Ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema: a meta-analysis of randomized controlled trials.

Guohai Chen,Fangzheng Jiang,Wensheng Li,Sihong Mao,Yuhua Tong,Radouil Tzekov,Mary Elizabeth Hartnett

doi:10.1371/journal.pone.0115797

Guohai Chen, Fangzheng Jiang + Show 5 more

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https://doi.org/10.1371/journal.pone.0115797

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Abstract

ObjectiveTo evaluate the relative efficacy of ranibizumab (RBZ) monotherapy or combined with laser (RBZ + Laser) versus laser monotherapy for the treatment of diabetic macular edema (DME).MethodsA comprehensive literature search using PUBMED, ClinicalTrials.gov, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing RBZ or RBZ + Laser to laser monotherapy in patients with DME. Efficacy estimates were determined by comparing weighted mean differences (WMD) in the change of best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline, and the risk ratios (RR) for the proportions of patients with at least 15 letters change from baseline. Safety analysis estimated the RR of cardiac disorders at 6 to 12 months in RBZ therapy vs. laser monotherapy. Statistical analysis was performed using the RevMan 5.1 software.ResultsSeven RCTs were selected for this meta-analysis, including 1749 patients (394 patients in the RBZ group, 642 patients in the RBZ + Laser group, and 713 patients in the laser group). RBZ and RBZ + Laser were superior to laser monotherapy in the mean change of BCVA and CMT from baseline (WMD = 5.65, 95% confidence interval (CI), 4.44–6.87, P<0.00001; WMD = 5.02, 95% CI, 3.83–6.20, P<0.00001, and WMD = −57.91, 95% CI, −77.62 to −38.20, P<0.00001; WMD = −56.63, 95% CI, −104.81 to −8.44, P = 0.02, respectively). The pooled RR comparing the proportions of patients with at least 15 letters improvement or deterioration were also in favor of RBZ and RBZ + Laser (RR = 2.94, 95% CI, 1.82–4.77, P<0.00001; RR = 2.04, 95% CI, 1.50–2.78, P<0.00001, and RR = 0.21, 95% CI, 0.06–0.71, P = 0.01; RR = 0.52, 95% CI, 0.29–0.95, P = 0.03, respectively). There were no significant differences between RBZ and RBZ + Laser for any of the parameters. There were no difference in the safety profile between RBZ and laser.ConclusionRBZ and RBZ + Laser had better visual and anatomic outcomes than laser monotherapy in the treatment of DME. RBZ + Laser seemed to be equivalent to RBZ.

Highlights

Diabetic retinopathy (DR) is the most frequent and severe ocular complication of diabetes mellitus, the leading cause of blindness in the working age population in developed countries [1]
Articles were considered eligible for inclusion in the meta-analysis if the studies met the following inclusion criteria: 1. study design: randomized controlled trials (RCTs), 2. population: minimum age of 18 years with Diabetic macular edema (DME), 3. intervention: RBZ or RBZ + Laser versus laser monotherapy, and 4. outcome variables: at least one of the outcomes of interest discussed in the section Outcome Measures below
There were 1749 patients included in the meta-analysis: 394 patients were included in the RBZ group, 642 patients in the RBZ + Laser group, and 713 patients in the laser monotherapy group

Summary

Introduction

Diabetic retinopathy (DR) is the most frequent and severe ocular complication of diabetes mellitus, the leading cause of blindness in the working age population in developed countries [1]. Diabetic macular edema (DME) is a major contributor to vision loss and one of the main causes for decreased visual acuity in patients with DR [2]. The prevalence of DME increases from 0% to 3% in individuals recently diagnosed with diabetes to 28% to 29% in those with diabetes duration of over 20 years [3]. Focal/grid laser photocoagulation (laser), the standard of care for DME since 1985, was shown by the Early Treatment Diabetic Retinopathy Study (ETDRS) to reduce the risk for significant vision loss by 50%, but complete cessation of vision loss and/or improvements in visual acuity are rarely observed [4]. Based on the observation that vascular endothelial growth factor (VEGF) levels are increased in the retina and vitreous of eyes with DME [5], inhibiting VEGF may provide an alternative therapeutic approach for this condition. Various studies have demonstrated that ranibizumab monotherapy is well-tolerated and significantly more effective than sham treatment in clinical trials for DME [8, 10]

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