Intravitreal Anti-Vascular Endothelial Growth Factor Therapy and Retinal Nerve Fiber Layer Loss in Eyes With Age-Related Macular Degeneration: A Meta-Analysis

PURPOSE. Clinical study findings regarding the association between repeated injections of intravitreal anti-vascular endothelial growth factor (VEGF) and the risk of retinal nerve fiber layer (RNFL) thinning in patients with age-related macular degeneration (AMD) have been inconsistent. We investigated this association by using a meta-analysis. METHODS. In August 2015, we systematically reviewed PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Two independent evaluators identified eligible articles by using predetermined selection criteria. Average RNFL thickness before and after intravitreal anti-VEGF injections was examined by using data obtained at baseline and at the last follow-up visit. RESULTS. Six studies on 288 eyes were ultimately included. The meta-analysis revealed that average RNFL thickness following repeated anti-VEGF injections was not significantly different from baseline (mean difference [MD] = -0.171, 95% confidence interval [CI]: -0.371 to 0.029, P = 0.093) or control group measurements (MD = -0.091, 95% CI: -0.517 to 0.335, P = 0.674). However, subgroup analyses by the methodologic quality of study revealed a significant RNFL thickness loss in two low-biased, controlled experimental studies (MD = -0.534, 95% CI: -0.783 to -0.286, P = 0.001), but not in four observational studies (MD = - 0.038, 95% CI: -0.171 to 0.095, P = 0.576). CONCLUSIONS. There was no association between anti-VEGF injections and RNFL thickness changes when all studies were examined together. However, when two low-biased, controlled clinical trials were separately examined, repeated anti-VEGF injection was associated with RNFL loss. Large-scale, prospective studies are needed to determine long-term effects of anti-VEGF treatments on the RNFL in AMD patients.