Purpose: To determine the histologic and cellular correlates in the retina and retinal pigment epithelium (RPE) with the presence of optical coherence tomography-defined reticular pseudodrusen (RPD). Design: Observation case using immunocytochemistry of an exenterated eye with immediate fixation after removal. Participants: Two patients, one with confirmed RPD and the other with mid-peripheral drusen, underwent multimethod imaging before exenteration and immediate fixation of the posterior eyecup for high-resolution immunocytochemical analysis. Methods: Optical coherence tomography (OCT) was compared with high-resolution immunocytochemistry using a range of cellular markers to determine changes in the RPE, photoreceptors, and gliosis. Main Outcome Measures: Correlations of the appearance of reticular pseudodrusen on OCT and immunocytochemical analysis. Results: Reticular pseudodrusen were deposits juxtaposed to photoreceptor outer segments extending through the outer nuclear layer and even beyond the outer limiting membrane. Deposits were rich in vitronectin, photoreceptor-associated proteins, and Iba1-immunoreactive immune cells. In contrast to conventional drusen the lipid stain Oil Red O failed to stain RPD. Cellular analysis revealed that RPD were associated with photoreceptor disruption and loss and localized gliosis. In addition, anomalies in the RPE were observed. Conclusions: Reticular pseudodrusen represent subretinal deposits that extend through the outer nuclear layer, affect photoreceptor integrity, and are associated with retinal gliosis and RPE damage
