Hyperreflective Choroidal Foci Characterization Supports the Existence of Different Clinical Phenotypes of Geographic Atrophy

Purpose: To characterize and quantify optical coherence tomography (OCT) hyperreflective choroidal foci (HCF) in geographic atrophy (GA) of age-related macular degeneration (AMD) and to assess their distribution across different GA phenotypes. Methods: Eyes with bilateral GA (B-GA) or unilateral GA (U-GA) with macular neovascularization in the fellow eye, as well as controls, were included. HCF were classified in different subtypes according to size (small, ≤30 µm; large, >30 µm) and reflectivity (high or intermediate). Each subtype was also identified according to location (choriocapillaris vs. choroid). HCF counts were quantified within complete retinal pigment epithelium and outer retinal atrophy (cRORA), incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), and non-atrophic outer retinal alteration (noRORA). The comparison of HCF count between the GA groups and the controls was performed only in noRORA segments. Results: Seventy-seven eyes were enrolled (40 B-GA, 18 U-GA, and 19 controls). The extent of cRORA, iRORA, and noRORA regions did not differ between the two GA groups (P > 0.05 for all). In noRORA regions, both GA groups exhibited significantly higher HCF number compared to controls (P < 0.0001 for both). Total HCF count did not differ between the GA groups across all RORA regions (P > 0.05 for all). However, the analysis of HCF subtypes revealed significant differences. Small intermediate-reflectivity choriocapillaris HCF were significantly more numerous in U-GA eyes than in B-GA in cRORA and noRORA regions (P = 0.0006 and P = 0.006, respectively). Large high-reflectivity choriocapillaris HCF were significantly more numerous in B-GA eyes than in U-GA within cRORA regions (P = 0.025). In choroid, HCF subtypes did not differ between the two GA groups in the different RORA regions. Conclusions: Although overall HCF burden was similar between the two GA phenotypes, significant distinct distribution of HCF subtypes was documented. Detailed HCF characterization provides new insights into GA heterogeneity, supporting the value of novel biomarkers in further characterizing different GA phenotypes.