title: Sustained delivery fluocinolone acetonide vitreous implants: long-term benefit in patients with chronic diabetic macular edema.
abstract: OBJECTIVE
  To present the safety and efficacy of intravitreal implants releasing 0.2 μg/day fluocinolone acetonide (FAc) in patients with chronic versus nonchronic diabetic macular edema (DME). To assess ocular characteristics, anatomic changes, and re-treatment and ancillary therapies that may explain the differential treatment effect seen with intravitreal implants releasing FAc 0.2 μg/day in patients with chronic and nonchronic DME. An overall benefit-to-risk assessment for the FAc 0.2-μg/day and FAc 0.5-μg/day doses has been reported previously.
  
  
  METHODS
  Preplanned subgroup analysis of chronic (duration of diagnosis, ≥3 years) and nonchronic (duration of diagnosis, <3 years) DME in patients from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials.
  
  
  METHODS
  Patients with persistent DME despite 1 or more macular laser treatment were randomized 1:2:2 to sham injection (n = 185), FAc 0.2 μg/day (n = 375), or FAc 0.5 μg/day (n = 393).
  
  
  METHODS
  Patients received study drug or sham injection and after 6 weeks were eligible for rescue laser. Based on re-treatment criteria, additional masked study drug could be given after 1 year.
  
  
  METHODS
  Percentage of patients with improvement of 15 letters or more from baseline. Secondary outcomes included other parameters of visual function and foveal thickness.
  
  
  RESULTS
  At month 36, the difference between FAc 0.2 μg/day and sham control in the percentage of patients who gained 15 letters or more was significantly greater in chronic DME patients (FAc 0.2 μg/day, 34.0% vs. sham, 13.4%; P<0.001), compared with patients with nonchronic DME (FAc 0.2 μg/day, 22.3% vs. sham, 27.8%; P = 0.275). The greater response in patients with chronic DME was not associated with baseline ocular characteristics, changes in anatomic features, or differences in re-treatment or ancillary therapies. The ocular adverse event profile for FAc 0.2 μg/day was similar regardless of DME duration.
  
  
  CONCLUSIONS
  This is the first published analysis correlating duration of diagnosis of DME with treatment effect. In patients with chronic DME, FAc 0.2 μg/day provides substantial visual benefit for up to 3 years and would provide an option for patients who do not respond to other therapy.
authors.affiliation: Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal. Electronic address: cunhavaz@aibili.pt.
authors.forename: José
authors.initials: J
authors.lastname: Cunha-Vaz
authors.affiliation: pSivida Corp., Watertown, Massachusetts.
authors.forename: Paul
authors.initials: P
authors.lastname: Ashton
authors.affiliation: Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Raymond
authors.initials: R
authors.lastname: Iezzi
authors.affiliation: Departments of Ophthalmology and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Peter
authors.initials: P
authors.lastname: Campochiaro
authors.affiliation: Retinal Consultants of Arizona, Phoenix, Arizona.
authors.forename: Pravin U
authors.initials: PU
authors.lastname: Dugel
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Holz
authors.affiliation: Service d'ophtalmologie, CHU Hôtel-Dieu, Nantes, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Weber
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Danis
authors.affiliation: Gavin Herbert Eye Institute, University of California, Irvine, California.
authors.forename: Baruch D
authors.initials: BD
authors.lastname: Kuppermann
authors.affiliation: Bristol Eye Hospital, Bristol, United Kingdom.
authors.forename: Clare
authors.initials: C
authors.lastname: Bailey
authors.affiliation: Alimera Sciences, Inc, Alpharetta, Georgia.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Billman
authors.affiliation: Alimera Sciences, Inc, Alpharetta, Georgia.
authors.forename: Barry
authors.initials: B
authors.lastname: Kapik
authors.affiliation: Apropos Pharmaceutical Consulting LLC, Suwanee, Georgia.
authors.forename: Frances
authors.initials: F
authors.lastname: Kane
authors.affiliation: Alimera Sciences, Inc, Alpharetta, Georgia.
authors.forename: Ken
authors.initials: K
authors.lastname: Green
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D004311:Double-Blind Method; D004343:Drug Implants; D005260:Female; D005446:Fluocinolone Acetonide / Q000008:administration & dosage*; D006801:Humans; D008269:Macular Edema / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D014792:Visual Acuity; D014822:Vitreous Body
chemical_list: D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005446:Fluocinolone Acetonide