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Short-term results for brolucizumab in treatment-naïve neovascular age-related macular degeneration: a Japanese multicenter study



To investigate short-term treatment outcomes of intravitreal brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (AMD) in a Japanese multicenter study.

Study design

Retrospective case control study


The subjects were 58 eyes of 57 patients with neovascular AMD (43 men and 14 women, mean age 74.6 years) of whom 43 eyes of 42 patients completed initial loading of 3 monthly IVBr injections and were followed for more than 3 months. Best-corrected visual acuity (BCVA) changes, anatomical outcomes, and complications were investigated.


Of the 43 eyes that completed loading doses, the AMD subtype was type 1 and type 2 macular neovascularization (MNV) in 51%, polypoidal choroidal vasculopathy (PCV) in 42%, and type 3 MNV in 7%. At 3 months after initiating treatment, BCVA significantly improved (P = 0.002) and central retinal thickness significantly decreased (P < 0.0001). At 3 months, complete retinal and subretinal fluid resolution was achieved in 91% of all eyes and complete regression of polypoidal lesions was achieved in 82% of PCV eyes. Iritis occurred in 8 eyes of 8 patients (14%), but resolved using topical or subtenon corticosteroid injection without visual loss in all cases.


IVBr for treatment-naïve neovascular AMD was effective in the short-term, achieving significantly improved BCVA, good retinal fluid resolution, and a high rate of polypoidal lesion regression. However, iritis was noted in 14% of patients which may limit use of this drug.

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  1. Wong TY, Chakravarthy U, Klein R, Mitchell P, Zlateva G, Buggage R, et al. The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis. Ophthalmology. 2008;115:116–26.

    Article  Google Scholar 

  2. Hara C, Wakabayashi T, Fukushima Y, Sayanagi K, Kawasaki R, Sato S, et al. Tachyphylaxis during treatment of exudative age-related macular degeneration with aflibercept. Graefes Arch Clin Exp Ophthalmol. 2019;257:2559–69.

    CAS  Article  Google Scholar 

  3. Eghøj MS, Sørensen TL. Tachyphylaxis during treatment of exudative age-related macular degeneration with ranibizumab. Br J Ophthalmol. 2012;96:21–3.

    Article  Google Scholar 

  4. Honda S, Yanagi Y, Koizumi H, Chen Y, Tanaka S, Arimoto M, et al. Impact of neovascular age-related macular degeneration: burden of patients receiving therapies in Japan. Sci Rep. 2021;11: 13152.

    CAS  Article  Google Scholar 

  5. Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, HAWK and HARRIER Study Investigators, 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.

    Article  Google Scholar 

  6. Dugel PU, Singh RP, Koh A, Ogura Y, Weissgerber G, Gedif K, et al. HAWK and HARRIER: Ninety-six-week outcomes from the Phase 3 trials of Brolucizumab for neovascular age-related macular degeneration. Ophthalmology. 2021;128:89–99.

    Article  Google Scholar 

  7. Brolucizumab MA. First approval. Drugs. 2019;79:1997–2000.

    Article  Google Scholar 

  8. 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.

    Article  Google Scholar 

  9. Baumal CR, Spaide RF, Vajzovic L, Freund KB, Walter SD, John V, et al. Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab. Ophthalmology. 2020;127:1345–59.

    Article  Google Scholar 

  10. Monés J, Srivastava SK, Jaffe GJ, Tadayoni R, Albini TA, Kaiser PK, et al. Risk of inflammation, retinal vasculitis, and retinal occlusion-related events with brolucizumab: post hoc review of HAWK and HARRIER. Ophthalmology. 2021;128:1–10.

    Article  Google Scholar 

  11. Singer M, Albini TA, Seres A, Baumal CR, Parikh S, Gale R, et al. Clinical characteristics and outcomes of eyes with intraocular inflammation after brolucizumab: post hoc analysis of HAWK and HARRIER. Ophthalmol Retina. 2021;6:97–108.

    Article  Google Scholar 

  12. Hikichi T. 3 Japanese cases of intraocular inflammation after intravitreal brolucizumab injections in one clinic. Jpn J Ophthalmol. 2021;65:208–14.

    CAS  Article  Google Scholar 

  13. Kataoka K, Horiguchi E, Kawano K, Ushida H, Nakano Y, Ito Y, et al. 3 cases of brolucizumab-associated retinal vasculitis treated with systemic and local steroid therapy. Jpn J Ophthalmol. 2021;65:199–207.

    CAS  Article  Google Scholar 

  14. Maruko I, Okada AA, Iida T, Hasegawa T, Izumi T, Kawai M, Japan AMD Research Consortium, et al. Brolucizumab-related intraocular inflammation in Japanese patients with age-related macular degeneration: a short-term multicenter study. Graefes Arch Clin Exp Ophthalmol. 2021;259:2857–9.

    CAS  Article  Google Scholar 

  15. Enríquez AB, Baumal CR, Crane AM, Witkin AJ, Lally DR, Liang MC, et al. Early experience with brolucizumab treatment of neovascular age-related macular degeneration. JAMA Ophthalmol. 2021;139:441–8.

    Article  Google Scholar 

  16. Bulirsch LM, Saßmannshausen M, Nadal J, Liegl R, Thiele S, Holz FG. Short-term real-world outcomes following intravitreal brolucizumab for neovascular AMD: SHIFT study. Br J Ophthalmol. 2021; bjophthalmol-2020-318672.

  17. Matsumoto H, Hoshino J, Mukai R, Nakamura K, Akiyama H. 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. 2021;11:1–8.

    Article  Google Scholar 

  18. Spaide RF, Jaffe GJ, Sarraf D, Freund KB, Sadda SR, Staurenghi G, et al. Consensus nomenclature for reporting neovascular age-related macular degeneration data: consensus on neovascular age-related macular degeneration nomenclature study group. Ophthalmology. 2020;127:616–36.

    Article  Google Scholar 

  19. Spaide RF, Yannuzzi LA, Slakter JS, Sorenson J, Orlach DA. Indocyanine green videoangiography of idiopathic polypoidal choroidal vasculopathy. Retina. 1995;15:100–10.

    CAS  Article  Google Scholar 

  20. Yannuzzi LA, Negrão S, Iida T, Carvalho C, Rodriguez-Coleman H, Slakter J, et al. Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2001;21:416–34.

    CAS  Article  Google Scholar 

  21. Ogura Y, Jaffe GJ, Cheung CMG, Kokame GT, Iida T, Takahashi K, et al. Efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy in Japanese participants of HAWK. Br J Ophthalmol. 2021: bjophthalmol-2021-319090.

  22. Koizumi H, Kano M, Yamamoto A, Saito M, Maruko I, Kawasaki R, et al. Short-term changes in choroidal thickness after aflibercept therapy for neovascular age-related macular degeneration. Am J Ophthalmol. 2015;159:627–33.

    CAS  Article  Google Scholar 

  23. Pitkänen L, Ranta VP, Moilanen H, Urtti A. Permeability of retinal pigment epithelium: effects of permeant molecular weight and lipophilicity. Investig Ophthalmol Vis Sci. 2005;46:641–6.

    Article  Google Scholar 

  24. Tadayoni R, Sararols L, Weissgerber G, Verma R, Clemens A, Holz FG. Brolucizumab: a newly developed anti-VEGF molecule for the treatment of neovascular age-related macular degeneration. Ophthalmologica. 2021;244:93–101.

    CAS  Article  Google Scholar 

  25. He L, Silva RA, Moshfeghi DM, Blumenkranz MS, Leng T. Aflibercept for the treatment of retinal pigment epithelial detachments. Retina. 2016;36:492–8.

    CAS  Article  Google Scholar 

  26. Sarraf D, London NJ, Khurana RN, Dugel PU, Gune S, Hill L, et al. Ranibizumab treatment for pigment epithelial detachment secondary to neovascular age-related macular degeneration: post hoc analysis of the HARBOR study. Ophthalmology. 2016;123:2213–24.

    Article  Google Scholar 

  27. Veritti D, Sarao V, Gorni G, Lanzetta P. Anti-VEGF drugs dynamics: relevance for clinical practice. Pharmaceutics. 2022;14:265.

    CAS  Article  Google Scholar 

  28. Revised Oct 7, 2019. Accessed Nov 22, 2021.

  29. Revised Oct 2014. Accessed Nov 22, 2021.

  30. Revised Nov 2011. Accessed Nov 22, 2021

  31. Sharma A, Kumar N, Parachuri N, Singh S, Bandello F, Regillo CD, et al. Understanding retinal vasculitis associated with brolucizumab: complex pathophysiology or Occam’s razor? Ocul Immunol Inflamm. 2021;20:1–3.

    Google Scholar 

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Correspondence to Koji Tanaka.

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Conflicts of interest

K. Tanaka, None; H. Koizumi, None; T. Tamashiro, None; K. Itagaki, None; M. Nakayama, None; I. Maruko, None; S. Wakugawa, None; N. Terao, None; H. Onoe, None; Y. Wakatsuki, None; A. Kasai, None; M. Ogasawara, None; H. Shintake, None; Y. Sugano, None; A. Yamamoto, None; K. Kataoka, None; T. Hasegawa, None; T. Izumi, None; M. Kawai, None; R. Maruko, None; T. Sekiryu, None; A. A. Okada, None; T. Iida, None; R. Mori, None.

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Corresponding Author: Koji Tanaka

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Tanaka, K., Koizumi, H., Tamashiro, T. et al. Short-term results for brolucizumab in treatment-naïve neovascular age-related macular degeneration: a Japanese multicenter study. Jpn J Ophthalmol 66, 379–385 (2022).

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  • Age-related macular degeneration
  • Polypoidal choroidal vasculopathy
  • Brolucizumab
  • Multicenter study
  • Treatment