The neuroprotective role of citicoline treatment in glaucoma – 6 months results of a prospective therapeutic trial

Abstract

Objectives. Neuroprotective treatment, including citicoline, is a new perspective in glaucoma management, having the role of progression delay. The purpose of the present study was to observe the evolution of the different parameters in patients with glaucoma treated with citicoline.Methods. 22 patients with GPUD were enrolled in the study, and they received oral citicoline in addition to the ocular hypotensive therapy. Investigations were performed at the beginning of the current study, then at 3 months and 6 months, and included, besides full ophthalmologic checkup and IOP determination, optic nerve and RGCs OCT, and visual evoked potentials, pattern and flash. The data we obtained were statistically analyzed with the SPSS (Microsoft) program. Results. The outcomes of the study following VEP wave analysis indicated variations in P100 wave amplitude, but after 6 months period, an increase was found. Also, the P2 wave amplitude recorded statistically insignificant variations. The increase in P2 latency at 6 months was noted as statistically significant. Negative correlations were also met between the thickness of the RGC layer and the P100 latency, but also between the amplitude and the latency of this wave. At 6 months, a positive correlation between the RGC layer and the P100 amplitude was observed. The RNFL thickness at the optical disc had higher values at the 6 months visit, it was statistically significant, and a slight increase in the thickness of the RGC layer between successive visits was noted. These might be an examination artifact because clinically they are not possible. The RNFL thickness showed a positive correlation with the amplitude of P100 and P2 waves.Conclusions. The study of the parameters and their correlations demonstrated that citicoline had positive effects in glaucoma on certain aspects, data confirmed by literature.

Cholinergic system and the role it plays in the visual system

“…Therefore, over the last few years, the therapeutic involvement of cholinesterase inhibitors as part of neuroprotective therapy has gained relevance. 81,87,88 Similarly, some experimental studies have demonstrated that the activity of Ach precursors such as citicoline, improves retinal function, restoring the activity of the mitochondrial membrane of RGC, increasing the expression of neural growth factors, and improving cell survival, which confirms that there is a close correlation between retinal function and cholinergic activity [89][90][91] .…”

The Role of Citicoline and Coenzyme Q10 in Retinal Pathology

“…The oral administration of citicoline alone also showed benefits for the visual system in glaucoma patients. In a study [ 32 ] conducted in 22 patients with OAG and controlled IOP (<21 mmHg), citicoline was administered orally at 600 mg/day (4 capsules of 150 mg) for at least 3 months. A functional study was performed at the initial visit and at 3 and 6 months using perimetry, PEV-pattern, and PEV-flash (P100 and P2 waves) measurements.…”

“…The mechanism of action of citicoline in glaucoma is multifactorial, including, among others, the preservation of cardiolipin and sphingomyelin; the restoration of phosphatidylcholine; the stimulation of glutathione synthesis; the prevention of neural apoptosis; and the synthesis of glutathione, myelin, and acetylcholine [ 28 ]. In the studies analyzed in this bibliographic review, improvements in VA [ 27 ], VF [ 28 , 33 , 34 ], electrophysiological tests [ 29 , 30 , 32 ], measurements of RNFL thickness [ 28 , 32 , 33 ], CS [ 31 ] or subjective character tests such as the GQL-15 test were found [ 31 ].…”

“…According to the laboratory, it is recommended that people take 2 COQUN Combo ® tablets daily, which would mean a total dose of 500 mg of citicoline and 200 mg of CoQ10. In this review, it was pointed out that the recommended dose of citicoline in adults is between 425 and 550 mg/day [ 7 ], although these amounts have not been updated since 1998 [ 93 ];more specifically, in the reviewed studies, the doses of citicoline used orally equaled 500 mg/day [ 31 , 33 ], and only one study used a higher amount, of 600 mg [ 32 ]. In the case of CoQ10, there is less dependence on the diet, but the evidence indicates that biosynthesis decreases with age, and supplementation could be beneficial to improve CoQ10 levels in the body.…”

Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma

“…Citicoline functions as an intermediate in the biosynthesis of cell membrane phospholipids and as a precursor of the neurotransmitter acetylcholine [ 153 ]. As a dietary supplement, citicoline has been used as a neuroprotective agent in several neurological disorders, including Parkinson’s and Alzheimer’s diseases, dementia, stroke, and glaucoma [ 154 , 155 , 156 , 157 ]. The neuroprotective effects of citicoline are mediated by several mechanisms such as the maintenance of sphingomyelin and cardiolipin levels (a component of the inner mitochondrial membrane essential for mitochondrial electron transport), restoration of phosphatidylcholine levels, increased activity of glutathione synthesis, reduction of lipid peroxidation, and attenuation of free fatty acid release [ 158 ].…”