Abstract
Introduction
To report the development of intraocular inflammation (IOI) in three Japanese patients in the same clinic after intravitreal injections (IVI) of brolucizumab to treat neovascular age-related macular degeneration.
Cases reports
The major findings were: (1) all three eyes had a history of treatment with multiple anti-vascular endothelial growth factor (VEGF) agents; (2) the time to the onset of IOI after the first IVI of brolucizumab varied, i.e., onset occurred after the first IVI in two cases and after the second IVI in one case; (3) the degree of vitreous opacities resulting from the IOI varied among the three cases and directly affected the degree of the decrease in the visual acuity (VA) and the timing of the VA recovery; (4) an injection of triamcinolone acetonide into the sub-Tenon’s capsule (STTA) resulted in resolution of the IOI and improvement of the VA; and (5) the sheathed retinal vessels indicating vasculitis improved associated with reduction of the IOI after STTA.
Comments
Although all three cases responded well to the injection of triamcinolone acetonide into the sub-Tenon’s capsule, physicians should fully disclose to patients both the potential for this adverse effect, especially those patients with a history of anti-VEGF therapy, and the benefits of therapy with brolucizumab. Immediate steroid therapy is recommended to possibly reduce deterioration of the visual function caused by persistent IOI.
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Markham A. Brolucizumab: first approval. Drugs. 2019;79:1997–2000.
Dugel PU, Jaffe GJ, Sallstig P, Warburton J, Weichselberger A, Wieland M, et al. Brolucizumab versus aflibercept in participants with neovascular age-related macular degeneration: a randomized trial. Ophthalmology. 2017;124:1296–304.
Holz FG, Dugel PU, Weissgerber G, Hamilton R, Rufino Silva R, Bandello F, et al. Single-chain anti-body fragment VEGF inhibitor RTH258 for neovascular age-related macular degeneration: a randomized controlled study. Ophthalmology. 2016;123:1080–9.
Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, et al. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology. 2020;127:72–84.
American Society of Retina Specialists. Beovu update for ASRS members. https://www.asrs.org/clinical/clinical-updates Published February 23, 2020 and March 30, 2020.
American Society of Retina Specialists Research and Safety in Therapeutics Committee. Available at; 2020. https://www.asrs.org/about/committees/51. Accessed 3 May 2020.
Haug SJ, Hien DL, Uludag G, Ngoc TTT, Lajevardi S, Halim MS, et al. Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration. Am J Ophthalmol Case Rep. https://doi.org/10.1016/j.ajoc.2020.100680.
Jain A, Chea S, Matsumiya W, M Sohail Halim MS, Çigdem Yaşar C, Guoping Kuang C, et al. Severe vision secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations. Am J Ophthalmol Case Rep. https://doi.org/10.1016/j.ajoc.2020.100687.
Witkin AJ, Hahn P, Murray TG, Arevalo JF, Blinder KJ, Choudhry N, et al. Occlusive retinal vasculitis following intravitreal brolucizumab. J Vitreoretin Dis. 2020;4:269–79.
Baumal CR, Spaide RF, VajzovicL, Freund KB, Walter SD, John V, et al. Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab. Ophthalmology. 22;127:1345–59.
https://www.euretina.org/wp-content/uploads/2020/06/SRC-Report.pdf.
US Food and Drug Administration. Center for Drug Evaluation and Research. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761125Orig1s000SumR.pdf.
US Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761125s000lbl.pdf.
European Medicines Agency Committee for Medicinal Products for Human Use (CHMP). European Medicines Agency assessment report EMA/23630/2020. https://www.ema.europa.eu/en/documents/assessment-report/beovu-epar-public-assessment-report_en.pdf. Accessed 14 Mar 20.
Witkin AJ, Anjali R Shah AR, Engstrom RE, Kron-Gray MM, Baumal CR, et al. Postoperative hemorrhagic occlusive retinal vasculitis. Expanding the clinical spectrum and possible association with vancomycin. Ophthalmology. 2015;122:1438–51.
Witkin AJ, Chang DF, Jumper JM, SC, Eliott D, Hoffman RS, et al. Vancomycin-associated hemorrhagic occlusive retinal vasculitis: clinical characteristics of 36 eyes. Ophthalmology. 2017;124:583–95.
Kuriakose A, Chirmule N, Nair P. Immunogenicity of biotherapeutics: causes and association with posttranslational modifications. J Immunol Res. 2016;2016:1298473.
US Food and Drug Administration. Center for Drug Evaluation and Research. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/125156Orig1s114.pdf.
Food US and Administration Drug. Center for Drug Evaluation and Research. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/125418Orig1s000ClinPharmR.pdf.
Makhoul M, Dewispelaere R, Relvas LJ, et al. Characterization of retinal expression of vascular cell adhesion molecule (VCAM-1) during experimental autoimmune uveitis. Exp Eye Res. 2012;101:27–35.
Lee MT, Hooper LC, Kump L, Hayashi K, Nussenblatt R, Hooks JJ, et al. Interferon-beta and adhesion molecules (E-selectin and s-intracellular adhesion molecule-1) are detected in sera from patients with retinal vasculitis and are induced in retinal vascular endothelial cells by Toll-like receptor 3 signalling. Clin Exp Immunol. 2007;147:71–80.
Kohno T, IshibashiT, Inomata H. Electron microscopic studies of pipestem sheathed vessel in human retina. Jpn J Ophthalmol 1983;27:228–35.
https://drs-net.novartis.co.jp/siteassets/common/pdf/beo/ot/ot_beo_rmp_202006.pdf. (in Japanese).
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Hikichi, T. Three Japanese cases of intraocular inflammation after intravitreal brolucizumab injections in one clinic. Jpn J Ophthalmol 65, 208–214 (2021). https://doi.org/10.1007/s10384-021-00819-7
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DOI: https://doi.org/10.1007/s10384-021-00819-7