Comparison of ranibizumab with or without focal/grid laser for macular edema secondary to branch retinal vein occlusion: 12-month results from the ZIPANGU study

Abstract

Purpose : The ZIPANGU study is the first phase IV, prospective, randomized, 12-month, multicenter study for macular edema secondary to branch retinal vein occlusion (BRVO) in Japanese patients. The purpose of this study was to minimize the required number of ranibizumab (RBZ) injections while maintaining vision restoring efficacy. We tested whether 1+PRN RBZ combined with focal/grid short pulse laser (RBZ+laser arm) can reduce the number of RBZ injections compared with those for 1+PRN RBZ monotherapy (RBZ arm).

Methods : In this study, 59 patients were randomized (1:1) to the RBZ or RBZ+laser arm. Patients received 1+PRN RBZ and laser treatment applied to the affected area, which corresponded to capillary dropout within vascular arcades. RBZ PRN criteria was defined by meeting any one or more of the following conditions: central subfield foveal thickness (CSFT) ≥300 μm, ≥20% increase from the lowest value in CSFT, decrease in visual acuity (VA) due to disease activity. The difference in the mean number of RBZ injections over 12 months (primary endpoint) and the mean change of VA, CSFT, and safety of the two treatment arms (secondary endpoints) were evaluated.

Results : The mean number of RBZ injections in the RBZ and RBZ+laser arms was not statistically different (4.3±0.5 and 4.1±0.4, respectively, p=0.432). VA (ETDRS letters) improved in both arms at 12 months compared with baseline (from 52.9±2.5 to 74.8±1.8 and from 54.0±1.8 to 69.6±1.6, respectively, p<0.01) and was significantly better in the RBZ than in the RBZ+laser arm (+22.0±2.7 vs +15.0±1.9, p=0.035). CSFT also improved in both arms at 12 months compared with baseline (from 563.3±27.3 to 257.0±8.1 and from 553.3±33.3 to 285.1±15.4, respectively, p<0.01). No serious ocular adverse events occurred.

Conclusions : The ZIPANGU study showed that 1+PRN RBZ combined with laser therapy did not reduce the mean number of RBZ injections. However, the 1+PRN regimen suggested that four RBZ injections per year, which is fewer than that in previous clinical trials of RBZ, BRAVO (8.4 ranibizumab injections, +18.3 letters improvement/year), and the BRIGHTER studies (11.4 ranibizumab injections, +15.5 letters improvement/2year), led to similar VA improvement. (ClinicalTrials.gov: NCT02953938)

This is a 2020 ARVO Annual Meeting abstract.