Outer Retinal Hyperreflective Foci as a Predictor of Hyperreflective Material Boundary Remodeling and Visual Outcomes in Neovascular Age-Related Macular Degeneration

Purpose: The purpose of this study was to characterize the distribution and longitudinal evolution of intraretinal and subretinal hyperreflective foci (HF) in treatment-naive neovascular age-related macular degeneration (nAMD), and to examine associations between HF burden, hyperreflective material boundary remodeling (HRM-BR), and best-corrected visual acuity (BCVA) outcomes following bevacizumab treat-and-extend therapy. Methods: This was a retrospective observational study of 84 treatment-naive nAMD eyes receiving intravitreal bevacizumab via a treat-and-extend protocol. Spectral-domain OCT (Revo FC, Optopol) was performed at baseline (M0), month 3 (M3), and month 6 (M6). HF were quantified in the intraretinal and subretinal compartments using ImageJ software (version 1.54, National Institutes of Health, Bethesda, MD, USA) by two masked graders, with inter-rater agreement assessed by intraclass correlation coefficient (ICC). Eyes were classified into four HRM evolution patterns following the framework of Yu et al. Primary outcome was BCVA change from M0 to M6. Multivariable linear regression was performed to assess independent predictors of BCVA change. Results: Baseline intraretinal HF counts increased significantly across HRM Patterns 1 through 4 (median 0, 6, 4, and 8, respectively; Kruskal–Wallis p < 0.001; 95% CI for Spearman r = 0.471: [0.286, 0.623]). A higher baseline intraretinal HF count correlated with worse BCVA change at M6 (r = −0.300, 95% CI [−0.483, −0.092], p_adj = 0.010). In the primary multivariable model (n = 67), both intraretinal HF burden (β = −0.449, 95% CI [−0.879, −0.020], p = 0.041) and HRM width (β = −0.003, 95% CI [−0.005, −0.001], p = 0.014) were independent predictors of BCVA change. The transient M3 intraretinal HF peak in Pattern 3 eyes (median 4 → 12 → 4) was statistically confirmed by Wilcoxon signed-rank testing (M0 → M3: p = 0.004; M3 → M6: p = 0.001). Conclusions: Intraretinal HF burden is a graded marker of HRM pattern severity and an independent predictor of visual outcomes in nAMD, alongside HRM width. The statistically validated transient M3 HF peak in Pattern 3 may represent an early OCT signal of active boundary remodeling.