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

Paolo Fogagnolo, Ettore Melardi, Laura Tranchina, Luca Rossetti, Paolo Fogagnolo, Ettore Melardi, Laura Tranchina, Luca Rossetti

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 30 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: Trial registration NCT03906513 , retrospectively registered on 08 April 2019.

Keywords: Citicoline; Cornea innervation; Corneal sensitivity; Diabetes; Dry eye disease; Vitamin B12.

Conflict of interest statement

The authors have no financial interest in the material or products discussed in the article. Paolo Fogagnolo and Luca Rossetti are Editors of BMC Ophthalmology.

Figures

Fig. 1
Fig. 1
An example of the effects of Cit-B12 during the study. Confocal images of the central cornea at a) baseline (FLD 7.1 mm/m2) and b) 18 months (FLD 10.3 mm/mm2)
Fig. 2
Fig. 2
Changes of the frequency of stages of the Ocular Surface Disease Index at baseline vs month 18 in the two groups (Cit-B12, P = 0.05). Normal, OSDI = 12 or less; mild, OSDI between 13 and 22; moderate, OSDI between 23 and 32
Fig. 3
Fig. 3
Changes of conjunctival staining according to Van Bijelsterveld scale at baseline vs month 18 in the two groups (Cit-B12, P = 0.04)

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