Fursova A Zh, Nikulich I F, Vasilyeva M A, Derbeneva A S, Karlash Yu A
Novosibirsk State Regional Hospital, Novosibirsk, Russia.
Novosibirsk State Medical University, Novosibirsk, Russia.
Vestn Oftalmol. 2025;141(3):71-78. doi: 10.17116/oftalma202514103171.
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.
新生血管性年龄相关性黄斑变性（nAMD）是一种进行性视网膜疾病，尽管有有效的抗血管内皮生长因子（VEGF）药物，但仍可导致严重且不可逆的视力丧失。nAMD治疗效果欠佳的潜在原因之一是治疗不足，这可能是由于需要频繁注射和随访、公共医疗资金有限以及在实现疾病活动（DA）的持续长期控制方面存在挑战所致。阿柏西普8mg是一种新型制剂，具有更高的浓度和更好的分子稳定性，能使输送到玻璃体的活性物质摩尔剂量增加四倍。III期PULSAR试验是一项为期96周的随机、双盲、活性对照研究，评估了8mg阿柏西普与标准2mg剂量相比，在初治nAMD患者中的疗效和安全性。参与者按1:1:1随机分为三组：在最初每月三次负荷剂量后，每8周注射2mg阿柏西普（2q8）、每12周注射8mg阿柏西普（8q12）或每16周注射8mg阿柏西普（8q16）。该研究证明了8mg剂量在延长注射间隔方面的益处。到96周时，88%的患者实现了≥12周的间隔，71%实现了≥16周的间隔，47%实现了≥20周的间隔；在8q16组中，53%的患者达到了≥20周的间隔，31%达到了20 - 24周的间隔。在两年期间，8q16组的患者接受了约8次注射，而2q8组约为13次，两组的解剖学和功能结果相当，且无额外的安全问题。鉴于在改善最佳矫正视力（BCVA）方面已证实的有效性、在解决视网膜内和/或视网膜下液（IRF/SRF）方面的卓越结果以及减轻治疗负担，无论治疗阶段或注射间隔如何，将已接受2mg阿柏西普治疗的患者广泛转换为更高摩尔浓度（阿柏西普8mg）似乎是最佳选择。这种方法旨在通过尽可能少的注射次数实现更长的抗VEGF作用持续时间和持续的DA控制。
