Macular Neovascularization Subtype Determines Visual Consequences of Early Fibro-atrophic Remodelling in Neovascular AMD: PRECISE Study Report 11

Purpose: To investigate how baseline optical coherence tomography (OCT) biomarkers of early fibro-atrophic remodeling defined as well-delineated hyperreflective material [wdHRM] associated with atrophic surrogates and fluid resolution influence early visual outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD), and whether effects differ by macular neovascularization (MNV) subtype. Methods: In the PRECISE cohort completing aflibercept 2 mg induction of three loading injections, baseline wdHRM and fluid status at Visit 4 (V4 mean = 112 days) were examined as independent predictors of best-corrected visual acuity (BCVA). Regression models included MNV subtype, baseline BCVA and V4 fluid status. Results: Baseline wdHRM independently predicted poorer short-term vision. Paradoxically, the BCVA penalty attributable to wdHRM was greater in eyes achieving complete fluid resolution (6.4 letters worse) than in those with residual fluid (3.4 letters worse), revealing that fluid itself masks the true structural deficit. The impact of wdHRM varied by MNV subtype: Type 3 MNV showed the largest visual penalty (9 letters), moderate penalties in Types 1, 2 and mixed (4 letters), and negligible effects in polypoidal choroidal vasculopathy. Baseline wdHRM is strongly associated with outer retinal disruption and choroidal hypertransmission, particularly in Type 3 MNV, suggesting a fibro-atrophic rather than purely fibrotic state. Conclusions: The impact of OCT biomarkers indicative of fibrosis is heterogeneous across MNV subtypes and modified by fluid resolution. wdHRM, particularly in Type 3 MNV, likely represents mixed fibro-atrophic remodeling, explaining disproportionate early visual penalties despite low overall fibrosis incidence. These findings refine baseline prognostication and emphasize the need to counsel patients based on these likely consequences of MNV subtype.