Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study.
The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.
                This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age>18 years, type 1 or 2 diabetes, central retinal thickness [CRT]≥300 μm, and best corrected visual acuity [BCVA] of 73-39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n=51 each) or sham (n=49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set (n=151, patients receiving≥1 injection).
                At month 12, mean±SD BCVA improved from baseline by 10.3±9.1 letters with ranibizumab and declined by 1.4±14.2 letters with sham (P<0.0001). Mean CRT reduction was 194.2±135.1 μm with ranibizumab and 48.4±153.4 μm with sham (P<0.0001). Gain of ≥10 letters BCVA from baseline occurred in 60.8% of ranibizumab and 18.4% of sham eyes (P<0.0001). Safety data were consistent with previous studies of intravitreal ranibizumab.
                Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety. Assess 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after branch retinal vein occlusion (BRVO).
                Prospective, randomized, sham injection-controlled, double-masked, multicenter trial.
                A total of 397 patients with macular edema after BRVO.
                Eligible patients were randomized 1:1:1 to 6 monthly injections of 0.3 mg or 0.5 mg ranibizumab or sham injections. After 6 months, all patients with study eye best-corrected visual acuity (BCVA) ≤20/40 or central subfield thickness ≥250 μm were to receive ranibizumab. Patients could receive rescue laser treatment once during the treatment period and once during the observation period if criteria were met.
                The main efficacy outcome reported is mean change from baseline BCVA letter score at month 12. Additional visual and anatomic parameters were assessed.
                Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 16.4 (14.5-18.4) and 18.3 (15.8-20.9) in the 0.3 mg and 0.5 mg groups, respectively, and 12.1 (9.6-14.6) in the sham/0.5 mg group (P<0.01, each ranibizumab group vs. sham/0.5 mg). The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 56.0% and 60.3% in the 0.3 mg and 0.5 mg groups, respectively, and 43.9% in the sham/0.5 mg group. On average, there was a marked reduction in central foveal thickness (CFT) after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group, which was sustained through month 12. No new ocular or nonocular safety events were identified.
                At month 12, treatment with ranibizumab as needed during months 6-11 maintained, on average, the benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after BRVO, with low rates of ocular and nonocular safety events. In the sham/0.5 mg group, treatment with ranibizumab as needed for 6 months resulted in rapid reduction in CFT to a similar level as that in the 0.3 mg ranibizumab treatment group and an improvement in BCVA, but not to the extent of that in the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an effective treatment for macular edema after BRVO.
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                Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
The available RCT evidence suggests that repeated treatment of non-ischaemic MO secondary to BRVO with the anti-VEGF agent ranibizumab may improve clinical and visual outcomes at six and 12 months. However, the frequency of re-treatment has not yet been determined and the impact of prior or combined treatment with laser photocoagulation on the primary outcome is unclear. Results from ongoing studies should assess not only treatment efficacy but also, the number of injections needed for maintenance and long-term safety and the effect of any prior treatment.