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Tachyphylaxis during treatment of exudative age-related macular degeneration with aflibercept

  • Medical Ophthalmology
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Abstract

Purpose

At present, the standard treatment of neovascular age-related macular degeneration (AMD) is the repeated administration of antivascular endothelial growth factor (VEGF) agents. However, we often encounter patients who develop tachyphylaxis for anti-VEGF agents. In this study, we investigated the characteristics of patients who developed tachyphylaxis on repeated intravitreal aflibercept (IVA) injections for neovascular AMD and the frequency of tachyphylaxis.

Methods

Three hundred thirteen eyes (313 patients) with treatment-naïve AMD who achieved resolution soon after starting IVA and were followed up for ≥ 12 months were enrolled in this retrospective, interventional, consecutive case series. The eyes were investigated for tachyphylaxis to aflibercept. Tachyphylaxis was defined as absence of any improvement (more than 100 μm) in or worsening of CRT within 1 month after more than two repeated monthly IVA injections when the exudative change remained.

Results

Twenty-eight (8.9%) of the 313 eyes developed tachyphylaxis (occult with no classic, n = 14; polypoidal choroidal vasculopathy, n = 14) at an annual rate of about 3%. The mean number of IVA injections was 10.5 ± 7.8, and the mean interval until tachyphylaxis was 20.9 ± 14.0 months. There was a significant difference in the AMD subtypes between the group with tachyphylaxis and the group without it (p = 0.0029). Occult with no classic type and polypoidal choroidal vasculopathy were the only AMD subtypes in the eyes with tachyphylaxis. In the analysis of the eyes that had occult with no classic or polypoidal choroidal vasculopathy, only intraretinal edema was significantly less common (p = 0.042). A combination of photodynamic therapy and aflibercept was effective in 13 (87%) of 15 eyes with tachyphylaxis, and switching to intravitreal ranibizumab was effective in 5 (56%) of 9 eyes.

Conclusions

Tachyphylaxis occurs after repeated IVA injections in a minority of patients with AMD for a long term and is more likely to occur in eyes with lesions beneath the retinal pigment epithelium and no intraretinal edema. Treatment of AMD should be performed keeping this fact in mind, while considering the consecutive treatment.

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Authors and Affiliations

  1. Department of Ophthalmology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Chikako Hara, Taku Wakabayashi, Yoko Fukushima, Kaori Sayanagi, Ryo Kawasaki, Shigeru Sato, Hirokazu Sakaguchi & Kohji Nishida

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  1. Chikako Hara
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Correspondence to Chikako Hara.

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Conflict of interest

None of the authors has a proprietary interest or conflict of interest in any product mentioned in this article. Dr. Hara has received lecture fees from Alcon pharma, Bayer, Santen, Pfizer, and Senju. Dr. Wakabayashi has received lecture fees from Santen and Senju. Dr. Sayanagi has received lecture fees from Alcon pharma, Bayer, Senju, and Otsuka. Dr. Sakaguchi heads an affiliated endowed department (Menicon) and has received lecture fees from Alcon pharma, Santen, and Nihon Alcon. Dr. Kawasaki also heads an affiliated endowed department (Topcon) and has received lecture fees from Alcon pharma, Bayer, Novartis, Senju, Pfizer, Kowa, Takeda, Astellas, Santen, Nitto Medic, and Topcon, as well as consultancy fees from Novartis, Novo Nordisk, Roche, Office Future, Predictive Analytic Group, and MICIN. Dr. Nishida has received lecture fees from Alcon, Carl Zeiss, Otsuka, Pfizer, Santen, and Senju, as well as grants from HOYA and Santen. Dr. Fukushima and Dr. Sato have no disclosures to make.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethics Committee of Osaka University Graduate School of Medicine; approval number 10039) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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The need for informed consent was waived in view of the retrospective nature of the research.

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Hara, C., Wakabayashi, T., Fukushima, Y. et al. Tachyphylaxis during treatment of exudative age-related macular degeneration with aflibercept. Graefes Arch Clin Exp Ophthalmol 257, 2559–2569 (2019). https://doi.org/10.1007/s00417-019-04456-2

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