Clinical Studies:
Protocol U
Citation: Maturi RK, Glassman AR, Liu D, et al. Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema: A DRCR Network Phase 2 Randomized Clinical Trial. JAMA Ophthalmol. 2018;136(1):29–38. doi:10.1001/jamaophthalmol.2017.4914
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Objective
To compare continued intravitreal ranibizumab alone with ranibizumab plus intravitreal dexamethasone implant in eyes with persistent DME.
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STUDY DESIGN
Multicenter phase 2 randomized clinical trial. Data analysis was according to intent to treat.
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DURATION
24 months
STUDY SUBJECTS
Major inclusion criteria:
- Subject with persistent DME, and visual acuity of 20/32 to 20/320 after at least 3 anti-VEGF injections before a run-in phase, which included an additional 3 monthly 0.3-mg ranibizumab injections.
RANDOMIZATION SCHEME AND INTERVENTIONS
Following the run-in phase, study eyes were randomly assigned to receive 700 μg of dexamethasone or sham treatment in addition to continued 0.3-mg ranibizumab in both treatment arms as often as every 4 weeks based on a structured re-treatment protocol.
RESULTS (36 months)
Study population
- 129 eyes of 116 participants randomly assigned to the dexamethasone + ranibizumab group (combination, 65 eyes) or the sham + ranibizumab group (ranibizumab, 64 eyes)
- The 24-week primary outcome visit completed by 114 (98.3%).
Visual acuity end-points
- Similar Mean (SD) improvement in visual acuity from randomization: 2.7 (9.8) letters in the combination group and 3.0 (7.1) letters in the ranibizumab group, with the adjusted treatment group difference (combination minus ranibizumab) of –0.5 letters (95% CI, −3.6 to 2.5; 2-sided P = .73)
- Similar mean change in visual acuity (area under the curve): 1.9 letters for combination and 2.5 letters for ranibizumab therapy (adjusted difference, −0.3; 95% CI, −2.3 to 1.7; P = .76).
- Gain of 10 letters: 14 of the 63 eyes (22%) in the combination group and 9 of the 64 eyes (14%) in the ranibizumab group (adjusted difference, 6%; 95 CI, −6% to 18%; P = .34).
- Gain of 15 letters: 7 eyes (11%) in the combination group and 1 eye (2%) in the ranibizumab group (adjusted difference, 9%; 95 CI, 1% to 17%; P = .03).
- Loss of 10 letters: 8 eyes (13%) in combination vs 4 (6%) in the ranibizumab group (adjusted difference, 7%; 95% CI, −1% to 16%; P = .09)
- Loss of 15 letters: 4 eyes (6%) in the combination group and 3 eyes (5%) in the ranibizumab group (adjusted difference, 2%; 95 CI, −5% to 9%; P = .62).
Anatomic outcomes
- Mean (SD) change in central subfield thickness in the combination group was –110 (86) μm compared with –62 (97) μm for the ranibizumab group (adjusted difference, –52; 95% CI, −82 to −22; P < .001).
Adverse events
- There were no cases of endophthalmitis.
- Nineteen eyes (29%) in the combination group experienced increased intraocular pressure or initiated treatment with antihypertensive eyedrops compared with 0 in the ranibizumab group (P < .001).
- Fifteen eyes in the combination group (23%) experienced increases of 10 mm Hg or more in IOP compared with 0 in the ranibizumab group.
- In the combination group, 3 of 65 eyes (5%) received postrandomization cataract extractions compared with 0 of 64 eyes in the ranibizumab group (P = .24).
Conclusions
- Although its use is more likely to reduce retinal thickness and increase intraocular pressure, the addition of intravitreal dexamethasone to continued ranibizumab therapy does not improve visual acuity at 24 weeks more than continued ranibizumab therapy alone among eyes with persistent DME following anti-VEGF therapy.