Clinical Studies:
Mead
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.
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Objective
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).
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STUDY DESIGN
Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols and pooled data.
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DURATION
36 months
STUDY SUBJECTS
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)
Study population
- 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.
Anatomic outcomes
- 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.
Adverse events
- 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.
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.