Place of intravitreal dexamethasone implant in the treatment armamentarium of diabetic macular edema

Table 1 Summary of major clinical trials of dexamethasone implant in patients with diabetic macular edema

Ref.	Study design, number of patients, mean or median follow-up period after the first injection	Treatment indications	Anatomical and functional outcomes
Boyer et al[24], Ozurdex MEAD study group	Multicenter, randomized, sham-controlled, phase III clinical study	DME	Statistically significantly higher mean CMT reduction from baseline during the study in both DEX implant groups than the sham group
	1048 patients		DEX implant 0.7 mg: -111.6 µm
	DEX implant 0.7 mg (351)		DEX implant 0.35 mg: -107.9 µm
	DEX implant 0.35 mg (347)		Sham group: - 41.9 µm
	Sham (350)		Statistically significant improvement in BVCA with DEX implant at year 3. A significantly greater percentage of patients with a ≥ 15-letter improvement in BCVA from baseline in both DEX implant groups than sham at year 3
	3 yr		DEX implant 0.7 mg: 22.2%
			DEX implant 0.35 mg: 18.4%
			Sham group: 12%
Haller et al[25]	Multicenter, randomized-controlled clinical trial	DME	A statistically significant improvement in CMT and fluorescein leakage after DEX implant compared with the observation group. Change in CMT from baseline at month 3: 0.7 mg DEX implant: -132 µm, observation group: +30 µm
	315 patients		A statistically significantly higher proportion of eyes improving in BCVA (≥ 10 letters) in 0.7 mg DEX implant (26% and 33%) than in observation group (9% and 12%) at months 2 and 3. The difference between the 0.7 mg DEX implant (30%) and observation group (23%) was maintained through month 6, but not statistically significant after month 3
	DEX implant 0.7 mg (105)
	DEX implant 0.35 mg (105)
	Observation group (105)
	6 m
Boyer et al[26], Ozurdex CHAMPLAIN study group	Multicenter, prospective, open-label, phase II clinical study	DME	Significant decrease in CMT at 2 mo and 6 mo after the first injection. The mean change from baseline CMT (403 µm): -156 µm at month 2 and -39 µm month 6
	55 patients		Significant improvement in BCVA at month 2 and 6. The mean increase in BCVA from baseline (54.5 letters): 6.0 letters at month 2 and 3.0 letters at month 6. 30.4% of patients gained ≥ 10 letters in BCVA at month 2
	6 mo
Callanan et al[27], Ozurdex PLACID study group	Multicenter, randomized, sham-controlled, double-masked, phase II clinical study	DME	Significant decrease in CMT and area of leakage in the combination of DEX implant with the laser than in the laser alone
	253 patients		The percentage of patients who gained ≥ 10 letters in BVCA in the combination of DEX implant with laser was significantly higher at week 1 and months 1, 4, and 9 (ranged from 22.2%-30.3%), but not month 12
	DEX implant plus laser (126 patients)
	Laser alone (127 patients)
	12 mo
Gillies et al[28], BEVORDEX Study Group	Multicenter, prospective, randomized, phase II study	DME	Greater mean CMT reduction in the DEX group than in bevacizumab
	88 eyes of 61 patients		DEX implant: -187 µm
	Bevacizumab (42 eyes)		Bevacizumab: -122 µm
	DEX implant (46 eyes)		The percentage of patients with a ≥ 10-letter improvement in BCVA
	12 mo		Bevacizumab: 40% (17 eyes of 42)
			DEX implant: 41% (19 eyes of 46)
Guigou et al[29], MOZART study	Multicenter, retrospective study	DME	Decrease in mean CMT: 239 μm at month 2 and 135 μm at month 6
	74 patients		Improvement in mean BCVA from the baseline: 8.5 letters at month 2 and 7.6 letters at month 6. The percentage of patients who gained greater than 15 letters in BVCA at month 6 was 27%
	6 mo
Singer et al[30], REINFORCE Study	Multicenter, prospective, observational, phase IV clinical study	DME	Statistically significant decrease in CMT (from -121.2 μm to -140.3 μm) from the baseline after the first three DEX injections at all months through month 12
	177 patients (180 eyes)		Statistically significant improvement in BCVA (ranged from +7.0 approximate ETDRS letters to +9.1 letters from baseline) after the first three DEX injections. The percentage of patients who gained greater than 15 approximate EDTRS letters in BVCA: 36%
	12 m
Mello Filho et al[31]	Multicenter, retrospective observational clinical study	DME	Statistically significant reduction in median CMT
	282 patients (329 eyes)		Baseline: 425 μm
			After DEX implant: 270 μm
			Statistically significant improvement in median BCVA.
			Baseline: 0.7 log-MAR/50 letters
			After DEX implant: 0.3 logMAR/70 letters
Malclès et al[32] RELDEX study	128 eyes of 89 patients	DME	A statistically significant improvement in CMT
	16 mo		Baseline: 451 μm, month 12: 370 μm, month 24: 377 μm, and month 36: 280 μm
			Statistically significant improvement in mean BCVA from the baseline (50.5 letters): 54 letters at month 2, 54.7 letters at month 12, 56 letters at month 24 and
			60.6 letters at month 36. The percentage of eyes achieving at least a 15-letter improvement from the baseline at month 36: 25.4%
Rosenblatt et al[33], ARTES study group	Multicenter, retrospective, cohort study	DME	Statistically significant CMT reduction was obtained throughout the first 6 mo. This effect diminished after month 3 but maintained until month 6. Mean change in CMT: -174 μm
	287 patients (340 eyes)		Significant improvement in BCVA during the first six months. The percentage of eyes with a ≥ 10-letter improvement in BCVA after DEX implant injections: 37.8%
	1.7 yr

BCVA: Best-corrected visual acuity; CMT: Central macular thickness; DEX: Dexamethasone phosphate; DME: Diabetic macular edema; EDTRS: Early treatment diabetic retinopathy study.