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PurposeTo characterize the association of reticular pseudodrusen (RPD) with late-onset retinal degeneration (L-ORD) using multimodal imaging.DesignProspective, 2-center, longitudinal case series.ParticipantsTwenty-nine patients with L-ORD.MethodsAll patients were evaluated within a 3-year interval with near-infrared reflectance, fundus autofluorescence, and spectral-domain OCT. In addition, a subset of patients also underwent indocyanine green angiography, fundus fluorescein angiography, mesopic microperimetry, and multifocal electroretinography.Main outcome measuresPrevalence, topographic distribution, and temporal phenotypic changes of RPD in L-ORD.ResultsA total of 29 patients with molecularly confirmed L-ORD were included in this prospective study. Reticular pseudodrusen was detected in 18 patients (62%) at baseline, 10 of whom were men. The prevalence of RPD varied with age. The mean age of RPD patients was 57.3 ± 7.2 years. Reticular pseudodrusen was not seen in patients younger than the fifth decade of life (n = 3 patients) or in the eighth decade of life (n = 5 patients). Reticular pseudodrusen were found commonly in the macula with relative sparing of the fovea and also were identified in the peripheral retina. The morphologic features of RPD changed with follow-up. Two patients (3 eyes) demonstrated RPD regression.ConclusionsReticular pseudodrusen is found frequently in patients with L-ORD and at a younger age than in individuals with age-related macular degeneration (AMD). Reticular pseudodrusen exhibits quick formation and collapse, change in type and morphologic features with time, and relative foveal sparing and also has a peripheral retinal location in L-ORD.