Noninfectious Inflammatory Response following Intravitreal Bevacizumab Injections: Description of a Cluster of Cases in Two Centers and a Review of the Literature

Abstract

Purpose: To report a cluster of high incidence of noninfectious inflammatory reaction shortly after bevacizumab injection. Methods: Data were collected from medical records of consecutive patients who underwent bevacizumab injections and presented with acute uveitis within 1–4 days. Results: All 7 patients were injected intravitreally with bevacizumab from different batches and presented with visual deterioration. One patient with anterior uveitis complained of pain. None had hypopyon. Three patients with vitritis underwent a vitreous tap with an intravitreal injection of vancomycin and ceftazidime for possible infectious endophthalmitis. All patients received intensive topical antibiotic drops and steroids, and the intraocular inflammation resolved completely within 1 month. Five patients continued to receive bevacizumab injections without recurrent episodes. Conclusions: Our series demonstrates an incidence of noninfectious inflammatory reaction shortly after bevacizumab injection that is higher than that reported in the literature. The cause is more likely the preparation process in the same compounding pharmacy.

<p>Evaluation of the Safety of Bilateral Same-Day Intravitreal Injections of Anti-Vascular Endothelial Growth Factor Agents: Experience of a Large Korean Retina Center</p>

“…Trivizki et al analyzed non-infectious inflammatory reactions after intravitreal bevacizumab injections in 2018 and concluded that 1.78% of patients with uveitis presented with anterior inflammatory cells after injection. 22 However, when classifying the degree of inflammation as mild-to-moderate, they did not include traces and defined the minimum level of cell count as 1+. Therefore, according to their classification criteria, the frequency of acute intraocular inflammation in our study would be 0.85%, which was less than that reported by Trivizki et al Wickremasinghe et al analyzed acute intraocular inflammation after monocular bevacizumab injection.…”

Manifestations of intraocular inflammation over time in patients on brolucizumab for neovascular AMD

“…In the pivotal nAMD trials for the approved anti-VEGF drugs, rates of IOI were reported to be ≤ 2.1% in ANCHOR and MARINA (any ocular inflammation of grade 3 or 4), ≤ 1.5% in VIEW 1 and VIEW 2, and ≤ 4.7% in HAWK and HARRIER [3][4][5][6]. IOI following anti-VEGF treatment often manifests as presence of cells in the anterior chamber or vitreous with reduced or blurred vision, which is typically treated with topical steroids and generally resolves without complication [2,[7][8][9][10][11][12]. Since FDA approval of brolucizumab in October 2019, there have been post-marketing reports of events of retinal vasculitis (RV) and retinal vascular occlusion (RO) associated with IOI following administration of brolucizumab [13,14].…”

<p>Issues with Intravitreal Administration of Anti-VEGF Drugs</p>

“…Several small series of intraocular inflammation after intravitreal injections of anti-VEGF presenting as uveitis have been described in the literature. 39 Non-infectious vitritis has been reported by Williams et al in 0.10% after 66,356 bevacizumab injections, 0.02% after 26,161 ranibizumab injections and 0.16% after 8071 aflibercept injections. 40 A true immune reaction to the anti-VEGF drug itself might be the explanation for the sporadic cases in which a rechallenge does result in a recurrent uveitis event.…”