Purpose-To determine the risk of progression to advanced age-related macular degeneration (AMD) conferred by reticular pseudodrusen (RPD), an imaging presentation of reticular macular disease (RMD), in high-risk fellow eyes of subjects with AMD and unilateral choroidal neovascularization (CNV) in a large prospective study. Design-Cohort study.Participants-271 subjects with AMD; 94 with RPD and 177 without RPD.Methods-We studied images from a cohort of 271 subjects with AMD in the NAT 2 Study, a 3-year prospective study of subjects with unilateral CNV and large soft drusen in the fellow eye. The fellow eye, at high risk for developing advanced AMD, was the study eye. There were 5 visits per subject. Imaging at each visit consisted of color, red free, and blue light photography and fluorescein angiography. We analyzed the images for the presence of RPD, following disease progression throughout the 3-year study. Main Outcome Measures-The development of advanced AMD (CNV or geographic atrophy).Results-For the 271 subjects who completed the full 3-year study, there was a significantly higher rate of advanced AMD (56% or 53/94) in fellow eyes with RPD at any visit compared to eyes without RPD (32% or 56/177; p = 7.7E-05, χ 2 test; relative risk (RR) 1.8; 95% confidence interval (CI) 1.4-2.4). The chance of developing advanced AMD in the fellow eye in females with RPD (66%) was more than double compared to females without RPD (30%, p = 5.1E-06, RR 2.2, 95% CI 1.6-3.1).Conclusion-To our knowledge, this is the first comprehensive prospective study of reticular macular disease (RMD), a distinct clinical phenotype of AMD which includes RPD. It provides strong confirmation that RMD, a disease entity with stereotypical presentations across imaging

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