Evolution of Anti-Vascular Endothelial Growth Factor Clinical Trial Design for Treating Neovascular Age-Related Macular Degeneration.

Anti-vascular endothelial growth factor (anti-VEGF) treatment protocols for neovascular age-related macular degeneration (nAMD) have evolved from fixed, monthly, or bimonthly dosing to individualized, extended dosing regimens. Although a PRN (as-needed) injection protocol may reduce the number of injections, it confers a similar treatment burden by requiring regimented follow-up visits, and disease activity may resurface between visits. Various personalized treatment intervals have been implemented in more recent randomized controlled clinical trials (RCTs), reflecting a shifting focus toward individualized, variable, extended treatment intervals rather than the frequent, fixed regimens used in older RCTs. Newer agents, such as faricimab and aflibercept 8.0 mg, have been evaluated in phase 3 RCTs and potentially offer extended durability of dosing in intervals of up to 12-16 weeks or longer. Recently introduced anti-VEGF agents were tested in pivotal trials using individualized, variable, extended treatment intervals, with results showing adequate nAMD control compared to older, fixed dosing regimens, but additional studies are needed to determine the real-world durability of these agents compared to older anti-VEGF agents.