Effectiveness and Safety of Non-Invasive Neuromodulation for Vision Restoration: A Systematic Review and Meta-Analysis.

We carried out a systematic review and meta-analysis to determine the effectiveness and safety of non-invasive electrical stimulation (NES) for vision restoration. We systematically searched for randomised controlled trials (RCTs) comparing NES with sham stimulation, for vision restoration between 2000 and 2022 in CENTRAL, MEDLINE, EMBASE, and LILACS. The main outcomes were as follows: visual acuity (VA); detection accuracy; foveal threshold; mean sensitivity as the parameter for the visual field; reading performance; contrast sensitivity (CS); electroencephalogram; quality of life (QoL), and safety. Two reviewers independently selected studies, extracted data, and evaluated the risk of bias using the Cochrane risk of bias 2.0 tool. The certainty in the evidence was determined using the GRADE framework. Protocol registration: CRD42022329342. Thirteen RCTs involving 441 patients with vision impairment indicate that NES may improve VA in the immediate post-intervention period (mean difference [MD] = -0.02 logMAR, 95% confidence intervals [CI] -0.08 to 0.04; low certainty), and probably increases QoL and detection accuracy (MD = 0.08, 95% CI -0.25 to 0.42 and standardised MD [SMD] = 0.09, 95% CI -0.58 to 0.77, respectively; both moderate certainty). NES likely results in little or no difference in mean sensitivity (SMD = -0.03, 95% CI -0.53 to 0.48). Compared with sham stimulation, NES increases the risk of minor adverse effects (risk ratio = 1.24, 95% CI 0.99 to 1.54; moderate certainty). The effect of NES on CS, reading performance, and electroencephalogram was uncertain. Our study suggests that although NES may slightly improve VA, detection accuracy, and QoL, the clinical relevance of these findings remains uncertain. Future research should focus on improving the available evidence's precision and consistency.