title: Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE.
abstract: OBJECTIVE
  To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME).
  
  
  METHODS
  Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection-controlled for 2 years.
  
  
  METHODS
  Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥ 275 μm on optical coherence tomography.
  
  
  METHODS
  Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser was available to all patients starting at month 3; panretinal laser was available as necessary.
  
  
  METHODS
  The proportion of patients gaining ≥15 Early Treatment Diabetic Retinopathy Study letters in BCVA from baseline at month 24.
  
  
  RESULTS
  Visual acuity (VA) outcomes seen at month 24 in ranibizumab groups were consistent through month 36; the proportions of patients who gained ≥15 letters from baseline at month 36 in the sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab groups were 19.2%, 36.8%, and 40.2%, respectively, in RIDE and 22.0%, 51.2%, and 41.6%, respectively, in RISE. In the ranibizumab arms, reductions in CFT seen at 24 months were, on average, sustained through month 36. After crossover to 1 year of treatment with ranibizumab, average VA gains in the sham/0.5 mg group were lower compared with gains seen in the ranibizumab patients after 1 year of treatment (2.8 vs. 10.6 and 11.1 letters). Per-injection rates of endophthalmitis remained low over time (∼0.06% per injection). The incidence of serious adverse events potentially related to systemic vascular endothelial growth factor inhibition was 19.7% in patients who received 0.5 mg ranibizumab compared with 16.8% in the 0.3 mg group.
  
  
  CONCLUSIONS
  The strong VA gains and improvement in retinal anatomy achieved with ranibizumab at month 24 were sustained through month 36. Delayed treatment in patients receiving sham treatment did not seem to result in the same extent of VA improvement observed in patients originally randomized to ranibizumab. Ocular and systemic safety was generally consistent with the results seen at month 24.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Retina Consultants of Houston, The Methodist Hospital, Houston, Texas.
authors.forename: David M
authors.initials: DM
authors.lastname: Brown
authors.forename: Quan Dong
authors.initials: QD
authors.lastname: Nguyen
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Marcus
authors.forename: David S
authors.initials: DS
authors.lastname: Boyer
authors.forename: Sunil
authors.initials: S
authors.lastname: Patel
authors.forename: Leonard
authors.initials: L
authors.lastname: Feiner
authors.forename: Patricio G
authors.initials: PG
authors.lastname: Schlottmann
authors.forename: Amy Chen
authors.initials: AC
authors.lastname: Rundle
authors.forename: Jiameng
authors.initials: J
authors.lastname: Zhang
authors.forename: Roman G
authors.initials: RG
authors.lastname: Rubio
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Adamis
authors.forename: Jason S
authors.initials: JS
authors.lastname: Ehrlich
authors.forename: J Jill
authors.initials: JJ
authors.lastname: Hopkins
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D000069579:Ranibizumab; D014792:Visual Acuity / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000069579:Ranibizumab