**Background:** Age-related macular degeneration (AMD) is a leading cause of blindness, and anti-VEGF therapy for neovascular AMD (nAMD) often yields suboptimal outcomes. The ellipsoid zone (EZ) is a qualitative OCT biomarker for photoreceptor function, but it can be affected by image quality and media opacity. The outer nuclear layer (ONL) contains photoreceptor cell bodies and its thickness may serve as a quantitative biomarker. This study investigated whether ONL thickness changes during anti-VEGF treatment predict visual prognosis in type 1 choroidal neovascularization (CNV) of nAMD.
**Methods:** This retrospective case-control study included 94 eyes of 94 patients with treatment-naïve type 1 CNV (confirmed by OCT, FA, ICGA) treated with three monthly intravitreal aflibercept loading doses followed by a treat-and-extend regimen, and 35 normal control eyes. Exclusion criteria included other CNV types, secondary CNV, pachychoroid neovasculopathy, complete outer retinal atrophy, and poor image quality. OCT parameters (foveal ONL thickness, SRF height, subfoveal choroidal thickness, foveal EZ presence) were measured manually by two graders (ICC excellent). BCVA was measured in logMAR. The study group was divided into poor responders (group A, ONL change ≤ +10 µm, n=46) and good responders (group B, ONL change > +10 µm, n=48) based on the median ONL change after loading. Multivariate linear regression identified predictors of 1-year BCVA.
**Key Results:** At baseline, type 1 CNV eyes had significantly thinner foveal ONL (54.0 ± 19.8 µm vs 89.5 ± 10.3 µm, p<0.001), worse BCVA (0.48 ± 0.28 vs 0.04 ± 0.05 logMAR, p<0.001), and higher SRF height (174.4 ± 103.8 µm vs 0 µm, p<0.001) compared to controls. After three aflibercept loading doses, ONL thickness increased from 54.68 ± 19.49 µm to 65.02 ± 23.84 µm (p<0.001), SRF height decreased, and BCVA improved to 0.34 ± 0.27. These improvements were maintained at 1 year (mean injections 7.1 ± 3.8). Multivariate regression showed that baseline SRF height (β=-0.001, p=0.004) and baseline BCVA (β=0.511, p<0.001) were significant predictors of 1-year BCVA. After loading, ONL thickness (β=-0.003, p=0.002) and BCVA (β=0.444, p<0.001) were significant predictors. ONL change during loading also correlated with 1-year BCVA (p=0.001). Eyes with present foveal EZ after loading had greater ONL recovery (p=0.001) and better 1-year BCVA (0.26 ± 0.22 vs 0.48 ± 0.27, p<0.001). Subgroup analysis: group B (good ONL response) had better BCVA at 1 year (0.22 ± 0.19 vs 0.43 ± 0.27, p<0.001) and fewer subfoveal CNV (45.5% vs 76.0%, p=0.012) compared to group A.
**Clinical Implications:** Foveal ONL thickness recovery after anti-VEGF loading may serve as a quantitative, reproducible biomarker for photoreceptor viability and visual prognosis in type 1 CNV. ONL improvement indicates salvageable photoreceptors, while lack of recovery suggests irreversible damage. This could help clinicians identify patients likely to benefit from continued therapy and set realistic expectations. The study also highlights that subfoveal CNV location is associated with poorer ONL recovery. Limitations include manual measurements, single-center design, and use of BCVA as the sole functional measure.