Vascular endothelial growth factor Trap-Eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study

Ophthalmology. 2012 May;119(5):1024-32. doi: 10.1016/j.ophtha.2012.01.042. Epub 2012 Mar 21.


Objective: To assess the efficacy and safety of intravitreal vascular endothelial growth factor (VEGF) Trap-Eye in eyes with macular edema secondary to central retinal vein occlusion (CRVO).

Design: Multicenter, randomized, prospective, controlled trial.

Participants: One hundred eighty-nine eyes with macular edema secondary to CRVO.

Methods: Eyes were randomized 3:2 to receive VEGF Trap-Eye 2 mg or sham injection monthly for 6 months.

Main outcome measures: The proportion of eyes with a ≥15-letter gain or more in best-corrected visual acuity (BCVA) at week 24 (primary efficacy end point), mean changes in BCVA and central retinal thickness (CRT), and proportion of eyes progressing to neovascularization of the anterior segment, optic disc, or elsewhere in the retina.

Results: At week 24, 56.1% of VEGF Trap-Eye treated eyes gained 15 letters or more from baseline versus 12.3% of sham-treated eyes (P<0.001). The VEGF Trap-Eye treated eyes gained a mean of 17.3 letters versus sham-treated eyes, which lost 4.0 letters (P<0.001). Central retinal thickness decreased by 457.2 μm in eyes treated with VEGF Trap-Eye versus 144.8 μm in sham-treated eyes (P<0.001), and progression to any neovascularization occurred in 0 and 5 (6.8%) of eyes treated with VEGF Trap-Eye and sham-treated eyes, respectively (P = 0.006). Conjunctival hemorrhage, reduced visual acuity, and eye pain were the most common adverse events (AEs). Serious ocular AEs were reported by 3.5% of VEGF Trap-Eye patients and 13.5% of sham patients. Incidences of nonocular serious AEs generally were well balanced between both groups.

Conclusions: At 24 weeks, monthly intravitreal injection of VEGF Trap-Eye 2 mg in eyes with macular edema resulting from CRVO improved visual acuity and CRT, eliminated progression resulting from neovascularization, and was associated with a low rate of ocular AEs related to treatment.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Double-Blind Method
  • Eye Pain / etiology
  • Female
  • Humans
  • Intravitreal Injections
  • Macular Edema / drug therapy*
  • Macular Edema / etiology
  • Macular Edema / physiopathology
  • Male
  • Prospective Studies
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use*
  • Retinal Vein Occlusion / complications
  • Retinal Vein Occlusion / drug therapy*
  • Retinal Vein Occlusion / physiopathology
  • Surveys and Questionnaires
  • Treatment Outcome
  • Visual Acuity / physiology


  • Angiogenesis Inhibitors
  • Recombinant Fusion Proteins
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor