Brolucizumab, the most recent approved anti–vascular endothelial growth factor (VEGF) for neovascular age-related macular degenration, demonstrated potential for increased durability as well as superior resolution of fluid on optical coherence tomography in the pivotal phase 3 HAWK and HARRIER trials.¹ Clinicians looked forward to this promising, novel anti-VEGF agent to reduce the treatment burden, and to be a new option for patients with an incomplete response to the other anti-VEGF agents. However, in the months following approval, there were reports of unexpected findings after intravitreal injection of brolucizumab consisting of retinal vascular occlusion (RO) and/or retinal vasculitis (RV), often accompanied with intraocular inflammation (IOI).^2,3 While sterile IOI has been described after intravitreal injection of other anti-VEGFs at an estimated rate between 0.3% to 2.9% per injection, IOI was noted in 4.4% of brolucizumab-treated eyes in HAWK and HARRIER.¹ Noninfectious RO and/or RV have not been reported after the other US Food and Drug Adminstration–approved anti-VEGF agents, so this does not appear to be an anti-VEGF class effect.⁴ Retinal vasculitis and IOI were noted after the investigational anti-VEGF agent abicipar-pegol, which did not receive Food and Drug Adminstration approval. Both brolucizumab and abicipar are novel structures with small molecular weights; these features allow for a higher molar concentration and potential increased tissue penetration, which may increase exposure to the systemic immune system from the eye.⁴

Brolucizumab 是最近获批用于治疗新生血管性年龄相关性黄斑变性的抗血管内皮生长因子 (VEGF)，在关键的 3 期 HAWK 和 HARRIER 试验中，在光学相干断层扫描中显示出提高耐久性和出色流体分辨率的潜力。¹临床医生期待这种有前途的新型抗 VEGF 药物能够减轻治疗负担，并成为对其他抗 VEGF 药物反应不完全的患者的新选择。然而，在批准后的几个月内，有报道称玻璃体内注射 brolucizumab 后出现意外发现，包括视网膜血管阻塞 (RO) 和/或视网膜血管炎 (RV)，通常伴有眼内炎症 (IOI)。^{2 ,3}虽然在玻璃体内注射其他抗 VEGF 后已描述了无菌 IOI，估计每次注射的比率在 0.3% 至 2.9% 之间，但在 HAWK 和 HARRIER 中，4.4% 的 brolucizumab 治疗的眼睛出现了 IOI。¹在美国食品和药物管理局批准的其他抗 VEGF 药物之后，未报告非感染性 RO 和/或 RV，因此这似乎不是抗 VEGF 类效应。⁴在研究性抗 VEGF 药物 abicipar-pegol 后发现视网膜血管炎和 IOI，该药物未获得食品和药物管理局的批准。brolucizumab 和 abicipar 都是具有小分子量的新型结构；这些特征允许更高的摩尔浓度和潜在的增加组织渗透，这可能会增加眼睛对全身免疫系统的暴露。⁴