Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration

Haug, Sara J.; Hien, Doan Luong; Uludağ, Günay; Than, Ngoc Trong Tuong; Lajevardi, Sherin; Halim, Muhammad Sohail; Sepah, Yasir J.; Diana, V.; Khanani, Arshad M.

doi:10.1016/j.ajoc.2020.100680

Cited by 118 publications

(135 citation statements)

References 19 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: 98%

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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: 98%

“…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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“…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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“…7 , 8 Recently, two case reports and one case series published a variety of presentations for brolucizumab-related intraocular inflammation and occlusive vasculitis, including arterial sheathing, retinal whitening, plaque deposition, venous phlebitis, perivascular hemorrhages, optic disc swelling, and others. 9 , 10 , 11 The American Society of Retinal Specialists (ASRS) also released their Research and Safety in Therapeutics (ReST) committee report on 26 eyes with retinal vasculitis after treatment with brolucizumab. 12 To date, although multiple hypotheses have been made, the mechanism of action for intraocular inflammation and vasculitis due to brolucizumab has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Brolucizumab-related retinal vasculitis with exacerbation following ranibizumab retreatment: A clinicopathologic case study

Iyer¹,

Peden

Suñer

et al. 2020

American Journal of Ophthalmology Case Reports

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Purpose To describe the clinical and pathologic characteristics of a case of retinal vasculitis and vitritis following brolucizumab administration and subsequent ranibizumab treatment. Observations A 76-year old Caucasian woman experienced pain, decreased vision and floaters one week after receiving her third monthly intravitreal brolucizumab injection in the right eye for exudative age-related macular degeneration. Examination was significant for 0.5+ anterior chamber cells, vitritis, mild peripheral vascular sheathing, and decreased vision from 20/70 to 20/200. She was started on topical 1% prednisolone acetate with improvement in her examination. She was switched to ranibizumab one month after her last brolucizumab injection of the right eye. Three weeks after her ranibizumab injection, she noticed photophobia, pain and decreased vision. Examination revealed worsening uveitis, vitritis, vascular sheathing, and decreased vision to count fingers. Despite starting on 0.05% difluprednate drops every 2 hours and oral high-dose methylprednisolone, the patient did not have any significant improvement in her symptoms or examination. She underwent pars plana vitrectomy and vitreous biopsy with intravitreal triamcinolone injection to the right eye. Vitreous biopsy and culture ruled out infectious endophthalmitis, and further cytopathologic analysis revealed chronic inflammatory infiltrate. Conclusion and importance Treatment with brolucizumab can result in intraocular inflammation and retinal vasculitis likely due to a delayed hypersensitivity reaction to the drug, supported by cytopathologic analysis of a vitreous sample. We demonstrate a case where retreatment with an alternative anti-VEGF agent resulted in worsening vision and vasculitis.

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Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration

Cited by 118 publications

References 19 publications

Occlusive Retinal Vasculitis Following Intravitreal Brolucizumab

Occlusive Retinal Vasculitis Following Intravitreal Brolucizumab

RETRACTED ARTICLE: Pharmacological agents in development for diabetic macular edema

Brolucizumab-related retinal vasculitis with exacerbation following ranibizumab retreatment: A clinicopathologic case study

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