Intravitreal anti-vascular endothelial growth factor (VEGF) injections are essential for treating neovascular age-related macular degeneration (nAMD), but patient responses vary significantly, complicating standardized regimens. This study identifies early optical coherence tomography (OCT) biomarkers and best-corrected visual acuity (BCVA) as predictors of injection frequency in a one-year treat-and-extend (T&E) regimen to optimize individualized treatment. A retrospective analysis of treatment-naïve nAMD patients receiving intravitreal aflibercept was conducted. Patients underwent three initial monthly loading injections, followed by a modified T&E regimen. OCT parameters and BCVA were assessed at baseline, during, and after the loading phase to identify associations with injection frequency and recurrence intervals. Post-loading central subfield thickness (CST) significantly predicted injection frequency (p <
0.001) and recurrence timing (p = 0.013), while baseline CST and BCVA showed no correlation. BCVA remained similar between high- and low-treatment-need groups despite differing injection frequencies. Type 2 macular neovascularization responded more rapidly to treatment than type 1, reflecting varying dynamics. CST after the loading phase is a reliable predictor of treatment needs within one year, superior to baseline biomarkers. Early response monitoring during loading enables personalized anti-VEGF therapy, minimizing overtreatment and preserving vision, underscoring the value of individualized management in nAMD.