Retinal pigment epithelium morphology indicates multiple pathways in GA and CNV. Atrophic/scarred areas have numerous cells capable of transcribing genes and generating imaging signals. Shed granule aggregates, possibly apoptotic, are visible in SDOCT, as are 'Dissociated' and 'Sloughed' cells. The significance of RPE phenotypes is addressable in longitudinal, high-resolution imaging in clinic populations. Data can motivate future molecular phenotyping studies.

Purpose To inform the interpretation of clinical optical coherence tomography and fundus autofluorescence?imaging in geographic atrophy (GA) of age-related macular degeneration (AMD) by determining the distribution of retinal pigment epithelium (RPE) phenotypes in the transition from health to atrophy (GA) in donor eyes. Method In RPE-Bruch’s membrane flat mounts of 2 GA eyes the terminations of organized RPE cytoskeleton and autofluorescent material were compared. In high-resolution histological sections of 13 GA eyes, RPE phenotypes were assessed at ±500 and ±100 µm from the descent of the external limiting membrane (ELM) towards Bruch’s membrane. The ELM descent was defined as curved, reflected, or oblique in shape. Thicknesses of RPE, basal laminar deposit (BLamD), and RPE+BLamD were measured. Results A border of atrophy that can be precisely delimited is the ELM descent, as opposed to the termination of the RPE layer itself, because of dissociated RPE in the atrophic area. Approaching the ELM descent, the percentage of abnormal RPE morphologies increases, the percentage of age-normal cells decreases, overall RPE thickens, and BLamD does not thin. The combination of RPE plus BLamD is 19.7% thicker at −100 µm from the ELM descent than at −500 µm (23.1 ± 10.7 vs 19.3 ± 8.2 µm; p=0.05). Conclusion The distribution of RPE phenotypes at the GA transition support the idea that these morphologies represent defined stages of a degeneration sequence. The idea RPE dysmorphia including rounding and stacking helps explain variable autofluorescence patterns in GA 14 is reinforced. The ELM descent and RPE+BLamD thickness profile may have utility as SDOCT metrics in clinical trials.

'Dissociated' RPE within atrophic areas may be the source of 'Subducted' cells. 'Entombed' RPE within fibrovascular and fibrocellular scars may be the source of 'Melanotic' cells. An imaging correlate for 'Subducted' cells awaits discovery; 'Melanotic' cells appear gray-black in the CNV fundus. Results provide a basis for future molecular phenotyping studies.