Özge SARI TAŞ, Yasin TOKLU
Retina-Vitreus - 2026;35(1):1-12
Neovascular age-related macular degeneration (nAMD) continues to represent a major cause of irreversible central vision loss despite substantial therapeutic progress over the past two decades. The advent of intravitreal anti-vascular endothelial growth factor (VEGF) therapy fundamentally altered the natural course of the disease, enabling sustained visual stabilization and, in many patients, meaningful visual improvement. However, long-term management remains dependent on repeated injections and continuous monitoring, imposing a considerable burden on both patients and healthcare systems. Contemporary therapeutic development has therefore shifted from maximizing short-term efficacy toward enhancing durability and reducing injection frequency. High-dose formulations, such as aflibercept 8 mg, aim to intensify VEGF suppression, whereas dual-pathway inhibitors such as faricimab target both VEGF-A and angiopoietin-2, addressing complementary pathways implicated in vascular destabilization. Agents designed to optimize pharmacokinetics, including antibody-biopolymer conjugates, represent an alternative strategy aimed at prolonging intraocular residence time through pharmacokinetic optimization. In parallel, biosimilars are expanding treatment accessibility through regulatory frameworks based on analytical and clinical comparability. Sustained drug delivery systems and gene-based strategies further attempt to provide prolonged intraocular anti-angiogenic activity while minimizing injection burden. This review summarizes current and emerging treatment strategies in nAMD, with emphasis on mechanistic diversity, durability optimization, safety considerations, and real-world applicability. As the field evolves, the central challenge lies not only in suppressing VEGF effectively but in achieving sustainable, individualized disease control over years of treatment.
