Extremely discordant sib-pair study design to determine risk factors for neovascular age-related macular degeneration

Objective: To search for factors that contribute to the development of neovascular age-related macular degeneration (AMD). Methods: In a matched-pair case-control study, we studied sib pairs in which the index sibling had neovascular AMD in at least 1 eye and the unaffected sibling had normal maculae (or at most only a few small drusen) and was past the age at which the index case was diagnosed. Factors studied included sex, iris color, education, alcohol consumption, body mass index, vitamin use, smoking history, hypercholesterolemia, aspirin use, hypertension, other cardiovascular disease, any autoimmune disease, and non-insulin-dependent diabetes mellitus. Conditional logistic regression was performed to identify predictors of neovascular AMD. Results: On the basis of 73 sib pairs, multivariate regression analysis revealed statistically significant 2% increase in risk of neovascular AMD with each pack-year of smoking (odds ratio, 1.02; 95% confidence interval, 1.01-1.04; P=.007). Suggestive but nonsignificant associations were also observed for mean lifetime alcohol consumption, adult lifetime body mass index, and hypertension in multivariate regression analyses. Conclusion: Using extremely discordant sib pairs to study risk factors for AMD, a novel approach in epidemiological design, we found evidence that smoking is a risk factor for neovascular AMD.