Purpose
Drusenoid pigment epithelium detachment (D-PED) is a known precursor to geographic atrophy in age-related macular degeneration (AMD). We sought histological correlates for spectral-domain optical coherence tomography (SD-OCT) signatures in D-PED and determined the frequency and origin of these OCT signatures in a clinical cohort of D-PED eyes.
Design
Laboratory imaging-histology comparison; Retrospective, observational cohort study.
Participants
Four donor eyes with histopathologic diagnosis of AMD (2 non-neovascular D-PED and 2 neovascular PED); 49 eyes of 33 clinic patients with non-neovascular D-PED > 2 mm in diameter.
Method
Donor eyes underwent multimodal ex vivo imaging including SD-OCT then processing for high-resolution histology. All clinic patients were imaged with SD-OCT, near-infrared reflectance and color photography.
Main Outcome Measures
Histologic correlates for SD-OCT signatures in D-PED; Estimate of coverage by different RPE phenotypes in the D-PED surface; Frequency and origin of histologically-verified SD-OCT signatures in a clinical cohort of D-PED eyes; Comparisons of histological features between neovascular PED and D-PED due to AMD.
Results
Intraretinal and subretinal hyperreflective foci as seen on SD-OCT correlated to RPE cells on histology. Hypertransmission of light below the RPE+basal lamina band correlated with dissociated RPE. Subretinal hyperreflective material due to acquired vitelliform lesions corresponded to regions of apically expelled RPE organelles. In the clinical cohort, all histologically verified reflectivity signatures were visible and quantifiable. The appearance of intraretinal hyperreflective foci was preceded by thickening of the RPE-basal lamina band. Compared to PEDs associated with neovascular AMD, D-PEDs had different crystallization patterns, no lipid-filled cells, and thinner basal laminar deposits.
Conclusion
Multiple RPE fates in AMD, including intraretinal cells that are highly prognostic for progression, can be reliably followed and quantified using eye-tracked serial SD-OCT. This information may be particularly useful for obtaining an accurate timeline of incipient geographic atrophy in clinic populations and for quantifying anatomic endpoints and response to therapy in AMD clinical trials.