Occlusive Retinal Vasculitis Following Intravitreal Brolucizumab

Abstract

Purpose: To analyze a case series of retinal vasculitis reported to the American Society of Retina Specialists (ASRS) following Food and Drug Administration approval of brolucizumab for treatment of neovascular age-related macular degeneration.

Methods: The ASRS Research and Safety in Therapeutics Committee analyzed clinical and imaging characteristics from submitted reports of retinal vasculitis after brolucizumab.

Results: Retinal vasculitis was reported in 26 eyes of 25 patients (22 [88%] female) after treatment with brolucizumab. Imaging studies were available for 24 of 26 eyes. Most cases (92%) were associated with intraocular inflammation, which presented at a mean of 25 days (range, 3-63 days) after the most recent brolucizumab injection. Mean visual acuity (VA) was 20/52 (range, 20/25-4/200) before the adverse event, 20/151 (range, 20/25-hand motion) at presentation of the adverse event, and 20/243 (range, 20/30-light perception) at last follow-up. Twelve eyes (46%) had a greater than 3-line decrease in VA at final follow-up, and 12 eyes (46%) had a final VA of 20/200 or worse. Analysis of retinal imaging identified vasculopathy that involved retinal arteries (91%), retinal veins (79%), and choroidal vessels (48%). Occlusive disease was apparent on imaging in 83% of eyes. Treatment approaches were varied.

Conclusions: Retinal vasculitis has been identified in a series of eyes following brolucizumab. Although a few eyes in this series were asymptomatic or minimally symptomatic, some eyes had significant vision loss. A careful examination for signs of active inflammation prior to brolucizumab injection is recommended. Once vasculopathy is suspected, angiographic imaging may help define the spectrum of involvement. Optimal treatment strategies remain unknown.

Keywords: anti-VEGF agents; branch retinal artery occlusion; central retinal artery occlusion; uveitis; vitritis.

Conflict of interest statement

Declaration of Conflicting Interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Relevant potential conflicts of interest are reported as follows: A.J.W.: none; P.H.: Genentech (consultant, lecture fees) and Allergan (consultant); T.G.M.: none; J.F.A.: Springer SBM LLC (patents/royalties), DORC International B.V. (consultant, lecture fees), Allergan Inc (consultant, lecture fees), Bayer (consultant, lecture fees), Mallinckrodt (consultant), and TOPCON (grant support); K.J.B.: Bausch&Lomb (consultant, lecture fees), Allergan (consultant, lecture fees), Regeneron (consultant, lecture fees), Novartis (consultant, lecture fees), and Genentech (consultant); N.C.: Allergan (consultant), Bayer (consultant), Novartis (consultant); G.G.E.: Novartis (stock), and Regeneron (stock); R.A.G: Genentech (research, speaker, advisory), Regeneron (advisory), Novartis (research, speaker, advisory), Allergan (research, speaker, advisory), Aerie (research), Santen (research), Graybug (research), and NovoNordisk (research); S.J.K.: none; J.P.: none; E.W.S.: none; H.T.: Alimera (stock); R.W.W.: Novartis (research).

Figures

Figure 1.

A 72-year-old woman with asymptomatic brolucizumab-associated occlusive retinal vasculopathy in the left eye, noted on routine follow-up 63 days after her third brolucizumab injection. (A) No intraocular inflammation was reported, but occlusion of an inferotemporal arteriole was visible. (B) Fluorescein angiography demonstrated arterial and venous filling defects with associated ischemia in this area, which persisted into the late phase and spared the macula.

Figure 2.

A 92-year-old woman with intraocular inflammation in the right eye that subsequently progressed to symptomatic occlusive retinal vasculitis, noted 24 days after her first (and only) brolucizumab injection. (A) Posterior examination revealed vitritis, arterial sheathing/occlusion, and patchy retinal whitening most prominently in the peripapillary region. (B) Early-phase fluorescein angiography revealed retinal arterial and venous filling defects and choroidal hypofluorescence consistent with hypoperfusion in a large patch around the optic nerve as well as in several smaller multifocal areas. (C) Middle- and late-phase fluorescein angiography images demonstrated slowly resolving choroidal hypoperfusion, persistent arterial and venous filling defects, and focal leakage around arterioles superiorly and inferiorly.

Figure 3.

A 78-year-old man with intraocular inflammation progressing to symptomatic occlusive retinal vasculitis in the left eye 34 days after his first (and only) brolucizumab injection. (A) Early-phase fluorescein angiography revealed diffuse retinal arterial and venous filling defects with extensive ischemia and choroidal hypoperfusion in several small multifocal areas. (B) Late-phase fluorescein angiography images demonstrated persistent arterial and venous filling defects, focal leakage around arterioles and venules, slowly resolving choroidal hypoperfusion, and mild optic nerve hyperfluorescence. (C) Optical coherence tomography showed hyperreflective thickening of the inner retinal layers in the nasal macula, consistent with acute retinal ischemia.

Figure 4.

An 87-year-old woman with intraocular inflammation progressing to symptomatic occlusive retinal vasculitis in the right eye, noted 58 days following her only brolucizumab injection. Visualization is hazy with 3+ anterior chamber cells, but retinal arterial occlusion/sheathing is visible along the superotemporal arcade with prominent macular whitening and a cherry-red spot.