Clinical Studies:
RESTORE
Citation: Mitchell P, Bandello F, Schmidt-Erturth U, et al. Ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011;118: 615-625.
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Objective
To demonstrate the superiority of ranibizumab 0.5mg monotherapy or combined with laser over laser alone in diabetic macular edema (DME)
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STUDY DESIGN
Phase 3, multicenter, randomized, double-masked, laser controlled trial
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DURATION
12 months
STUDY SUBJECTS
Major inclusion criteria:
- ≥ 18 years of age with type 1 or type 2 diabetes
- Stable medication for diabetes management
- Visual impairment due to focal or diffuse DME in at least 1 eye that was eligible for laser treatment
- BCVA letter score between 78 and 39 base on Early Treatment Diabetic Retinopathy Study (ETDRS)-like VA testing charts
- Decreased vision due to DME and no other causes
RANDOMIZATION SCHEME AND INTERVENTIONS
Randomized 1:1:1 to:
(a) intravitreal ranibizumab 0.5mg injection + sham laser
(b) intravitreal ranibizumab 0.5mg injection + active laser
(c) laser treatment + sham injection
RESULTS (12 months)
Study population
- 345 subjects
Visual acuity end-points
- Mean average change in BCVA letter score from baseline to month 1 to 12 : ranibizumab 0.5mg 6.1 ± 6.4, ranibizumab 0.5mg + laser 5.9 ±7.9, laser 0.8 ±8.6
- Proportion of patients with BCVA letter score >73 at month 12: ranibizumab 0.5mg 61(53%), ranibizumab 0.5mg + laser 53(44.9%), laser 26(23.6%)
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Categorized BCVA letter score outcome at month 12
- Gain of ≥ 5: ranibizumab 0.5mg 75(65.2%), ranibizumab 0.5mg + laser 75(63.6%), and laser 37(33.6%)
- Gain of ≥ 10: ranibizumab 0.5mg 43(37.4,%), ranibizumab 0.5mg + laser 51(43.2%), laser 17(15.5%)
- Gain of ≥ 15: ranibizumab 0.5mg 26(22.6%), ranibizumab 0.5mg + laser 27(22.9%), laser 9(8.2%)
- Loss of ≥ 10: ranibizumab 0.5mg 4(3.5%), ranibizumab 0.5mg + laser 5(4.2%), laser 14(12.7%)
- Loss of ≥ 15: ranibizumab 0.5mg 1(0.9%), ranibizumab 0.5mg + laser 4(3.4%), laser 9(8.2%)
- Mean central retinal thickness (CRT) reduction month 12 (μm): ranibizumab 0.5mg -118.7±115.07, ranibizumab 0.5mg + laser -128.3±114.34, laser -61.3±132.29
Angiographic end-points
Resolution of leakage on fluorescein: ranibizumab 0.5mg 19.4%, ranibizumab 0.5mg + laser 13.7%, laser 2.2%
Adverse events
- Rates of any serious and non-serious ocular events, overall similar between all groups
- There were no reported cases of endophthalmitis
CONCLUSIONS
Ranibizumab monotherapy and combined with laser provided greater visual acuity gain over standard laser in patients with visual impairment due to DME.