title: Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME).
  
  
  METHODS
  Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis.
  
  
  METHODS
  Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 μm by optical coherence tomography.
  
  
  METHODS
  Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months.
  
  
  METHODS
  The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP).
  
  
  RESULTS
  Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (-111.6 μm) and DEX implant 0.35 mg (-107.9 μm) than sham (-41.9 μm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy.
  
  
  CONCLUSIONS
  The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports.
authors.affiliation: Retina-Vitreous Associates Medical Group, Los Angeles, California. Electronic address: vitdoc@aol.com.
authors.forename: David S
authors.initials: DS
authors.lastname: Boyer
authors.affiliation: Asan Medical Center, University of Ulsan, Seoul, South Korea.
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Yoon
authors.affiliation: Vision Institute, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Rubens
authors.initials: R
authors.lastname: Belfort
authors.affiliation: University Vita-Salute, Hospital San Raffaele, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bandello
authors.affiliation: Midwest Eye Institute, Indianapolis, Indiana.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Maturi
authors.affiliation: Department of Ophthalmology, Staedtisches Klinikum Karlsruhe, Karlsruhe, Germany.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Augustin
authors.affiliation: Allergan, Inc, Irvine, California.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Li
authors.affiliation: Allergan, Inc, Irvine, California.
authors.forename: Harry
authors.initials: H
authors.lastname: Cui
authors.affiliation: Allergan, Inc, Irvine, California.
authors.forename: Yehia
authors.initials: Y
authors.lastname: Hashad
authors.affiliation: Allergan, Inc, Irvine, California.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Whitcup
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D019540:Area Under Curve; D003907:Dexamethasone / Q000008:administration & dosage*; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D004343:Drug Implants; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D014792:Visual Acuity
chemical_list: D000893:Anti-Inflammatory Agents; D004343:Drug Implants; D003907:Dexamethasone