Three-year, Randomized, Sham-controlled, Phase III Study of Dexamethasone Intravitreal Implant in Patients with Diabetic Macular Edema

Abstract

Purpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 mg and 0.35 mg in the treatment of diabetic macular edema (DME).

Methods: Pooled data analysis of results from two 3-year, randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols. Patients (n=1048) with DME, best-corrected visual acuity (BCVA) between 34 and 68 ETDRS letters, and central subfield retinal thickness (CRT) ≥300 µm by optical coherence tomography (OCT) were randomized in a 1:1:1 ratio to treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months. The primary endpoint for the United States FDA was achievement of ≥15-letter improvement in BCVA from baseline at study end in the intent-to-treat population with last-observation-carried-forward for missing values. Safety measures included adverse events (AEs) and intraocular pressure (IOP).

Results: Mean number of treatments received over 3 years was 4.1 for DEX implant 0.7 mg, 4.4 for DEX implant 0.35 mg, and 3.3 for sham. 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 during the study was greater with DEX implant 0.7 mg (-111.6 µm) and DEX implant 0.35 mg (-107.9 µm) than sham (-41.9 µm) (P<0.001, area-under-the-curve approach). Rates of cataract-related AEs 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. IOP increases were usually controlled with medication or no therapy; only 1 (0.3%) patient treated with DEX implant 0.7 mg and 1 (0.3%) treated with DEX implant 0.35 mg underwent glaucoma incisional surgery for steroid-induced IOP increases.

Conclusions: DEX implant 0.7 mg and 0.35 mg provided statistically and clinically significant improvement in BCVA and reduction in CRT with an average of only 4-5 injections over 3 years. The safety profile was favorable.

Keywords: 499 diabetic retinopathy • 487 corticosteroids • 505 edema