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To determine whether comorbidities are more prevalent among individuals with neovascular age-related macular degeneration (NV-AMD) than individuals without AMD.This 2-year, retrospective, case-control study included Medicare beneficiaries (standard 5% analytic sample) continuously enrolled from January 1, 2003, to December 31, 2004, excluding those in managed care plans. The NV-AMD cohort included individuals ≥65 at baseline with a diagnosis of NV-AMD in 2003 and 2004. Age-, gender-, and race-matched controls were selected from those with no AMD. Comparisons were made for 13 general categories of non-eye-related diseases and 18 specific comorbidities based on ICD-9-CM codes. Two-year prevalence was calculated by condition and cohort; odds ratios and 99% confidence intervals were calculated (logistic regression).Analyses included 26,057 subjects and an equal number of controls. Nearly all subjects had at least one comorbidity, and >80% in each cohort had five or more comorbidities across general disease categories. Prevalence of 7/13 general disease categories exceeded 50% in both cohorts; rates for 12/13 categories were significantly higher in those with NV-AMD (P < 0.001). Prevalence of 13/14 non-eye-related and 4/4 eye-related specific comorbidities was significantly higher among NV-AMD subjects (P < 0.05). A more than 20% greater odds for NV-AMD subjects was noted for hypertension, hypercholesterolemia, emphysema, chronic obstructive pulmonary disease, atherosclerosis, arthritis, coronary heart disease, cataract, glaucoma, and myopia.Patients with NV-AMD are significantly more likely to have comorbidities, many of which could be life-threatening.