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      Can Treatment With Citicoline Eyedrops Reduce Progression in Glaucoma? The Results of a Randomized Placebo-controlled Clinical Trial

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          Abstract

          Precis:

          Citicoline eyedrops in patients with progressing glaucoma.

          Purpose:

          This study aimed to test whether the additional therapy with citicoline eyedrops to intraocular pressure (IOP)-lowering treatment could slow glaucoma progression in patients with worsening of damage and IOP 18 mm Hg or less.

          Design:

          This was a randomized, double-masked, placebo-controlled, multicenter 3-year study.

          Outcomes:

          The outcomes studied were difference in the visual field (mean deviation, MD, of 24-2; MD of 10-2) rates of progression and difference in retinal nerve fiber layer (RNFL) thickness change between the 2 study groups at 3 years.

          Methods:

          Patients with mild to moderate open-angle glaucoma (OAG) showing damage progression of at least −0.5 dB/y in the 2 years before enrollment despite IOP ≤18 mm Hg were randomized to receive citicoline eyedrops or placebo 3 times daily for 3 years. Patients were followed every 3 months and underwent a visual field examination with 24-2 and 10-2 strategies and RNFL assessment. Analysis of variance and linear models were used to test the differences between groups.

          Results:

          Eighty patients were randomized in the trial. The mean 3-year rates of progression were −1.03 (2.14) dB in the citicoline group and −1.92 (2.23) dB in the placebo group ( P=0.07) for 24-2 MD and −0.41 (3.45) dB in the citicoline group and −2.22 (3.63) dB in the placebo group ( P=0.02) for 10-2 MD. On average, patients receiving citicoline eyedrops lost 1.86 μm of RNFL in 3 years, versus 2.99 μm in the placebo group ( P=0.02).

          Conclusions:

          Additional treatment with citicoline eyedrops to IOP-lowering treatment might reduce disease progression in patients with progressing glaucoma despite IOP ≤18 mm Hg.

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          Most cited references29

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          Cholinergic nervous system and glaucoma: From basic science to clinical applications

          The cholinergic system has a crucial role to play in visual function. Although cholinergic drugs have been a focus of attention as glaucoma medications for reducing eye pressure, little is known about the potential modality for neuronal survival and/or enhancement in visual impairments. Citicoline, a naturally occurring compound and FDA approved dietary supplement, is a nootropic agent that is recently demonstrated to be effective in ameliorating ischemic stroke, traumatic brain injury, Parkinson’s disease, Alzheimer’s disease, cerebrovascular diseases, memory disorders and attention-deficit/hyperactivity disorder in both humans and animal models. The mechanisms of its action appear to be multifarious including (i) preservation of cardiolipin, sphingomyelin, arachidonic acid content of phosphatidylcholine and phosphatidylethanolamine, (ii) restoration of phosphatidylcholine, (iii) stimulation of glutathione synthesis, (iv) lowering glutamate concentrations and preventing glutamate excitotoxicity, (v) rescuing mitochondrial function thereby preventing oxidative damage and onset of neuronal apoptosis, (vi) synthesis of myelin leading to improvement in neuronal membrane integrity, (vii) improving acetylcholine synthesis and thereby reducing the effects of mental stress and (viii) preventing endothelial dysfunction. Such effects have vouched for citicoline as a neuroprotective, neurorestorative and neuroregenerative agent. Retinal ganglion cells are neurons with long myelinated axons which provide a strong rationale for citicoline use in visual pathway disorders. Since glaucoma is a form of neurodegeneration involving retinal ganglion cells, citicoline may help ameliorate glaucomatous damages in multiple facets. Additionally, trans-synaptic degeneration has been identified in humans and experimental models of glaucoma suggesting the cholinergic system as a new brain target for glaucoma management and therapy.
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            Neuroprotection for treatment of glaucoma in adults.

            Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells, and ultimately visual field loss. It is a leading cause of blindness worldwide. Open angle glaucoma (OAG), the most common form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death.
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              • Article: not found

              Treatment with citicoline eye drops enhances retinal function and neural conduction along the visual pathways in open angle glaucoma.

              To evaluate the retinal function and the neural conduction along the visual pathways after treatment with citicoline eye drops in patients with open angle glaucoma (OAG).
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                Author and article information

                Journal
                J Glaucoma
                J. Glaucoma
                IJG
                Journal of Glaucoma
                Wolters Kluwer Health, Inc
                1057-0829
                1536-481X
                July 2020
                11 June 2020
                : 29
                : 7
                : 513-520
                Affiliations
                [* ]Eye Clinic, ASST Santi Paolo e Carlo, University of Milan, Milan
                []Eye Clinic, DiNOGMI, University of Genoa
                []IRCCS Policlinico San Martino Hospital, Genova
                [§ ]Department of Clinical Sciences and Translational Medicine, University of Tor Vergata
                []Bietti Foundation, IRCCS, Rome, Italy
                Author notes
                Reprints: Luca Rossetti, MD, Clinica Oculistica, ASST Santi Paolo e Carlo, Via di Rudinì, 8, Milano 20142, Italy (e-mail: luca.rossetti@ 123456unimi.it ).
                Article
                00003
                10.1097/IJG.0000000000001565
                7337116
                32541370
                92128410-81e4-4b1d-bade-b7af5038e1da
                Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/

                History
                : 10 January 2020
                : 17 May 2020
                Categories
                Original Studies
                Custom metadata
                TRUE

                glaucoma,neuroprotection,clinical trial,citicoline
                glaucoma, neuroprotection, clinical trial, citicoline

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