Brolucizumab-related intraocular inflammation in Japanese patients with age-related macular degeneration: a short-term multicenter study

Ichiro Maruko & Annabelle A. Okada & Tomohiro Iida & Taiji Hasegawa & Takahiko Izumi & Moeko Kawai & Ruka Maruko & Makiko Nakayama & Akiko Yamamoto & Hideki Koizumi & Tamaki Tamashiro & Nobuhiro Terao & Sorako Wakugawa & Ryusaburo Mori & Hajime Onoe & Koji Tanaka & Yu Wakatsuki & Kanako Itagaki & Akihito Kasai & Masashi Ogasawara & Tetsuju Sekiryu & Hiroaki Shintake & Yukinori Sugano & for the Japan AMD Research Consortium

Brolucizumab was approved in Japan in May 2020 and used to treat 149 eyes of 149 patients over the 6-month period May-November 2020 by the Japan AMD Research Consortium. Clinical data for 127 eyes of 127 consecutive patients who had at least 1 follow-up visit after the first brolucizumab injection were retrospectively analyzed. Fortythree patients were treatment-naive (36 men, 7 women) and 84 patients were switched from other anti-VEGF agents (73 men, 11 women).
Mean follow-up after the first brolucizumab injection was 12.4 ± 4.7 (range 4-24) weeks. Of 127 eyes, 12 (9.4%) developed IOI consisting of anterior chamber cells and/or vitreous cells, with retinal vasculitis documented in 4 eyes (3.1%) and retinal vascular occlusion in 2 eyes (1.6%) ( Table 1). The IOI was noted after the first injection in 9 eyes at a mean of 23.2 ± 9.3 (range 10-36) days post-injection; in the remaining 3 eyes, it occurred after the second or third injections. Rates of IOI were similar for treatment-naive cases (9.3%) and switched cases (9.5%), and were not higher in women (Table 2). IOI was treated with topical corticosteroids (0.1% betamethasone eyedrops) in all eyes and additional sub-Tenon's injection of triamcinolone acetonide (20 mg) in the 4 eyes with retinal vasculitis. No patient received systemic corticosteroids. Active inflammation resolved within 2 months in all patients. Although the retinal vascular occlusion observed in 2 eyes was located outside the vascular arcades, visual acuity decreased markedly from 74 to 35 Early Treatment of Diabetic Retinopathy Study letters then improved to 65 letters in 1 month for one eye, and decreased from 59 to 50 letters then improved to 65 letters in 1 month for the other eye.
Overall, the SRC found IOI in 4.6% of patients, retinal vasculitis in 3.3%, and retinal vascular occlusion in 2.1%. However, among 101 Japanese patients enrolled in the HAWK study, the rates were 2-to 3-fold higher; IOI in 12.9%, retinal vasculitis in 9.9%, and retinal vascular occlusion in 4.95% [5]. In addition, Heier et al. reported that female gender was associated with higher risk for IOI [4]. Previous case reports of IOI associated with brolucizumab were also predominantly in women [6]. The reasons for higher rates of inflammatory adverse effects in Japanese or women have yet to be delineated.
Because Japanese patients may be at higher risk, we believe it is important to report our early experience with brolucizumab over our first 6 months of use. We found IOI rates to be between 9 and 10%, still high but slightly lower than reported by the SRC for Japanese trial patients. The majority (75%) occurred after the first injection, and one-third developed retinal vasculitis or retinal vascular occlusion.

Declarations
Ethics approval This was a retrospective study, and the procedures used conformed to the tenets of the Declaration of Helsinki. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.