title: A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of pegaptanib sodium injection (pegaptanib) in the treatment of diabetic macular edema (DME).
  
  
  METHODS
  Randomized, double-masked, multicenter, dose-ranging, controlled trial.
  
  
  METHODS
  Individuals with a best-corrected visual acuity (VA) between 20/50 and 20/320 in the study eye and DME involving the center of the macula for whom the investigator judged photocoagulation could be safely withheld for 16 weeks.
  
  
  METHODS
  Intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections at study entry, week 6, and week 12 with additional injections and/or focal photocoagulation as needed for another 18 weeks. Final assessments were conducted at week 36.
  
  
  METHODS
  Best-corrected VA, central retinal thickness at the center point of the central subfield as assessed by optical coherence tomography measurement, and additional therapy with photocoagulation between weeks 12 and 36.
  
  
  RESULTS
  One hundred seventy-two patients appeared balanced for baseline demographic and ocular characteristics. Median VA was better at week 36 with 0.3 mg (20/50), as compared with sham (20/63) (P = 0.04). A larger proportion of those receiving 0.3 mg gained VAs of > or =10 letters (approximately 2 lines) (34% vs. 10%, P = 0.003) and > or =15 letters (18% vs. 7%, P = 0.12). Mean central retinal thickness decreased by 68 microm with 0.3 mg, versus an increase of 4 microm with sham (P = 0.02). Larger proportions of those receiving 0.3 mg had an absolute decrease of both > or =100 microm (42% vs. 16%, P = 0.02) and > or =75 microm (49% vs. 19%, P = 0.008). Photocoagulation was deemed necessary in fewer subjects in each pegaptanib arm (0.3 mg vs. sham, 25% vs. 48%; P = 0.04). All pegaptanib doses were well tolerated. Endophthalmitis occurred in 1 of 652 injections (0.15%/injection; i.e., 1/130 [0.8%] pegaptanib subjects) and was not associated with severe visual loss.
  
  
  CONCLUSIONS
  In this phase II trial, subjects assigned to pegaptanib had better VA outcomes, were more likely to show reduction in central retinal thickness, and were deemed less likely to need additional therapy with photocoagulation at follow-up.
authors.affiliation: Stanford University, USA.
authors.forename: Emmett T
authors.initials: ET
authors.lastname: Cunningham
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Adamis
authors.forename: Michael
authors.initials: M
authors.lastname: Altaweel
authors.forename: Lloyd P
authors.initials: LP
authors.lastname: Aiello
authors.forename: Neil M
authors.initials: NM
authors.lastname: Bressler
authors.forename: Donald J
authors.initials: DJ
authors.lastname: D'Amico
authors.forename: Mauro
authors.initials: M
authors.lastname: Goldbaum
authors.forename: David R
authors.initials: DR
authors.lastname: Guyer
authors.forename: Barrett
authors.initials: B
authors.lastname: Katz
authors.forename: Manju
authors.initials: M
authors.lastname: Patel
authors.forename: Steven D
authors.initials: SD
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052157:Aptamers, Nucleotide; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007267:Injections; D008269:Macular Edema / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000008:administration & dosage*; D012449:Safety; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014792:Visual Acuity / Q000502:physiology; D014822:Vitreous Body
chemical_list: D052157:Aptamers, Nucleotide; D009841:Oligonucleotides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C495058:pegaptanib