title: Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of intravitreal aflibercept injection (IAI) for the treatment of macular edema secondary to central retinal vein occlusion (CRVO).
  
  
  METHODS
  Randomized, double-masked, phase 3 trial.
  
  
  METHODS
  A total of 188 patients with macular edema secondary to CRVO.
  
  
  METHODS
  Patients received IAI 2 mg (IAI 2Q4) (n = 114) or sham injections (n = 74) every 4 weeks up to week 24. During weeks 24 to 52, patients from both arms were evaluated monthly and received IAI as needed, or pro re nata (PRN) (IAI 2Q4 + PRN and sham + IAI PRN). During weeks 52 to 100, patients were evaluated at least quarterly and received IAI PRN.
  
  
  METHODS
  The primary efficacy end point was the proportion of patients who gained ≥ 15 letters in best-corrected visual acuity (BCVA) from baseline to week 24. This study reports week 100 results.
  
  
  RESULTS
  The proportion of patients gaining ≥ 15 letters was 56.1% versus 12.3% (P<0.001) at week 24, 55.3% versus 30.1% (P<0.001) at week 52, and 49.1% versus 23.3% (P<0.001) at week 100 in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively. The mean change from baseline BCVA was also significantly higher in the IAI 2Q4 + PRN group compared with the sham + IAI PRN group at week 24 (+17.3 vs. -4.0 letters; P<0.001), week 52 (+16.2 vs. +3.8 letters; P<0.001), and week 100 (+13.0 vs. +1.5 letters; P<0.0001). The mean reduction from baseline in central retinal thickness was 457.2 versus 144.8 μm (P<0.001) at week 24, 413.0 versus 381.8 μm at week 52 (P = 0.546), and 390.0 versus 343.3 μm at week 100 (P = 0.366) in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively. The mean number (standard deviation) of PRN injections in the IAI 2Q4 + PRN and sham + IAI PRN groups was 2.7 ± 1.7 versus 3.9 ± 2.0 during weeks 24 to 52 and 3.3 ± 2.1 versus 2.9 ± 2.0 during weeks 52 to 100, respectively. The most frequent ocular serious adverse event from baseline to week 100 was vitreous hemorrhage (0.9% vs. 6.8% in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively).
  
  
  CONCLUSIONS
  The visual and anatomic improvements after fixed dosing through week 24 and PRN dosing with monthly monitoring from weeks 24 to 52 were diminished after continued PRN dosing, with a reduced monitoring frequency from weeks 52 to 100.
authors.affiliation: Ophthalmic Consultants of Boston, Boston, Massachusetts.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Heier
authors.affiliation: Palmetto Retina Center, West Columbia, South Carolina.
authors.forename: W Lloyd
authors.initials: WL
authors.lastname: Clark
authors.affiliation: Retina-Vitreous Associates Medical Group, Beverly Hills, California.
authors.forename: David S
authors.initials: DS
authors.lastname: Boyer
authors.affiliation: Retina Consultants of Houston, The Methodist Hospital, Houston, Texas.
authors.forename: David M
authors.initials: DM
authors.lastname: Brown
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
authors.forename: Robert
authors.initials: R
authors.lastname: Vitti
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
authors.forename: Alyson J
authors.initials: AJ
authors.lastname: Berliner
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
authors.forename: Husain
authors.initials: H
authors.lastname: Kazmi
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Bayer HealthCare, Berlin, Germany; Department of Neurology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Stemper
authors.affiliation: Bayer HealthCare, Berlin, Germany; Klinik und Poliklinik fur Augenheilkunde, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Zeitz
authors.affiliation: Bayer HealthCare, Berlin, Germany; Department of Neurology, Heinrich-Heine-Universitat, Dusseldorf, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Sandbrink
authors.affiliation: Wills Eye Hospital, Philadelphia, Pennsylvania. Electronic address: jhaller@willseye.org.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Haller
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012160:Retina / Q000473:pathology; D012170:Retinal Vein Occlusion / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014792:Visual Acuity / Q000502:physiology
chemical_list: D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor