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

• Published in: PloS one Vol. 14; no. 7; p. e0220435
• Main Authors: Parisi, Vincenzo, Barbano, Lucilla, Di Renzo, Antonio, Coppola, Gianluca, Ziccardi, Lucia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.07.2019; Public Library of Science (PLoS)
• Subjects: Acuity; Administration, Oral; Age; Aged; Apoptosis; Biology and Life Sciences; Citicoline; Correlation analysis; Cytidine diphosphate choline; Cytidine Diphosphate Choline - administration & dosage; Cytidine Diphosphate Choline - pharmacology; Degeneration; Disease; Drug Administration Schedule; Drug therapy; Electroretinography; Evoked Potentials, Visual - drug effects; Eye; Eye (anatomy); Female; Ganglion cysts; Glaucoma; Health aspects; Humans; Ischemia; Male; Medicine and Health Sciences; Middle Aged; Nerve conduction; Nerve degeneration; Nervous system; Neurodegeneration; Neuropathy; Neuroprotection; Neuroprotective agents; Optic nerve; Optic nerve diseases; Optic neuropathy; Optic Neuropathy, Ischemic - drug therapy; Optic Neuropathy, Ischemic - physiopathology; Optical fibers; Optics; Oral drugs; Pathways; Pharmaceutical Solutions; Pilot Projects; Preservation; Research and Analysis Methods; Retina; Retinal ganglion cells; Social Sciences; Stroke; Studies; Testing; Thickness; Tomography; Treatment Outcome; Variance analysis; Vision Tests; Visual acuity; Visual evoked potentials; Visual field; Visual fields; Visual pathways; Visual perception; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0220435

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. 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. 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. 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. ClinicalTrials.gov NCT03758118.