臨床眼科76巻5号

2022年05月発行

連載 今月の話題

抗VEGF薬に関連した感染性/非感染性眼内炎症

著者： 安藤亮¹ 石田晋¹

所属機関： ¹北海道大学大学院医学研究院眼科学教室

ページ範囲：P.581 - P.588

　2020年5月，待望の滲出型加齢黄斑変性に対する新しい薬剤が販売された。しかし，これには網膜血管炎，網膜血管閉塞という今までにない副作用があった。実は，硝子体内注射には無菌性眼内炎という炎症性有害事象が以前からあった。本稿では，忌むべき感染性眼内炎を含めて，これらの炎症性有害事象について述べていきたい。

参考文献

1）Singh RP：Global Trends in Retina. American Society of Retina Specialists：2018〔https://www.asrs.org/cotent/documents/2018-global-trends-in-retina-survey-highlights-website.pdf（閲覧日：2021年12月22日）〕

2）Cox JT, Eliott D, Sobrin L：Inflammatory complications of intravitreal anti-VEGF injections. J Clin Med 10：981, 2021

3）Reyes-Capo DP, Yannuzzi NA, Smiddy WE et al：Trends in endophthalmitis associated with intravitreal injection of anti-VEGF agents at a tertiary referral center. Ophthalmic Surg Lasers Imaging Retina 52：319-326, 2021

4）Shah CP, Garg SJ, Vander JF et al：Outcomes and risk factors associated with endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. Ophthalmology 118：2028-2034, 2011

5）McCannel CA：Meta-analysis of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents：causative organisms and possible prevention strategies. Retina 31：654-661, 2011

6）Storey P, Dollin M, Pitcher J et al：The role of topical antibiotic prophylaxis to prevent endophthalmitis after intravitreal injection. Ophthalmology 121：283-289, 2014

7）Morioka M, Takamura Y, Nagai K et al：Incidence of endophthalmitis after intravitreal injection of an anti-VEGF agent with or without topical antibiotics. Sci Rep 10：22122, 2020

8）Avery RL, Bakri SJ, Blumenkranz MS et al：Intravitreal injection technique and monitoring：updated guidelines of an expert panel. Retina 34：S1-S18, 2014

9）Williams PD, Chong D, Fuller T et al：Noninfectious vitritis after intravitreal injection of anti-VEGF agents：variations in rates and presentation by medication. Retina 36：909-913, 2016

10）Daien V, Nguyen V, Essex RW et al：Incidence and outcomes of infectious and noninfectious endophthalmitis after intravitreal injections for age-related macular degeneration. Ophthalmology 125：66-74, 2018

11）Greenberg JP, Belin P, Butler J et al：Aflibercept-related sterile intraocular inflammation outcomes. Ophthalmol Retina 3：753-759, 2019

12）Hahn P, Chung MM, Flynn HW Jr et al：Postmarketing analysis of aflibercept-related sterile intraocular inflammation. JAMA Ophthalmol 133：421-426, 2015

13）Sharma A, Kumar N, Parachuri N et al：Brolucizumab and immunogenicity. Eye（Lond）34：1726-1728, 2020

14）Souied EH, Dugel PU, Ferreira A et al：Severe ocular inflammation following ranibizumab or aflibercept injections for age-related macular degeneration：a retrospective claims database analysis. Ophthalmic Epidemiol 23：71-79, 2016

15）Sahni J, Dugel PU, Patel SS et al：Safety and efficacy of different doses and regimens of faricimab vs ranibizumab in neovascular age-related macular degeneration：the AVENUE phase 2 randomized clinical trial. JAMA Ophthalmol 138：955-963, 2020

16）Heier JS, Antoszyk AN, Pavan PR et al：Ranibizumab for treatment of neovascular age-related macular degeneration：a phase I/II multicenter, controlled, multidose study. Ophthalmology 113：633-642, 2006

17）Anderson WJ, da Cruz NFS, Lima LH et al：Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs：a narrative review. Int J Retina Vitreous 7：37, 2021

18）Krayukhina E, Yokoyama M, Hayashihara KK et al：An assessment of the ability of submicron- and micron-size silicone oil droplets in dropped prefillable syringes to invoke early- and late-stage immune responses. J Pharm Sci 108：2278-2287, 2019

19）Melo GB, Figueira ACM, Batista FAH et al：Inflammatory reaction after aflibercept intravitreal injections associated with silicone oil droplets released from syringes：a case-control study. Ophthalmic Surg Lasers Imaging Retina 50：288-294, 2019

20）Haug SJ, Hien DL, Uludag G et al：Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration. Am J Ophthalmol Case Rep 18：100680, 2020

21）Monés J, Srivastava SK, Jaffe GJ et al：Risk of inflammation, retinal vasculitis and retinal occlusion-related events with brolucizumab：post hoc review of HAWK and HARRIER. Ophthalmology 128：1050-1059, 2021

22）Maruko I, Okada AA, Iida T et al：Brolucizumab-related intraocular inflammation in Japanese patients with age-related macular degeneration：a short-term multicenter study. Graefes Arch Clin Exp Ophthalmol 259：2857-2859, 2021

23）Matsumoto H, Hoshino J, Mukai R et al：Short-term outcomes of intravitreal brolucizumab for treatment-naïve neovascular age-related macular degeneration with type 1 choroidal neovascularization including polypoidal choroidal vasculopathy. Sci Rep 11：6759, 2021

24）Kataoka K, Horiguchi E, Kawano K et al：Three cases of brolucizumab-associated retinal vasculitis treated with systemic and local steroid therapy. Jpn J Ophthalmol 65：199-207, 2021

25）Baumal CR, Bodaghi B, Singer M et al：Expert opinion on management of intraocular inflammation, retinal vasculitis, and vascular occlusion after brolucizumab treatment. Ophthalmol Retina 5：519-527, 2021

26）European Medicines Agency Committee for Medicinal Products for Human Use（CHMP）. Beovu Public Assessment Report. 2019〔Available online：https://www.ema.europa.eu/en/documents/assessment-report/beovu-epar-public-assessment-report_en.pdf（閲覧日：2021年12月22日）〕

27）Australian Public Assessment Report for Brolucizumab（rbe）〔Available online：https://www.tga.gov.au/auspar/auspar-brolucizumab-rbe（閲覧日：2021年12月22日）〕

28）Sharma A, Kumar N, Parachuri N et al：Understanding retinal vasculitis associated with brolucizumab：complex pathophysiology or Occam's razor? Ocul Immunol Inflamm 20：1-3, 2021

29）Hikichi T：Three Japanese cases of intraocular inflammation after intravitreal brolucizumab injections in one clinic. Jpn J Ophthalmol 65：208-214, 2021