| Clinical Study “Common” Name (formal title) | Study design | Treatment arms | Primary outcomes | Results | Author conclusions | Real-world impact |
|---|---|---|---|---|---|---|
| BRAVO, (RanibizumaB for the Treatment of Macular Edema following BRAnch Retinal Vein Occlusion) | Prospective, randomized, sham injection-controlled, double-masked, multicenter trial | Ranibizumab 0.3mg (n-134) Ranibizumab 0.5 mg (n=131) Sham (n=132) | Mean change from baseline BCVA letter score at month 6 | The mean change from baseline BCVA letter score was 16.6 in the 0.3 mg ranibizumab group, 18.3 in the 0.5 mg ranibizumab group, and 7.3 in the sham group (P<0.0001 for each ranibizumab group vs sham). | Monthly intravitreal ranibizumab injections provided important benefits for patients with macular edema following RVO, but several important questions remained, notably what percentage of patients would remain edema-free after ranibizumab treatment discontinuation as well as the impact of delays or gaps in treatment. [Campochiaro.2010] As-needed injections of ranibizumab maintained the improvement in visual acuity and central foveal thickness seen at month 6. | This was the first study to demonstrate anti-VEGF as an alternative to laser treatment for BRVOs with macular edema. The study design did not randomize patients to laser on day 0 so there is no direct head-to-head comparison. Nevertheless, treatment with laser resulted in suboptimal visual outcomes even when the patients were transitioned to anti-VEGF implying the 6 month delay in treatment is a significant concern. [Brown.2011] |
| BRVO (Comparing the Efficacy of Bevacizumab and Ranibizumab in Patients with Retinal Vein Occlusion) | Comparative, randomized, double-masked, multicenter, noninferiority clinical trial. | Bevacizumab 1.25 mg (n=144) Ranibizumab 0.5 mg (n-142) 133 diagnosed with BRVO 97 diagnosed with CRVO 47 diagnosed with hemi-CRVO | Change in BCVA of the study eye from baseline to 6 months, with a noninferiority margin of 4 letters. |
At 6 months, overall: BRVO Bevacizumab : 14.2 letter gain Bevacizumab : 16.1 letter gain |
Monthly administration of bevacizumab 1.25 mg is noninferior to monthly administration of ranibizumab 0.5 mg through month 6 in the treatment of patients with macular edema resulting from RVO. [Vader.2020] |
Patients in this study were treated monthly for 6 months, which is more than most real-world clinics will do. However, this adds to the literature and re-confirms noninferiority between bevacizumab and ranibizumab. |
| BVOS (Branch Vein Occlusion Study) | Multicenter, randomized trial | Group 1 included eyes at risk for the development of neovascularization, [BVOS.1984] group 2 included eyes at risk for the development of vitreous hemorrhage, [BVOS.1984] and group 3 included eyes at risk for vision loss from macular edema. [BVOS.1984] Group 3: Grid laser (n=71) No laser (n=68) |
For group 3, efficacy of macular grid laser for the treatment of macular edema secondary to BRVO
(Of note, there were no specific primary endpoints) |
At 3 years, the efficacy of laser treatment was clear; treated eyes in group 3 gained an average of 1.33 lines compared with 0.23 lines in a control group. [BVOS.1984] | Argon laser photocoagulation improved VA in patients with 20/40 or worse. Study authors recommended the treatment for those with VA reduced as a result of macular edema, not for those whose vision loss was a result of intraretinal hemorrhage in the fovea or fovea capillary nonperfusion. [BVOS.AJO.1984/p281/col1/para3] | Based on these data, macular grid laser photocoagulation became the first-line treatment for patients with macular edema following RVO. Laser treatment is considered a second-line treatment today only if patients are contraindicated for an anti-VEGF or if they are unlikely to keep up with monthly treatments. [Flaxel.2020] |
|
VIBRANT [Study to Assess the Clinical Efficacy and Safety of Intravitreal Aflibercept Injection (IAI;EYLEA;BAY86-5321) in Patients With Branch Retinal Vein Occlusion (BRVO) |
Phase 3, multicenter, randomized, double-masked, active-controlled trial | Macular grid laser photocoagulation (n=92) Aflibercept 2mg Q4 weeks (n=91) |
Treatment to week 20 Primary endpoint: proportion of patients 15 letters in BCVA from baseline [Campochiaro.2015] |
Week 24: Macular grid laser photocoagulation: 26.7% Aflibercept 2mg Q4 weeks: 52.7% [Campochiaro.2015] Week 52: Macular grid laser photocoagulation: 41.1% Aflibercept 2mg Q4 weeks: 57.1% [Clark.2016] | Treatment with aflibercept 2 mg every 4 weeks was superior to laser treatment through week 24 in visual acuity gains and anatomic outcomes. [Clark.2016] Continued treatment with an every 8-week regimen maintained visual and anatomic gains through week 52 after 6 monthly injections. [Clark.2016] | The study randomized patients in a head-to-head fashion on day 0 to either laser or aflibercept treatment.The results further validated that anti-VEGF treatment is superior to laser treatment. [Clark.2016] |