Sustained Delivery Fluocinolone Acetonide Vitreous Implants Long-Term Benefit in Patients with Chronic Diabetic Macular Edema

Purpose: To present the safety and efficacy of intravitreal implants releasing 0.2 mg/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 mg/day in patients with chronic and nonchronic DME. An overall benefit-to- risk assessment for the FAc 0.2-mg/day and FAc 0.5-mg/day doses has been reported previously. Design: 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. Participants: Patients with persistent DME despite 1 or more macular laser treatment were randomized 1: 2: 2 to sham injection (n = 185), FAc 0.2 mg/day (n = 375), or FAc 0.5 mg/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. Main Outcome Measures: 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 mg/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 mg/day, 34.0% vs. sham, 13.4%; P < 0.001), compared with patients with nonchronic DME (FAc 0.2 mg/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 mg/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 mg/day provides substantial visual benefit for up to 3 years and would provide an option for patients who do not respond to other therapy. (C) 2014 by the American Academy of Ophthalmology.