Skip to main content

Advertisement

SpringerLink
Log in

Switching from aflibercept to brolucizumab for the treatment of refractory neovascular age-related macular degeneration

  • Clinical Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To examine the 16-week outcomes of switching to brolucizumab in eyes with neovascular age-related macular degeneration (nAMD) refractory to aflibercept.

Study design

Retrospective observational study.

Methods

Data of eyes with nAMD who switched to brolucizumab because of resistance to aflibercept were collected. The best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status on optical coherence tomography were analyzed.

Results

A total of 48 eyes of 48 patients were reviewed. At 4 to 7 weeks after switching, BCVA changed from 0.26 ± 0.19 to 0.25 ± 0.21 (not significant; P = 0.95), but CRT significantly decreased from 298.9 ± 108.4 µm to 241.9 ± 92.5 µm (P < 0.001) and CCT from 182.6 ± 89.3 µm to 169.7 ± 82.6 µm (P < 0.001). Of the 23 eyes refractory to monthly aflibercept injections, 12 (52.2%) achieved a dry macula, and 8 (34.8%) reduced exudative changes at 1 month. At 16 weeks, 31 eyes (64.6%) achieved the treatment interval ≥ 8 weeks. Two patients (4.2%) dropped out, 7 eyes (14.6%) developed intraocular inflammation (IOI), and 8 eyes (16.7%) switched back to aflibercept because of the failure to extend the treatment interval ≥ 8 weeks.

Conclusion

Switching to brolucizumab in eyes refractory to aflibercept conferred favorable outcomes in controlling exudative changes. However, IOI and the regulation of the treatment interval to at least 8 weeks during the maintenance phase disrupted the continuation of brolucizumab treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Traine PG, Pfister IB, Zandi S, Spindler J, Garweg JG. Long-term outcome of intravitreal aflibercept treatment for neovascular age-related macular degeneration using a “treat-and-extend” regimen. Ophthalmol Retina. 2019;3:393–9.

    Article  Google Scholar 

  2. Tsunekawa Y, Kataoka K, Asai K, Ito Y, Terasaki H. Four-year outcome of aflibercept administration using a treat-and-extend regimen in eyes with recurrent neovascular age-related macular degeneration. Jpn J Ophthalmol. 2021;65:69–76.

    Article  CAS  Google Scholar 

  3. 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.

    Article  Google Scholar 

  4. 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 

  5. Augsburger M, Sarra GM, Imesch P. Treat and extend versus pro re nata regimens of ranibizumab and aflibercept in neovascular age-related macular degeneration: a comparative study. Graefes Arch Clin Exp Ophthalmol. 2019;257:1889–95.

    Article  CAS  Google Scholar 

  6. DeCroos FC, Reed D, Adam MK, Salz D, Gupta OP, Ho AC, et al. Treat-and-extend therapy using aflibercept for neovascular age-related macular degeneration: a prospective clinical trial. Am J Ophthalmol. 2017;180:142–50.

    Article  CAS  Google Scholar 

  7. Ohji M, Takahashi K, Okada AA, Kobayashi M, Matsuda Y, Terano Y, et al. Efficacy and safety of intravitreal aflibercept treat-and-extend regimens in exudative age-related macular degeneration: 52- and 96-week findings from ALTAIR : a randomized controlled trial. Adv Ther. 2020;37:1173–87.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Enriquez 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 

  10. 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. https://doi.org/10.1136/bjophthalmol-2020-318672.

    Article  PubMed  Google Scholar 

  11. Matsumoto H, Hoshino J, Mukai R, Nakamura K, Akiyama H. Short-term outcomes of intravitreal brolucizumab for treatment-naive neovascular age-related macular degeneration with type 1 choroidal neovascularization including polypoidal choroidal vasculopathy. Sci Rep. 2021;11:6759.

    Article  CAS  Google Scholar 

  12. Yamamoto A, Okada AA, Kano M, Koizumi H, Saito M, Maruko I, et al. One-year results of intravitreal aflibercept for polypoidal choroidal vasculopathy. Ophthalmology. 2015;122:1866–72.

    Article  Google Scholar 

  13. Lee WK, Iida T, Ogura Y, Chen SJ, Wong TY, Mitchell P, et al. Efficacy and safety of intravitreal aflibercept for polypoidal choroidal vasculopathy in the PLANET study: a randomized clinical trial. JAMA Ophthalmol. 2018;136:786–93.

    Article  Google Scholar 

  14. Yonekawa Y, Andreoli C, Miller JB, Loewenstein JI, Sobrin L, Eliott D, et al. Conversion to aflibercept for chronic refractory or recurrent neovascular age-related macular degeneration. Am J Ophthalmol. 2013;156:29–35.

    Article  CAS  Google Scholar 

  15. 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. 2020;18:100680.

    Article  Google Scholar 

  16. Kondapalli SSA. Retinal vasculitis after administration of brolucizumab resulting in severe loss of visual acuity. JAMA Ophthalmol. 2020;138:1103–4.

    Article  Google Scholar 

  17. Maruko I, Okada AA, Iida T, Hasegawa T, Izumi T, Kawai M, 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.

    Article  CAS  Google Scholar 

  18. 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 

  19. Witkin AJ, Hahn P, Murray TG, Arevalo JF, Blinder KJ, Choudhry N, et al. Occlusive retinal vasculitis following intravitreal brolucizumab. J Vitreoretin Dis. 2020;4:69–279.

    Article  Google Scholar 

  20. Gharbiya M, Cruciani F, Mariotti C, Grandinetti F, Marenco M, Cacace V. Choroidal thickness changes after intravitreal antivascular endothelial growth factor therapy for age-related macular degeneration: ranibizumab versus aflibercept. J Ocul Pharmacol Ther. 2015;31:357–62.

    Article  CAS  Google Scholar 

  21. Koizumi H, Kano M, Yamamoto A, Saito M, Maruko I, Sekiryu T, et al. Subfoveal choroidal thickness during aflibercept therapy for neovascular age-related macular degeneration: twelve-month results. Ophthalmology. 2016;123:617–24.

    Article  Google Scholar 

  22. Kim JH, Lee TG, Chang YS, Kim CG, Cho SW. Short-term choroidal thickness changes in patients treated with either ranibizumab or aflibercept: a comparative study. Br J Ophthalmol. 2016;100:1634–9.

    Article  Google Scholar 

  23. Mazaraki K, Fassnacht-Riederle H, Blum R, Becker M, Michels S. Change in choroidal thickness after intravitreal aflibercept in pretreated and treatment-naive eyes for neovascular age-related macular degeneration. Br J Ophthalmol. 2015;99:1341–4.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan

    Hikaru Ota, Jun Takeuchi, Yuyako Nakano, Etsuyo Horiguchi, Yosuke Taki, Yasuki Ito, Hiroko Terasaki, Koji M. Nishiguchi & Keiko Kataoka

  2. Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan

    Keiko Kataoka

  3. Department of Ophthalmology, Fujita Health University, Aichi, Japan

    Yasuki Ito

Authors
  1. Hikaru Ota
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Takeuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuyako Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Etsuyo Horiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yosuke Taki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yasuki Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroko Terasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Koji M. Nishiguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Keiko Kataoka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keiko Kataoka.

Ethics declarations

H. Ota, None; J. Takeuchi, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (Novartis, Santen, Bayer); Y. Nakano, None; E. Horiguchi, None; Y. Taki, None; Y. Ito, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (Bayer, Canon, ZEISS, Kowa, Novartis, Pfizer, Santen); H. Terasaki, Grant (ZEISS, Kowa, Otsuka, Senju, Santen, Alcon, Sanofi, Novartis, ROHTO, Bayer, Wakamoto, HOYA, Johnson&Johnson), Consulting fees (Bayer), Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (Otsuka, Kowa, Santen, Senju, Sanofi, Alcon, ROHTO, Novartis, Wakamoto, Bayer), Support for attending meetings and/or travel (Bayer); K. M. Nishiguchi, Grant (Takara Bio, Takeda, JCR Pharma, Alcon, Bayer, Novartis, Santen), Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (Alcon, Bayer, Novartis, Santen, Chugai, Kowa, Senju, Otsuka, Wakamoto), Patents planned, issued or pending (A gene therapy using genome editing with a single AAV vector); K. Kataoka, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (Novartis, Senju, Santen, Bayer, Boehringer Ingelheim, Bayer).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Corresponding Author: Keiko Kataoka

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 16 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ota, H., Takeuchi, J., Nakano, Y. et al. Switching from aflibercept to brolucizumab for the treatment of refractory neovascular age-related macular degeneration. Jpn J Ophthalmol 66, 278–284 (2022). https://doi.org/10.1007/s10384-022-00908-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-022-00908-1

Keywords

Search

Navigation