Macular neovascularisation subtype determines visual consequences of early fibro-atrophic remodelling in neovascular AMD: PRECISE study report 11

PURPOSE: To evaluate whether baseline well-delineated hyperreflective material (wdHRM) is associated with short-term visual outcome in treatment-naïve neovascular age-related macular degeneration (nAMD), whether this association differs by macular neovascularisation (MNV) subtype, and how wdHRM relates to atrophy-related OCT biomarkers. METHODS: Multicentre observational analysis of 2036 treatment-naïve eyes (PRECISE cohort) completing three monthly aflibercept 2 mg injections. Best-corrected visual acuity (BCVA) at Visit 4 (V4) was modelled against baseline wdHRM using adjusted multivariable linear regression. Secondary analyses assessed subtype interaction and eye-level association with atrophy-related OCT biomarkers. RESULTS: Mean BCVA improved from 58.0 to 62.6 letters by V4. Baseline wdHRM was present in 14.6% of eyes, and foveal-involving wdHRM independently predicted lower V4 BCVA (β =-6.60 letters, 95%confidence interval [CI]-8.18 to -5.02; p < 0.001). Foveal-involving baseline choroidal hypertransmission (HTM) showed a stronger adverse association (β =-8.98, 95%CI-10.97 to -6.98; p < 0.001). The wdHRM association differed by subtype (interaction p = 0.016), with adjusted BCVA reductions of -10.6 letters in Type 3 MNV, -4.8 in Type 2/mixed MNV, -4.1 in Type 1 MNV, and -1.0 in polypoidal choroidal vasculopathy. By V4, wdHRM increased to 21.0% and was associated with HTM and greater outer retinal disruption. CONCLUSIONS: In treatment-naïve nAMD, baseline wdHRM is independently associated with poorer short-term visual outcome, particularly in Type 3 MNV. Short-term visual outcome should be interpreted in relation to both fibrosis-related and atrophy-related OCT biomarkers.