Choriocapillaris Flow Deficits Are Spatially Linked to Retinal Pigment Epithelium and Photoreceptor Integrity in Geographic Atrophy

Purpose: To assess the correlation between choriocapillaris (CC) flow deficits and structural biomarkers of outer retinal degeneration in eyes with geographic atrophy (GA) secondary to nonexudative age-related macular degeneration, using a novel histology-informed binarization method and multimodal image registration. Methods: Patients with GA underwent spectral-domain optical coherence tomography (SD-OCT; Spectralis HRA + OCT) and swept-source optical coherence tomography angiography (SS-OCT-A; PLEX Elite 9000) imaging. Flow deficit percentage (FD%) was quantified via a novel histology-informed binarization approach. Retinal pigment epithelium loss (RPEL), ellipsoid zone loss (EZL), and ellipsoid zone (EZ) thickness were derived from SD-OCT using previously validated segmentation algorithms. Exact interdevice registration enabled spatial mapping. Linear mixed-effects models assessed global and local FD% associations with structural biomarkers. Results: We analyzed 115 eyes of 64 patients. Global FD% predicted RPEL (β, estimated effect = 0.16 mm/%FD; 95% confidence interval [CI], 0.10-0.22; P < 0.001) and EZL (β = 0.11 mm/%FD; 95% CI, 0.07-0.15; P < 0.001). Local FD% was elevated in RPEL (β = 22.95%FD; 95% CI, 20.86-25.04; P < 0.001) and EZL (β = 12.03%FD; 95% CI, 9.94-14.12; P < 0.001) regions. FD% negatively correlated with EZ thickness independent of drusen (β = -0.05 µm/%FD; 95% CI, -0.05 to -0.05; P < 0.001). Conclusions: Using a novel multimodal pipeline combining structural SD-OCT, SS-OCT-A, and histology-informed choriocapillaris binarization, we demonstrate that CC flow deficits are spatially correlated with outer retinal degeneration and independently associated with photoreceptor integrity, supporting their potential as predictive biomarkers for GA severity. These findings support a model in which choriocapillaris hypoperfusion contributes to metabolic stress in the retinal pigment epithelium and compromises photoreceptor outer segment integrity in geographic atrophy.