Citicoline Oral Solution Induces Functional Enhancement and Synaptic Plasticity in Patients with Open-Angle Glaucoma

<b>Objectives:</b> To evaluate the changes in retinal function and neural conduction along the visual pathways after 12 months of treatment with Citicoline oral solution in patients with open-angle glaucoma (OAG). <b>Methods:</b> In this randomized, prospective, double-blind study, 29 OAG patients were enrolled. Fifteen patients (Citicoline Group, 15 eyes) received Citicoline oral solution (Neurotidine^®, 500 mg/day), and 14 patients (Placebo Group, 14 eyes) received placebo for 12 months. Visual field (VF), pattern electroretinogram (PERG), visual evoked potentials (VEP), and Retinocortical Time (RCT) were assessed at baseline and after 6 and 12 months. Brain Diffusion Tensor Imaging (DTI)-Magnetic Resonance Imaging (MRI) was performed at baseline and at 12 months. <b>Results:</b> PERG, VEP, and RCT baseline values were comparable between groups (<i>p</i> > 0.01) at baseline. After 12 months of Citicoline treatment, significant (<i>p</i> < 0.01) increases in PERG P50-N95 and VEP N75-P100 amplitudes, and significant shortening of PERG P50, VEP P100 implicit times and RCT were observed. VEP implicit times shortening significantly correlated with the changes in VF Mean Deviation, and RCT shortening was associated with changes in DTI-MRI metrics in the lateral geniculate nucleus and on optic radiations, without reaching the level of significance. No significant changes were found in the Placebo Group. <b>Conclusions:</b> In OAG, Citicoline oral solution enhances retinal function likely through neuromodulation processes and changes post-retinal visual pathway connectivity. This could explain the improvement of visual field defects.