Neuroenhancement and neuroprotection by oral solution citicoline in non-arteritic ischemic optic neuropathy as a model of neurodegeneration: A randomized pilot study

PLoS One. 2019 Jul 26;14(7):e0220435. doi: 10.1371/journal.pone.0220435. eCollection 2019.


Purpose: To evaluate whether treatment with Citicoline in oral solution (OS-Citicoline) would increase visual function, retinal ganglion cells (RGCs) function, and neural conduction along visual pathways (neuroenhancement), and/or induce preservation of RGCs fibers' loss (neuroprotection) in non-arteritic ischemic optic neuropathy (NAION), a human model of neurodegeneration.

Methods: Thirty-six patients with NAION and 20 age-matched controls were enrolled. Nineteen NAION patients received 500 mg/day of OS-Citicoline for a 6-month period followed by 3-month of wash-out (NC Group); 17 NAION patients were not treated (NN Group) from baseline to 9 months. In all subjects at baseline, and in NC and NN eyes at 6 and 9 months of follow-up, we assessed Visual Acuity (VA), Pattern Electroretinogram (PERG), Visual Evoked Potentials (VEP), retinal nerve fiber layer thickness (RNFL-T), and Humphrey 24-2 visual field mean deviation (HFA MD). Mean differences were statistically evaluated with ANOVA between Groups, and linear correlations were analysed with Pearson's test.

Results: At 6 months, significant differences between groups for all parameters were observed (ANOVA, p<0.01). In NC eyes, VA increased, PERG responses increased, VEP recordings improved and were significantly correlated with increases in HFA MD (p<0.01), and RNFL-T was unmodified or improved. In contrast, in NN eyes, VA, PERG, VEP responses, RNFL-T, and HFA MD were further worsened. Significant differences were still present at 9-month follow-up in the NN Group and after 3 months of OS-Citicoline wash-out in NC eyes.

Conclusions: OS-Citicoline treatment induced neuroenhancement (improvement in RGCs function and neural conduction along visual pathways related to improvement of visual field defects) and neuroprotection (unmodified or improved RNFL morphological condition) in a human model of NAION involving fast RGCs degeneration.

Trial registration: NCT03758118.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Cytidine Diphosphate Choline / administration & dosage*
  • Cytidine Diphosphate Choline / pharmacology
  • Drug Administration Schedule
  • Electroretinography
  • Evoked Potentials, Visual / drug effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Optic Neuropathy, Ischemic / drug therapy*
  • Optic Neuropathy, Ischemic / physiopathology
  • Pharmaceutical Solutions
  • Pilot Projects
  • Treatment Outcome
  • Vision Tests


  • Pharmaceutical Solutions
  • Cytidine Diphosphate Choline

Associated data


Grant support

Research for this study was financially supported partially by the Ministry of Health and partially by Fondazione Roma. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.