of eyes in which cataract surgery had been performed.

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TABLE 6. The Relation of Late Age-related Maculopathy by Location to Visual Acuity in Right Eyes With and Without Central Cateract Controlling for Age and Glaucoma in the Beaver Dam Eye Study, 1988-1990 Eyes Without Central Eyes With Central Cataract Cataract

Coefficient P

425 3434 Any subfield involvement -38.8 <0.001 -27.5 <0.001 Age (years) -0.38 <0.001 -0.20 <0.001 Glaucoma, present -2.25 0.26 -0.64 0.37 n 423 3429 Any central subfield involvement -35.4 <0.001 -33.4 <0.001 Age (years) -0.38 <0.001 -0.20 <0.001 Glaucoma, present -1.91 0.33 -1.24 0.08

in the case-control study of Hyman et al.26 These find- atrophic stage of age-related maculopathy is less likely ings are not unexpected given the high risk that cho- to be associated with decreased visual acuity. However, roidal neovascularization will develop in the unin- our data demonstrate that although pure geographic volved eye of people with unilateral involvement with atrophy is less common15 than exudative macular de- exudative macular degeneration and the increased generation, it seems to be associated with almost the risk of loss of vision in these eyes despite timely laser same frequency of blindness as the exudative form of 6 7 photocoagulation. ' These findings suggest the need the disease when it involves the foveal area. for further study of the early pathogenesis of age-re- Data from the Beaver Dam Eye Study show that lated maculopathy and for development of preventive although lesions associated with early age-related ma- measures before its late stages. culopathy were associated with a statistically significant In Beaver Dam, the frequency of visual acuity of decrease in visual acuity, the decrease was not clini- 20/200 or worse was not significantly higher in eyes cally meaningful. These findings are consistent with with exudative macular degeneration (48.0%) than in earlier observations8'9 and suggest that visual acuity eyes with pure geographic atrophy (41.9%). These criteria not be applied to define the presence of early data show that both late stages of age-related maculo- age-related maculopathy. The prognostic implications pathy, exudative macular degeneration and pure geo- of specific age-related maculopathy lesions and their graphic atrophy, have an important impact on vision. locations for the incidence and progression to the late Data from most earlier population-based studies have stages of age-related maculopathy with loss of vision lumped pure geographic atrophy with early distur- remain to be studied. bances of the retinal pigment epithelium and/or dru- Care must be taken in interpreting our data re- sen.2'89 This has resulted in the observation that the garding the relation between age-related maculopathy and visual acuity. First, attempts were made to remove from the analyses all eyes widi decreased visual acuity TABLE 7. Relationship of Early and Late Age- thought to be caused by ocular conditions other than Related Maculopathy by Location to Visual age-related maculopathy, cataract, and glaucoma. Fail- Impairment, Controlling for Age and ure to exclude some eyes with non-age-related ocular Central Cataract in the Beaver Dam Eye conditions associated widi loss of vision might obscure Study, 1988-1990 some of the relations observed! Second, age-related 27 Liang-Zeger Models maculopathy and cataract are associated. The magnitude of the effect of each cannot be completely deter- OR 95%. a mined from these analyses. However, even when age or cataract was not controlled for, the magnitude of Early age-related maculopathy the effect on visual acuity of early age-related maculo- Central circle subfield involvement 1.72 0.52, 5.62 Any subfield involvement 2.06 0.89, 4.78 pathy lesions was not clinically significant (Klein R, Late age-related maculopathy unpublished data, 1994). Central circle subfield involvement 27.09 10.36, 70.81 The rate of legal blindness that we report derives Any subfield involvement 19.77 5.91, 66.19 from the white population of Beaver Dam, Wisconsin. OR = Odds ratio; CI = confidence interval. We may anticipate that this rate, due largely to age-

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related macular degeneration, would differ in popula- Acknowledgments tions with heterogenous ethnic mixtures. In such pop- The authors thank Drs. Karen J. Cruickshanks, Matthew D. ulations, cataract and glaucoma, rather than age-re- Davis, and Polly Newcomb for collaboration, consultation, lated macular degeneration, may be more frequent and criticism. causes of legal blindness. Thus, extrapolating our findings must be done cautiously. References In the Beaver Dam Eye Study, central cataract was 1. National Society to Prevent Blindness. Vision Problems associated with significant but small decreases in visual in the United Stales. New York: National Society to Pre- acuity. It is possible that the exclusion of eyes ungradable vent Blindness; 1980. for age-related macular degeneration because of central 2. Leibowitz HM, Krueger DE, Maunder LR, et al. The cataract might have led to a small underestimation of Framingham Eye Study monograph. Surv Ophthalmol. the relationship between cataract and decrease in visual 1980; 24(suppl):335— 610. acuity. It also is possible that cataract surgery was per- 3. Ganley JP, RobertsJ. Eye conditions and related need formed in eyes widi severe central opacities and signifi- for medical care among persons 1 -74 years of age: cant decreases in visual acuity. This could explain why United States, 1971-72. Vital and Health Statistics. Se- only 1 % of eyes with central cataract and without late ries 11. 1983. age-related macular degeneration had visual acuities of 4. Sommer A, Tielsch JM, Katz J, et al. Racial differences 20/200 or worse. In contrast, in Mud Creek, Kentucky, in the cause-specific prevalence of blindness in East Baltimore. NEnglJMed. 1991;325:1412-1417. cataract has been shown to be an important cause of 5 5. Dana MR, Tielsch JM, Enger C, Joyce E, Santoli JM, significant loss of vision. In that study, decreased vision Taylor HR. Visual impairment in a rural Appalachian from cataract was probably related to a greater frequency community. JAMA. 1964; 264:2400-2405. of more severe cataracts than was true in die Beaver 6. Macular Photocoagulation Study Group. Argon laser Dam Eye Study. This may be related to lower relative photocoagulation for senile macular degeneration: rates of cataract surgery due, in part, to the absence of Results of a randomized trial. Arch Ophthalmol. ophthalmologic care, less education, and apprehension 1982;100:912-918. about surgery. Age-related cataract also was shown to be 7. Macular Photocoagulation Study Group. Five-year fol- an important cause of blindness in black people (27%) low-up of fellow eyes of patients with age-related macu- and to a lesser extent in white people (13%) in the lar degeneration and unilateral extrafoveal choroidal Baltimore Eye Survey.4 In developing countries, cataract neovascularization. Arch Ophthalmol. 1993; 111:1189- 1199. is a major cause of blindness.28 8. Ferris FL III, Fine SL, Hyman L. Age-related macular While controlling for age-related maculopathy degeneration and blindness due to neovascular macu- and cataract, we found that glaucoma was not associ- lopathy. Arch Ophthalmol. 1984; 102:1640-1642. ated with a clinically meaningful decrease in visual 9. Vinding T. Visual impairment of age-related macular acuity. These findings are consistent with the effect degeneration: An epidemiological study of 1000 aged of glaucoma on peripheral rather than central visual individuals. Ada Ophthalmol. 1990; 68:162-167. acuity early in the course of the disease. 10. Linton KLP, Klein BEK, Klein R. The validity of self- Two conditions that can be prevented, ocular reported and surrogate-reported ocular disease in the trauma and amblyopia, accounted for 34% of monoc- Beaver Dam Eye Study. Am J Epidemiol. 1991; 134: ular severe vision impairment. This was lower than the 1438-1446. 59% reported in the Mud Creek study, which used 11. Klein R, Klein BEK, Linton KLP, DeMets DL. The Beaver Dam Eye Study: Visual acuity. Ophthalmology. 20/400 or poorer visual acuity to define monocular 1991;98:1310-1315. severe vision impairment. These data suggest the value 12. Early Treatment Diabetic Retinopathy Study of screening for children for conditions that result in (ETDRS). Manual of Operations. Baltimore: ETDRS Co- amblyopia and education programs regarding strate- ordinating Center, University of Maryland, Depart- gies (such as the use of safety glasses and die safe ment of Epidemiology and Preventive Medicine, 1980, handling,of chemicals) at work and home to prevent ch. 12. Available from: National Technical Informa- traumatic ocular injury. tion Service, 5285 Port Royal Road, Springfield, VA In summary, these data demonstrate that late, not 22161 (accession no. PB85223006). early, stages of age-related maculopathy are associated 13. Klein R, Davis MD, Magli YL, Klein BEK. Wisconsin Age-Related Maculopathy Grading System. Madison: NTIS with significant decreases in Snellen visual acuity. Accession no. PB91 184267/AS. Available from: Na- Other visual function tests may provide more sensitive tional Technical Information Service, 5285 Port Royal measures of detecting functional changes associated Road, Springfield, VA 22161. with early age-related maculopathy. 14. Klein R, Davis MD, Magli YL, Segal P, Klein BEK, Key Words Hubbard L. The Wisconsin Age-related Maculopathy age-related maculopathy, cataract, glaucoma, visual acuity, Grading System. Ophthalmology. 1991;98:1128- prevalence 1134.

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