The randomized ZIPANGU trial of ranibizumab and adjunct laser for macular edema following branch retinal vein occlusion in treatment-na\xefve patients

Toshinori Murata,Yohei Ohashi,Mineo Kondo,Rie Osaka,Makoto Inoue,Chikatapu Chandrasekhar,Takeumi Kaneko,Shintaro Nakao,Chieko Shiragami,Akitaka Tsujikawa,Kenji Sogawa,Motohiro Kamei,Akikazu Mochizuki,Rumiko Shiraga

doi:10.1038/s41598-020-79051-1

Abstract

The ZIPANGU study assessed the efficacy and safety of ranibizumab as a one loading dose + pro re nata (one + PRN) regimen with/without focal/grid laser among treatment-naïve patients suffering from macular edema (ME) following branch retinal vein occlusion (BRVO). ZIPANGU was a phase IV, prospective, randomized, open-label, active-controlled, 12-month, two-arm, multicenter study. Treatment-naïve patients with visual impairment (19–73 letters) caused by ME, defined as central subfield thickness (CSFT) > 300 µm, due to BRVO were randomly assigned to ranibizumab monotherapy (n = 29) or combination therapy (ranibizumab + focal/grid short-pulse laser, n = 30). The primary endpoint was the number of ranibizumab injections. Secondary endpoints were mean changes in best-corrected visual acuity (BCVA) and CSFT, and safety. There were no statistically significant differences in the mean number of ranibizumab injections between monotherapy (4.3 injections) vs. combination (4.1 injections) therapy, or in CSFT. BCVA improvement in the monotherapy arm (22.0 letters) was better than the combination therapy arm (15.0 letters) (p = 0.035). Overall, both regimens appeared to be safe and well tolerated. One + PRN ranibizumab is safe and efficacious in treatment-naïve patients with ME secondary to BRVO. A conjunctive laser treatment did not lead to better functional outcomes or fewer ranibizumab injections.

Highlights

The ZIPANGU study assessed the efficacy and safety of ranibizumab as a one loading dose + pro re nata regimen with/without focal/grid laser among treatment-naïve patients suffering from macular edema (ME) following branch retinal vein occlusion (BRVO)
While some clinical studies demonstrated that macular focal/grid laser combined with an anti-vascular endothelial growth factor (VEGF) agent may have the potential to reduce the number of anti-VEGF injections and m aintain[26] or improve treatment efficacy[27,28,29], two multicenter randomized controlled clinical trials with large cohorts concluded that the use of additional laser did not have add-on efficacy for visual acuity (VA), edema resolution, or number of ranibizumab injections
Baseline characteristics were generally well-balanced between treatment arms, except for sex: more female patients were randomly assigned to treatment with combination therapy (63.3%), and more male patients received monotherapy (65.5%)

Summary

Introduction

The ZIPANGU study assessed the efficacy and safety of ranibizumab as a one loading dose + pro re nata (one + PRN) regimen with/without focal/grid laser among treatment-naïve patients suffering from macular edema (ME) following branch retinal vein occlusion (BRVO). In addition to increasing treatment efficacy, there is a need for further treatments that minimize the risk of systemic adverse events and the patient’s financial burden by reducing the number of intravitreal injections of anti-VEGF agents. While some clinical studies demonstrated that macular focal/grid laser combined with an anti-VEGF agent may have the potential to reduce the number of anti-VEGF injections and m aintain[26] or improve treatment efficacy[27,28,29], two multicenter randomized controlled clinical trials with large cohorts (the RELATE s tudy[30] and BRIGHTER study23) concluded that the use of additional laser did not have add-on efficacy for visual acuity (VA), edema resolution, or number of ranibizumab injections

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