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Association of an age-related maculopathy susceptibility 2 gene variant with the 12-month outcomes of intravitreal aflibercept combined with photodynamic therapy for polypoidal choroidal vasculopathy

  • Clinical Investigation
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Abstract

Purpose

To determine the association of age-related maculopathy susceptibility 2 (ARMS2) gene polymorphisms with the 12-month outcomes of intravitreal aflibercept combined with photodynamic therapy (IVA+PDT) in polypoidal choroidal vasculopathy (PCV).

Study design

Interventional cohort study.

Methods

This was a retrospective study of 48 consecutive treatment-naïve PCV patients. The patients underwent IVA+PDT as the initial therapy and were followed up for more than 12 months under a pro re nata regimen. The single nucleotide polymorphism (SNP) at rs10490924 in the ARMS2 gene was genotyped using the TaqMan assay. The clinical characteristics and outcomes of IVA+PDT were compared among the 3 genotypes at rs10490924. Multivariate regression analysis was performed to evaluate the influence of the clinical cofactors on the association of rs10490924 with the visual outcome at 12 months after the first IVA+PDT.

Results

No significant difference was found in the baseline characteristics among the 3 genotypes (n = 9, 23, and 16 for the GG, GT, and TT genotypes, respectively). All the patients, regardless of genotype, showed a significant improvement in vision, central retinal thickness, and subfoveal choroidal thickness at all time points measured after the initial IVA+PDT. The number of treatments was significantly smaller in the patients with the GG genotype than in those with the GT or the TT genotype. On multivariate logistic regression analysis, the number of the T allele at rs10490924 was significantly associated with the chance of retreatment after the initial IVA+PDT.

Conclusion

The presence of the G allele at rs10490924 in the ARMS2 gene is likely associated with a lower chance of retreatment after IVA+PDT in patients with PCV.

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References

  1. Cook HL, Patel PJ, Tufail A. Age-related macular degeneration: diagnosis and management. Br Med Bull. 2008;85:127–49.

    Article  CAS  PubMed  Google Scholar 

  2. Rein DB, Wittenborn JS, Zhang X, Honeycutt AA, Lesesne SB, Saaddine J, Vision Health Cost-Effectiveness Study Group. Forecasting age-related macular degeneration through the year 2050: the potential impact of new treatments. Arch Ophthalmol. 2009;127:533–40.

    Article  PubMed  Google Scholar 

  3. Maruko I, Iida T, Saito M, Nagayama D, Saito K. Clinical characteristics of exudative age-related macular degeneration in Japanese patients. Am J Ophthalmol. 2007;144:15–22.

    Article  PubMed  Google Scholar 

  4. Tsujikawa A, Akagi-Kurashige Y, Yuzawa M, Ishibashi T, Nakanishi H, Nakatani E, AMD2000 Study Group, et al. Baseline data from a multicenter, 5-year, prospective cohort study of Japanese age-related macular degeneration: an AMD2000 report. Jpn J Ophthalmol. 2018;62:127–36.

    Article  PubMed  Google Scholar 

  5. 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  PubMed  Google Scholar 

  6. Hara C, Sawa M, Sayanagi K, Nishida K. One-year results of intravitreal aflibercept for polypoidal choroidal vasculopathy. Retina. 2016;36:37–45.

    Article  CAS  PubMed  Google Scholar 

  7. Saito M, Kano M, Itagaki K, Sekiryu T. Efficacy of intravitreal aflibercept in Japanese patients with exudative age-related macular degeneration. Jpn J Ophthalmol. 2017;61:74–83.

    Article  CAS  PubMed  Google Scholar 

  8. Alexandru MR, Alexandra NM. Wet age related macular degeneration management and follow-up. Rom J Ophthalmol. 2016;60:9–13.

    PubMed  PubMed Central  Google Scholar 

  9. Enslow R, Bhuvanagiri S, Vegunta S, Cutler B, Neff M, Stagg B. Association of anti-VEGF injections with progression of geographic atrophy. Ophthalmol Eye Dis. 2016;8:31–2.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Nowak-Sliwinska P, van den Bergh H, Sickenberg M, Koh AH. Photodynamic therapy for polypoidal choroidal vasculopathy. Prog Retin Eye Res. 2013;37:182–99.

    Article  PubMed  Google Scholar 

  11. Gomi F, Oshima Y, Mori R, Kano M, Saito M, Yamashita A, Fujisan Study Group, et al. Initial versus delayed photodynamic therapy in combination with ranibizumab for treatment of polypoidal choroidal vasculopathy: the Fujisan Study. Retina. 2015;35:1569–76.

    Article  CAS  PubMed  Google Scholar 

  12. Honda S, Imai H, Yamashiro K, Kurimoto Y, Kanamori-Matsui N, Kagotani Y, et al. Comparative assessment of photodynamic therapy for typical age-related macular degeneration and polypoidal choroidal vasculopathy: a multicenter study in Hyogo prefecture, Japan. Ophthalmologica. 2009;223:333–8.

    Article  PubMed  Google Scholar 

  13. Koh A, Lai TYY, Takahashi K, Wong TY, Chen LJ, Ruamviboonsuk P, EVEREST II study group, et al. Efficacy and safety of ranibizumab with or without verteporfin photodynamic therapy for polypoidal choroidal vasculopathy: a randomized clinical trial. JAMA Ophthalmol. 2017;135:1206–13.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Tsuchihashi T, Mori K, Horie-Inoue K, Gehlbach PL, Kabasawa S, Takita H, et al. Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration. Ophthalmology. 2011;118:93–100.

    Article  PubMed  Google Scholar 

  15. Brantley MA Jr, Edelstein SL, King JM, Plotzke MR, Apte RS, Kymes SM, et al. Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to photodynamic therapy. Eye (Lond). 2009;23:626–31.

    Article  CAS  PubMed  Google Scholar 

  16. Sakurada Y, Kubota T, Imasawa M, Mabuchi F, Tanabe N, Iijima H. Association of LOC387715 A69S genotype with visual prognosis after photodynamic therapy for polypoidal choroidal vasculopathy. Retina. 2010;30:1616–21.

    Article  PubMed  Google Scholar 

  17. Bessho H, Honda S, Kondo N, Negi A. The association of age-related maculopathy susceptibility 2 polymorphisms with phenotype in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Mol Vis. 2011;17:977–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Nakai S, Honda S, Matsumiya W, Miki A, Nakamura M. ARMS2 variants may predict the 3-year outcome of photodynamic therapy for wet age-related macular degeneration. Mol Vis. 2017;23:514–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Brunicardi FC, Gibbs RA, Wheeler DA, Nemunaitis J, Fisher W, Goss J, et al. Overview of the development of personalized genomic medicine and surgery. World J Surg. 2011;35:1693–9.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kikushima W, Sakurada Y, Sugiyama A, Yoneyama S, Tanabe N, Matsubara M, et al. Comparison of two-year outcomes after photodynamic therapy with ranibizumab or aflibercept for polypoidal choroidal vasculopathy. Sci Rep. 2017;7:16461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Japanese Study Group of Polypoidal Choroidal Vasculopathy. Criteria for diagnosis of polypoidal choroidal vasculopathy [in Japanese]. Nippon Ganka Gakkai Zasshi. 2005;109:417–27.

    Google Scholar 

  22. Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin One-year results of 2 randomized clinical trials: TAP report 1. Arch Ophthalmol. 1999;117:1329–45.

    Article  Google Scholar 

  23. Matsumiya W, Honda S, Otsuka K, Miki A, Nagai T, Imai H, et al. One-year outcome of combination therapy with intravitreal aflibercept and verteporfin photodynamic therapy for polypoidal choroidal vasculopathy. Graefes Arch Clin Exp Ophthalmol. 2017;255:541–8.

    Article  CAS  PubMed  Google Scholar 

  24. Kondo N, Honda S, Ishibashi K, Tsukahara Y, Negi A. LOC387715/HTRA1 variants in polypoidal choroidal vasculopathy and age-related macular degeneration in a Japanese population. Am J Ophthalmol. 2007;144:608–12.

    Article  CAS  PubMed  Google Scholar 

  25. Hayashi H, Yamashiro K, Gotoh N, Nakanishi H, Nakata I, Tsujikawa A, et al. CFH and ARMS2 variations in age-related macular degeneration, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation. Invest Ophthalmol Vis Sci. 2010;51:5914–9.

    Article  PubMed  Google Scholar 

  26. Goto A, Akahori M, Okamoto H, Minami M, Terauchi N, Haruhata Y, et al. Genetic analysis of typical wet-type age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese population. J Ocul Biol Dis Inform. 2009;2:164–75.

    Article  Google Scholar 

  27. Gotoh N, Nakanishi H, Hayashi H, Yamada R, Otani A, Tsujikawa A, et al. ARMS2 (LOC387715) variants in Japanese patients with exudative age-related macular degeneration and polypoidal choroidal vasculopathy. Am J Ophthalmol. 2009;147(1037–41):e2.

    Google Scholar 

  28. Hu Z, Xie P, Ding Y, Yuan D, Liu Q. Association between variants A69S in ARMS2 gene and response to treatment of exudative AMD: a meta-analysis. Br J Ophthalmol. 2015;99:593–8.

    Article  PubMed  Google Scholar 

  29. Tsujikawa A, Ojima Y, Yamashiro K, Nakata I, Ooto S, Tamura H, et al. Association of lesion size and visual prognosis to polypoidal choroidal vasculopathy. Am J Ophthalmol. 2011;151:961–72.

    Article  PubMed  Google Scholar 

  30. Joachim N, Mitchell P, Burlutsky G, Kifley A, Wang JJ. The incidence and progression of age-related macular degeneration over 15 years: the Blue Mountains Eye Study. Ophthalmology. 2015;122:2482–9.

    Article  PubMed  Google Scholar 

  31. Seddon JM, Silver RE, Kwong M, Rosner B. Risk prediction for progression of macular degeneration: 10 common and rare genetic variants, demographic, environmental, and macular covariates. Invest Ophthalmol Vis Sci. 2015;56:2192–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kanda A, Chen W, Othman M, Branham KE, Brooks M, Khanna R, et al. A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration. Proc Natl Acad Sci USA. 2007;104:16227–32.

    Article  PubMed  Google Scholar 

  33. van den Bergh H. Photodynamic therapy of age-related macular degeneration: history and principles. Semin Ophthalmol. 2001;16:181–200.

    Article  PubMed  Google Scholar 

  34. Tanaka K, Nakayama T, Mori R, Sato N, Kawamura A, Mizutani Y, et al. Associations of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotypes with subtypes of polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci. 2011;52:7441–4.

    Article  CAS  PubMed  Google Scholar 

  35. Miki A, Honda S, Kondo N, Negi A. The association of age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) variants with two angiographic subtypes of polypoidal choroidal vasculopathy. Ophthalmic Genet. 2013;34:146–50.

    Article  CAS  PubMed  Google Scholar 

  36. Honda S, Miki A, Yanagisawa S, Matsumiya W, Nagai T, Tsukahara Y. Comparison of the outcomes of photodynamic therapy between two angiographic subtypes of polypoidal choroidal vasculopathy. Ophthalmologica. 2014;232:92–6.

    Article  CAS  PubMed  Google Scholar 

  37. Kikushima W, Sakurada Y, Yoneyama S, Sugiyama A, Tanabe N, Kume A, et al. Incidence and risk factors of retreatment after three-monthly aflibercept therapy for exudative age-related macular degeneration. Sci Rep. 2017;7:44020.

    Article  PubMed  PubMed Central  Google Scholar 

  38. She H, Nakazawa T, Matsubara A, Connolly E, Hisatomi T, Noda K, et al. Photoreceptor protection after photodynamic therapy using dexamethasone in a rat model of choroidal neovascularization. Invest Ophthalmol Vis Sci. 2008;49:5008–14.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Financial Support: this study was supported by a grant-in aid (C) (16K11286 to S. H.) from the Japan Society for the Promotion of Science. The funding organization had no role in the design or conduct of this research.

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Authors and Affiliations

  1. Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Shunichiro Nakai, Wataru Matsumiya, Akiko Miki, Shigeru Honda & Makoto Nakamura

  2. Department of Ophthalmology and Visual Sciences, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan

    Shigeru Honda

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  1. Shunichiro Nakai
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Correspondence to Shigeru Honda.

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Conflicts of interest

S Nakai, None; W. Matsumiya, None; A. Miki, None; S. Honda, None; M. Nakamura, Lecture fee (Santen, Alcon Pharma, Senju).

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Corresponding author: Shigeru Honda

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Nakai, S., Matsumiya, W., Miki, A. et al. Association of an age-related maculopathy susceptibility 2 gene variant with the 12-month outcomes of intravitreal aflibercept combined with photodynamic therapy for polypoidal choroidal vasculopathy. Jpn J Ophthalmol 63, 389–395 (2019). https://doi.org/10.1007/s10384-019-00683-6

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  • DOI: https://doi.org/10.1007/s10384-019-00683-6

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