Dataset Information

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

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.

SUBMITTER: Murata T

PROVIDER: S-EPMC7804316 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Murata Toshinori T Kondo Mineo M Inoue Makoto M Nakao Shintaro S Osaka Rie R Shiragami Chieko C Sogawa Kenji K Mochizuki Akikazu A Shiraga Rumiko R Ohashi Yohei Y Kaneko Takeumi T Chandrasekhar Chikatapu C Tsujikawa Akitaka A Kamei Motohiro M

Scientific reports 20210112 1

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 ( ...[more]

PMID: 33436683

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Project description:BackgroundIt is not clear whether macular laser combined with anti-vascular endothelial growth factor (VEGF) can reduce the number of anti-VEGF injections in the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Our study aimed to investigate the effects of intravitreal ranibizumab with or without macular laser for ME secondary to BRVO and its associated number of anti-VEGF injections.MethodsThis is a prospective, randomized, double-blind, monocentric trial.80 patients were enrolled and 64 patients fulfilled the study requirements. All patients received a minimum of 3 initial monthly ranibizumab injections, pro re nata (PRN) dosing thereafter VA and CRT stabilization criteria-driven PRN treatment. Laser was given 7 days after third ranibizumab injection in ranibizumab with laser group. The follow-up time of this study was 1 year. Best corrected visual acuity (BCVA) improvement, central retinal thickness (CRT) reduction and number of injections of patients were compared between two groups. T-test, non-parametric Wilcoxon test and chis-square tests were adopted for between-group comparisons.ResultsThirty patients received intravitreal ranibizumab 0.5 mg alone and 34 patients received intravitreal ranibizumab 0.5 mg with macular laser. At 52 week, BCVA increased significantly and CRT decreased significantly in both groups (P < 0.001). However, there was no significant difference in BCVA improvement with baseline BCVA adjusted (p = 0.5226), and in the CRT reduction (P = 0.4552) between two groups after 52 weeks. There was also no significant difference in the number of injections between the two groups. (P = 0.0756). There was also no significant difference between ischemic and non-ischemic groups in BCVA improvement, CRT reduction and number of injections (P > 0.05).ConclusionsOur study suggests that ranibizumab combined with macular laser is effective in the treatment of ME secondary to BRVO after 1 year of treatment with 3 + PRN regimen. However, combination of macular grid photocoagulation showed no beneficial anatomical or functional effect during follow-up period, nor did it reduce the number of ranibizumab injections, either in ischemic group or non-ischemic group. We suggest that there is no need to combine macular grid photocoagulation in the treatment of ME secondary to BRVO in the future.Trial registrationClinical Trials NCT03054766. https://register.clinicaltrials.gov.Prospectively registered.

Project description:IntroductionRanibizumab and aflibercept are anti-vascular endothelial growth factor agents licensed for the treatment of visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). The aim of this study was to estimate, from a UK healthcare payer's perspective, the cost-effectiveness of ranibizumab versus aflibercept in this indication.MethodsA Markov model was used to simulate the outcomes and costs of treating BRVO. Patient baseline characteristics and efficacy data for ranibizumab were obtained from the BRAVO trial. The relative efficacy of aflibercept was derived from a published network meta-analysis. Injection frequencies were derived from ranibizumab and aflibercept studies included in the network meta-analysis. Health states were defined by increments of 10 letters in best corrected visual acuity (BCVA). Patients could gain or lose a maximum of two health states between cycles. The first cycle was 6 months, followed by monthly cycles. Different utility values were assigned to the better-seeing and worse-seeing eyes based on BCVA. A 2-year treatment time frame and a lifetime time horizon were used. Future costs and health outcomes were discounted at 3.5% per annum. Sensitivity analyses were used to test the robustness of the model.ResultsThe lifetime cost per patient treated was £15,273 with ranibizumab and £17,347 with aflibercept. Ranibizumab was dominant over aflibercept, producing incremental health gains of 0.0120 quality-adjusted life-years (QALYs) and cost savings of £2074. Net monetary benefit for ranibizumab at a willingness-to-pay threshold of £20,000/QALY was £2314. Sensitivity analyses showed that the results were robust to variations in model parameters.ConclusionsRanibizumab provides greater health gains at a lower overall cost than aflibercept in the treatment of visual impairment due to macular edema secondary to BRVO. Ranibizumab is therefore cost-effective from a UK healthcare payer's perspective.FundingNovartis Pharma AG, Basel, Switzerland.

Project description:BackgroundBranch retinal vein occlusion (BRVO) is a common retinal vascular disease leading to severe vision loss and blindness. This study aimed to investigate and reveal the pathophysiological mechanisms underlying macular edema (ME) recurrence in patients with BRVO through a proteomic approach.MethodsWe detected proteins in the aqueous humor of 14 untreated, four refractory, and four post-operative patients with BRVO-ME and 12 age-matched cataract controls using four-dimensional label-free proteomic and bioinformatics analyses.ResultsIn total, 84 proteins exhibited significant differential expression between the BRVO and control samples (fold change [FC] ≥ 1.2 and adjusted p-value < 0.05). Compared to the control group, 43 and 41 proteins were upregulated and downregulated, respectively, in the BRVO group. These proteins were involved in cell adhesion, visual perception, retina homeostasis, and platelet activation. Several significantly enriched signaling pathways included complement and coagulation cascades and platelet activation. In the protein-protein interaction networks generated using the search tool for retrieval of interacting genes (STRING), the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. Many common protein expression trends, such as the fibrinogen alpha chain and fibrinogen beta chain, were observed in both the recurrent and refractory groups. Differentially expressed proteins in the two groups were involved in complement activation, acute-phase response, platelet activation, and platelet aggregation. Important signaling pathways include the complement and coagulation cascades, and platelet activation. Protein-protein interaction analysis suggested that the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. The expression of some differentially expressed proteins shared by the BRVO and the recurrent and refractory groups was reversed in the post-operative group.ConclusionsOur study is the first to analyze the proteomics of recurrent, refractory, and post-operative groups treated for BRVO-ME, and may potentially provide novel therapeutic interventions for the recurrence of ME.

Project description:PurposeTo evaluate spectral-domain (SD)-OCT features associated with baseline vision and visual outcomes in the prospective, multicenter Study Evaluating Dosing Regimens for Treatment with Intravitreal Ranibizumab Injections in Subjects with Macular Edema following Retinal Vein Occlusion (SHORE).DesignPost hoc analysis of prospective clinical trial data.ParticipantsTwo hundred two participants in the 15-month, phase 4 SHORE study comparing monthly versus pro re nata ranibizumab after 7 monthly doses in eyes with retinal vein occlusion (RVO) with macular edema.MethodsBaseline SD-OCT images were assessed for (1) central subfield thickness (CST); (2) presence of vitreomacular adhesion, vitreomacular traction, or epiretinal membrane; (3) presence, location, and amount of intraretinal fluid or subretinal fluid (SRF); (4) presence, location, and amount of hyperreflective foci (HF); (5) disorganization of retinal inner layers (DRIL); and (6) disruption of external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ). Univariate and multivariate regression analyses were performed to evaluate the association of these features with baseline best-corrected visual acuity (BCVA) and change in BCVA after 7 monthly ranibizumab injections.Main outcome measuresAssociation of SD-OCT features with baseline BCVA and change in BCVA after 7 monthly ranibizumab injections.ResultsBefore therapy, worse baseline BCVA was associated with ERM presence (P = 0.0045), thicker SRF (P = 0.0006), larger intraretinal cysts (P = 0.0015), and higher percentage of DRIL (P < 0.0001), percentage of ELM disruption (P < 0.0001), percentage of EZ disruption (P = 0.0003), and percentage of IZ disruption (P = 0.0018). In multivariate models, only percentage of ELM disruption independently impacted baseline BCVA (P < 0.0001). After 7 monthly ranibizumab injections, mean BCVA improved by 18.3±12.6 Early Treatment Diabetic Retinopathy Study letters in treated eyes. The only factors independently associated with BCVA gain after 7 monthly ranibizumab treatments were younger age (P < 0.0001) and worse baseline BCVA (P < 0.0001).ConclusionsAlthough SD-OCT features may be associated with presenting vision in eyes with macular edema and RVO, most eyes treated with ranibizumab achieve substantial vision gains, and only older age and better baseline BCVA limited visual improvements.

Dataset Information

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

Publications

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

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