Purpose: To describe the association of demographic, behavioral, medical, and nonretinal ocular factors with the incidence of neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA) in the Age-Related Eye Disease Study (AREDS), a randomized trial of antioxidants and zinc supplementat ion prophylaxis for development of advanced AMD. Design: Clinic-based prospecti ve cohort study. Participants: Of individuals with early or intermediate AMD at baseline with a median follow-up of 6.3 years, 788 were at risk of developing a dvanced AMD in one eye (the fellow eye had advanced AMD), and 2506 were at risk in both eyes. Methods: The incidence of neovascular AMD and CGA was assessed fro m stereoscopic color fundus photographs taken at baseline and at annual visits b eginning at year 2. Main Outcome Measures: Neovascular AMD was defined as photoc oagulation for choroidal neovascularization, or photographic documentation at th e reading center of any of the following: nondrusenoid retinal pigment epithelia l detachment, serous or hemorrhagic retinal detachment, hemorrhage under the ret ina or the retinal pigment epithelium, and subretinal fibrosis. Central geograph ic atrophy was defined as geographic atrophy involving the center of the macula. Results: In multivariable models, in persons at risk of advanced AMD in both ey es, while controlling for age, gender, and AREDS treatment group, the following variables were statistically significantly associated with the incidence of neov ascularAMD: race (odds ratio [OR], white vs. black, 6.77; 95%confidence inter va l [CI], 1.24-36.9) and larger amount smoked (OR, >10 vs. ≤10 pack-years [a pa ck-year is an average of 1 pack of cigarette smoked per day for a year], 1.55; 95%CI, 1.15-2.09). The following were statistically significantly associated w ith the incidence of CGA: less education (OR, high school graduate or less vs. c ollege graduate, 1.75; 95%CI, 1.10-2.78), greater body mass index (BMI) (OR, o bese vs. nonobese, 1.93; 95%CI, 1.25-2.65), larger amount smoked (OR, >10 pack -years vs. ≤10 pack-years, 1.82; 95%CI, 1.25-2.65), and antacid use (OR, 0. 29; 95%CI, 0.09-0.91). In persons at risk of developing advanced AMD in one ey e, the incidence of neovascular AMD was associated with diabetes (OR, 1.88; 95% CI, 1.07-3.31), and the incidence of CGA was associated with use of antiinflamm atorymedications (OR, 0.22; 95%CI, 0.08-0.59). Conclusions: Results suggest th at, among persons with early or intermediate AMD, smoking and BMI are modifiable factors associated with progression to advanced AMD, and suggest other associat ions (e.g., use of antacids and antiinflammatory medications) that warrant furth er study. Purpose: To describe the association of demographic, behavioral, medical, and nonretinal ocular factors with the incidence of neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA) in the Age-Related Eye Disease Study (AREDS), a randomized trial of antioxidants and zinc supplementat ion prophylaxis for development of advanced AMD. Design: Clinic-based prospecti ve cohort study. Participants: Of individuals with early or intermediate AMD at baseline with a median follow-up of 6.3 years, 788 were at risk of developing a dvanced AMD in one eye (the fellow eye had advanced AMD), and 2506 were at risk in both eyes. Methods: The incidence of neovascular AMD and CGA was assessed fro stereoscopic color fundus photographs taken at baseline and at annual visits b eginning at year 2. Main Outcome Measures: Neovascular AMD was defined as photoc oagulation for choroidal neovascularization, or photographic documentation at th e reading center of any of the followin g: nondrusenoid retinal pigment epithelia l detachment, serous or hemorrhagic retinal detachment, hemorrhage under the ret ina or the retinal pigment epithelium, and subretinal fibrosis. Central geograph ic atrophy was defined as geographic atrophy involving the center of the macula. Results: In multivariable models, in persons at risk of advanced AMD in both ey es, while controlling for age, gender, and AREDS treatment group, the following variables were been significantly associated with the incidence of neov ascularAMD: race (odds ratio [OR], white vs black, 6.77; 95% confidence inter va l [CI], 1.24-36.9) and larger amount smoked (OR,> 10 vs. ≤10 pack- years [a pa ck-year is an average of 1 pack of cigarette smoked per day for a year], 1.55; 95% CI, 1.15-2.09). The following were was significant for associated with the incidence of CGA: less education (OR, high school graduate or less vs. c ollege graduate, 1.75; 95 % CI, 1.10-2.78), greater body mass index (BMI) (O R,obese vs. nonobese, 1.93; 95% CI, 1.25-2.65), larger amount smoked (OR,> 10 pack-years vs. ≤10 pack- years, 1.82; 95% CI, 1.25-2.65), and antacid use (OR, 0.29; 95% CI, 0.09-0.91). In persons at risk of developing advanced AMD in one ey e, the incidence of neovascular AMD was associated with diabetes (OR, 1.88; 95% CI, 1.07-3.31 ), and the incidence of CGA was associated with use of antiinflammy atications medications (OR, 0.22; 95% CI, 0.08-0.59). Conclusions: Results suggest th at, among persons with early or intermediate AMD, smoking and BMI are modifiable factors associated with progression to advanced AMD, and suggest other associat ions (eg, use of antacids and antiinflammatory medications) that warrant furth er study.