To estimate the effect of dietary intake of lutein and zeaxanthin (L/Z) and fats on the progression of age-related macular degeneration (AMD).Two hundred and fifty-four subjects identified with early age-related macular degeneration (AMD) were re-examined to determine 7-year AMD progression. Intakes of L/Z and fatty acids were estimated from food frequency questionnaires. Progression was defined by 3 different definitions, 2 quantitative and 1 qualitative, which varied in the stringency of the change required for the AMD to be deemed to have progressed. Covariates included age, smoking, AMD family history, source study, and follow-up duration.Energy-adjusted L/Z intake as a continuous variable was associated with AMD progression in the worse affected eye when defined by the most stringent criterion (odds ratio [OR] = 2.65, 95% confidence interval [CI] 1.13-6.22, p = 0.02). Similar associations were observed for the 2 other progression definitions (p = 0.18 and p = 0.13). Energy-adjusted omega-3 fatty acid intake modelled as a quintile median was associated with AMD progression only in the side-by-side assessment (OR = 2.56, 95% CI 1.11-5.91, p = 0.03), with borderline significance in the other 2 definitions (p = 0.05 and p = 0.08). No association of AMD progression was observed with the intake of either total fat or other subgroups: saturated, polyunsaturated, or monounsaturated fats; trans fatty acids; or omega-6 fatty acids.The findings of the study are counterintuitive, suggesting that increased intakes of dietary L/Z and omega-3 fatty acids are associated with progression of AMD. These results may indicate that too much of a good thing might be harmful. It is possible that in this study participants adopted a more healthy diet, having been aware of their AMD status at the beginning of the study. This healthy diet was then reflected in the dietary questionnaire completed at the end of study. However, this explanation may not adequately explain why those whose AMD had progressed, on the basis of fundus signs and not symptoms such as visual acuity decline, adopted a healthier lifestyle more aggressively than those without progression.