title: Intravitreal aflibercept for diabetic macular edema.
abstract: OBJECTIVE
  A head-to-head comparison was performed between vascular endothelial growth factor blockade and laser for treatment of diabetic macular edema (DME).
  
  
  METHODS
  Two similarly designed, double-masked, randomized, phase 3 trials, VISTA(DME) and VIVID(DME).
  
  
  METHODS
  We included 872 patients (eyes) with type 1 or 2 diabetes mellitus who presented with DME with central involvement.
  
  
  METHODS
  Eyes received either intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation.
  
  
  METHODS
  The primary efficacy endpoint was the change from baseline in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52. Secondary efficacy endpoints at week 52 included the proportion of eyes that gained ≥ 15 letters from baseline and the mean change from baseline in central retinal thickness as determined by optical coherence tomography.
  
  
  RESULTS
  Mean BCVA gains from baseline to week 52 in the IAI 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (P < 0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (P < 0.0001) in VIVID. The corresponding proportions of eyes gaining ≥ 15 letters were 41.6% and 31.1% versus 7.8% (P < 0.0001) in VISTA, and 32.4% and 33.3% versus 9.1% (P < 0.0001) in VIVID. Similarly, mean reductions in central retinal thickness were 185.9 and 183.1 versus 73.3 μm (P < 0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (P < 0.0001) in VIVID. Overall incidences of ocular and nonocular adverse events and serious adverse events, including the Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events and vascular deaths, were similar across treatment groups.
  
  
  CONCLUSIONS
  At week 52, IAI demonstrated significant superiority in functional and anatomic endpoints over laser, with similar efficacy in the 2q4 and 2q8 groups despite the extended dosing interval in the 2q8 group. In general, IAI was well-tolerated.
authors.affiliation: Service d'ophtalmologie, Hôpital Pellegrin-CHU de Bordeaux, Bordeaux, France; Université Bordeaux Segalen, Bordeaux, France; INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Korobelnik
authors.affiliation: Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Diana V
authors.initials: DV
authors.lastname: Do
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Schmidt-Erfurth
authors.affiliation: Retina-Vitreous Associates Medical Group, Beverly Hills, California.
authors.forename: David S
authors.initials: DS
authors.lastname: Boyer
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Holz
authors.affiliation: Ophthalmic Consultants of Boston and Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Heier
authors.affiliation: Department of Ophthalmology, University of Padova, Padova, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Midena
authors.affiliation: Cole Eye Institute, Cleveland, Ohio.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Kaiser
authors.affiliation: Nagoya University Hospital, Nagoya, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Terasaki
authors.affiliation: Southeast Retina Center, Augusta, Georgia.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Marcus
authors.affiliation: Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Quan D
authors.initials: QD
authors.lastname: Nguyen
authors.affiliation: Department of Ophthalmology, Duke University, Durham, North Carolina.
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Jaffe
authors.affiliation: Vitreous-Retina-Macula Consultants of New York, New York, New York.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Slakter
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Simader
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
authors.forename: Yuhwen
authors.initials: Y
authors.lastname: Soo
authors.affiliation: Bayer HealthCare, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmelter
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
authors.forename: Neil
authors.initials: N
authors.lastname: Stahl
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: Bayer HealthCare, Berlin, Germany; University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Zeitz
authors.affiliation: Bayer HealthCare, Berlin, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Metzig
authors.affiliation: Retina Consultants of Houston, Houston, Texas. Electronic address: dmbmd@houstonretina.com.
authors.forename: David M
authors.initials: DM
authors.lastname: Brown
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D017075:Laser Coagulation; D008269:Macular Edema / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D040262:Receptors, Vascular Endothelial Growth Factor / Q000009:adverse effects / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor