Identification of Molecular Signals in Vitreous Humor Associated With Suboptimal Response to Vascular Endothelial Growth Factor (VEGF) Inhibition in Neovascular Age-related Macular Degeneration (nAMD) Within a Clinical Trial Setting

Neovascular age-related macular degeneration (nAMD), also called wet AMD, can cause serious vision loss. While anti-VEGF (anti Vascular Endothelial Growth Factor) treatments such as ranibizumab help many patients, about 20 40% have a suboptimal response. In this study, the investigators want to identify other factors (beyond VEGF) that might be driving the disease in these non-responding patients. By looking at samples from inside the eye (vitreous humor) and comparing "good responders" to "suboptimal responders", the investigators hope to find potential new treatment approaches or biomarkers for nAMD.

Neovascular age-related macular degeneration (nAMD) is a leading cause of severe vision loss worldwide. Although intravitreal anti-VEGF injections have markedly improved outcomes, 20-40% of patients show a suboptimal response, indicating the involvement of additional molecular pathways. This study investigates whether profiling the vitreous humor can reveal alternative angiogenic pathways-beyond VEGF-that drive persistent disease. If such pathways are identified, switching from anti-VEGF monotherapy (ranibizumab) to a bispecific anti-VEGF/anti-Ang2 agent (faricimab) may improve disease control and provide better vision outcomes for patients with inadequate response to standard therapy. Additionally, the dosage regimens (monthly injections over 24 weeks), and selection of treatment-naïve nAMD patients will minimize confounding variables. This approach ensures a clear comparison between good responders and suboptimal responders. By correlating clinical/imaging outcomes with vitreous biomarker profiles, the investigators aim to develop personalized treatment strategies for nAMD.