Comparison of efficacy of conbercept, aflibercept, and ranibizumab ophthalmic injection in the treatment of macular edema caused by retinal vein occlusion: a Meta-analysis

Abstract

Aim: To evaluate and compare the anatomical and functional outcomes and negative effects of the three anti-vascular endothelial growth factor (VEGF) drugs in the treatment of macular edema (ME) due to retinal vein occlusion (RVO) based on the evidence pooled from current clinical trials and observational studies.

Methods: A systematic literature search was conducted on nine online databases from inception until April 30, 2022. The main endpoints were best corrected visual acuity (BCVA), central macular thickness (CMT), and adverse events (AEs). Cumulative Meta-analysis was conducted to synthesize the outcomes of the drugs. The retrieved data were analyzed using Stata software (version 12.0).

Results: A total of 20 studies comprising 1674 eyes met the inclusion criteria to the Meta-analysis. It was observed that conbercept and aflibercept had better visual acuity effects compared with ranibizumab at 1mo [weight mean difference (WMD)=-0.03, P=0.001; WMD=-0.05, P=0.019], but the effects were not different from that of ranibizumab at 6mo. Moreover, there was not statistically significant difference in the proportion of patients gaining ≥15 letters at 12-24mo between aflibercept and ranibizumab [odds ratio (OR)=1.16, P=0.427]. Conbercept had higher mean CMT change effects at 1mo (WMD=-14.43, P=0.014) and 6mo (WMD=-35.63, P≤0.001) compared with ranibizumab. Meanwhile, the mean CMT change effects at 1mo (WMD=-10.14, P=0.170), 6mo (WMD=-26.98, P=0.140) and 12-24mo (WMD=-12.34, P=0.071) were comparable among the groups. Similarly, AEs were not significantly different among the treatments (OR=0.75, P=0.305; OR=1.04, P=0.89). The stability of effect size of mean BCVA and CMT improved with the increase in sample size. Aflibercept and conbercept required fewer injections compared with ranibizumab.

Conclusion: This is the first study to evaluate the efficacy and AEs of intravitreal administration of conbercept, ranibizumab, and aflibercept in the treatment of RVO-ME. Intravitreal aflibercept or conbercept results in better mean change in vision and CMT reduction compared with ranibizumab. Conbercept can be considered to be a promising and innovative drug with good anti-VEGF effects.

Keywords: aflibercept; anti-vascular endothelial growth factor; conbercept; macular edema; ranibizumab; retinal vein occlusion.

Figure 1. A flow diagram of the eligibility of studies for inclusion in Meta-analysis.

Figure 2. Forest plot of Meta-analysis and cumulative Meta-analysis in mean BCVA change comparing with baseline

A: After 1-month treatment of IVC versus IVR; B: After 1-month treatment of IVA versus IVR; C: Cumulative Meta-analysis of IVC versus IVR after 1-month; D: Cumulative Meta-analysis of IVA versus IVR after 1mo; E: After 6-month treatment of IVC versus IVR; F: After 6-month treatment of IVA versus IVR; G: Cumulative Meta-analysis of IVC versus IVR after 6-month; H: Cumulative Meta-analysis of IVA versus IVR after 6-month. BCVA: Best corrected visual acuity; IVC: Intravitreal conbercept; IVR: Intravitreal ranibizumab; IVA: Intravitreal aflibercept.

Figure 3. Forest plot of Meta-analysis and cumulative Meta-analysis in mean CMT change comparing with baseline

A: After 1-month treatment of IVC versus IVR; B: After 1-month treatment of IVA versus IVR; C: Cumulative Meta-analysis of IVC versus IVR after 1-month; D: Cumulative Meta-analysis of IVA versus IVR after 1-month; E: After 6-month treatment of IVC versus IVR; F: After 6-month treatment of IVA versus IVR; G: Cumulative Meta-analysis of IVC versus IVR after 6-month; H: Cumulative Meta-analysis of IVA versus IVR after 6-month. CMT: Central macular thickness; IVC: Intravitreal conbercept; IVR: Intravitreal ranibizumab; IVA: Intravitreal aflibercept.

Figure 4. Forest plot of Meta-analysis in other outcomes

A: Proportion of patients gaining ≥15 letters after 12-24mo treatment of IVA versus IVR; B: Mean CMT change after 12-24mo treatment of IVA versus IVR; C: Systemic adverse events of IVA versus IVR; D: Ocular adverse events of IVC versus IVR; E: Ocular adverse events of IVA versus IVR. IVC: Intravitreal conbercept; IVR: Intravitreal ranibizumab; IVA: Intravitreal aflibercept.