A meta-analysis of anti-vascular endothelial growth factor remedy for macular edema secondary to central retinal vein occlusion

Peirong Huang; Wenquan Niu; Zhentian Ni; Renzuo Wang; Xiaodong Sun

doi:10.1371/journal.pone.0082454

A meta-analysis of anti-vascular endothelial growth factor remedy for macular edema secondary to central retinal vein occlusion

PLoS One. 2013 Dec 23;8(12):e82454. doi: 10.1371/journal.pone.0082454. eCollection 2013.

Authors

Peirong Huang¹, Wenquan Niu², Zhentian Ni³, Renzuo Wang³, Xiaodong Sun⁴

Affiliations

¹ Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² State Key Laboratory of Medical Genomics, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China ; Department of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China ; Eye Research Institute of Shanghai Jiao Tong University, Shanghai, China.

Abstract

Background: Central retinal vein occlusion (CRVO) associates with severe vision outcome and no proven beneficial treatment. Our meta-analysis intended to appraise the efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents in macular edema (ME) following CRVO.

Methods: Data were collected and analyzed by Review Manager 5.2.1. We employed a random-effects model to eliminate between-study heterogeneity. Nfs (called fail-safe number) was calculated to evaluate the publication bias.

Results: We included 5 trials consisting 323 cases and 281 controls. Primary outcomes showed that overall comparison of anti-VEGF agents with placebo control yielded a 374% and 136% increased tendency for a gain of 15 letters or more on Early Treatment Diabetic Retinopathy Study (ETDRS) chart (95% confidence interval [95% CI]: 2.43-9.23; P<0.00001; I(2) = 59%, 95% CI: 1.60-3.49; P<0.0001; I(2) = 0%, respectively) at 6 and 12 months. Secondary outcomes showed that a 90% and 77% decreased risk at 6 and 12 months for a loss of 15 letters or more. The overall mean difference showed a statistically significance in best-corrected visual acuity (BCVA) on each time point. However, changes of central retinal thickness (CRT) lost significance at 12 months after 6-month as-needed treatment. The incidence of adverse events (AEs) had no statistical difference between anti-VEGF and placebo groups. Subgroup analyses indicated that patients receiving Aflibercept got the highest tendency to gain 15 letters or more (OR = 9.78; 95% CI: 4.43-21.56; P<0.00001). Age controlled analysis suggested a weaken tendency of BCVA improvement in age over 50 (MD = 12.26; 95% CI: 7.55-16.98; P<0.00001). Subgroup analysis by clinical classification showed a strengthen difference of BCVA changes at 6 months in ischemic type (MD = 19.65 letters, 95% CI: 13.15 to 26.14 letters, P<0.00001).

Conclusions: Our results showed that anti-VEGF agents were superior to placebo in CRVO-ME treatment with no statistically significant AEs, especially in younger people and for ischemic type.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Angiogenesis Inhibitors / adverse effects
Angiogenesis Inhibitors / pharmacology
Angiogenesis Inhibitors / therapeutic use*
Diabetic Retinopathy / complications
Female
Humans
Macular Edema / drug therapy*
Macular Edema / etiology*
Macular Edema / physiopathology
Male
Middle Aged
Randomized Controlled Trials as Topic
Retinal Vein Occlusion / complications*
Retinal Vein Occlusion / physiopathology
Vascular Endothelial Growth Factor A / antagonists & inhibitors*
Visual Acuity

Substances

Angiogenesis Inhibitors
Vascular Endothelial Growth Factor A

Grants and funding

This study was supported by the National Basic Research Program of China P-RHa longer-te(2011CB707506), the National Natural Science Foundation of China Grant (81271030 and 81170861), Shanghai Key Basic Research Grant (11JC141601), Shanghai Scholar Leadship Grant (12XD1404100). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.