A preliminary study of the neuroprotective role of citicoline eye drops in glaucomatous optic neuropathy

Gloria Roberti, Lucia Tanga, Vincenzo Parisi, Massimo Sampalmieri, Marco Centofanti, Gianluca Manni, Gloria Roberti, Lucia Tanga, Vincenzo Parisi, Massimo Sampalmieri, Marco Centofanti, Gianluca Manni

Abstract

Purpose: To study the neuroprotective effect of topical citicoline.

Materials and methods: Experimental phase to evaluate the ability of citicoline eye drops to reach the vitreous and the retina: The right eyes of 5 mice CD1 were treated with two drops per day for three days of citicoline 1% and 2% (OMK1, Omikron Italia s.r.l.), and then the vitreous was analyzed with the liquid chromatography and spectrometry mass (LC-MS/MS). Clinical phase to determine if topical citicoline is able to delay glaucoma progression, considering perimetric parameters and electro functional tests. Patients were randomized in two groups, OMK1 and OAG. The first group was treated with OMK1 three times per day, plus hypotensive therapy for two months and one month of wash out. The second group was treated only with hypotensive treatment for three months.

Results: LC-MS/MS detected the molecule very well, and only OMK1 showed systemic absorption. Thirty-four patients were enrolled, 16 in the OMK1 and 18 in the OAG group. Perimetric parameters showed a positive trend in individual eyes of patients in OMK1 group, but these values were not statistically significant in the whole group. Retinal ganglion cells function improved as shown by reduced P50 latency (P = 0.04) and increased P50-N95 amplitude (P < 0.0001) of pattern electroretinogram, up to 30 days after the washout (P = 0.01; P = 0.002). Visual evoked potential and retino-cortical time improvement regressed after 30 days of washout. In OAG group, there was any change during the follow-up. No adverse reactions were reported in both groups.

Conclusions: Topical citicoline seems to have a neuroprotective action.

Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1
Figure 1
The graph shows the spectrometry result: The peak corresponds to the presence of citicoline in the vitreous.
Figure 2
Figure 2
The graph shows the spectrometry result of the left eye of Group A mouse: Citicoline is not in the vitreous.
Figure 3
Figure 3
An example of visual field MD improvement after 30 and 60 days
Figure 4
Figure 4
An example of visual field MD improvement after 30 and 60 days

References

    1. Sommer A, Miller NR, Pollack I, Maumenee AE, George T. The nerve fiber layer in the diagnosis of glaucoma. Arch Ophthalmol. 1977;95:2149–56.
    1. Harwerth RS, Carter-Dawson L, Shen F, Smith EL, 3rd, Crawford ML. Ganglion cell losses underlying visual field defects from experimental glaucoma. Invest Ophthalmol Vis Sci. 1999;40:2242–50.
    1. Sakugawa M, Chihara E. Blockage at two points of axonal transport in glaucomatous eyes. Graefes Arch Clin Exp Ophthalmol. 1985;223:214–8.
    1. Burgoyne CF, Downs JC, Bellezza AJ, Suh JK, Hart RT. The optic nerve head as a biomechanical structure: A new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage. Prog Retin Eye Res. 2005;24:39–73.
    1. Secades JJ. Citicoline: Pharmacological and clinical review, 2010 update. Rev Neurol. 2011;52(Suppl 2):S1–62.
    1. Chang EE, Goldberg JL. Glaucoma 2.0: Neuroprotection, neuroregeneration, neuroenhancement. Ophthalmology. 2012;119:979–86.
    1. Ottobelli L, Manni GL, Centofanti M, Iester M, Allevena F, Rossetti L. Citicoline oral solution in glaucoma: Is there a role in slowing disease progression? Ophthalmologica. 2013;229:219–26.
    1. Pecori Giraldi J, Virno M, Covelli G, Grechi G, De Gregorio F. Therapeutic value of citicoline in the treatment of glaucoma (computerized and automated perimetric investigation) Int Ophthalmol. 1989;13:109–12.
    1. Virno M, Pecori-Giraldi J, Liguori A, De Gregorio F. The protective effect of citicoline on the progression of the perimetric defects in glaucomatous patients (perimetric study with a 10-year follow-up) Acta Ophthalmol Scan Suppl. 2000;232:56–7.
    1. Rejdak R, Toczo³owski J, Kurkowski J, Kamiñski ML, Rejdak K, Stelmasiak Z, et al. Oral citicoline treatment improve visual pathway function in glaucoma. Med Sci Monit. 2003;9:P124–8.
    1. Parisi V, Manni G, Colacino G, Bucci MG. Cytidine-5’-diphosphocholine (citicoline) improves retinal and cortical responses in patients with glaucoma. Ophthalmology. 1999;106:1126–34.
    1. Parisi V. Electrophysiological assessment of glaucomatous visual dysfunction during treatment with cytidine-5’-diphosphocholine (citicoline): A study of 8 years of follow-up. Doc Ophthalmol. 2005;110:91–102.
    1. Parisi V, Coppola G, Centofanti M, Oddone F, Angrisani AM, Ziccardi L, et al. Evidence of the neuroprotective role of citicoline in glaucoma patients. Prog Brain Res. 2008;173:541–54.
    1. Bubella RM, Carità S, Badalamenti R, Bubella DM. Neuroprotezione del paziente con glaucoma cronico ad an golo aperto: Ruolo della citicolina in soluzione orale. Ottica fisiopatologica. 2011;XVI:171–7.
    1. Oshitari T, Fujimoto N, Adachi-Usami E. Citicoline has a protective effect on damaged retinal ganglion cells in mouse culture retina. Neuroreport. 2002;13:2109–11.
    1. Chan KC, So KF, Wu EX. Proton magnetic resonance spectroscopy revealed choline reduction in the visual cortex in an experimental model of chronic glaucoma. Exp Eye Res. 2009;88:65–70.
    1. Ashton P, Podder SK, Lee VH. Formulation influence on conjunctival penetration of four beta blockers in the pigmented rabbit: A comparison with corneal penetration. Pharm Res. 1991;8:1166–74.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться