title: Long-term effects of ranibizumab on diabetic retinopathy severity and progression.
abstract: OBJECTIVE
  To evaluate effects of intravitreal ranibizumab on diabetic retinopathy (DR) severity over time in 2 phase 3 clinical trials (RIDE, NCT00473382; RISE, NCT00473330) of ranibizumab for diabetic macular edema.
  
  
  METHODS
  Participants with diabetic macular edema (n=759) were randomized to monthly sham, 0.3-mg ranibizumab, or 0.5-mg ranibizumab intravitreal injections. Macular laser was available per protocol-specified criteria. Fundus photographs, taken at baseline and periodically, were graded by a central reading center; clinical examinations were performed monthly. The main outcome measures of this report are secondary/exploratory analyses including a 2-step or more and 3-step or more change on the Early Treatment Diabetic Retinopathy Study severity scale in the study eye and a composite DR progression outcome including photographic changes plus clinically important events such as occurrence of vitreous hemorrhage or need for panretinal laser.
  
  
  RESULTS
  At 2 years, the percentage of participants with DR progression (worsening by ≥ 2 or ≥ 3 steps) was significantly reduced in ranibizumab-treated eyes compared with sham-treated eyes, and DR regression (improving by ≥ 2 or ≥ 3 steps) was significantly more likely. The cumulative probability of clinical progression of DR as measured by the composite outcome at 2 years was 33.8% of sham-treated eyes compared with 11.2% to 11.5% of ranibizumab-treated eyes.
  
  
  CONCLUSIONS
  Intravitreal ranibizumab reduced the risk of DR progression in eyes with diabetic macular edema, and many ranibizumab-treated eyes experienced improvement in DR severity. Because these results are exploratory, the use of intravitreal ranibizumab specifically to reduce DR progression or cause DR regression requires further study.
authors.affiliation: Department of Ophthalmology and Visual Services, University of Wisconsin Medical School, Madison, WI 53717, USA. msip@wisc.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Ip
authors.forename: Amitha
authors.initials: A
authors.lastname: Domalpally
authors.forename: J Jill
authors.initials: JJ
authors.lastname: Hopkins
authors.forename: Pamela
authors.initials: P
authors.lastname: Wong
authors.forename: Jason S
authors.initials: JS
authors.lastname: Ehrlich
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D017075:Laser Coagulation; D008269:Macular Edema / Q000188:drug therapy* / Q000503:physiopathology; D000069579:Ranibizumab; D012160:Retina / Q000503:physiopathology; D012720:Severity of Illness Index; D013997:Time Factors; D014792:Visual Acuity / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000069579:Ranibizumab