BackgroundTransitions between different stages of age-related macular degeneration (AMD) are not completely captured by traditional survival models with an endpoint of advanced AMD. ObjectiveThis study aimed to explore the transitions from early and intermediate AMD to higher non-advanced and advanced stages and determine the contributions of nutritional factors to these outcomes. MethodsEyes with early or intermediate AMD at baseline, classified according to the Age-Related Eye Disease Study severity score, were included in this prospective longitudinal analysis. Foods and the biologically active nutrients associated with AMD [green leafy vegetables, fish, lutein/zeaxanthin (LZ), and ω-3 fatty acids] were determined by a baseline food frequency questionnaire. Progression was defined as eyes transitioning to higher severity groups including non-advanced and advanced stages over 5 years, confirmed at 2 consecutive visits. Cox proportional hazards models for foods and nutrients were analyzed adjusting for demographics, lifestyle, baseline macular status, family history of AMD, caloric intake and genetic risk. ResultsAmong 2697 eyes, 616 (23%) progressed to higher severity groups. In the food group model, higher intake of green leafy vegetables reduced incidence of transitions [hazard ratio (HR) (≥ 2.7 servings/week vs. none) = 0.75 (95% confidence interval 0.59 - 0.96), P = 0.02]. Higher fish intake was also protective [HR (≥ two 4-ounce servings/week vs. < 2) = 0.79 (0.65 - 0.95), P = 0.01]. In the nutrient model, LZ intake was protective [HR (≥ 2 mg/day vs. < 2) = 0.76 (0.60 - 0.96), P = 0.02]. Higher intake of ω-3 fatty acids also tended to be beneficial [HR (≥ 0.7 g/week vs. < 0.7) = 0.85 (0.71 - 1.01), P = 0.06]. ConclusionsIncreased consumption of green leafy vegetables, LZ, and fish nutritionally rich in ω-3 fatty acids during the initial stages of AMD may reduce rates of progression to higher severity of this debilitating disease. Clinical TrialNCT00594672