[New options determining the success of treatment for neovascular age-related macular degeneration].

Abstract

Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that can lead to severe and irreversible vision loss despite the availability of effective anti-VEGF agents. One of the potential causes of suboptimal treatment outcomes in nAMD is undertreatment, which may result from the need for frequent injections and follow-up visits, limitations in public healthcare funding, and challenges in achieving sustained and long-term control of disease activity (DA). Aflibercept 8 mg is a novel formulation with a higher concentration and improved molecular stability, enabling a fourfold increase in the molar dose of the active substance delivered to the vitreous body. The phase III PULSAR trial, a 96-week randomized, double-masked, active-controlled study, evaluated the efficacy and safety of 8 mg aflibercept compared with the standard 2 mg dose in treatment-naïve patients with nAMD. Participants were randomized 1:1:1 into three groups: aflibercept 2 mg every 8 weeks (2q8), 8 mg every 12 weeks (8q12), or 8 mg every 16 weeks (8q16) after three initial monthly loading doses. The study demonstrated the benefits of the 8 mg dose in extending interinjection intervals. By week 96, 88% of patients achieved an interval of ≥12 weeks, 71% ≥16 weeks, and 47% ≥20 weeks; in the 8q16 group, 53% of patients reached an interval of ≥20 weeks and 31% - 24 weeks. Over the 2-year period, patients in the 8q16 group received approximately 8 injections, compared to around 13 in the 2q8 group, with comparable anatomical and functional outcomes and no additional safety concerns. Given the proven effectiveness in improving best-corrected visual acuity (BCVA), superior outcomes in resolving intra- and/or subretinal fluid (IRF/SRF), and reduced treatment burden, it appears optimal to broadly transition patients already receiving aflibercept 2 mg to the higher molar concentration (aflibercept 8 mg) regardless of treatment phase or the interinjection interval. This approach aims to achieve a longer anti-VEGF effect duration and sustained DA control with the fewest possible injections.