title: Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema.
abstract: BACKGROUND
  The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown.
  
  
  METHODS
  At 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year.
  
  
  RESULTS
  From baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P=0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P=0.003 for aflibercept vs. ranibizumab, and P=0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P=0.40), hospitalization (P=0.51), death (P=0.72), or major cardiovascular events (P=0.56).
  
  
  CONCLUSIONS
  Intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01627249.).
authors.forename: John A
authors.initials: JA
authors.lastname: Wells
authors.forename: Adam R
authors.initials: AR
authors.lastname: Glassman
authors.forename: Allison R
authors.initials: AR
authors.lastname: Ayala
authors.forename: Lee M
authors.initials: LM
authors.lastname: Jampol
authors.forename: Lloyd Paul
authors.initials: LP
authors.lastname: Aiello
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Antoszyk
authors.forename: Bambi
authors.initials: B
authors.lastname: Arnold-Bush
authors.forename: Carl W
authors.initials: CW
authors.lastname: Baker
authors.forename: Neil M
authors.initials: NM
authors.lastname: Bressler
authors.forename: David J
authors.initials: DJ
authors.lastname: Browning
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Elman
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ferris
authors.forename: Scott M
authors.initials: SM
authors.lastname: Friedman
authors.forename: Michele
authors.initials: M
authors.lastname: Melia
authors.forename: Dante J
authors.initials: DJ
authors.lastname: Pieramici
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Sun
authors.forename: Roy W
authors.initials: RW
authors.lastname: Beck
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000069579:Ranibizumab; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage* / Q000009:adverse effects; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D012160:Retina / Q000187:drug effects / Q000473:pathology; D013810:Therapeutic Equivalency; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014792:Visual Acuity / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab