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Invited Commentary
November 24, 2021

Risk Factors for Intraocular Inflammation After Brolucizumab Treatment

Author Affiliations
  • 1New England Eye Center, Tufts Medical Center, Boston, Massachusetts
JAMA Ophthalmol. 2022;140(1):28-29. doi:10.1001/jamaophthalmol.2021.4586

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

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