Three-year randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema.

Purpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME). Design: Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis. Participants: Patients (n 1⁄4 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of 300 mm by optical coherence tomography. Methods: Patientswere randomized in a 1:1:1 ratio to study treatmentwithDEX implant 0.7mg,DEX implant 0.35 mg, or shamprocedure andfollowedfor 3 years (or 39months for patients treatedatmonth36) at40 scheduledvisits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months. Main Outcome Measures: The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of 15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP). Results: Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with 15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (111.6 mm) and DEX implant 0.35 mg (107.9 mm) than sham (41.9 mm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy. Conclusions: The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports. Ophthalmology 2014;121:1904- 1914 a 2014 by the American Academy of Ophthalmology