Real-world durability challenges with nAMD treatments and the potential promise of gene therapy.

The introduction of anti-vascular endothelial growth factor (VEGF) therapies changed the treatment landscape for neovascular age-related macular degeneration (nAMD), slowing the progression of central vision loss. However, current anti-VEGF therapies are limited by the need for frequent intravitreal injections to maintain disease control, which places a substantial burden on patients, caregivers, and healthcare systems, and contributes to poorer treatment adherence and persistence in the real-world setting. To extend the dosing interval, flexible dosing strategies were implemented; however, they carry the risk of both undertreatment and overtreatment. Emerging longer-acting strategies include continuous-release delivery systems (e.g. ranibizumab port delivery system) and gene therapy. Investigational gene therapies have been designed to preferentially target non-dividing retinal cells, enabling sustained expression of a therapeutic protein for the lifespan of these cells. While the therapeutic effect is designed to persist for years following the one-time administration of gene therapy, early clinical trials show that a subset of patients do receive supplemental anti-VEGF injections. Emerging patterns of retreatment support the concept that supplemental treatment does not necessarily indicate waning efficacy, but rather the adjuvant treatment may be used transiently to fine tune for increased disease activity levels at the patient level. In summary, multiple factors need to be considered to understand the durability of future therapies, not only reduced procedural frequency but also continuous disease control and improved quality of life - key metrics that will guide the evolution of care in nAMD.