Choriocapillaris Flow Signal Deficits Are Associated With AMD Onset and Early Progression Over Three Years: ALSTAR2 Follow-Up.

Purpose: To determine if a baseline choriocapillaris flow signal deficits (CCFD%), as a marker of impaired transport, is associated with age-related macular degeneration (AMD) onset and progression at the 3-year follow-up. Methods: Participants ≥ 60 years old with normal macular health, early AMD (eAMD), and intermediate AMD (iAMD) were staged at baseline and follow-up with the Age-Related Eye Disease Study (AREDS) 9-step classification system and were then classified as stable and progressing based on whether their stage advanced. Spectral-domain optical coherence tomography angiography (OCTA) quantified baseline CCFD% across the Early Treatment Diabetic Retinopathy Study (ETDRS) central subfield (CS), inner ring (IR), and an outer area (OA, extending superiorly). Adjusted baseline CCFD% values were compared between stable and progressing eyes. Results: Of 332 included eyes at baseline (mean age, 71.1 ± 5.8 years), 173 eyes were normal, 101 were eAMD, and 58 were iAMD. Over 3 years, 284 eyes remained stable (85.5%), and 48 eyes progressed (14.5%). In the overall cohort, progressing eyes demonstrated significantly higher baseline CCFD% than stable eyes in the CS (57.7% vs. 53.5%; P = 0.007) and IR (56.1% vs. 53.9%; P = 0.045), but not in the OA. When stratified by baseline AMD stage, stable versus progressor differences were exclusively observed in eAMD (51.4% vs. 60.7% and 52.6 vs. 58.0% for CS and IR, respectively) but not in OA or in normal eyes (all P > 0.05). Conclusions: CCFD% in the CS and IR, one aspect of impaired transport between circulation and photoreceptors, is associated with AMD progression in early-stage disease; this spatial specificity implicates the fovea.