Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations

Jain, Atul; Chea, Sophaktra; Matsumiya, Wataru; Halim, Muhammad Sohail; Yaşar, Çigdem; Kuang, Guo-Ping; Sepah, Yasir J.; Khanani, Arshad M.; Diana, V.; Nguyen, Quan Dong

doi:10.1016/j.ajoc.2020.100687

Cited by 96 publications

(99 citation statements)

References 16 publications

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“…First, voluntary reporting of AEs is inherently subject to underreporting, and we are aware of other cases of retinal vasculitis after brolucizumab that have not been reported to the ASRS, including 2 recently published case reports. 2,3 We are also aware of other case series being collected, and there is likely some overlap of cases with our series. Second, cases of retinal vasculitis may be mild and difficult to detect without a careful dilated fundus examination and/or angiography.…”

Section: Epidemiologymentioning

confidence: 99%

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Occlusive Retinal Vasculitis Following Intravitreal Brolucizumab

Witkin

Hahn

Murray³

et al. 2020

Journal of VitreoRetinal Diseases

146

211

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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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Section: Epidemiologymentioning

confidence: 99%

“…Two case reports were recently published describing this phenomenon. 2,3 The purpose of this study is to analyze the characteristics of postapproval cases of retinal vasculitis voluntarily reported to the ASRS as of April 1, 2020.…”

Section: Introductionmentioning

confidence: 99%

Occlusive Retinal Vasculitis Following Intravitreal Brolucizumab

Witkin

Hahn

Murray³

et al. 2020

Journal of VitreoRetinal Diseases

146

211

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“…In February 2020, only months after brolucizumab’s FDA approval, the American Society of Retinal Specialists (ASRS) announced it had “received reports of [brolucizumab-associated] inflammation which included more than a dozen cases of vasculitis, of which greater than two-thirds were designated as occlusive retinal vasculitis by the reporting providers” [ 58 ]. Early case reports outlined post-injection inflammation and retinal vasculitis that was often occlusive and associated with significant vision loss [ 59 , 60 ].…”

Section: Brolucizumab-associated Retinal Vasculitismentioning

confidence: 99%

Inflammatory Complications of Intravitreal Anti-VEGF Injections

Cox

Eliott

Sobrin

2021

JCM

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Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents is a commonly used therapy for numerous retinal diseases. The most commonly used of these medications are bevacizumab, ranibizumab, aflibercept, and brolucizumab. However, intravitreal administration of these agents is also associated with several inflammatory and non-inflammatory adverse events. The three inflammatory adverse events are sterile intraocular inflammation, brolucizumab-associated retinal vasculitis, and post-injection endophthalmitis. This narrative review summarizes the current literature regarding these conditions, including their epidemiology, presentation, management, outcomes, and pathogenesis. The inflammatory adverse events also share a number of overlapping features, which can make them difficult to discern from one another in a clinical context. This review discusses certain distinguishing features of these conditions that may aid providers in discerning between them and establishing the correct diagnosis.

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“…Although the initial results with brolucizumab have been promising, the drug's safety is currently under review due to reports of clinically significant intraocular inflammation and occlusive retinal vasculitis associated with the study drug in the HAWK and HARRIER studies as well as in patients with neovascular AMD treated with brolucizumab after the drug was approved by the FDA [26][27][28][29][30]. In addition, Novartis, the manufacturer of brolucizumab, has also reported the occurrence of vitritis and retinal vasculitis in subjects with DME being treated with RTH 258 in current studies [31,32].…”

Section: Brolucizumabmentioning

confidence: 99%

RETRACTED ARTICLE: Pharmacological agents in development for diabetic macular edema

et al. 2020

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Background: Diabetic macular edema (DME) is the leading cause of visual loss in patients with diabetic retinopathy. There has been a paradigm shift in the treatment of DME since the advent of anti-vascular endothelial growth factor (anti-VEGF) therapy. The safety and efficacy of anti-VEGF therapy has been well established. Although efficacious, currently approved anti-VEGF agents are associated with certain limitations, which include, among others: frequent need for injections, high treatment cost and variable response to treatment. These challenges have led to an active search for more novel agents that may be able to overcome these limitations. Areas covered: The index review focuses on novel treatment agents that target various pathways in patients with DME. These agents are used either as monotherapy or in combination with other agents in the management of DME. Drugs discussed include novel anti-VEGF inhibitors, TIE-2 receptor modulators, integrin peptide inhibitors, rho kinase inhibitors, and future therapies such as neuroprotection and gene therapy. Conclusions: The future of investigational pharmacological therapy appears promising for patients with DME. Results from early clinical trials indicate that newer agents highlighted in the study may be safe and efficacious treatment options for patients with DME. However, data from large multicenter clinical trials need to be analyzed before these agents can be incorporated into clinical practice.

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Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations

Cited by 96 publications

References 16 publications

Occlusive Retinal Vasculitis Following Intravitreal Brolucizumab

Occlusive Retinal Vasculitis Following Intravitreal Brolucizumab

Inflammatory Complications of Intravitreal Anti-VEGF Injections

RETRACTED ARTICLE: Pharmacological agents in development for diabetic macular edema

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