Baseline Biomarkers for Three-Year Fibrosis Development on OCT in Treatment-Naïve Neovascular AMD

Aims: To explore how baseline biomarkers on optical coherence tomography (OCT) predict fibrotic development in eyes with neovascular age-related macular degeneration (nAMD) commencing intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: Medical records at a single institution were retrospectively searched to identify eyes starting anti-vascular endothelial growth factor therapy with 36-month follow-up. Baseline OCT images were graded for central subfield thickness (CST) and nAMD lesion features. The development of fibrosis was determined after three years using an OCT-based approach, and multivariable logistic regression was used to identify independent predictors. Results: A total of 201 eyes were included, of mean age 77.3 years. At baseline, median visual acuity (VA) was 67 (IQR 58–77) letters, and mean central subfield thickness (CST) was 398.6 ± 135.3 µm. Mean injections received were 9.8 ± 1.9, 8.1 ± 3.1, and 7.3 ± 3.2 in years 1, 2, and 3, respectively. Fibrosis developed in 53 eyes (26.4%) by three years. Lower baseline VA (OR 0.68 per 10 letters, p = 0.006), as well as presence of subretinal hyperreflective material (SHRM; OR 10.80, p < 0.001), intraretinal fluid (IRF; OR 2.60, p = 0.025), and type 2 macular neovascularisation (MNV; OR 2.98, p = 0.033) were each independently associated with fibrosis, while drusen presence was protective (OR 0.25, p = 0.002). Fibrosis occurred in 4.6% of eyes without SHRM and 43.0% with SHRM. In exploratory unadjusted analyses, odds of fibrosis were higher with SHRM height 1–99 µm (OR 6.2, 95% CI 1.8–21.7) and ≥100 µm (OR 23.7, 95% CI 7.9–71.3) than with no SHRM, and higher with ≥100 µm than 1–99 µm (OR 3.8, 95% CI 1.6–9.1; p = 0.003). Conclusions: Subretinal hyperreflective material was the strongest baseline biomarker for developing subretinal fibrosis following anti-VEGF therapy in this historical cohort, with exploratory analyses suggesting higher risk at SHRM ≥ 100 µm. In combination with other biomarkers, these features may support future risk stratification in treatment-naïve neovascular age-related macular degeneration.