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Margaret M. DeAngelis, PhD; Anne Marie Lane, MPH; Chirag P. Shah, BA; Jurg Ott, PhD; Thaddeus P. Dryja, MD; Joan W. Miller, MD

Arch Ophthalmol. 2004;122:575-580.

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 a 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.

From the Harvard Medical School, Ocular Molecular Genetics Institute, Boston, Mass (Drs DeAngelis and Dryja and Mr Shah); the Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Mass (Dr Miller and Ms Lane); and the Laboratory of Statistical Genetics, Rockefeller University, New York, NY (Dr Ott). The authors have no relevant financial interest in this article.

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Cigarette Smoking, CFH, APOE, ELOVL4, and Risk of Neovascular Age-Related Macular Degeneration
DeAngelis et al.
Arch Ophthalmol 2007;125:49-54.
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