Brolucizumab, the most recent approved anti–vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration, 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
Baumal CR. Risk Factors for Intraocular Inflammation After Brolucizumab Treatment. JAMA Ophthalmol. 2022;140(1):28–29. doi:10.1001/jamaophthalmol.2021.4586
Artificial Intelligence Resource Center
Customize your JAMA Network experience by selecting one or more topics from the list below.