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Graefe's Archive for Clinical and Experimental Ophthalmology
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 8/2015

01-08-2015 | Glaucoma

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

Authors: Vincenzo Parisi, Marco Centofanti, Lucia Ziccardi, Lucia Tanga, Manuele Michelessi, Gloria Roberti, Gianluca Manni

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 8/2015

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Abstract

Purpose

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).

Methods

Fifty-six OAG patients (mean age 52.4 ± 4.72 years, IOP <18 mmHg with beta-blocker monotherapy only) were enrolled. Of these, 47 eyes completed the study: 24 OAG eyes were treated with topical citicoline (OMK1®, Omikron Italia, 3 drops/day) (GC eyes) over a 4-month period (month 4) followed by a 2-month period of citicoline wash-out (month 6), and another 23 OAG eyes were only treated with beta-blocker monotherapy (GP eyes). In GC and GP eyes, pattern electroretinogram (PERG) and visual evoked potentials (VEP) were assessed at baseline and at months 4 and 6 in both groups.

Results

At baseline, similar (ANOVA, p > 0.01) PERG and VEP values in GC and GP eyes were observed. After treatment with topical citicoline, a significant (p < 0.01) increase of PERG P50-N95 and VEP N75-P100 amplitudes, and a significant (p < 0.01) shortening of VEP P100 implicit times were found. In GC eyes, the shortening of VEP P100 implicit times was correlated significantly (p < 0.01) with the increase of PERG P50-N95 amplitudes. After a 2-month period of topical Citicoline wash-out, PERG and VEP values were similar (p > 0.01) to baseline ones. GP eyes showed not significant changes of PERG and VEP values during the entire follow-up.

Conclusions

Topical treatment with citicoline in OAG eyes induces an enhancement of the retinal bioelectrical responses (increase of PERG amplitude) with a consequent improvement of the bioelectrical activity of the visual cortex (shortening and increase of VEP implicit time and amplitude, respectively).
Literature
1.
2.
Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M, Early Manifest Glaucoma Trial Group (2002) Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 120:1268–1279PubMedCrossRef
3.
The Advanced Glaucoma Intervention Study (AGIS): 7 (2000) The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol 130:429–440CrossRef
4.
Maier PC, Funk J, Schwarzer G, Antes G, Falck-Ytter YT (2005) Treatment of ocular hypertension and open angle glaucoma: meta-analysis of randomised controlled trials. Br Med J 331:134CrossRef
5.
Holopigian K, Sieple W, Mayron C, Koty R, Lorenzo M (1990) Electrophysiological and psychophysical flicker sensitivity in patients with primary open angle glaucoma and ocular hypertension. Invest Ophthalmol Vis Sci 31:1863–1869PubMed
6.
Parisi V, Ziccardi L, Centofanti M, Tanga L, Gallinaro G, Falsini B, Bucci MG (2012) Macular function in eyes with open-angle glaucoma evaluated by multifocal electroretinogram. Invest Ophthalmol Vis Sci 53:6973–6980PubMedCrossRef
7.
Porciatti V, Falsini B, Brunori S, Colotto A, Moretti G (1987) Pattern electroretinogram as a function of spatial frequency in ocular hypertension and early glaucoma. Doc Ophthalmol 65:349–355PubMedCrossRef
8.
Bach M, Speidel-Fiaux A (1989) Pattern electroretinogram in glaucoma and ocular hypertension. Doc Ophthalmol 73:173–181PubMedCrossRef
9.
10.
Hood DC, Xu L, Thienprasiddhi P, Greenstein VC, Odel JG, Grippo TM, Liebmann JM, Ritch R (2005) The pattern electroretinogram in glaucoma patients with confirmed visual field deficits. Invest Ophthalmol Vis Sci 46:2411–2418PubMedCrossRef
11.
Parisi V, Manni G, Centofanti M, Gandolfi SA, Olzi D, Bucci MG (2001) Correlation between optical coherence tomography, pattern electroretinogram and visual evoked potentials in open angle glaucoma patients. Ophthalmology 108:905–912PubMedCrossRef
12.
Parisi V (1997) Neural conduction in the visual pathways in ocular hypertension and glaucoma. Graefes Arch Clin Exp Ophthalmol 235:136–146PubMedCrossRef
13.
Colotto A, Falsini B, Salgarello T, Iarossi G, Galan ME, Scullica L (2000) Photopic negative response of the human ERG: losses associated with glaucomatous damage. Invest Ophthalmol Vis Sci 41:2205–2211PubMed
14.
Hung L, Shen X, Fan N, He J (2012) Clinical application of photopic negative response of the flash electroretinogram in primary open-angle glaucoma. Eye Sci 27:113–118
15.
Parisi V, Bucci MG (1992) Visual evoked potentials after photostress in patients with primary open-angle glaucoma and ocular hypertension. Invest Ophthalmol Vis Sci 33:436–442PubMed
16.
Horn FK, Jonas JB, Budde WM, Jünemann AM, Mardin CY, Korth M (2002) Monitoring glaucoma progression with visual evoked potentials of the blue-sensitive pathway. Invest Ophthalmol Vis Sci 43:1828–1834PubMed
17.
Falsini B, Colotto A, Porciatti V, Porrello G (1992) Follow-up study with pattern ERG in ocular hypertension and glaucoma patients under timolol maleate treatment. Clin Vision Sci 7:341–347
18.
Ventura L, Porciatti V (2005) Restoration of retinal ganglion cell function in early glaucoma after intraocular pressure reduction. Ophthalmology 1:20–27CrossRef
19.
Papst N, Bopp M, Schnaudigel OE (1984) The pattern evoked electroretinogram associated with elevated intraocular pressure. Graefes Arch Clin Exp Ophthalmol 222:34–37PubMedCrossRef
20.
Arden GB, O’Sullivan F (1992) Longitudinal follow up of glaucoma suspects tested with pattern electroretinogram. Bull Soc Belge Ophtalmol 244:147–154PubMed
21.
Nesher R, Trick GL, Kass MA, Gordon MO (1990) Steady-state pattern electroretinogram following long term unilateral administration of timolol to ocular hypertensive subjects. Doc Ophthalmol 75:101–109PubMedCrossRef
22.
Colotto A, Salgarello T, Giudiceandrea A, De Luca LA, Coppè A, Buzzonetti L, Falsini B (1995) Pattern electroretinogram in treated ocular hypertension: a cross-sectional study after timolol maleate therapy. Ophthalmic Res 27:168–177PubMedCrossRef
23.
Parisi V, Colacino G, Milazzo G, Scuderi AC, Manni G (1999) Effects of nicergoline on the retinal and cortical electrophysiological responses in glaucoma patients: a preliminary open study. Pharmacol Res 40:249–255PubMedCrossRef
24.
Parisi V, Centofanti M, Gandolfi S, Marangoni D, Rossetti L, Tanga L, Tardini M, Traina S, Ungaro N, Vetrugno M, Falsini B (2014) Effects of Coenzyme Q10 in conjunction with vitamin E on retinal-evoked and cortical-evoked responses in patients with open-angle glaucoma. J Glaucoma 23:391–404PubMedCrossRef
25.
Secades JJ, Lorenzo JL (2006) Citicoline: pharmacological and clinical review, 2006 update. Methods Find Exp Clin Pharmacol 28(suppl B):1–56PubMed
26.
Parisi V, Manni GL, Colacino G, Bucci MG (1999) Cytidine-5′-diphosphocholine (Citicoline) improves retinal and cortical responses in patients with glaucoma. Ophthalmology 106:1126–1134PubMedCrossRef
27.
Parisi V (2005) Electrophysiological assessment of glaucomatous visual dysfunction during treatment with Cytidine-5′-diphosphocholine (citicoline): a study of 8 years of follow-up. Doc Ophthalmol 110:91–102PubMedCrossRef
28.
Parisi V, Coppola G, Centofanti M, Oddone F, Angrisani AM, Ziccardi L, Ricci B, Quaranta L, Manni G (2008) Evidence of the neuroprotective role of citicoline in glaucoma patients. Prog Brain Res 173:541–554PubMedCrossRef
29.
30.
Virno M, Pecori-Giraldi J, Liguori A, De Gregorio F (2000) 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 Scand Suppl 232:56–57PubMedCrossRef
31.
Ottobelli L, Manni GL, Centofanti M, Iester M, Allevena F, Rossetti L (2013) Citicoline oral solution in glaucoma: is there a role in slowing disease progression? Ophthalmologica 229:219–226PubMedCrossRef
32.
Fresina M, Dickmann A, Salerni A, De Gregorio F, Campos EC (2008) Effect of oral CDP-choline on visual function in young amblyopic patients. Graefes Arch Clin Exp Ophthalmol 246:143–150PubMedCrossRef
33.
Porciatti V, Schiavi C, Benedetti P, Baldi A, Campos EC (1998) Cytidine-5 ′-diphosphocholine improves visual acuity, contrast sensitivity and visually evoked potentials of amblyopic subjects. Curr Eye Res 17:141–148PubMedCrossRef
34.
Parisi V, Coppola G, Ziccardi L, Gallinaro G, Falsini B (2008) Cytidine-5′ -diphosphocholine (citicoline): a pilot study in patients with nonarteritic ischaemic optic neuropathy. Eur J Neurol 15:465–474PubMedCrossRef
35.
Roberti G, Tanga L, Parisi V, Sampalmieri M, Centofanti M, Manni G (2014) A preliminary study of the neuroprotective role of citicoline eye drops in glaucomatous optic neuropathy. Indian J Ophthalmol 62:549–553PubMedCentralPubMedCrossRef
36.
Parisi V, Scarale ME, Balducci N, Fresina M, Campos EC (2010) Electrophysiological detection of delayed post-retinal neural conduction in human amblyopia. Invest Ophthalmol Vis Sci 51:5041–5048PubMedCrossRef
37.
Parisi V, Miglior S, Manni G, Centofanti M, Bucci MG (2006) Clinical ability of pattern electroretinograms and visual evoked potentials in detecting visual dysfunction in ocular hypertension and glaucoma. Ophthalmology 113:216–228PubMedCrossRef
38.
Bach M, Brigell MG, Hawlina M, Holder GE, Johnson MA, McCulloch DL, Meigen T, Viswanathan S (2013) ISCEV standard for clinical pattern electroretinography (PERG) – 2012 update. Doc Ophthalmol 126:1–7PubMedCrossRef
39.
Odom JV, Bach M, Brigell M, Holder GE, McCulloch DL, Tormene AP, Vaegan (2010) ISCEV standard for clinical visual evoked potentials (2009 update). Doc Ophthalmol 120:111–119PubMedCrossRef
40.
Fiorentini A, Maffei L, Pirchio M, Spinelli D, Porciatti V (1981) The ERG in response to alternating gratings in patients with diseases of the peripherheral visual pathway. Invest Ophthalmol Vis Sci 21:490–493PubMed
41.
Hawlina M, Konec B (1992) New non-corneal HK-loop electrode for clinical electroretinography. Doc Ophthalmol 81:253–259PubMedCrossRef
42.
Porciatti V, Falsini B (1993) Inner retina contribution to the flicker electroretinogram: a comparison with the pattern electroretinogram. Clin Vision Sci 8:435–447
43.
Jasper HH (1958) The ten-twenty electrode system of the international federation of electroencephalography. Electronceph Clin Neurophysiol 10:371–375
44.
Quigley HA, Sanchez RM, Dunkelberger GR, L’Hernault NL, Baginski TA (1987) Chronic glaucoma selectively damages large optic nerve fibers. Invest Ophthalmol Vis Sci 28:913–920PubMed
45.
Quigley HA, Dunkelberger GR, Green WR (1988) Chronic human glaucoma causing selectively greater loss of large optic nerve fibers. Ophthalmology 95:357–363PubMedCrossRef
46.
Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zack DJ (1995) Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci 36:774–786PubMed
47.
Orzalesi N, Miglior S, Lonati C, Rosetti L (1998) Microperimetry of localized retinal nerve fiber layer defects. Vision Res 38:763–771PubMedCrossRef
48.
Shuman JS, Hee MR, Puliafito CA, Wong C, Pedut-Kloizman T, Lin CP, Hertzmark E, Izatt JA, Swanson EA, Fujimoto JG (1995) Quantification of nerve layer thickness in normal and glaucomatous eyes using optical coherence tomography. Arch Ophthalmol 113:586–596CrossRef
49.
Falsini B, Colotto A, Porciatti V, Buzzonetti L, Coppe’ A, De Luca LA (1991) Macular flicker-and pattern ERGs are differently affected in ocular hypertension and glaucoma. Clin Vision Sci 6:422–429
50.
Holopigian K, Seiple W, Greenstein VC (1993) Electrophysiological evidence for outer retinal deficits in primary open angle glaucoma. Invest Ophthalmol Vis Sci 34(supp):1269
51.
Holder GE (1997) The pattern electroretinogram in anterior visual pathways dysfunction and its relationship to the pattern visual evoked potential: a personal clinical review of 743 eyes. Eye 11:924–934PubMedCrossRef
52.
Viswanathan S, Frishman LJ, Robson JG (2000) The uniform field and pattern ERG in macaques with experimental glaucoma: removal of spiking activity. Invest Ophthalmol Vis Sci 41:2797–2810PubMed
53.
Viswanathan S, Frishman LJ, Robson JG, Harwerth RS, Smith EL 3rd (1999) The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma. Invest Ophthalmol Vis Sci 40:1124–1136PubMed
54.
Bode SF, Jehle T, Bach M (2011) Pattern electroretinogram in glaucoma suspects: new findings from a longitudinal study. Invest Ophthalmol Vis Sci 52:4300–4306PubMedCrossRef
55.
Bach M, Unsoeld AS, Philippin H, Staubach F, Maier P, Walter HS, Bomer TG, Funk J (2006) Pattern ERG as an early glaucoma indicator in ocular hypertension: a long-term, prospective study. Invest Ophthalmol Vis Sci 47:4881–4887PubMedCrossRef
56.
Bach M, Poloschek CM (2013) Electrophysiology and glaucoma: current status and future challenges. Cell Tissue Res 353:287–296PubMedCrossRef
57.
Kennedy EP (1957) Biosynthesis of phospholipides. Fed Proc 16:847–853PubMed
58.
Goracci G, Francescangeli E, Mozzi R, Porcellati S, Porcellati G (1985) Regulation of phospholipid metabolism by nucleotides in brain and transport of CDP-choline into brain. In: Zappia V, Kennedy EP, Nilsson BI, Galletti P (eds) Novel biochemical, pharmacological and clinical aspects of cytidine-diphosphocholine. Elsevier, New York, pp 105–109
59.
Secades JJ, Frontera G (1995) CDP-choline: pharmacological and clinical review. Methods Find Exp Clin Pharmacol 17(suppl B):1–54PubMed
60.
Weiss GB (1995) Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. Life Sci 56:637–660PubMedCrossRef
61.
Oshitari T, Fujimoto N, Adachi-Usami E (2002) Citicoline has a protective effect on damaged retinal ganglion cells in mouse culture retina. Neuroreport 13:2109–2111PubMedCrossRef
62.
Oshitari T, Yoshida-Hata N, Yamamoto S (2010) Effect of neurotrophic factors on neuronal apoptosis and neurite regeneration in cultured rat retinas exposed to high glucose. Brain Res 1346:43–51PubMedCrossRef
63.
Matteucci A, Varano M, Gaddini L, Mallozzi C, Villa M, Pricci F, Malchiodi-Albedi F (2014) Neuroprotective effects of citicoline in in vitro models of retinal neurodegeneration. Int J Mol Sci 15:6286–6297PubMedCentralPubMedCrossRef
64.
Gupta N, Yucel YH (2003) Brain changes in glaucoma. Eur J Ophthalmol 3(suppl):32–35
65.
Yucel YH, Zhang Q, Weinreb RN, Kaufman PL, Gupta N (2003) Effects of retinal ganglion cell loss on magno-, parvo-, koniocellular pathways in the lateral geniculate nucleus and visual cortex in glaucoma. Prog Retin Eye Res 22:465–481PubMedCrossRef
66.
Chaturvedi N, Hedley-Whyte T, Dreyer EB (1993) Lateral geniculate nucleus in Glaucoma. Am J Ophthalmol 116:182–188PubMedCrossRef
67.
68.
Gottlob I, Stangler-Zuschrott E (1990) Effect of levodopa on contrast sensitivity and scotomas in human amblyopia. Invest Ophthalmol Vis Sci 31:776–780PubMed
69.
Gottlob I, Charlier J, Reinecke RD (1992) Visual acuities and scotomas after one week levodopa administration in human amblyopia. Invest Ophthalmol Vis Sci 33:2722–2728PubMed
70.
Leguire LE, Rogers GL, Bremer DL, Walson PD, McGregor ML (1993) Levodopa/carbidopa for childhood amblyopia. Invest Ophthalmol Vis Sci 34:3090–3095PubMed
71.
Eberhardt R, Birbamer G, Gerstenbrand F, Rainer E, Traegner H (1990) Citicoline in the treatment of Parkinson’s disease. Clin Ther 12:489–495PubMed
Metadata
Title
Treatment with citicoline eye drops enhances retinal function and neural conduction along the visual pathways in open angle glaucoma
Authors
Vincenzo Parisi
Marco Centofanti
Lucia Ziccardi
Lucia Tanga
Manuele Michelessi
Gloria Roberti
Gianluca Manni
Publication date
01-08-2015
Publisher
Springer Berlin Heidelberg
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 8/2015
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-015-3044-9

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