Intravitreal anti-VEGF injections for treating wet age-related macular degeneration: a systematic review and meta-analysis

Abstract

Aims: Age-related macular degeneration (AMD) is the main cause of blindness. Anti-vascular endothelial growth factor is used to prevent further neovascularization due to wet AMD. The purpose of this systematic review was to investigate the effect and protocol of anti-vascular endothelial growth factor treatment on wet AMD.

Methods: A comprehensive literature search was performed in PubMed, Embase, the Cochrane Library, CNKI, and reference lists. Meta-analysis was performed using Stata12.0 software, best corrected visual acuity (BCVA), retinal thickness, and lesion size were evaluated.

Results: Twelve randomized controlled trials spanning from 2010 to 2014 and involving 5,225 patients were included. A significant difference was observed between the intravitreal ranibizumab (IVR) group and the intravitreal bevacizumab group (standard mean difference = -0.14, 95% confidence interval [CI] = -0.23 to -0.05). No significant differences were observed in best corrected VA, retinal thickness, or lesion size between IVR and the intravitreal aflibercept group. Compared to monthly injection, IVR as-needed injections (PRN) can raise VA by 1.97 letters (weighted mean difference = 1.97, 95% CI = 0.14-3.794). Combination therapy of IVR and photodynamic therapy can significantly raise VA by 2.74 letters when combined with IVR monotherapy (weighted mean difference = 2.74, 95% CI = 0.26-5.21).

Conclusion: The superiority remains unclear between IVR and intravitreal bevacizumab in the treatment of neovascular AMD. Intravitreal aflibercept dosed every 2 months required fewer injection times, but produced similar efficacy as monthly IVR. IVR PRN could significantly increase VA. Combined with photodynamic therapy, IVR therapy could also increase VA effectively.

Keywords: VEGF; aflibercept; age-related macular degeneration; bevacizumab; meta-analysis; ranibizumab.

Figure 1

Search strategy flow diagram regarding anti-VEGF agents for treating wet AMD. Abbreviations: AMD, age-related macular degeneration; CNV, choroidal neovascularization; RCT, randomized controlled trial; VEGF, vascular endothelial growth factor.

Figure 2

Forest plot of BCVA of IVR vs IVB for treating wet AMD. Note: No significant difference was observed between the IVR group and the IVB group. Abbreviations: AMD, age-related macular degeneration; BCVA, best corrected visual acuity; IVB, intravitreal bevacizumab; IVR, intravitreal ranibizumab; WMD, weighted mean difference; CI, confidence interval.

Figure 3

Forest plot of BCVA of monthly IVR vs PRN for treating wet AMD. Notes: A significant difference was shown between the two groups. Compared to monthly injection, PRN treatment can raise VA by 1.97 letters (WMD =1.97, 95% CI =0.14–3.794, P=0.04). Abbreviations: AMD, age-related macular degeneration; BCVA, best corrected visual acuity; CI, confidence interval; IVR, intravitreal ranibizumab; PRN, injection as-needed; WMD, weighted mean difference; VA, visual acuity.

Figure 4

Forest plot of BCVA of IVR monotherapy vs IVR+PDT for treating wet AMD. Notes: A significant difference was shown between the two groups. Compared to monotherapy, the combination therapy can raise VA by 2.74 letters (WMD =2.74, 95% CI =0.26–5.21, P=0.03). Abbreviations: AMD, age-related macular degeneration; BCVA, best corrected visual acuity; CI, confidence interval; IVR, intravitreal ranibizumab; PDT, photodynamic therapy; WMD, weighted mean difference; VA, visual acuity.