title: A multicenter, 12-month randomized study comparing dexamethasone intravitreal implant with ranibizumab in patients with diabetic macular edema.
abstract: OBJECTIVE
  To evaluate whether treatment with dexamethasone intravitreal implant (DEX implant) 0.7 mg every 5 months provides a similar average change in best-corrected visual acuity (BCVA) from baseline as ranibizumab 0.5 mg administered as per its European Summary of Product Characteristics in patients with diabetic macular edema (DME).
  
  
  METHODS
  This was a multicenter, open-label, 12-month, randomized, parallel-group, noninferiority study in patients with DME (one eye/patient). The primary efficacy measure was BCVA using the Early Treatment Diabetic Retinopathy Study (ETDRS) method. Secondary efficacy measures included area of leakage on fluorescein angiography and central retinal thickness (CRT) on optical coherence tomography.
  
  
  RESULTS
  Baseline patient characteristics were similar in the two treatment groups (DEX implant, n = 181; ranibizumab, n = 182); mean DME duration was ∼33 months. The mean average BCVA change from baseline over 12 months was 4.34 letters with DEX implant and 7.60 letters with ranibizumab. The lower limit of the 95 % confidence interval of the between-group difference was -4.74 letters, and therefore, DEX was demonstrated to be noninferior to ranibizumab based on the prespecified noninferiority margin of 5 letters. At monthly follow-up visits, the percentage of patients with ≥15-letter BCVA gain from baseline ranged from 7.2 to 17.7 % with DEX implant and 4.4 to 26.9 % with ranibizumab. Both DEX implant and ranibizumab effectively reduced CRT and reduced the area of fluorescein leakage. Between-group differences in change from baseline CRT favored DEX implant at 1, 2, 6, and 7 months (p ≤ 0.007) and ranibizumab at 4, 5, 9, and 10 months (p < 0.001); the decrease in fluorescein leakage area was greater with DEX implant than ranibizumab at month 12 (p < 0.001). Ocular adverse events in the study eye were more frequent in the DEX implant group because of the occurrence of intraocular pressure (IOP) increases and cataract. IOP increases were transient and generally managed with topical medication.
  
  
  CONCLUSIONS
  Both DEX implant and ranibizumab were well tolerated and improved BCVA and anatomic outcomes in patients with DME. DEX implant met the a priori criterion for noninferiority to ranibizumab in average change from baseline BCVA over 12 months. Noninferiority was achieved with an average of 2.85 DEX implant injections and 8.70 ranibizumab injections per patient.
authors.affiliation: Texas Retina Associates, 801 W Randol Mill Rd, Suite 101, Arlington, TX, 76012, USA. dcallanan@texasretina.com.
authors.forename: David G
authors.initials: DG
authors.lastname: Callanan
authors.affiliation: Tel Aviv Medical Center, Tel Aviv, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Loewenstein
authors.affiliation: West Texas Retina, Abilene, TX, USA.
authors.forename: Sunil S
authors.initials: SS
authors.lastname: Patel
authors.affiliation: Paris Diderot University, Lariboisière Hospital, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Massin
authors.affiliation: Institute of Ocular Microsurgery, Barcelona, Spain.
authors.forename: Borja
authors.initials: B
authors.lastname: Corcóstegui
authors.affiliation: Allergan plc, Irvine, CA, USA.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Li
authors.affiliation: Allergan plc, Irvine, CA, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Allergan plc, Irvine, CA, USA.
authors.forename: Yehia
authors.initials: Y
authors.lastname: Hashad
authors.affiliation: Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Whitcup
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage*; D003930:Diabetic Retinopathy / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D058449:Intravitreal Injections; D008266:Macula Lutea / Q000473:pathology*; D008269:Macular Edema / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D000069579:Ranibizumab / Q000008:administration & dosage*; D013997:Time Factors; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014792:Visual Acuity; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D004343:Drug Implants; D005938:Glucocorticoids; D003907:Dexamethasone; D000069579:Ranibizumab
keywords: Dexamethasone; Diabetic macular edema; Intravitreal; Noninferiority; Randomized clinical trial; Ranibizumab