Recognizing Atrophy and Mixed-Type Neovascularization in Age-Related Macular Degeneration Via Clinicopathologic Correlation

Purpose: We explored via multimodal imaging and histology an eye with mixed-types 1 and 2 macular neovascularization (MNV) and complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) in age-related macular degeneration.

Methods: An 82-year-old white man was followed 7 years by optical coherence tomography and treated with intravitreal anti-vascular endothelial growth factor for 3 years. At the last clinic visit, visual acuity was stable at 20/50. Two months later the patient died, and eyes were preserved at 8.33 hours after death. Submicrometer epoxy resin sections of osmicated tissue were stained with toluidine blue and evaluated by oil immersion microscopy.

Results: A shallow irregular RPE elevation on optical coherence tomography correlated with type 1 MNV with fibrocellular scar and neocapillaries (close to RPE), at a density similar to underlying native choriocapillaris (0.37 vs. 0.42). Type 2 MNV covered the native RPE and was enveloped at the margins by RPE, without neocapillaries. Native RPE cells transdifferentiated from age-normal to melanotic and entered type 1 MNV and choroid. Some photoreceptors persisted over MNV. The cRORA initiated at a collapsed druse, expanded during follow-up, and exhibited low choriocapillaris density (0.05).

Conclusions: An eye with maintained vision on 3 years of anti-vascular endothelial growth factor therapy had type 1 MNV sustaining RPE. Type 2 MNV enveloped by RPE was visible in optical coherence tomography and histology. Persistence of photoreceptors and RPE over MNV contrasted with drusen-associated cRORA.

Translational Relevance: Vision during long-term anti-vascular endothelial growth factor treatment persists by MNV partially preserving outer retinal cells and by RPE enveloping type 2 MNV.