Bressler SB, Muñoz B, Solomon SD, West SK, the Salisbury Eye Evaluation (SEE) Study Team. Racial Differences in the Prevalence of Age-Related Macular DegenerationThe Salisbury Eye Evaluation (SEE) Project. Arch Ophthalmol. 2008;126(2):241–245. doi:10.1001/archophthalmol.2007.53
To determine differences in the prevalence of age-related macular degeneration (AMD) and its fundus manifestations in a population-based sample of older black and white Americans.
Cross-sectional population-based study of 2520 participants of whom 1854 are white and 666 are black. Mean age was 73.5 years. Stereoscopic color fundus photographs were graded for presence, severity, and location of drusen, retinal pigment epithelium abnormalities, and choroidal neovascularization or disciform scarring.
Drusen at least 64 μm in size were identified in 56% of black and white individuals within 3000 μm of the foveal center, but drusen larger than 125 μm were more common among white participants (16% white vs 11% black individuals). Drusen at least 250 μm in size, confluent drusen, or a larger area (> 10%) occupied by drusen were each more common among white participants. White individuals were 3 times more likely to have focal hyperpigmentation than black individuals. Racial differences were most pronounced for features within the central 1500-μm macular zone. Neovascular AMD was present in 1.7% of white participants and 1.1% of black participants (age-adjusted, P = .38), whereas geographic atrophy was more common in white than black individuals (1.8% vs 0.3%; age-adjusted, P = .02).
White persons are generally more likely than black persons to have medium or large drusen, focal pigment abnormalities, and advanced AMD. Racial differences were prominent for nonneovascular AMD features only when present in the central zone. These data suggest that black individuals may have a mechanism for protection in the central zone against these critical fundus features, which themselves convey high risk of progression to advanced AMD.
The prevalence of drusen larger than 125 μm and advanced age-related macular degeneration (AMD) has been summarized using population-based data from several studies performed in the United States and abroad by the Eye Diseases Prevalence group.1While the goal of their study was to provide estimates of AMD in the United States, it also pointed out potential differences between black and white individuals in rates of advanced AMD and one particular early AMD characteristic, large drusen. Data on other characteristics of early AMD are not available in comparable populations of the 2 racial groups. Although some fundus features are available from the Baltimore Eye Survey's black and white populations, 19% of photographs, particularly those from individuals aged 65 years or older, were missing or ungradeable.2The Barbados Eye Study only reported characteristics of AMD in its black population.3A better understanding of how the fundus features of AMD differ in the 2 racial populations may provide insight into the etiology of AMD.
The Salisbury Eye Evaluation (SEE) Project is based on a population composed of older individuals (aged ≥ 65 years) from a heterogeneous racial community.4The purpose of this article is to describe the differences in prevalence of early fundus lesions associated with AMD by racial group in the SEE population. We expand on data already reported by the Eye Disease Prevalence research group by using a variety of other fundus characteristics.
Details on the identification, recruitment, and enrollment of the population appear in previous reports.4,5Briefly, a random sample of white individuals and a complete sample of black individuals were drawn from the Health Care Financing Administration Medicare database for the greater Salisbury area. Eligibility criteria for participants were as follows: (1) aged 65 to 84 years as of July 1, 1993, (2) residence in the Salisbury, Maryland, metropolitan area, (3) noninstitutionalized and able to communicate with interviewer, and (4) a score of at least 17 on the Mini-Mental State Examination. The final eligible sample consisted of 3906 persons, of whom 65% (2520) participated.
All procedures were approved by the institutional review board of the Johns Hopkins University School of Medicine and all participants completed an informed consent document prior to study participation. A comparison of participants and nonparticipants demonstrated that those who refused were older and more likely to be women, but comparable recruitment rates were achieved for black and white individuals.5
Every participant had an ocular examination in the SEE clinic. Following pupillary dilation, each eye underwent film-based stereoscopic 30° color fundus photography using a Topcon TRC-FET fundus camera (Topcon, Tokyo, Japan). Views were centered on the disc and the macula. The slide transparencies were read in the Wilmer Reading Center, Johns Hopkins University. Photographs of eye pairs were separated into different plastic sheets and readers were masked to all demographic data of the individual participants and results of companion eyes. Two experienced fundus photograph readers independently performed a detailed grading of the photographs. A grid consisting of 3 circles concentric with the macular center was superimposed on one photograph of the macular stereo pair.6The radius of the innermost circle corresponded to 500 μm in the fundus. This small circle was used to center the position of the grid with reference to the foveal avascular zone center on the fundus image. The radii of the middle and outer circles corresponded to 1500 and 3000 μm, respectively. The middle circle (inclusive of the area contained within the innermost circle) encapsulates the central macular zone, whereas the space between the middle and outer circle defines the pericentral macular zone. Macular lesions associated with AMD were graded in each of these 2 macular zones using the Wilmer Reading Center system.7An additional clear plastic template illustrating circles with diameters of 64, 125, and 250 μm was used to estimate drusen size.8Discrepancies between the 2 photograph readers were openly adjudicated, and unresolved differences were decided by the ophthalmologist (S.B.B.). The ophthalmologist also reviewed a random 10% sample of all gradings in addition to all cases of neovascular AMD, geographic atrophy, and all diseases classified as other (eg, diabetic retinopathy).
A set of 48 fundus photographs were recycled through the grading process so that possible drift in the photograph grading during the 2-year enrollment period could be detected. Comparing the first and last gradings on this set of photographs resulted in weighted κ values of 0.72 or higher for each fundus characteristic graded.
Of the 2520 participants, only 112 (4.5%) did not have photographs taken. Eyes were not photographed mainly because of camera failure, inability to dilate the pupil, refusal of the participant, significant corneal opacity, or inability to maintain fixation. Among the 2408 participants with fundus photographs of at least 1 eye, 2403 (99.8%) had gradable photographs in at least 1 eye. Sixteen individuals with gradable photographs were excluded from the AMD analysis owing to the presence of other widespread posterior pole disease that interfered with grading AMD, such as pattern dystrophy or bilateral venous occlusive disease-producing maculopathy. For the purposes of this report, only the 2387 (95%) participants with at least 1 eye with gradable fundus photographs for advanced AMD without an excluded lesion are included in the analyses.
Advanced AMD is defined as the definite presence of signs of neovascular AMD (choroidal neovascularization, disciform scarring, or focal confluent areas of atrophy judged to be due to laser photocoagulation of choroidal neovascularization) in either macular zone or geographic atrophy in the central zone. We categorized an individual by findings in the more severely involved eye or, if only 1 eye was graded, in the single eye.
Current age was defined as the age at the time of the examination. Identification of each participant's race originated from self-reports.
Prevalence of early AMD features and the advanced signs of neovascular AMD and geographic atrophy, stratified by age and race, are presented. The χ2test and Fisher exact test were used to compare proportions between the races, each adjusted for age and gender. The McNemar test for correlated proportions was used to examine differences in drusen type and size between the central and the pericentral zones. Logistic regression models were used to examine the relationship between fundus characteristics and race, adjusting for age and gender. When analysis was performed at eye level, standard errors were adjusted to account for the correlation between eyes of the same participant.
The mean age of participants for these analyses was 73.5 years (Table 1). The white and black populations were balanced by mean age (73.3 vs 73.6 years, respectively).
Drusen of any size were common in both racial groups (Table 2), present in 93% of the population. Drusen of any size were more frequently identified in the pericentral than in the central macular zone (P < .001, McNemar test for discordant pairs), but there was no difference by race in drusen (of any size) in the pericentral zone. Drusen 64 μm or larger (medium or large size) were identified in 56% of white and 54% of black participants; however, white participants were more likely to have this characteristic in the central macular zone than black participants (36% vs 28%, P = .001). Only 15% had large drusen (> 125 μm). White participants were more likely to have large drusen, particularly in the central zone (11% vs 5%, P = .001), compared with black participants. Drusen 250 μm or larger were uncommon, present in 41 participants, or 1.7% of the population. However, drusen of this size were more common in white than in black participants (2.1% vs 0.65%; P = .02). White participants were more likely to have confluent macular drusen than black participants (24% vs 19%; P = .01) owing to a difference in the prevalence of this characteristic within the central macular zone (16% vs 8%, respectively; P < .001) (Table 2). Black and white participants had the same prevalence of confluent drusen in the pericentral zone.
In each macular zone, the area covered by medium or large drusen was assessed. It was more common for these drusen to cover more than 10% of the area of the central zone than the pericentral zone (1.2%
vs 0.4%; P < .001). In part, this difference may be because of the relatively smaller macular area contained within the central zone compared with the pericentral zone. White participants were more likely to have more than 10% of the central zone occupied by medium or large drusen than black participants (1.6% vs 0.2%; P < .001) (Table 3). There was no difference by race in the pericentral zone for the area covered by drusen.
Focal hyperpigmentation was 4 times more common in the central macular zone compared with the pericentral zone (5.9% vs 1.4%; P < .001). White participants were approximately 3 times more likely to have focal hyperpigmentation compared with black participants, but only in the central zone (age-adjusted P < .001) (Table 4). Nongeographic atrophy was uncommon in this population, occurring in 1.4% overall; racial differences were not observed.
Drusen size was strongly related to the presence of pigmentary abnormalities in both races (Table 5). Eyes with medium or large drusen were more likely to have pigmentary abnormalities compared with eyes that had no or small drusen. In a multivariate model of pigmentary abnormalities using all eyes (in which drusen size, race, and age were included), white race (P = .04) and drusen size (64-125 μm, P = .004; > 125 μm, P < .001) were independent factors. Such data suggest that, though large drusen were more common, this alone cannot explain the higher rates of focal hyperpigmentation in white individuals.
There were 37 (1.6%) participants in this population who had evidence of choroidal neovascularization. The observed rate of neovascular AMD was slightly higher in white participants (1.7%) than in black participants (1.1%) but not significantly (age-adjusted P = .38). Only 1 of 7 black individuals had bilateral evidence of neovascular AMD, whereas 15 of 30 white participants had both eyes involved. Comparison of the fellow eye's AMD characteristics among the 6 black and 15 white individuals with unilateral neovascular maculopathy revealed similar distributions of medium and large drusen.
Thirty-four (1.4%) individuals had geographic atrophy, including 24 participants (1.0%) in whom it occupied the foveal center. White participants had a greater prevalence of geographic atrophy than black participants (1.8% vs 0.3%; age- and gender-adjusted, P = .02). Fundus photographs of both eyes were available in 29 of the 34 (85%) individuals with geographic atrophy of whom 15 (52%) had bilateral geographic atrophy. Three individuals had geographic atrophy in one eye and neovascular AMD in the contralateral eye.
These data on fundus characteristics have suggested several key differences between black and white individuals. First, while there was no racial difference in the prevalence of any size drusen, larger drusen (especially those > 125 μm) were more common in white individuals. Moreover, other signs, such as confluent drusen, greater drusen area, and focal hyperpigmentation, were also more common in white participants. Second, this racial difference was only apparent when these features were required to exist within 1500 μm of the foveal center. Such data suggest that small drusen are ubiquitous, while prevalence of medium and large drusen may be different. The data also suggest that black individuals have similar rates of fundus features in the pericentral zone but do not seem to manifest AMD features, particularly those that impart risk for disease progression, in the central zone. Perhaps both races are equally likely to develop at least medium drusen in the posterior pole, but drusen in white individuals are more likely to progress to large drusen in the central macular zone. This prevalence analysis cannot address progression.
Focal hyperpigmentation was largely identified in the central rather than the pericentral zone in both races. However, the greater prevalence seen in white individuals might confirm again that white individuals develop or progress to AMD features in the central macular zone at a different rate than black individuals, placing them at greater risk of ultimately developing the advanced forms of AMD. Hypopigmentation was an infrequent feature of AMD in this cohort and our data did not suggest any distinguishing aspects of this AMD characteristic between the races.
As in other population-based AMD studies, the absolute number of advanced AMD cases (either geographic atrophy or neovascular AMD) was relatively small; therefore prevalence estimates are not precise and it is difficult to determine if the prevalence of either or both of the features of advanced disease is different between white and black individuals. Our sample size did not have sufficient power to detect a significant difference between prevalence rates of 1.7% and 1.1% for neovascular AMD among white and black participants, respectively. Nevertheless, white individuals appear to be more likely than black individuals to have bilateral evidence of advanced AMD (in particular neovascular AMD). This finding is consistent with that of the black population of the Barbados Eye Study, in which all 17 cases of neovascular AMD were unilateral.3
Comparison with other AMD studies involving both black and white participants is difficult owing to differing definitions of AMD and study methods. The National Health and Nutrition Examination Survey III (NHANES III) categorized AMD status based on 1 nonstereoscopic 45° fundus image of 1 eye using only a nonmydriatic camera. Therefore, it is unlikely that much of the pericentral zone could be graded in NHANES III. Nevertheless, our findings of excess risk in white participants is consistent with NHANES III findings that black participants were less likely to have early AMD (odds ratio, 0.49; 95% confidence interval, 0.37-0.65).9Features of advanced AMD were so infrequent in each NHANES III racial group that statistical comparison between them was not possible.
Reasonable similarity in the methods used to categorize and define early AMD in the Baltimore Eye Survey2and the SEE Study potentially allow more direct descriptive comparisons to be made, though the Baltimore Eye Survey had many more missing photographs. We compare the subgroup of older (≥ 60 years) Baltimore Eye Survey participants with SEE participants aged 65 years and older. In the Baltimore Eye Survey and the SEE Study, the prevalence rates of drusen at least 64 μm within the central 1500-μm macular zone appear similar. However, the age-adjusted prevalence rates between the 2 racial groups do not differ statistically in the Baltimore Eye Survey; whereas, in the SEE Study, the difference does achieve statistical significance. In each study, the prevalence of large drusen (> 125 μm) within the central zone was significantly more common in older white participants than black participants. Focal hyperpigmentation was more frequently recognized in the SEE Study than in the Baltimore Eye Survey. This AMD feature may be subtle, its recognition dependent on image quality. It is possible that the overall photograph quality was better in the SEE population than in the Baltimore Eye Survey, as there were significant differences in the photography protocol between the 2 studies. In each study, focal hyperpigmentation was found to be roughly 3 times more prevalent in white than black participants. Each study demonstrated higher rates of geographic atrophy and neovascular AMD among white than black participants, though the difference between the races was found to significantly differ only for geographic atrophy in the SEE Study. There was a lower prevalence of neovascular AMD in black participants in the Baltimore Eye Survey than in the SEE Study; however, this may be because of a greater proportion of black participants and persons with poorer vision not having photographs available for review in the Baltimore Eye Survey. While both studies reported similar prevalences, our finding of the importance of the central vs pericentral area for explaining racial differences is unique.
Comparison of our findings with those of the Barbados Eye Study is more problematic. Barbados was specifically selected because of its relatively high prevalence of glaucoma, but the population may not be representative of the AMD prevalence in an African American community. Also, differences in age group and grading protocol preclude a detailed comparison between the black participants in the SEE Study and the Barbados Eye Study for many aspects of early AMD.3However, both studies found drusen larger than 250 μm to be uncommon (1.1% prevalence in Barbados and 0.65% in the SEE Study). A higher proportion of the Barbados Eye Study group manifested retinal pigment epithelium abnormalities than was apparent in black participants in the SEE Study, but we have no comparable white Barbadian participants with whom to compare the white SEE population.
There are some limitations to these findings. First, the response rate to the SEE Study was 65%, which is comparable with other epidemiologic studies in this age range.10There was no difference between the individuals who elected not to participate and those who did participate in self-reported vision problems or race, suggesting that, on these factors, the sample in the study likely was representative. Our estimates based on the recruited sample may be representative of the AMD prevalence in these racial groups at least for severe AMD. Clinical examination by SEE ophthalmologists documented the absence of severe AMD in those few individuals who did not have photographs. A strength of our investigation is the detailed grading, using a reproducible, standardized system in a large population of older black and white individuals.
Larger drusen size, a greater area occupied by drusen, and presence of focal hyperpigmentation increase the risk that an eye will progress to the advanced stages of AMD.7,11- 14The SEE data suggest that these drusen and retinal pigment epithelium characteristics are more common in the central zone in white than in black individuals. Such data strongly suggest that white individuals are more likely to progress to advanced vision-disabling AMD (certainly to geographic atrophy) than black individuals. The absence of racial differences in these early lesions in the pericentral area suggest that further research is warranted on factors that protect black individuals from lesions in the central zone or promote central lesions in white individuals.
Correspondence:Susan B. Bressler, MD, Maumenee Bldg, Room 229, The Wilmer Eye Institute, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287-9228 (email@example.com).
Submitted for Publication:September 8, 2005; final revision received January 31, 2007; accepted February 10, 2007.
Financial Disclosure:None reported.
Funding/Support:This study was supported by Research to Prevent Blindness through an Olga Keith Weiss Scholars Award (Dr Bressler) and a senior scientist award (Dr West); an unrestricted grant from Alcon Research Institute (Dr West); and grant AG16294 from the National Institute on Aging.