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Occlusive Retinal Vasculitis Following Intravitreal Brolucizumab
Open accessAbstract
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.
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Average time to presentation was 53 days after the last brolucizumab injection (range 8-137 days).
“Average time to presentation was 53 days after the last brolucizumab injection (range 8–137 days).”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [37]
The Results (Demographics; page not provided) report a mean time to presentation of 26 days after the most recent brolucizumab injection (range 3–63 days). The 53-day mean and 8–137-day range appear in Results (Outcomes), but measure time from the last injection to the most recent follow-up visit, not to presentation. (LLM, conf=0.94)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe largest study outside of the clinical trials to date evaluating retinal vasculitis after brolucizumab is a retrospective analysis of 26 eyes from 25 patients that were reported to the ASRS.
“The largest study outside of the clinical trials to date evaluating retinal vasculitis after brolucizumab is a retrospective analysis of 26 eyes from 25 patients that were reported to the ASRS [37].”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [37]
The Methods and Results > Demographics sections describe an analysis of ASRS reports covering 26 eyes from 25 patients after brolucizumab treatment. The Conclusions > Epidemiology section mentions other case reports and series being collected, but does not establish that this was the largest study outside clinical trials to date. Page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe average time to presentation in recent case series has ranged from 30 to 53 days after injection.
“The average time to presentation in recent case series has ranged from 30 to 53 days after injection [37, 38].”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [37]
The Results > Demographics section reports a mean time to presentation of 46 days from the first brolucizumab injection, which falls within the claimed range. But it reports 26 days from the most recent injection, below the claimed 30-day lower bound. The 53 days in Results > Outcomes measures time to the most recent follow-up visit, not time to presentation; page numbers were not provided in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredFemale predominance in brolucizumab-associated retinal vasculitis may point towards an auto-immune response.
“The female predominance of brolucizumab-associated retinal vasculitis reported by Witkin et al. (22 of 25 patients were female) may point towards an auto-immune response, although no definitive correlation to auto-immune disease has been made [37].”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [37]
Results > Demographics reports that 22 of 25 patients were women. Conclusions > Etiology considers a possible immune-mediated mechanism, but Conclusions > Epidemiology says the apparent sex disparity could be due to chance and does not link it to an autoimmune response; it also finds no indication of an association with autoimmune disease. Page numbers are not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAnterior chamber cell was present in 65% of eyes.
“Anterior chamber cell was present in 65% of eyes.”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [37]
Occlusive vasculitis was noted in 85% of eyes.
“Occlusive vasculitis was noted in 85% of eyes [37].”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [37]
Patients had variable extent of retinal vasculitis, with involvement of retinal arteries, veins or choroidal vessels.
“Patients had variable extent of retinal vasculitis, with involvement of retinal arteries, veins or choroidal vessels.”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [37]
Choroidal ischemia was noted in 10 of 21 eyes.
“Choroidal ischemia was noted in 10 of 21 eyes.”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [37]
At final follow up, mean final BCVA was 20/243 and 46% had a greater than 3-line decrease in visual acuity.
“At final follow up, mean final BCVA was 20/243 and 46% had a greater than 3-line decrease in visual acuity.”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [37]
Clinical presentation was variable, however 92% of eyes exhibited signs of either anterior inflammation and/or posterior inflammation.
“Clinical presentation was variable, however 92% of eyes exhibited signs of either anterior inflammation and/or posterior inflammation.”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [37]
This study showed that BCVA worsened from an average baseline of 20/52 to 20/151 at time of presentation.
“This study showed that BCVA worsened from an average baseline of 20/52 to 20/151 at time of presentation.”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [37]
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Metadata
- Authors
- Witkin, A. J., Hahn, P., Murray, T. G., Arevalo, J. F., Blinder, K. J., Choudhry, N., Emerson, G. G., Goldberg, R. A., Kim, S. J., Pearlman, J., Schneider, E. W., Tabandeh, H., & Wong, R. W.
- Affiliations
- Tufts Medical Center, Boston, MA, USA
- NJ Retina, Teaneck, NJ, USA
- Murray Ocular Oncology and Retina, Miami, FL, USA
- Wilmer Eye Institute at Johns Hopkins Hospital, Baltimore, MD, USA
- Retina Institute (US)
- Vitreous Retina Macula Specialists of Toronto, Toronto, ON, Canada
- The Retina Center (US)
- Bay Area Retina Associates (US)
- Vanderbilt University Medical Center (US)
- Retinal Consultants, Sacramento, CA, USA
- Tennessee Retina (US)
- Retina Vitreous Associates Medical Group (US)
- Austin Retina Associates, Austin, TX, USA
- Corresponding author
- Hahn, Paul
- ORCID
- Venue
- Journal of VitreoRetinal Diseases
- Publisher
- SAGE Publications
- Published
- 2020-07
- Volume
- 4
- Issue
- 4
- Pages
- 269-279
- ISSN
- 2474-1264 (ISSN-L)
- 2474-1272
- PMC
- PMC7418897
- OpenAlex
- W3040108021
- Cited by
- 183
- References
- 19
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 27 · 2023: 34 · 2022: 41 · 2021: 46 · 2020: 3
- FWCI
- 24.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of VitreoRetinal Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (EY027691)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Keywords
- brolucizumab, occlusive retinal vasculitis, neovascular age-related macular degeneration, intraocular inflammation, retinal vascular disease, vision loss, anti-VEGF therapy, drug safety
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