Rethinking strategies for rescue treatment in wet AMD and retinal vascular disease clinical trials

Frequent anti-VEGF treatment has demonstrated efficacy in wet age-related macular degeneration (wet AMD) and retinal vascular diseases, but continued treatment is necessary to maintain initial gains in visual acuity. As a result, extending the duration of action and durability has become a primary focus of retinal drug development.

Developers are pursuing longer-acting approaches, including higher-dose anti-VEGF products, continuous anti-VEGF delivery products, combination therapies, and transgene products that encode anti-VEGF. Trials must incorporate rescue treatment when the effect of the investigational product appears to be wearing off to help protect participants from vision loss.

Designing rescue criteria is a delicate balancing act. They must distinguish true disease progression from normal test–retest variability while remaining sensitive enough to detect disease activity before clinically meaningful or irreversible progression occurs. At the same time, the specific criteria and definitions selected directly affect rescue-related outcome measures and the interpretation of trial efficacy and durability results.