Neovascular age-related macular degeneration management – Beyond anti-VEGF

Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has transformed neovascular age-related macular degeneration (nAMD) into a chronic, treatable condition. However, real-world outcomes remain limited by treatment burden, limited durability, variable response, and progression of atrophy or fibrosis, highlighting the need for strategies beyond VEGF-A suppression. This narrative review summarizes emerging therapeutic approaches aimed at addressing these unmet needs. Adjunctive pharmacologic targets, including angiopoietin/Tie2 signaling, VEGF-C/D, integrins, hypoxia-inducible pathways, and intracellular tyrosine kinase inhibition, are discussed. Gene-based therapies offering the potential for prolonged intraocular VEGF suppression are discussed, though challenges related to inflammation, irreversibility, and patient selection persist. Finally, surgical and regenerative strategies such as retinal pigment epithelium monolayer transplantation are reviewed as investigational options for highly selected patients. Collectively, these developments signal a shift toward individualized, multipronged nAMD management, with anti-VEGF therapy remaining foundational, while biomarkers, intraocular biochemical milieu, and patient adherence may guide future care.