The REVOLUTIONARY trial: A pilot study to assess the efficacy, durability, and safety of combination ranibizumab + peripheral scatter laser for macular edema secondary to branch retinal vein occlusion associated with peripheral nonperfusion on ultrawide-field angiography. Ivan J. Suñer * , Isabel A. Suñer, Marc C. Peden, Mark E. Hammer, Janet Traynom Retina Associates of Florida, Tampa, Florida, USA Abstract Purpose: To determine the efficacy, durability, and safety of combination intravitreal ranibizumab plus peripheral scatter laser in patients with macular edema secondary to branch retinal vein occlusion associated with peripheral retinal nonperfusion on ultrawide-field fluorescein angiography. Methods: A 12-month, randomized, controlled, prospective, single center phase I/II study of 12 treatment-naïve eyes of 12 patients with visual impairment secondary to macular edema secondary to branch retinal vein occlusion associated with peripheral nonperfusion on ultrawide-field fluorescein angiography. Patients were randomized in 1:1 fashion to study and control groups. Patients in the study group received angiography-guided peripheral scatter laser treatment at baseline. All patients received six monthly intravitreal injections of ranibizumab followed by six months of observation with pro re nata treatment with ranibizumab if prespecified visual acuity or optical coherence tomography criteria were met. Results: At the 6-month primary outcome, both groups had significant improvement in mean change in best-corrected visual acuity (treatment: +16.8 letters v/s control +14.5 letters) and reduction in central foveal thickness (treatment: -207 μ m v/s control -241 μ m). Both groups also had an improvement at 12 months in mean change in best-corrected visual acuity (treatment: +19.1 letters v/s control +15.3 letters) and reduction in central foveal thickness (treatment: -282 μ m v/s control -281 μ m). The differences between groups were not statistically significant. In the 6-month observation period, the REVOLUTIONARY group had a statistically-significant fewer number of retreatments (median of 1 in the treatment group v/s 2.5 in the control group p=0.03), and there was a trend in the reduction of patients needing retreatment (67% in the treatment group v/s 100% in the control group, p=0.14). Conclusion: This pilot study suggests safety and durability of combination ranibizumab + angiography-guided peripheral scatter laser in treatment-naïve patients with macular edema secondary to branch retinal vein occlusion and peripheral nonperfusion on ultrawide-field fluorescein angiography. Further investigation is warranted to demonstrate the efficacy and long-term benefit of this treatment strategy. Keywords: Anti-VEGF, branch retinal vein occlusion, combination therapy, laser photocoagulation, macular edema, peripheral nonperfusion, peripheral scatter laser, ranibizumab, REVOLUTIONARY, ultrawide-field fluorescein angiography. Accepted on September 21, 2018 Introduction Retinal Vein Occlusion (RVO) is the second most common cause of retinal vascular disease leading to visual impairment after diabetic retinopathy [1]. RVO is typically classified by the location of the occlusion as either branch RVO (BRVO) or central RVO (CRVO). There are approximately 180,000 cases of RVO in the United States alone each year, and the vast majority (approximately 150,000) are BRVOs [2]. Macular edema is the major cause of vision loss in BRVO. The current gold standard for therapy of macular edema secondary to BRVO is treatment with intravitreal Anti-Vascular Endothelial Growth Factor (Anti-VEGF) agents as demonstrated in BRAVO with ranibizumab [3] and in VIBRANT with aflibercept [4]. In these studies, patients received monthly intravitreal injections for the first six months, followed by subsequent injections if there was loss of vision or increase in central foveal thickness (CFT) on optical coherence tomography (OCT). The visual acuity and anatomical results were superior as compared to control groups, and they validate the VEGF pathway as a key therapeutic target in BRVO. Peripheral nonperfusion has been observed in patients with various retinal vascular diseases, including BRVO and CRVO by utilizing novel, commercially-available imaging systems for ultrawide-field angiography (UWFA) [5-12]. The long-term need for anti-VEGF injections to treat recurrent macular edema Research Article http://www.alliedacademies.org/clinical-ophthalmology-and-vision-science/ J Clin Ophthalmol. 2018 Volume 2 Issue 2 80