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

Abstract

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 ClinicalTrials.gov NCT03758118 .

Citicoline and Vitamin B12 Eye Drops in Type 1 Diabetes: Results of a 3-year Pilot Study Evaluating Morpho-Functional Retinal Changes

“…After administration of citicoline plus vitamin B 12 , we observed no significant changes in both the INL and OPL thicknesses, which suggests that treatment with citicoline eye drops may prevent the retinal morphological changes related to DR. Neuroprotective effects from the structural activity of citicoline may contribute to the differences between the DC and DP groups, which is supported by another study on non-arteritic ischemic optic neuropathy in humans [30] and the review by Faiq et al [21] on experimental models. With regard to OCTA, the DC group showed no significant changes of VD at SCP and DCP, while the DP group showed significant reduction of that over time.…”

Visual Evoked Potentials in Joubert Syndrome: A Suggested Useful Method for Evaluating Future Approaches Targeted to Improve Visual Pathways’ Function

“…VEP findings detected in the present cohort of JS patients were overall similar to those observed in patients with other diseases inducing a visual pathway dysfunction (see Creel for a review [27]). Recently, to improve the visual pathway function, several clinical trials have been started in patients with different types of optic neuropathies (LHON, ischemic optic neuropathy, glaucoma) by using treatments with idebenone [19,20], citicoline [40][41][42][43], coenzyme Q10 [44] or nerve growth factor [45]. In many of these studies [40][41][42][43][44][45], the efficacy of the supplementation treatment was evaluated by measuring the changes of the VEP responses, and it can be foreseen that VEP can be adopted as a useful methodology to evaluate the outcome of future trials aimed at improving visual function in JS patients.…”

Cytidine 5′-Diphosphocholine (Citicoline): Evidence for a Neuroprotective Role in Glaucoma

“…In amblyopia, citicoline, with or without patching, improved visual acuity [65][66][67][68][69] and contrast sensitivity and visually-evoked potentials (VEP) [69]. Similarly, citicoline improved visual acuity, VEP, and pattern electroretinogram (PERG) responses in patients with non-arteritic ischemic optic neuropathy (a human model of neurodegeneration) [70,71]. Furthermore, evidence from several preclinical and clinical studies suggest that citicoline has potential beneficial neuroprotective or neurorestorative activity in glaucoma.…”