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

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.

Figure 1. Flow chart of search strategy and study selection.

RCCT: Randomize Case Controlled Trial, IVR: IntraViteal Ranibizumab, IVB: IntraViteal Bevacizumab, IVT: IntraViteal Triamcinolone acetonide (IVT), PRN: Pro Re Nata.

Figure 2. Forrest plots for the proportion of patients with an improvement from baseline in best-corrected visual acuity (BCVA) of greater than or equal to 15 letters on Early Treatment in Diabetic Retinopathy Study (ETDRS) Chart at six and twelve months between anti-VEGF and placebo group.

Figure 3. Forrest plots for the proportion of patients with a loss from baseline in best-corrected visual acuity (BCVA) of greater than or equal to 15 letters on Early Treatment in Diabetic Retinopathy Study (ETDRS) Chart at six and twelve months between anti-VEGF and placebo group.

Figure 4. Forrest plots for the mean visual acuity change on Early Treatment in Diabetic Retinopathy Study (ETDRS) Chart at one, six and twelve months between anti-VEGF and placebo group.

Figure 5. Forrest plots for the mean change in central retinal thickness (µm) at one, six and twelve months between anti-VEGF and placebo group.