Gene therapy for wet AMD: a paradigm shift in the standard of care

Neovascular age-related macular degeneration (nAMD), or wet AMD, remains a leading cause of vision loss in older adults. Current standard of care relies on repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, which create significant treatment burdens for patients and healthcare systems. Emerging gene therapies aim to address these challenges by delivering sustained therapeutic effects via single administration.

Next-generation gene therapies are transforming AMD treatment by enabling sustained, autonomous production of therapeutic proteins within ocular tissues, enabling the eye to synthesize its own anti-VEGF agents. A comprehensive literature search was performed using both PubMed and ClinicalTrials.gov to identify pertinent manuscripts and clinical trials for this narrative review. Keywords utilized included: Gene therapy, wet AMD, neovascular AMD, Viral Vectors, Adeno-associated viral vectors, Subretinal, Suprachoroidal, and Retinal Pigment Epithelium.

Advances in gene therapy for wet AMD may revolutionize treatment by enabling sustained intraocular anti-VEGF protein, reducing frequent injections, improving patient adherence, and potentially lowering long-term healthcare costs. Although promising, challenges including long-term safety, complex delivery procedures, immune responses, regulatory hurdles, and the need for optimized vectors and clinical protocols must be addressed before widespread adoption and integration into standard care.