SUBRETINAL DRUSENOID DEPOSITS IN NON-NEOVASCULAR AGE-RELATED MACULAR DEGENERATION

In Brief Purpose: To characterize the morphology, prevalence, and topography of subretinal drusenoid deposits, a candidate histological correlate of reticular pseudodrusen, with reference to basal linear deposit (BlinD), a specific lesion of age-related macular degeneration, and to propose a biogenesis model for both lesion. Methods: Donor eyes with median death-to-preservation of 2:40 hours were postfixed in osmium tannic acid paraphenylenediamine and prepared for macula-wide high-resolution digital sections. Annotated thicknesses of 21 chorioretinal layers were determined at standard locations in sections through the fovea and the superior perifovea. Results: In 22 eyes of 20 white donors (83.1 ± 7.7 years), SDD appeared as isolated or confluent drusenoid dollops punctuated by tufts of retinal pigment epithelium apical processes and associated with photoreceptor perturbation. Subretinal drusenoid deposits and BlinD were detected in 85 and 90% of non-neovascular age-related macular degeneration donors, respectively. Subretinal drusenoid deposit was thick (median, 9.4 μm) and more abundant in the perifovea than in the fovea (P < 0.0001). BlinD was thin (median, 2.1 μm) and more abundant in the fovea than in the perifovea (P < 0.0001). Conclusion: Subretinal drusenoid deposits and BlinD prevalence in age-related macular degeneration eyes are high. Subretinal drusenoid deposits organized morphology, topography, and impact on surrounding photoreceptors imply specific processes of biogenesis. Contrasting topographies of subretinal drusenoid deposits and BlinD suggest relationships with differentiable aspects of rod and cone physiology, respectively. A 2-lesion 2-compartment biogenesis model incorporating outer retinal lipid homeostasis is presented. The largest series of eyes devoted to histological characterization of subretinal drusenoid deposit, a candidate correlate of reticular pseudodrusen, shows that it is a stereotyped extracellular lesion that is as prevalent in age-related macular degeneration eyes as basal linear deposit. A 2-lesion 2-compartment biogenesis model invoking photoreceptor lipid homeostasis is proposed.