Five-year treatment outcomes following intravitreal ranibizumab injections for neovascular age-related macular degeneration in Japanese patients
To assess the real-world 5-year treatment outcomes of ranibizumab therapy in Japanese patients with neovascular age-related macular degeneration (AMD).
This was a retrospective, observational, and open-label effectiveness study that included 295 eyes. The participants were patients with treatment-naïve neovascular AMD who received intravitreal ranibizumab (IVR) monthly injection at least three times as the loading phase, followed by further injections as needed (pro re nata (PRN)) and follow-up assessments for 5 years. Outcomes were determined at least 5 years after the first ranibizumab injection.
Mean logMAR best-corrected visual acuity (BCVA) at baseline was 0.52. The mean BCVA significantly improved after three loading injections; however, it declined gradually. The BCVA at 1 year was significantly better than the baseline BCVA, whereas the 3-year, 4-year, and 5-year BCVA values were significantly lower than the baseline values. The average central foveal thickness improved significantly from 366 ± 125 μm to 268 ± 134 μm (p < 0.0001). Macular atrophy was significantly more likely to occur in cases with classic choroidal neovascularization (CNV) than in cases with other AMD (p = 0.01).
IVR is well tolerated in eyes with AMD. However, a PRN regimen for AMD may have limited real-world effectiveness for long-term maintenance of improved visual acuity. Macular atrophy may occur more frequently in classic CNV. To maintain good vision, IVR treatment should be started earlier and performed continuously.
KeywordsAge-related macular degeneration Ranibizumab Long-term treatment Pro re nata treatment Macular atrophy
This study was funded by the JSPS KAKENHI Grant Number (Kiban C 17K11454 (to Y.O.)).
Compliance with ethical standards
Conflict of interest
Author T.I. has received research grants from Bayer Yakuhin, Ltd., and Santen Pharmaceutical Co., Ltd. Author K.S. has received research grants from Santen Pharmaceutical Co., Ltd.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all the participants included in the study.
- 1.Gheorghe A, Mahdi L, Musat O (2015) Age-related macular degeneration. Rom J Ophthalmol 59:74–77Google Scholar
- 4.Macular Photocoagulation Study Group (1991) Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 109:1220–1231Google Scholar
- 5.Treatment of age-related macular degeneration with photodynamic therapy (TAP) Study Group (1999) Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin one-year results of 2 randomized clinical trials—TAP report. Arch Ophthalmol 117:1329–1345Google Scholar
- 8.Brown DM, Heier JS, Ciulla T, Benz M, Abraham P, Yancopoulos G, Stahl N, Ingerman A, Vitti R, Berliner AJ, Yang K, Nguyen QD, Investigators C-I (2011) Primary endpoint results of a phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration. Ophthalmology 118:1089–1097. https://doi.org/10.1016/j.ophtha.2011.02.039 CrossRefGoogle Scholar
- 9.Singer MA, Awh CC, Sadda S, Freeman WR, Antoszyk AN, Wong P, Tuomi L (2012) HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology 119:1175–1183. https://doi.org/10.1016/j.ophtha.2011.12.016 CrossRefGoogle Scholar
- 11.Comparison of Age-related Macular Degeneration Treatments Trials Research G, Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, Grunwald JE, Toth C, Redford M, Ferris FL 3rd (2012) Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology 119:1388–1398. https://doi.org/10.1016/j.ophtha.2012.03.053 CrossRefGoogle Scholar
- 12.Comparison of Age-related Macular Degeneration Treatments Trials Research G, Maguire MG, Martin DF, Ying GS, Jaffe GJ, Daniel E, Grunwald JE, Toth CA, Ferris FL 3rd, Fine SL (2016) Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration: the comparison of age-related macular degeneration treatments trials. Ophthalmology 123:1751–1761. https://doi.org/10.1016/j.ophtha.2016.03.045 CrossRefGoogle Scholar
- 13.Boulanger-Scemama E, Sayag D, Ha Chau Tran T, Quaranta-El Maftouhi M, Rumen F, Creuzot-Garcher C, Blanco Garavito R, Jung C, Souied E (2016) Ranibizumab and exudative age-related macular degeneration: 5-year multicentric functional and anatomical results in real-life practice. J Fr Ophtalmol 39:668–674. https://doi.org/10.1016/j.jfo.2016.06.001 CrossRefGoogle Scholar
- 14.Heimes B, Lommatzsch A, Zeimer M, Gutfleisch M, Spital G, Dietzel M, Pauleikhoff D (2011) Long-term visual course after anti-VEGF therapy for exudative AMD in clinical practice evaluation of the German reinjection scheme. Graefes Arch Clin Exp Ophthalmol 249:639–644. https://doi.org/10.1007/s00417-010-1524-5 CrossRefGoogle Scholar
- 17.Sunness JS, Gonzalez-Baron J, Applegate CA, Bressler NM, Tian Y, Hawkins B, Barron Y, Bergman A (1999) Enlargement of atrophy and visual acuity loss in the geographic atrophy form of age-related macular degeneration. Ophthalmology 106:1768–1779. https://doi.org/10.1016/S0161-6420(99)90340-8 CrossRefGoogle Scholar
- 18.Grunwald JE, Pistilli M, Ying GS, Maguire MG, Daniel E, Martin DF, Comparison of Age-related Macular Degeneration Treatments Trials Research G (2015) Growth of geographic atrophy in the comparison of age-related macular degeneration treatments trials. Ophthalmology 122:809–816. https://doi.org/10.1016/j.ophtha.2014.11.007 CrossRefGoogle Scholar
- 19.Grunwald JE, Pistilli M, Daniel E, Ying GS, Pan W, Jaffe GJ, Toth CA, Hagstrom SA, Maguire MG, Martin DF, Comparison of Age-Related Macular Degeneration Treatments Trials Research G (2017) Incidence and growth of geographic atrophy during 5 years of comparison of age-related macular degeneration treatments trials. Ophthalmology 124:97–104. https://doi.org/10.1016/j.ophtha.2016.09.012 CrossRefGoogle Scholar
- 21.Takahashi A, Ooto S, Yamashiro K, Oishi A, Tamura H, Nakanishi H, Ueda-Arakawa N, Tsujikawa A, Yoshimura N (2016) Photoreceptor damage and reduction of retinal sensitivity surrounding geographic atrophy in age-related macular degeneration. Am J Ophthalmol 168:260–268. https://doi.org/10.1016/j.ajo.2016.06.006 CrossRefGoogle Scholar
- 22.Wecker T, Ehlken C, Buhler A, Lange C, Agostini H, Bohringer D, Stahl A (2017) Five-year visual acuity outcomes and injection patterns in patients with pro-re-nata treatments for AMD, DME, RVO and myopic CNV. Br J Ophthalmol 101:353–359. https://doi.org/10.1136/bjophthalmol-2016-308668 Google Scholar
- 23.Takahashi Y, Koizumi H, Hasegawa T, Izumi T, Maruko I, Sonoda S, Sakamoto T, Iida T (2018) Comparison of subfoveal choroidal structures in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Jpn J Ophthalmol 62:576–583. https://doi.org/10.1007/s10384-018-0615-4 CrossRefGoogle Scholar
- 24.Ogasawara M, Koizumi H, Yamamoto A, Itagaki K, Saito M, Maruko I, Okada AA, Iida T, Sekiryu T (2018) Prognostic factors after aflibercept therapy for typical age-related macular degeneration and polypoidal choroidal vasculopathy. Jpn J Ophthalmol 62:584–591. https://doi.org/10.1007/s10384-018-0605-6 CrossRefGoogle Scholar
- 25.Bhisitkul RB, Mendes TS, Rofagha S, Enanoria W, Boyer DS, Sadda SR, Zhang K (2015) Macular atrophy progression and 7-year vision outcomes in subjects from the ANCHOR, MARINA, and HORIZON studies: the SEVEN-UP study. Am J Ophthalmol 159:915–924 e912. https://doi.org/10.1016/j.ajo.2015.01.032 CrossRefGoogle Scholar
- 27.Koh A, Lai TYY, Takahashi K, Wong TY, Chen LJ, Ruamviboonsuk P, Tan CS, Feller C, Margaron P, Lim TH, Lee WK, group EIs (2017) Efficacy and safety of ranibizumab with or without verteporfin photodynamic therapy for polypoidal choroidal vasculopathy: a randomized clinical trial. JAMA Ophthalmol 135:1206–1213. https://doi.org/10.1001/jamaophthalmol.2017.4030 CrossRefGoogle Scholar
- 28.Oshima Y, Kimoto K, Yoshida N, Fujisawa K, Sonoda S, Kubota T, Murata T, Sakamoto T, Yoshida S, Sonoda KH, Ishibashi T (2017) One-year outcomes following intravitreal aflibercept for polypoidal choroidal vasculopathy in Japanese patients: the APOLLO study. Ophthalmologica 238:163–171. https://doi.org/10.1159/000477448 CrossRefGoogle Scholar