title: Alternating Current Stimulation for Vision Restoration after Optic Nerve Damage: A Randomized Clinical Trial.
abstract: BACKGROUND
  Vision loss after optic neuropathy is considered irreversible. Here, repetitive transorbital alternating current stimulation (rtACS) was applied in partially blind patients with the goal of activating their residual vision.
  
  
  METHODS
  We conducted a multicenter, prospective, randomized, double-blind, sham-controlled trial in an ambulatory setting with daily application of rtACS (n = 45) or sham-stimulation (n = 37) for 50 min for a duration of 10 week days. A volunteer sample of patients with optic nerve damage (mean age 59.1 yrs) was recruited. The primary outcome measure for efficacy was super-threshold visual fields with 48 hrs after the last treatment day and at 2-months follow-up. Secondary outcome measures were near-threshold visual fields, reaction time, visual acuity, and resting-state EEGs to assess changes in brain physiology.
  
  
  RESULTS
  The rtACS-treated group had a mean improvement in visual field of 24.0% which was significantly greater than after sham-stimulation (2.5%). This improvement persisted for at least 2 months in terms of both within- and between-group comparisons. Secondary analyses revealed improvements of near-threshold visual fields in the central 5° and increased thresholds in static perimetry after rtACS and improved reaction times, but visual acuity did not change compared to shams. Visual field improvement induced by rtACS was associated with EEG power-spectra and coherence alterations in visual cortical networks which are interpreted as signs of neuromodulation. Current flow simulation indicates current in the frontal cortex, eye, and optic nerve and in the subcortical but not in the cortical regions.
  
  
  CONCLUSIONS
  rtACS treatment is a safe and effective means to partially restore vision after optic nerve damage probably by modulating brain plasticity. This class 1 evidence suggests that visual fields can be improved in a clinically meaningful way.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01280877.
authors.affiliation: Institute of Medical Psychology, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Gall
authors.affiliation: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Sein
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Department of Ophthalmology, University Medical Center, Georg-August University of Goettingen, Goettingen, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schittkowski
authors.affiliation: Department of Clinical Neurophysiology, University Medical Center, Georg-August University, Goettingen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antal
authors.affiliation: Department of Clinical Neurophysiology, University Medical Center, Georg-August University, Goettingen, Germany.
authors.forename: Géza Gergely
authors.initials: GG
authors.lastname: Ambrus
authors.affiliation: Department of Clinical Neurophysiology, University Medical Center, Georg-August University, Goettingen, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Paulus
authors.affiliation: Center for Integrative Biomedical Computing and the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Moritz
authors.initials: M
authors.lastname: Dannhauer
authors.affiliation: Institute of Medical Psychology, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Romualda
authors.initials: R
authors.lastname: Michalik
authors.affiliation: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Alf
authors.initials: A
authors.lastname: Mante
authors.affiliation: Institute of Medical Psychology, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Michal
authors.initials: M
authors.lastname: Bola
authors.affiliation: Institute for Biometry and Medical Informatics, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Lux
authors.affiliation: Institute for Biometry and Medical Informatics, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kropf
authors.affiliation: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Brandt
authors.affiliation: Institute of Medical Psychology, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Bernhard A
authors.initials: BA
authors.lastname: Sabel
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004599:Electric Stimulation Therapy / Q000379:methods*; D004560:Electricity; D004569:Electroencephalography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009900:Optic Nerve / Q000503:physiopathology*; D009901:Optic Nerve Diseases / Q000503:physiopathology / Q000628:therapy*; D020221:Optic Nerve Injuries / Q000503:physiopathology / Q000628:therapy*; D011446:Prospective Studies; D011788:Quality of Life; D057566:Self Report; D013997:Time Factors; D016896:Treatment Outcome; D014786:Vision Disorders / Q000628:therapy*; D014785:Vision, Ocular; D014792:Visual Acuity; D058609:Visual Field Tests; D014794:Visual Fields