Epidemiological Study of Extremely Discordant Sibpairs with Neovascular Age-related Macular Degeneration

Abstract

Abstract: : Purpose: To analyze extremely discordant sibpairs to search for epidemiological factors that may contribute to the development of the neovascular form of age-related macular degeneration (AMD). Methods: We ascertain sibships in which one member has the neovascular form of AMD in at least one eye and a sibling has normal maculae (or at most only a few hard drusen) and is past the age at which the index patient was diagnosed with neovascular AMD. Disease status is confirmed by fundus photography of every participant by at least two of the investigators. Epidemiological data are collected through interviews with participants. Risk factors under investigation include sex, body mass index, iris color, smoking history, vitamin use, aspirin use, alcohol consumption, hypertension, hypercholesterolemia, and history of autoimmune disease (rheumatoid arthritis, thyroid disease, eczema/psoriasis). The reference age for both the affected and unaffected siblings in a pair was the age at diagnosis of AMD of the affected member. Conditional logistic regression (StataCorp software) was performed to identify risk factors for AMD. Blood samples were also collected and analyzed with microsatellite markers to evaluate whether the siblings are truly full sibs. Results: So far, we have collected 56 extremely discordant sibpairs, and for 48 of these we have obtained complete epidemiological data. To date, analysis of 43 of these pairs with 3 unlinked microsatellite markers, each having a heterozygosity of 94%, indicates that there is little if any contamination of the sibpairs with pairs that are unknowingly half sibs or unrelated individuals. The mean age of our index cases is 69.9 years and the mean age for our controls is 71.8 years. Preliminary multivariate analysis of these 48 pairs revealed that presence of hypertension (measured as an ever/never phenomena, with taking medication as the threshold) was associated with an almost 4-fold increase in risk of AMD, but this was of borderline statistical significance (O.R.:3.8, 95% C.I.: 1.02-14.2, p = .046). Pack years of smoking (measured as a continuous variable) and alcohol consumption (>9.5 glasses of wine/wk, or > 8.6 beers/wk or > 7 shots of liquor/wk), although statistically significant factors in univariate analysis, were not associated with AMD in the multivariate age-adjusted model. Conclusions: Hypertension may be a risk factor for AMD. Other associations may be demonstrated in future analyses of a larger cohort; therefore recruitment is ongoing.

Keywords: age-related macular degeneration • choroid: neovascularization • clinical (human) or epidemiologic studies: ris