title: Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial.
abstract: OBJECTIVE
  We studied the 3-year efficacy and safety results of a 4-year study evaluating fluocinolone acetonide (FA) intravitreal implants in eyes with persistent or recurrent diabetic macular edema (DME).
  
  
  METHODS
  Prospective, evaluator-masked, controlled, multicenter clinical trial.
  
  
  METHODS
  We included 196 eyes with refractory DME.
  
  
  METHODS
  Patients were randomized 2:1 to receive 0.59-mg FA implant (n = 127) or standard of care (SOC additional laser or observation; n = 69). The implant was inserted through a pars plana incision. Visits were scheduled on day 2, weeks 1, 3, 6, 12, and 26, and thereafter every 13 weeks through 3 years postimplantation.
  
  
  METHODS
  The primary efficacy outcome was ≥15-letter improvement in visual acuity (VA) at 6 months. Secondary outcomes included resolution of macular retinal thickening and Diabetic Retinopathy Severity Score (DRSS). Safety measures included incidence of adverse events (AEs).
  
  
  RESULTS
  Overall, VA improved ≥3 lines in 16.8% of implanted eyes at 6 months (P=0.0012; SOC, 1.4%); in 16.4% at 1 year (P=0.1191; SOC, 8.1%); in 31.8% at 2 years (P=0.0016; SOC, 9.3%); and in 31.1% at 3 years (P=0.1566; SOC, 20.0%). The number of implanted eyes with no evidence of retinal thickening at the center of the macula was higher than SOC eyes at 6 months (P<0.0001), 1 year (P<0.0001; 72% vs 22%), 2 years (P=0.016), and 3 years (P=0.861). A higher rate of improvement and lower rate of decline in DRSS occurred in the implanted group versus the SOC group at 6 months (P=0.0006), 1 year (P=0.0016), 2 years (P=0.012), and 3 years (P=0.0207). Intraocular pressure (IOP) ≥30 mmHg was recorded in 61.4% of implanted eyes (SOC, 5.8%) at any time and 33.8% required surgery for ocular hypertension by 4 years. Of implanted phakic eyes, 91% (SOC, 20%) had cataract extraction by 4 years.
  
  
  CONCLUSIONS
  The FA intravitreal implant met the primary and secondary outcomes, with significantly improved VA and DRSS and reduced DME. The most common AEs included cataract progression and elevated IOP. The 0.59-mg FA intravitreal implant may be an effective treatment for eyes with persistent or recurrent DME.
  
  
  BACKGROUND
  Proprietary or commercial disclosure may be found after the references.
authors.affiliation: Department of Ophthalmology and Visual Science, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Pearson
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Comstock
authors.forename: Michael
authors.initials: M
authors.lastname: Ip
authors.forename: David
authors.initials: D
authors.lastname: Callanan
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Morse
authors.forename: Paul
authors.initials: P
authors.lastname: Ashton
authors.forename: Brian
authors.initials: B
authors.lastname: Levy
authors.forename: Eric S
authors.initials: ES
authors.lastname: Mann
authors.forename: Dean
authors.initials: D
authors.lastname: Eliott
mesh_terms: D002386:Cataract / Q000139:chemically induced; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004343:Drug Implants; D005260:Female; D005446:Fluocinolone Acetonide / Q000008:administration & dosage* / Q000009:adverse effects; D005451:Fluorescein Angiography; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology; D008269:Macular Edema / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D012160:Retina / Q000187:drug effects / Q000473:pathology; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014792:Visual Acuity / Q000187:drug effects / Q000502:physiology; D014822:Vitreous Body / Q000187:drug effects*
chemical_list: D004343:Drug Implants; D005938:Glucocorticoids; D005446:Fluocinolone Acetonide