Quantitative Features of Neovascularization in Fibrotic Age-Related Macular Degeneration and Their Associations With Visual Changes After a Single Anti-VEGF Therapy

Background: Macular fibrosis represents an advanced manifestation of neovascular age-related macular degeneration (nAMD), but active neovascularization may persist within fibrotic lesions. Reliable biomarkers for predicting short-term visual changes after anti-vascular endothelial growth factor (VEGF) therapy in eyes with fibrotic lesions remain limited. This study aimed to identify predictors associated with short-term visual changes 4 weeks after a single anti-VEGF therapy in patients with macular fibrosis (MF).Methods: Patients with active nAMD, either treatment-naïve or without anti-VEGF therapy for ≥6 months, were included and classified into fibrotic and non-fibrotic groups. Within the MF cohort, associations between baseline clinical, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) parameters and continuous changes in best-corrected visual acuity (BCVA) after a single injection were initially explored. Subsequently, patients were further divided into vision-improved (ΔBCVA ≥5 letters) and vision-unimproved (ΔBCVA <5 letters) groups after a single injection. Baseline clinical and OCTA parameters were compared. Quantitative vascular features were explored using logistic regression analysis.Results: Seventy-five patients were included (48 with MF, 27 without). Within the fibrotic cohort, macular neovascularization (MNV) lesions showed a larger vessel area, greater vessel length, more endpoints, greater central macular thickness, and worse baseline BCVA. However, these differences cannot be fully separated from the potential effects of previous treatment exposure, as fibrosis status was completely confounded with treatment history in this cohort. After adjustment for lesion area, the differences in absolute vascular parameters, including vessel area, total vessel length, and endpoint, were no longer statistically significant. In addition, fibrotic lesions exhibited significant quantitative vascular changes after anti-VEGF therapy, characterized by reductions in total vessel length, endpoint count, and exudation, accompanied by an increase in lacunarity (p < 0.001). Within the MF cohort, the vision-improved group was younger (p = 0.039) and had higher baseline junction density (p = 0.002) compared with the vision-unimproved group. Receiver operating characteristic (ROC) analysis showed that the combination of age and junction density predicted short-term visual improvement with good accuracy (area under the curve (AUC) = 0.77, 95% CI: 0.64–0.91). Junction density alone was also predictive (AUC = 0.77, 95% CI: 0.62–0.93).Conclusion: OCTA revealed that fibrotic MNV exhibited measurable vascular responsiveness after a single anti-VEGF therapy, as evidenced by significant post-treatment reductions in total vessel length, endpoint count, and exudation, together with an increase in lacunarity. More importantly, quantitative OCTA parameters, particularly junction density, predicted 4-week visual improvement with acceptable accuracy. These findings suggest that quantitative OCTA parameters may serve as candidate biomarkers of short-term visual change after a single anti-VEGF injection in patients with fibrotic nAMD.