Topical citicoline and vitamin B12 versus placebo in the treatment of diabetes-related corneal nerve damage: a randomized double-blind controlled trial.

Abstract

Background: To evaluate the effects of topical citicoline and vitamin B12 (Cit-B12; OMK2, Omikron Italia srl, Italy) on corneal innervation of patients with diabetic neuropathy.Methods: This prospective, randomized, double blind, placebo-controlled study included thirty patients randomised with a 2:1 ratio to Cit-B12 or placebo 3 times daily for 18 months. At baseline and at months 4,8,12,18 patients underwent the Ocular Surface Disease Index questionnaire (OSDI), tear break-up time, evaluation of corneal and conjunctival staining, Schirmer I test, Cochet-Bonnet esthesiometry, and confocal biomicroscopy of corneal sub-basal plexus (SBP). Fiber lenght density (FLD) was calculated using NeuronJ and expressed in mm/mm2. Raw data and differences from baseline were analysed in the two groups. Results: 29/30 patients concluded the study. The two groups had similar FLD at baseline; it progressively improved up to month 18 in both groups (Cit-B12, p<0.0001; controls, <0.0001-0.03); improvement at month 18 vs baseline was higher in Cit-B12 than placebo (33% vs 15%, p=0.04). A progressive amelioration of corneal sensitivity (baseline, 28±18 mm; month 18, 52±10 mm, p<0.0001), conjunctival staining (P=0.04) and OSDI questionnaire (P=0.05) were shown on Cit-B12 group alone. Both treatments were well tolerated and adherence during the study was high.Conclusions: Cit-B12 ameliorated both morphology and function of corneal nerves in patients with diabetes, thus suggesting a neuroregenerative effect. Trial registration NCT03906513, retrospectively registered on 08 April 2019

Citicoline and Vitamin B12 Eye Drops in Type 1 Diabetes: Results of a 36-Month Pilot Study Evaluating Macular Electrophysiological Changes

“…In patients with DM1, long-term stabilization and positive changes of psychophysical macular responses (i.e., FDT 10-2 mean sensitivity) and microvascular involvement were obtained by the administration for 36 months of eye drops containing citicoline and vitamin B 12 [14]. In addition, in patients with DR the same combination improved the morphology and sensitivity of corneal nerves [15].…”