Purpose <p>This study evaluated the clinical outcomes and aqueous humor cytokine levels in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept to ranibizumab biosimilar (BS).</p> Study design <p>Prospective observational study.</p> Methods <p>Thirty-eight eyes of 38 patients with nAMD who received aflibercept under a treat-and-extend (TAE) regimen were prospectively switched to ranibizumab BS. Eight eyes with cataracts undergoing surgery served as controls for aqueous humor cytokine analysis. Best-corrected visual acuity (BCVA) and anatomical outcomes were assessed over one year. The aqueous humor levels of vascular endothelial growth factor (VEGF)-A, angiopoietin-2 (Ang-2), and placental growth factor (PlGF) were measured before and after switching in eyes with nAMD and at surgery in controls.</p> Results <p>Disease activity remained controlled in 94.3% of patients with nAMD for over one year. No significant changes were observed in the BCVA (<i>P</i>=0.65) after one year. Ang-2 levels remained unchanged (<i>P</i>=0.66) and were not significantly different between eyes with nAMD and controls both before (<i>P</i>=0.64) and after switching (<i>P</i>=0.30). PlGF levels also remained stable (<i>P</i>=0.12) but were significantly higher in eyes with nAMD than in controls both before (<i>P</i>&lt;0.01) and after switching (<i>P</i>=0.03). VEGF-A levels significantly increased after switching (<i>P</i>&lt;0.01) but remained lower than in the controls both before (P&lt;0.01) and after switching (<i>P</i>=0.02).</p> Conclusion <p>Switching from aflibercept to ranibizumab BS effectively maintained disease stability and cytokine balance in eyes with nAMD. These findings support ranibizumab BS as a viable and cost-effective alternative for long-term treatment.</p>