title: Association of Baseline Visual Acuity and Retinal Thickness With 1-Year Efficacy of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema.
abstract: OBJECTIVE
  Comparisons of the relative effect of 3 anti-vascular endothelial growth factor agents to treat diabetic macular edema warrant further assessment.
  
  
  OBJECTIVE
  To provide additional outcomes from a randomized trial evaluating 3 anti-vascular endothelial growth factor agents for diabetic macular edema within subgroups based on baseline visual acuity (VA) and central subfield thickness (CST) as evaluated on optical coherence tomography.
  
  
  METHODS
  Post hoc exploratory analyses were conducted of randomized trial data on 660 adults with diabetic macular edema and decreased VA (Snellen equivalent, approximately 20/32 to 20/320). The original study was conducted between August 22, 2012, and August 28, 2013. Analysis was conducted from January 7 to June 2, 2015.
  
  
  METHODS
  Repeated 0.05-mL intravitreous injections of 2.0 mg of aflibercept (224 eyes), 1.25 mg of bevacizumab (218 eyes), or 0.3 mg of ranibizumab (218 eyes) as needed per protocol.
  
  
  METHODS
  One-year VA and CST outcomes within prespecified subgroups based on both baseline VA and CST thresholds, defined as worse (20/50 or worse) or better (20/32 to 20/40) VA and thicker (≥400 µm) or thinner (250 to 399 µm) CST.
  
  
  RESULTS
  In the subgroup with worse baseline VA (n = 305), irrespective of baseline CST, aflibercept showed greater improvement than bevacizumab or ranibizumab for several VA outcomes. In the subgroup with better VA and thinner CST at baseline (61-73 eyes across 3 treatment groups), VA outcomes showed little difference between groups; mean change was +7.2, +8.4, and +7.6 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively. However, in the subgroup with better VA and thicker CST at baseline (31-43 eyes), there was a suggestion of worse VA outcomes in the bevacizumab group; mean change from baseline to 1 year was +9.5, +5.4, and +9.5 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively, and VA letter score was greater than 84 (approximately 20/20) in 21 of 33 (64%), 7 of 31 (23%), and 21 of 43 (49%) eyes, respectively. The adjusted differences and 95% CIs were 39% (17% to 60%) for aflibercept vs bevacizumab, 25% (5% to 46%) for ranibizumab vs bevacizumab, and 13% (-8% to 35%) for aflibercept vs ranibizumab.
  
  
  CONCLUSIONS
  These post hoc secondary findings suggest that for eyes with better initial VA and thicker CST, some VA outcomes may be worse in the bevacizumab group than in the aflibercept and ranibizumab groups. Given the exploratory nature of these analyses and the small sample size within subgroups, caution is suggested when using the data to guide treatment considerations for patients.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01627249.
authors.affiliation: Palmetto Retina Center, West Columbia, South Carolina.
authors.forename: John A
authors.initials: JA
authors.lastname: Wells
authors.affiliation: Jaeb Center for Health Research, Tampa, Florida.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Glassman
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Jampol
authors.affiliation: Beetham Eye Institute, Joslin Diabetes Center, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lloyd Paul
authors.initials: LP
authors.lastname: Aiello
authors.affiliation: Charlotte Eye, Ear, Nose and Throat Associates, PA, Charlotte, North Carolina.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Antoszyk
authors.affiliation: Paducah Retinal Center, Paducah, Kentucky.
authors.forename: Carl W
authors.initials: CW
authors.lastname: Baker
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland8Editor, JAMA Ophthalmology.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Bressler
authors.affiliation: Charlotte Eye, Ear, Nose and Throat Associates, PA, Charlotte, North Carolina.
authors.forename: David J
authors.initials: DJ
authors.lastname: Browning
authors.affiliation: Jaeb Center for Health Research, Tampa, Florida.
authors.forename: Crystal G
authors.initials: CG
authors.lastname: Connor
authors.affiliation: Elman Retina Group, Baltimore, Maryland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Elman
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ferris
authors.affiliation: Florida Retina Consultants, Winter Haven.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Friedman
authors.affiliation: Jaeb Center for Health Research, Tampa, Florida.
authors.forename: Michele
authors.initials: M
authors.lastname: Melia
authors.affiliation: California Retina Consultants, Santa Barbara.
authors.forename: Dante J
authors.initials: DJ
authors.lastname: Pieramici
authors.affiliation: Beetham Eye Institute, Joslin Diabetes Center, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Sun
authors.affiliation: Jaeb Center for Health Research, Tampa, Florida.
authors.forename: Roy W
authors.initials: RW
authors.lastname: Beck
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000069579:Ranibizumab / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012160:Retina / Q000473:pathology*; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; 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; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab