Japanese Journal of Ophthalmology

, Volume 62, Issue 5, pp 584–591 | Cite as

Prognostic factors after aflibercept therapy for typical age-related macular degeneration and polypoidal choroidal vasculopathy

  • Masashi Ogasawara
  • Hideki Koizumi
  • Akiko Yamamoto
  • Kanako Itagaki
  • Masaaki Saito
  • Ichiro Maruko
  • Annabelle A. Okada
  • Tomohiro Iida
  • Tetsuju SekiryuEmail author
Clinical Investigation



To determine factors predictive of visual outcomes in eyes treated with intravitreal aflibercept injections (IAIs) for typical neovascular age-related macular degeneration (AMD) or polypoidal choroidal vasculopathy (PCV).

Study design

Retrospective, multicenter, institutional, consecutive, interventional case series.


One hundred nine eyes (107 patients) with treatment-naïve neovascular AMD at 3 university hospitals were studied. After a loading phase of 3 monthly 2.0-mg IAIs, injections were administered every 2 months. The baseline clinical characteristics were investigated in relation to the 12-month visual outcomes. Changes in the mean best-corrected visual acuity (BCVA) were measured at 12 months after initiation of aflibercept therapy.


Forty-five eyes (41.3%) had typical neovascular AMD, and 64 eyes (58.7%) had PCV. The changes in the mean BCVA at 12 months compared with baseline did not differ significantly (P = .737) between the 2 groups. Stepwise analysis showed that larger gains in the BCVA at 12 months were associated with poor BCVA (P < .001), no pigment epithelial detachment (P = .004), and subretinal fluid (P = .039) at baseline in eyes with typical neovascular AMD; larger gains in the BCVA were associated with poorer BCVA (P < .001), presence of choroidal vascular hyperpermeability (CVH) (P = .013), and subretinal fluid (P = .044) at baseline in eyes with PCV.


Although poorer BCVA and the presence of subretinal fluid predicted larger gains in BCVA in both subtypes treated with aflibercept, eyes with typical neovascular AMD had greater improvement if no pigment epithelial detachment was present, while eyes with PCV had greater improvement if CVH was present.


Aflibercept Age-related macular degeneration Choroidal vascular hyperpermeability Polypoidal choroidal vasculopathy 


Conflicts of interest

M. Ogasawara, None; Hideki Koizumi, Grant (Novartis Pharma), Moderator fees (Alcon, Bausch & Lomb, Bayer, Canon, HOYA, Kowa, NIDEK, Novartis Pharma, Santen Pharmaceutical, Senju Pharmaceutical, Topcon, Wakamoto Pharmaceutical); A. Yamamoto, Lecture fees (Bayer, Novartis Pharma, Pfizer, Santen Pharmaceutical); K. Itagaki, None; M. Saito, Grant (Bayer, Novartis Pharma, Santen Pharmaceutical), Moderator fees (Alcon, AMO, Bayer, HOYA, Novartis Pharma, Santen Pharmaceutical, Senju Pharmaceutical); I. Maruko, Moderator fees (Alcon, Bayer, NIDEK, Novartis Pharma, Santen Pharmaceutical, Topcon); A. A. Okada, Grant (Bayer, Mitsubishi Tanabe Pharma), Advisory board fee (Bayer), Consultant fee (XOMA), Lecture fees (Bayer, Novartis Pharma, Santen Pharmaceutical), Research funds (Bayer, Mitsubishi Tanabe Pharma); T. Iida, Grant (Bayer, Nidek, Novartis Pharma, Santen Pharmaceutical), Lecture fees (Bayer, Novartis Pharma, Santen Pharmaceutical); T. Sekiryu, None.


  1. 1.
    Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, et al. Risk factors for age-related macular degeneration: pooled findings from three continents. Ophthalmology. 2001;108:697–704.CrossRefPubMedGoogle Scholar
  2. 2.
    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.CrossRefPubMedGoogle Scholar
  3. 3.
    Yannuzzi LA, Sorenson J, Spaide RF, Lipson B. Idiopathic polypoidal choroidal vasculopathy (IPCV). Retina. 1990;10:1–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Yuzawa M, Mori R, Haruyama M. A study of laser photocoagulation for polypoidal choroidal vasculopathy. Jpn J Ophthalmol. 2003;47:379–84.CrossRefPubMedGoogle Scholar
  5. 5.
    Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2011;119:2537–48.CrossRefGoogle Scholar
  6. 6.
    Yamamoto A, Okada AA, Koizumi H, Maruko I, Sekiryu T, Iida T, et al. One-year results of intravitreal aflibercept for polypoidal choroidal vasculopathy. Ophthalmology. 2015;122:1866–72.CrossRefPubMedGoogle Scholar
  7. 7.
    Kaiser PK, Brown DM, Zhang K, Hudson HL, Holz FG, Shapiro H, et al. Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results. Am J Ophthalmol. 2007;144:850–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Yamashiro K, Tomita K, Tsujikawa A, Nakata I, Akagi-Kurashige Y, Miyake M, et al. Factors associated with the response of age-related macular degeneration to intravitreal ranibizumab treatment. Am J Ophthalmol. 2012;154:125–36.CrossRefPubMedGoogle Scholar
  9. 9.
    Simader C, Ritter M, Bolz M, Deak GG, Mayr-Sponer U, Golbaz I, et al. Morphologic parameters relevant for visual outcome during anti-angiogenic therapy of neovascular age-related macular degeneration. Ophthalmology. 2014;121:1237–45.CrossRefPubMedGoogle Scholar
  10. 10.
    Schmidt-Erfurth U, Waldstein SM, Deak GG, Kundi M, Simader C. Pigment epithelial detachment followed by retinal cystoid degeneration leads to vision loss in treatment of neovascular age-related macular degeneration. Ophthalmology. 2015;122:822–32.CrossRefPubMedGoogle Scholar
  11. 11.
    Broadhead GK, Hong T, Zhu M, Li H, Schlub TE, Wijeyakumar W, et al. Response of pigment epithelial detachments to intravitreal aflibercept among patients with treatment-resistant neovascular age-related macular degeneration. Retina. 2015;35:975–81.CrossRefPubMedGoogle Scholar
  12. 12.
    Koizumi H, Yamamoto A, Maruko I, Sekiryu T, Okada AA, Iida T, et al. Subfoveal choroidal thickness during aflibercept therapy for neovascular age-related macular degeneration: twelve-month results. Ophthalmology. 2016;123:617–24.CrossRefPubMedGoogle Scholar
  13. 13.
    Jaffe GJ, Martin DF, Toth CA, Daniel E, Maguire MG, Ying GS, et al. Macular morphology and visual acuity in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2013;120:1860–70.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Ikuno Y, Yasuno Y, Miura M, Sekiryu T, Nishida K, Iida T, et al. Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and high-penetration optical coherence tomography. Invest Ophthalmol Vis Sci. 2011;52:5536–40.CrossRefPubMedGoogle Scholar
  15. 15.
    Cho M, Barbazetto IA, Freund KB. Refractory neovascular age-related macular degeneration secondary to polypoidal choroidal vasculopathy. Am J Ophthalmol. 2009;148:70–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Koizumi H, Yamagishi T, Yamazaki T, Kinoshita S. Relationship between clinical characteristics of polypoidal choroidal vasculopathy and choroidal vascular hyperpermeability. Am J Ophthalmol. 2013;155:305–13.CrossRefPubMedGoogle Scholar
  17. 17.
    Saito M, Iida T, Kano M, Itagaki K. Two-year results of intravitreal ranibizumab for polypoidal choroidal vasculopathy with recurrent or residual exudation. Eye (Lond). 2013;27:931–9.CrossRefGoogle Scholar
  18. 18.
    Hikichi T, Kitamei H, Shioya S. Prognostic factors of 2-year outcomes of ranibizumab therapy for polypoidal choroidal vasculopathy. Br J Ophthalmol. 2015;99:817–22.CrossRefPubMedGoogle Scholar
  19. 19.
    Kang HM, Koh HJ. Long-term visual outcome and prognostic factors after intravitreal ranibizumab injections for polypoidal choroidal vasculopathy. Am J Ophthalmol. 2013;156:652–60.CrossRefPubMedGoogle Scholar
  20. 20.
    Koizumi H, Yamagishi T, Yamazaki T, Kinoshita S. Predictive factors of resolved retinal fluid after intravitreal ranibizumab for polypoidal choroidal vasculopathy. Br J Ophthalmol. 2011;95:1555–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Hikichi T, Higuchi M, Matsushita T, Kosaka S, Matsushita R, Takami K, et al. Factors predictive of outcomes 1 year after 3 monthly ranibizumab injections and as-needed reinjections for polypoidal choroidal vasculopathy in Japanese patients. Retina. 2013;33:1949–58.CrossRefPubMedGoogle Scholar
  22. 22.
    Kang HM, Kwon HJ, Yi JH, Lee CS, Lee SC. Subfoveal choroidal thickness as a potential predictor of visual outcome and treatment response after intravitreal ranibizumab injections for typical exudative age-related macular degeneration. Am J Ophthalmol. 2014;157:1013–21.CrossRefPubMedGoogle Scholar
  23. 23.
    Cho HJ, Kim HS, Jang YS, Han JI, Lew YJ, Lee TG, et al. Effects of choroidal vascular hyperpermeability on anti-vascular endothelial growth factor treatment for polypoidal choroidal vasculopathy. Am J Ophthalmol. 2013;156:1192–200.CrossRefPubMedGoogle Scholar
  24. 24.
    Julien S, Biesemeier A, Taubitz T, Schraermeyer U. Different effects of intravitreally injected ranibizumab and aflibercept on retinal and choroidal tissues of monkey eyes. Br J Ophthalmol. 2014;98:813–25.CrossRefPubMedGoogle Scholar
  25. 25.
    Stewart MW, Rosenfeld PJ. Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol. 2008;92:667–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Takahashi S. Vascular endothelial growth factor (VEGF), VEGF receptors and their inhibitors for antiangiogenic tumor therapy. Biol Pharm Bull. 2011;34:1785–8.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Ophthalmological Society 2018

Authors and Affiliations

  • Masashi Ogasawara
    • 1
  • Hideki Koizumi
    • 2
  • Akiko Yamamoto
    • 3
  • Kanako Itagaki
    • 1
  • Masaaki Saito
    • 1
  • Ichiro Maruko
    • 2
  • Annabelle A. Okada
    • 3
  • Tomohiro Iida
    • 2
  • Tetsuju Sekiryu
    • 1
    Email author
  1. 1.Department of OphthalmologyFukushima Medical UniversityFukushimaJapan
  2. 2.Department of OphthalmologyTokyo Women’s Medical UniversityTokyoJapan
  3. 3.Department of OphthalmologyKyorin University School of MedicineTokyoJapan

Personalised recommendations