Longitudinal Tracking of Photoreceptor Integrity in Neovascular AMD: Early Restoration Predicts 24-Month Structural and Visual Outcomes

Purpose: The purpose of this study was to longitudinally characterize photoreceptor band changes over 24 months and determine whether early restoration predicts long-term outcomes in neovascular age-related macular degeneration (nAMD). Methods: This prospective study enrolled treatment-naïve patients with nAMD receiving anti-vascular endothelial growth factor therapy following 3 + pro re nata (PRN) regimen. Impaired areas of outer nuclear layer (ONL), ellipsoid zone (EZ), external limiting membrane (ELM), and interdigitation zone (IZ) were quantified at baseline, 1 week, 1, 2, 3, 12, and 24 months, and associations between early restoration and long-term structural and visual outcomes were assessed. Results: Eighty-two eyes from 82 patients (mean age = 65.15 ± 7.47 years) completed a 24-month follow-up. All bands showed significant changes over 2 years (P < 0.05 for all). Only EZ demonstrated significant early restoration at 1 week and 1 month (P = 0.041 and 0.004, respectively). Month 3 restoration of all bands predicted corresponding 1- and 2-year structural changes (Stdβ = 0.432-0.912, P < 0.05, except for 2-year ONL and IZ: P = 0.201 and 0.304, respectively). Moreover, month 2 ONL changes also independently predicted long-term ONL changes (P = 0.011 and P < 0.001 for 1 and 2 years, respectively). For visual outcomes, month 3 IZ restoration predicted 1-year BCVA improvement (Stdβ = -0.334, P = 0.032), whereas month 2 ONL restoration predicted 2-year BCVA improvement (Stdβ = -0.378, P = 0.003). Conclusions: Photoreceptor bands showed layer-specific restoration patterns, with EZ responding earliest. Early restoration at months 2 to 3 predicted long-term outcomes, with ONL and IZ as independent visual predictors.