The Relationship of Atherosclerosis to the 10-Year Cumulative Incidence of Age-related Macular Degeneration: The Beaver Dam Studies

Objective: To describe the relationships of intima-media thickness (IMT), plaque in the carotid artery, angina, myocardial infarction (MI), and stroke to the 10-year cumulative incidence of early and late age-related macular degeneration (AMD) and progression of AMD. Design: Cohort study. Participants: A total of 1700 persons aged 53 to 96 years who participated in both the Epidemiology of Hearing Loss Study and the Beaver Dam Eye Study in 1998-2000, with photographs gradable for AMD at 5-year (2003-2005) and 10-year (2008-2010) follow-up examinations. Methods: The IMT and presence of plaque were assessed using B-mode ultrasonography of the carotid artery. Presence of angina, MI, and stroke were defined on the basis of a self-reported history of physician diagnosis. The presence and severity of AMD were determined by systematic grading of stereoscopic color fundus photographs. Main Outcome Measures: Age-related macular degeneration. Results: The 10-year cumulative incidence of early AMD was 15.7%, and the 10-year cumulative incidence of late AMD was 4.0%. After adjusting for age, sex, body mass index, smoking status, age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) genotypes, and other factors, mean IMT was associated with the 10-year incidence of early AMD (odds ratio [OR] per 0.1 mm IMT, 1.11; 95% confidence interval [CI], 1.00-1.21; P = 0.03) and late AMD (OR per 0.1 mm IMT, 1.27; CI, 1.10-1.47; P = 0.001). Mean IMT was associated with the 10-year incidence of pure geographic atrophy (OR per 0.1 mm IMT, 1.31; CI, 1.05-1.64; P = 0.02) but not exudative AMD (OR per 0.1 mm IMT, 1.14; CI, 0.97-1.34; P = 0.11). Similar associations were found for maximum IMT. The number of sites with plaque was related to the incidence of late AMD (OR per 0.1 mm IMT, 2.79 for 4-6 sites vs. none; CI, 1.06-7.37; P = 0.04) but not to early AMD. A history of angina, MI, or stroke was not related to any incident AMD outcome. Conclusions: In these population-based data, carotid artery IMT and carotid plaques had a weak relationship to the incidence of late AMD that was independent of systemic and genetic risk factors. Angina, MI, and stroke were not related to AMD. It is unclear whether the carotid IMT is a risk indicator of processes affecting Bruch's membrane and the retinal pigment epithelium, or a measure of atherosclerosis affecting susceptibility to AMD.