Citation: Boyer DS, Yoon YH, Belfort R Jr, Bandello F, Maturi RK, Augustin AJ, Li XY, Cui H, Hashad Y, Whitcup SM; Ozurdex MEAD Study Group. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology. 2014 Oct;121(10):1904-14.
doi: 10.1016/j.ophtha.2014.04.024. Epub 2014 Jun 4. PMID: 24907062.
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).
Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols and pooled data.
Major inclusion criteria:
- Patients with type 1 or 2 DM with fovea-involved macular edema associated with DR previously treated with medical or laser therapy as well as treatment-naïve patients who had refused laser treatment or who, in the opinion of the investigator, would not benefit from laser treatment.
RANDOMIZATION SCHEME AND INTERVENTIONS
Randomized 1:1:1 to
- (a) DEX implant 0.7 mg
- (b) DEX implant 0.35 mg
- (c) Sham procedure
Patients were eligible for retreatment with DEX implant only if there had been ≥6 months since the most recent study treatment and there was evidence of residual edema..
RESULTS (36 months)
- 1,048 patients randomized to receive a 0.7-mg implant (351 patients), a 0.35-mg implant (347 patients) or sham treatment (350 patients).
- The mean duration of DME before the study was 24.9 months.
Visual acuity end-points
- Gain of ≥15-letter: Greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018).
- Both DEX groups gained 15 letters significantly earlier than those in the sham treatment group (P < .001 and P =.005, respectively)
- Mean average BCVA change: 3.5 letters with the 0.7-mg implant, 3.6 letters with the 0.35-mg implant and 2 letters with sham treatment. Average change significantly greater in the 0.7-mg group (P = .023) and 0.35-mg group (P = .019) than in the sham treatment group.
- Mean reduction in CRT: 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)
- CRT increased after cataract surgery in the sham treatment group but not in the dexamethasone groups.
- Cataract-related adverse events in phakic eyes were 67.9% in the 0.7-mg group, 64.1% in the 0.35-mg group and 20.4% in the sham treatment group.
- IOP increased by at least 10 mm Hg in 27.7% of patients in the 0.7-mg group, 24.8% of patients in the 0.35-mg group and 3.7% of patients in the sham treatment group. Two patients in the 0.7-mg group and one patient in the 0.35-mg group required trabeculectomy.
- Vitreous hemorrhage was identified in 6.9% of eyes in the 0.7-mg group, 13.1% of eyes in the 0.35-mg group and 7.1% of patients in the sham group; no cases of vitreous hemorrhage required vitrectomy and most resolved quickly.
- Retinal tear, retinal detachment, vitreous loss, endophthalmitis, hypotony, and complication of device insertion (implant misplacement), were <2% of patients in each group
- Two reports of endophthalmitis out of 2928 DEX implant injections: One case occurred after cataract surgery and was considered unrelated to study treatment, and the other occurred after a DEX implant 0.7 mg injection.
- 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.