Intravitreal Aflibercept (VEGF Trap-Eye) in Wet Age-related Macular Degeneration

Published:October 18, 2012DOI:


      Two similarly designed, phase-3 studies (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD [VIEW 1, VIEW 2]) of neovascular age-related macular degeneration (AMD) compared monthly and every-2-month dosing of intravitreal aflibercept injection (VEGF Trap-Eye; Regeneron, Tarrytown, NY, and Bayer HealthCare, Berlin, Germany) with monthly ranibizumab.


      Double-masked, multicenter, parallel-group, active-controlled, randomized trials.


      Patients (n = 2419) with active, subfoveal, choroidal neovascularization (CNV) lesions (or juxtafoveal lesions with leakage affecting the fovea) secondary to AMD.


      Patients were randomized to intravitreal aflibercept 0.5 mg monthly (0.5q4), 2 mg monthly (2q4), 2 mg every 2 months after 3 initial monthly doses (2q8), or ranibizumab 0.5 mg monthly (Rq4).

      Main Outcome Measures

      The primary end point was noninferiority (margin of 10%) of the aflibercept regimens to ranibizumab in the proportion of patients maintaining vision at week 52 (losing <15 letters on Early Treatment Diabetic Retinopathy Study [ETDRS] chart). Other key end points included change in best-corrected visual acuity (BCVA) and anatomic measures.


      All aflibercept groups were noninferior and clinically equivalent to monthly ranibizumab for the primary end point (the 2q4, 0.5q4, and 2q8 regimens were 95.1%, 95.9%, and 95.1%, respectively, for VIEW 1, and 95.6%, 96.3%, and 95.6%, respectively, for VIEW 2, whereas monthly ranibizumab was 94.4% in both studies). In a prespecified integrated analysis of the 2 studies, all aflibercept regimens were within 0.5 letters of the reference ranibizumab for mean change in BCVA; all aflibercept regimens also produced similar improvements in anatomic measures. Ocular and systemic adverse events were similar across treatment groups.


      Intravitreal aflibercept dosed monthly or every 2 months after 3 initial monthly doses produced similar efficacy and safety outcomes as monthly ranibizumab. These studies demonstrate that aflibercept is an effective treatment for AMD, with the every-2-month regimen offering the potential to reduce the risk from monthly intravitreal injections and the burden of monthly monitoring.

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        • Congdon N.G.
        • Friedman D.S.
        • Lietman T.
        Important causes of visual impairment in the world today.
        JAMA. 2003; 290: 2057-2060
        • Macular Photocoagulation Study Group
        Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration.
        Arch Ophthalmol. 1991; 109: 1220-1231
        • 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: 1329-1345
        • Verteporfin in Photodynamic Therapy Study Group
        Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization–Verteporfin in Photodynamic Therapy report 2.
        Am J Ophthalmol. 2001; 131: 541-560
        • Yancopoulos G.D.
        Clinical application of therapies targeting VEGF.
        Cell. 2010; 143: 13-16
        • Ferrara N.
        VEGF-A: a critical regulator of blood vessel growth.
        Eur Cytokine Netw. 2009; 20: 158-163
        • Rosenfeld P.J.
        • Brown D.M.
        • Heier J.S.
        • et al.
        • MARINA Study Group
        Ranibizumab for neovascular age-related macular degeneration.
        N Engl J Med. 2006; 355: 1419-1431
        • Brown D.M.
        • Kaiser P.K.
        • Michels M.
        • et al.
        • ANCHOR Study Group
        Ranibizumab versus verteporfin for neovascular age-related macular degeneration.
        N Engl J Med. 2006; 355: 1432-1444
        • Schmidt-Erfurth U.
        • Eldem B.
        • Guymer R.
        • et al.
        • EXCITE Study Group
        Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study.
        Ophthalmology. 2011; 118: 831-839
        • Regillo C.D.
        • Brown D.M.
        • Abraham P.
        • et al.
        • PIER Study Group
        Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1.
        Am J Ophthalmol. 2008; 145: 239-248
        • Boyer D.S.
        • Heier J.S.
        • Brown D.M.
        • et al.
        A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration.
        Ophthalmology. 2009; 116: 1731-1739
        • Singer M.A.
        • Awh C.C.
        • Sadda S.
        • et al.
        HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration.
        Ophthalmology. 2012; 119: 1175-1183
        • Martin D.F.
        • Maguire M.G.
        • Ying G.S.
        • et al.
        • CATT Research Group
        Ranibizumab and bevacizumab for neovascular age-related macular degeneration.
        N Engl J Med. 2011; 364: 1897-1908
        • Martin D.F.
        • Maguire M.G.
        • Fine S.L.
        • et al.
        • Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group
        Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results.
        Ophthalmology. 2012; 119: 1388-1398
        • Chakravarthy U.
        • Harding S.P.
        • Rogers C.A.
        • et al.
        • IVAN Study Investigators
        Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial.
        Ophthalmology. 2012; 119: 1399-1411
        • Economides A.N.
        • Carpenter L.R.
        • Rudge J.S.
        • et al.
        Cytokine traps: multi-component, high-affinity blockers of cytokine action.
        Nat Med. 2003; 9: 47-52
        • Holash J.
        • Davis S.
        • Papadopoulos N.
        • et al.
        VEGF-Trap: a VEGF blocker with potent antitumor effects.
        Proc Natl Acad Sci U S A. 2002; 99: 11393-11398
        • Heier J.S.
        • Boyer D.
        • Nguyen Q.D.
        • et al.
        • CLEAR-IT 2 Investigators
        The 1-year results of CLEAR-IT 2, a phase 2 study of vascular endothelial growth factor Trap-Eye dosed as-needed after 12-week fixed dosing.
        Ophthalmology. 2011; 118: 1098-1106
        • Stewart M.W.
        • Rosenfeld P.J.
        Predicted biological activity of intravitreal VEGF Trap.
        Br J Ophthalmol. 2008; 92: 667-668
        • Brown D.M.
        • Heier J.S.
        • Ciulla T.
        • et al.
        • CLEAR-IT 2 Investigators
        Primary endpoint results of a phase II study of vascular endothelial growth factor Trap-Eye in wet age-related macular degeneration.
        Ophthalmology. 2011; 118: 1089-1097

      Linked Article

      • Erratum
        OphthalmologyVol. 120Issue 1
        • In Brief
          With apologies from the authors of “Intravitreal Aflibercept (VEGF Trap-Eye) in Wet Age-related Macular Degeneration” (Ophthalmology 2012;119:2537–48) one paragraph of the Discussion section was removed and the correctly edited version is bolded in the text below.
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