title: Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema.
abstract: OBJECTIVE
  To assess the efficacy and safety of intravitreal inserts releasing 0.2 μg/day (low dose) or 0.5 μg/day (high dose) fluocinolone acetonide (FA) in patients with diabetic macular edema (DME).
  
  
  METHODS
  Two parallel, prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trials.
  
  
  METHODS
  Subjects with persistent DME despite at least 1 macular laser treatment were randomized 1:2:2 to sham injection (n = 185), low-dose insert (n = 375), or high-dose insert (n = 393).
  
  
  METHODS
  Subjects received study drug or sham injection at baseline and after 6 weeks were eligible for rescue laser. Based on retreatment criteria, additional study drug or sham injections could be given after 1 year.
  
  
  METHODS
  The primary outcome was the percentage of patients with improvement from baseline best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Trial (ETDRS) letter score of 15 or more at month 24. Secondary outcomes included other parameters of visual function and foveal thickness (FTH).
  
  
  RESULTS
  The percentage of patients with improvement from baseline ETDRS letter score of 15 or more at month 24 was 28.7 and 28.6 in the low- and high-dose insert groups, respectively, compared with 16.2 in the sham group (P = 0.002 for each). Benefit occurred for both doses compared with sham at 3 weeks and all subsequent time points. The mean improvement in BCVA letter score between baseline and month 24 was 4.4 and 5.4 in the low- and high-dose groups, respectively, compared with 1.7 in the sham group (P = 0.02 and P = 0.016). At all time points compared with sham, there was significantly more improvement in FTH. Subjects requiring cataract surgery were more frequent in the insert groups, and their visual benefit was similar to that of subjects who were pseudophakic at baseline. Glaucoma requiring incisional surgery occurred in 3.7%, 7.6%, and 0.5% of the low-dose, high-dose, and sham groups, respectively.
  
  
  CONCLUSIONS
  Both low- and high-dose FA inserts significantly improved BCVA in patients with DME over 2 years, and the risk-to-benefit ratio was superior for the low-dose insert. This is the first pharmacologic treatment that can be administered by an outpatient injection to provide substantial benefit in patients with DME for at least 2 years.
authors: The Wilmer Eye Institute, the Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA. pcampo@jhmi.edu
authors: Peter A
authors: PA
authors: Campochiaro
authors: David M
authors: DM
authors: Brown
authors: Andrew
authors: A
authors: Pearson
authors: Thomas
authors: T
authors: Ciulla
authors: David
authors: D
authors: Boyer
authors: Frank G
authors: FG
authors: Holz
authors: Michael
authors: M
authors: Tolentino
authors: Amod
authors: A
authors: Gupta
authors: Lilianne
authors: L
authors: Duarte
authors: Steven
authors: S
authors: Madreperla
authors: John
authors: J
authors: Gonder
authors: Barry
authors: B
authors: Kapik
authors: Kathleen
authors: K
authors: Billman
authors: Frances E
authors: FE
authors: Kane
mesh_terms: D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004343:Drug Implants; D005260:Female; D005446:Fluocinolone Acetonide / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012160:Retina / Q000473:pathology; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014792:Visual Acuity / Q000502:physiology; D014822:Vitreous Body / Q000187:drug effects*
chemical_list: D004343:Drug Implants; D005938:Glucocorticoids; D005446:Fluocinolone Acetonide