Feliciana Menna, Laura De Luca, Alessandro Meduri, Antonio Baldascino, S. Lupo, Enzo Maria Vingolo
Neovascular age-related macular degeneration (nAMD) remains a major cause of visual morbidity worldwide, although its contribution to blindness in developed healthcare systems has declined in the era of anti-VEGF therapy. Although randomized clinical trials have consistently demonstrated meaningful visual gains under structured retreatment protocols, real-world outcomes frequently decline over time due to undertreatment, limited durability, and persistent disease activity. Recent therapeutic advances have shifted the focus from maximizing short-term efficacy to engineering sustained disease control. Faricimab, a bispecific antibody targeting both VEGF-A and angiopoietin-2, introduces dual-pathway vascular modulation, while high-dose aflibercept (8 mg) enhances VEGF suppression through pharmacokinetic intensification. This perspective critically examines the biological rationale, clinical evidence, real-world implications, and strategic positioning of these agents, proposing a durability-centered framework for next-generation management of nAMD.