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

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          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.

          Related collections

          Most cited references19

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          Glaucoma 2.0: neuroprotection, neuroregeneration, neuroenhancement.

          Glaucoma is a progressive neurodegenerative disease of retinal ganglion cells (RGCs) associated with characteristic axon degeneration in the optic nerve. Clinically, our only method of slowing glaucomatous loss of vision is to reduce intraocular pressure (IOP), but lowering IOP is only partially effective and does not address the underlying susceptibility of RGCs to degeneration. We review the recent steps forward in our understanding of the pathophysiology of glaucoma and discuss how this understanding has given us a next generation of therapeutic targets by which to maintain RGC survival, protect or rebuild RGC connections in the retina and brain, and enhance RGC function. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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            Ganglion cell losses underlying visual field defects from experimental glaucoma.

            To investigate the relationship between ganglion cell losses and visual field defects caused by glaucoma. Behavioral perimetry and histology data were obtained from 10 rhesus monkeys with unilateral experimental glaucoma that was induced by argon laser treatments to their trabecular meshwork. After significant visual field defects had developed, the retinas were collected for histologic analysis. The ganglion cells were counted by light microscopy in cresyl violet-stained retina sections, and the percentage of ganglion cell loss (treated to control eye counts) was compared with the depth of visual field defect (treated to control eye thresholds) at corresponding retinal and perimetry test locations. Sensitivity losses as a function of ganglion cell losses were analyzed for Goldmann III, white and Goldmann V, and short- and long-wavelength perimetry test stimuli. The relationship between the proportional losses of ganglion cells and visual sensitivity, measured with either white or colored stimuli, was nonlinear. With white stimuli, the visual sensitivity losses were relatively constant (approximately 6 dB) for ganglion cell losses of less than 30% to 50%, and then with greater amounts of cell loss the visual defects were more systematically related to ganglion cell loss (approximately 0.42 dB/percent cell loss). The forms of the neural-sensitivity relationships for visual defects measured with short- or long-wavelength perimetry stimuli were similar when the visual thresholds were normalized to compensate for differences in expected normal thresholds for white and colored perimetry stimuli. Current perimetry regimens with either white or monochromatic stimuli do not provide a useful estimate of ganglion cell loss until a substantial proportion have died. The variance in ganglion cell loss is large for mild defects that would be diagnostic of early glaucoma and for visual field locations near the fovea where sensitivity losses occur relatively late in the disease process. The neural-sensitivity relationships were essentially identical for both white and monochromatic test stimuli, and it therefore seems unlikely that the higher sensitivity for detecting glaucoma with monochromatic stimuli is based on the size-dependent susceptibility of ganglion cells to injury from glaucoma.
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              The nerve fiber layer in the diagnosis of glaucoma.

              Serial fundus photographs of 14 eyes that eventually developed glaucomatous visual field defects and 110 slides from 76 eyes of race- and age-matched controls were reviewed in randomized masked fashion. Each eye that lost visual field demonstrated consistent abnormalities of the nerve fiber layer, beginning as early as 5 years (mean, 1 1/2 years) before it developed glaucomatous visual field defects on routine Goldmann perimetry. Preliminary estimates, based on regression analysis of this small series, suggest that half of these eyes (median) might demonstrate such reproducible abnormalities between four and six years before onset of their visual field defects. Only 9% of the matched controls showed similar nerve fiber layer changes, and in the one instance where analysis was possible, these were inconsistent and nonreproducible. Nerve fiber layer assessment by means of fundus photographs may be the earliest, surest means of distinguishing ocular hypertension from true glaucoma.
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                Author and article information

                Journal
                Indian J Ophthalmol
                Indian J Ophthalmol
                IJO
                Indian Journal of Ophthalmology
                Medknow Publications & Media Pvt Ltd (India )
                0301-4738
                1998-3689
                May 2014
                : 62
                : 5
                : 549-553
                Affiliations
                [1 ]Istituto di Ricerca e Cura a Carattere Scientifico Fondazione GB Bietti, Via Livenza 3, 00198, Rome, Italy
                [2 ]Dipartimento di Scienze Cliniche e Medicina Traslazionale, University of Rome Tor Vergata, Viale Oxford 81, 00133, Rome, Italy
                Author notes
                Correspondence to: Dr. Gloria Roberti, IRCCS Fondazione GB Bietti, Rome, Italy. E-mail: gloriaroberti82@ 123456gmail.com
                Article
                IJO-62-549
                10.4103/0301-4738.133484
                4065503
                24881599
                cff08675-ce1d-4f12-8e23-b8d25c8e90e5
                Copyright: © Indian Journal of Ophthalmology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 July 2013
                : 16 February 2014
                Categories
                Original Article

                Ophthalmology & Optometry
                citicoline,glaucoma,neuroprotection,progression
                Ophthalmology & Optometry
                citicoline, glaucoma, neuroprotection, progression

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