In the original study design, the case categories (2, 3, and 4) were to be pooled to assess the effects of the 3 different treatment regimens on progression to advanced disease and visual acuity loss. In the first published report of AREDS results, the authors moved quickly to a subgroup analysis for categories 3 and 4, for reasons given subsequently. The presentation of the results in this manner led to significant controversy and doubt regarding the study findings, including letters to the editor and heated discussions at professional meetings. However, the authors' subsequent explanations seem to address the concerns raised. In a response to a letter to the editor, the AREDS authors explained that the analysis of all 3 case categories was indeed statistically significant, when the predefined design variable of AMD category was included as a covariate in the model. In this analysis, the 3-df test for differential treatment effect was significant (P = .006), as were the zinc main effect (P = .009) and the treatment effect for 2 individual treatment arms, zinc alone (P = .006) and zinc plus antioxidants (P = .001).13 However, in category 2, only 15 events of progression to advanced AMD occurred across all treatment groups, with 3 of those occurring in the placebo group. For this reason, and because the investigators believed that it would be inappropriate to recommend supplements to patients who would rarely progress to advanced AMD, the AMD category–adjusted analysis for the full cohort was not presented in the published report.10 Instead, the published report focused on the benefit to categories 3 and 4. Subjects in categories 3 and 4 assigned to placebo had a 28% probability of progression to advanced AMD compared with 23% for antioxidants, 22% for zinc, and 20% for the combination of antioxidants and zinc.