IS 5. Clinical efficacy of non-invasive transorbital alternating current stimulation in optic neuropathy: A double-blind, randomized, sham-controlled multi-center study

Abstract

Non-invasive brain current stimulation enhances neuronal plasticity in the visual system both in normal subjects and in patients with visual field loss ( Antal et al., 2012 , Sabel et al., 2011 ). In order to improve visual functions in patients with optic nerve damage we have now validated the efficacy of repetitive transorbital alternating current stimulation (rtACS) for the treatment of optic nerve damage in a randomized, multi-center clinical trial. A total of 98 patients were randomized in rtACS and sham group using stratified block randomisation considering the study center (3 levels) and the defect depth of visual fields at baseline (2 levels) as a potential prognostic factor. Patients were stimulated with 4 stimulation electrodes positioned near the closed eyes on 2 × 5 consecutive weekdays for 25–40 min daily with square pulse rtACS at 125% of individual phosphene threshold based on a preceding parameter optimization study (reported in an accompanying abstract). The sham group received a “minimal dose” of short-lasting single pulse phosphenes once per minute. Diagnostic sessions assessing visual field parameters, reaction times, visual acuity, and EEG were conducted 2 days before and after stimulation and at a 2-months follow-up. Eighty-two patients were finally included in the analyses. The primary analysis was directed to the comparison of percentage changes in detection rates in visual field diagnostics using the high resolution perimetry method (HRP) between the two treatment arms (rtACS vs. sham) with a significant difference in favor of rtACS ( p = 0.011; one-sided Mann–Whitney U ). RtACS-treated patients showed significant improvements after treatment (Hodges–Lehmann estimator for median increase 6.4%, 95%–CI (2.9%, 11.6%); p < 0.001 (Wilcoxon signed rank test one-sided). No significant change was seen in the sham-group (median change 1.1%, 95%–CI (−2.0%; 4.3%); p = 0.256. Due to a higher number of responders in the rtACS-group the mean improvement of visual fields was larger for visual field parameters after rtACS (23.96%) compared to sham (2.53%). RtACS-induced visual field changes were stable at a 2-months follow-up. Secondary perimetry measures confirmed this result, the most pronounced visual field changes being located in the central 5°. Covariance analysis for the logarithms of visual field change parameters did not reveal any significant differences between the study centers, neither as main factor nor as interaction with the treatment arm. EEG findings are reported in an accompanying abstract. RtACS treatment led to visual field improvement in patients with optic neuropathy suggesting that it is a viable clinical tool to improve visual fields in patients with long-lasting visual field loss. Together with the changes in EEG power spectra this finding supports the notion that visual system plasticity can be altered by non-invasive alternating current stimulation. The study was funded by EBS Technologies GmbH (Kleinmachnow, Germany) and the University of Magdeburg.