Abstract
Background
To determine the effect of memantine on axonal loss and visual function during the course of optic neuritis (ON).
Methods
Sixty ON patients in a single-center, institutional setting were randomly assigned to the memantine or placebo groups. Patients with first attack of acute unilateral optic neuritis, with visual symptoms of 8 days’ duration or less were enrolled in this trial. No patient had known multiple sclerosis, and none had taken immunomodulatory agent prior to or at the time of presentation. For all patients, the following characteristics were recorded and compared at initial presentation and 3 months afterward: visual acuity, retinal nerve fiber layer (RNFL) thickness, visual field parameters (mean deviation and pattern standard deviation), visual evoked potential, and contrast sensitivity.
Results
Fifty-four patients completed the 3-month follow up. There were no significant differences between the placebo and memantine groups for any of the characteristics at initial presentation. After 3 months, the only statistically significant difference between the two groups was in RNFL thickness. Memantine group subjects had higher thickness in nasal (P = 0.01), superior (P = 0.006), inferior (P = 0.01) quadrants and average (P = 0.01). However, temporal quadrant thickness was not different between two groups (P = 0.35).
Conclusion
Memantine was effective in reduction of RNFL thinning, although this structural difference was not associated with improved visual function.
Similar content being viewed by others
References
Smith CH (2005) Optic neuritis. In: Miller NR, Newman NJ (eds) Walsh and Hoyt’s clinical neuro-ophthalmology. Lippincott Williams & Wilkins, Baltimore, pp 293–349
Costello F, Coupland S, Hodge W, Lorello GR, Koroluk J, Pan YI, Freedman MS, Zackon DH, Kardon RH (2006) Quantifying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol 59:963–969
Klistorner A, Arvind H, Nguyen T, Garrick R, Paine M, Graham S, O’Day J, Grigg J, Billson F, Yiannikas C (2008) Axonal loss and myelin in early ON loss in postacute optic neuritis. Ann Neurol 64:325–331
Trip SA, Schlottmann PG, Jones SJ, Altmann DR, Garway-Heath DF, Thompson AJ, Plant GT, Miller DH (2005) Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis. Ann Neurol 58:383–391
Henderson AP, Altmann DR, Trip AS, Kallis C, Jones SJ, Schlottmann PG, Garway-Heath DF, Plant GT, Miller DH (2010) A serial study of retinal changes following optic neuritis with sample size estimates for acute neuroprotection trials. Brain 133:2592–2602
Costello F, Hadge W, Pan YI, Eggenberger E, Coupland S, Kardon RH (2008) Tracking retinal nerve fiber layer loss after optic neuritis: a prospective study using optical coherence tomography. Mult Scler 14:893–905
Lamirel C, Newman NJ, Biousse V (2010) Optical coherence tomography in optic neuritis and MS. Rev Neurol (Paris) 166:978–986
Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ (2003) Memantine Study Group. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 348:1333–1341
Beck RW, Cleary PA, Trobe JD, Dl K, Kupersmith MT, Paty DW, Brown CH (1993) The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis—The Optic Neuritis Study Group. N Engl J Med 329:1764–1769
Odom JV, Bach M, Barber C, Brigell M, Marmor MF, Tormene AP, Holder GE, Vaegan (2004) Visual evoked potentials standard. Doc Ophthalmol 108:115–123
Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS (2005) Diagnostic criteria for multiple sclerosis 2005 ravision to the "Mcdonald criteria". Ann Neurol 58:840–846
Basso AS, Frenkel D, Quintana FJ, Costa-Pinto FA, Petrovic-Stojkovic S, Puckett L, Monsonego A, Bar-Shir A, Engel Y, Gozin M, Weiner HL (2008) Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis. J Clin Invest 118:1532–1543
Sepulcre J, Murie-Femandez M, Salinas-Alaman A, Garcia-Layana A, Bejarano B, Villoslada P (2007) Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS. Neurology 68:1488–1494
Han IC, Jaffe GJ (2009) Comparison of spectral- and time-domain optical coherence tomography for retinal thickness measurements in healthy and diseased eyes. Am J Ophthalmol 147:847–858
Naismith RT, Tutlam NT, Xu J, Shepherd JB, Klawiter EC, Song SK et al (2009) Optical coherence tomography is less sensitive than visual evoked potentials in optic neuritis. Neurology 73:46–52
Danesh-Meyer HV, Levin LA (2009) Neuroprotection: extrapolating from neurologic diseases to the eye. Am J Ophthalmol 148:186–191
Hare WA, WoldeMussie E, Lai RK et al (2004) Efficacy and safety of memantine treatment for reduction of changes associated with experimental glaucoma in monkey, L functional measures. Invest Ophthalmol Vis Sci 45:2625–2639
Yücel YH, Gupta N, Zhang Q, Mizisin AP, Kalichman MW, Weinreb RN (2006) Memantine protects neurons from shrinkage in the lateral geniculate nucleus in experimental glaucoma. Arch Ophthalmol 124:217–225
Wallström E, Diener P, Ljungdahl A, Khademi M, Nilsson CG, Olsson T (1996) Memantine abrogates neurological deficits, but not CNS inflammation, in Lewis rat experimental autoimmune encephalomyelitis. J Neurol Sci 137:89–96
Paul C, Bolton C (2002) Modulation of blood–brain barrier dysfunction and neurological deficits during acute experimental allergic encephalomyelitis by the N-methyl-D-aspartate receptor antagonist memantine. J Pharmacol Exp Ther 302:50–57
Pitt D, Werner P, Raine CS (2000) Glutamate excitotoxicity in a model of multiple sclerosis. Nat Med 6:67–70
Matute C, Sánchez-Gómez MV, Martínez-Millán L, Miledi R (1997) Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes. Proc Natl Acad Sci U S A 94:8830–8835
Bock M, Brandt AU, Dörr J, Kraft H, Weinges-Evers N, Gaede G, Pfueller CF, Herges K, Radbruch H, Ohlraun S, Bellmann-Strobl J, Kuchenbecker J, Zipp F, Paul F (2010) Patterns of retinal nerve fiber layer loss in multiple sclerosis patients with or without optic neuritis and glaucoma patients. Clin Neurol Neurosurg 112:647–652
Talman LS, Bisker ER, Sackel DJ, Long DA Jr, Galetta KM, Ratchford JN, Lile DJ, Farrell SK, Loguidice MJ, Remington G, Conger A, Frohman TC, Jacobs DA, Markowitz CE, Cutter GR, Ying GS, Dai Y, Maguire MG, Galetta SL, Frohman EM, Calabresi PA, Balcer LJ (2010) Longitudinal study of vision and retinal nerve fiber layer thickness in multiple sclerosis. Ann Neurol 67:749–760
Danesh-Meyer HV, Carroll SC, Foroozan R, Savino PJ, Fan J, Jiang Y, Vander Hoorn S (2006) Relationship between retinal nerve fiber layer and visual field sensitivity as measured by optical coherence tomography in chiasmal compression. Invest Ophthalmol Vis Sci 47:4827–4835
Acknowledgements
Contributions of authors: design of the study (MRE, ZAH, MAF, MM), conduct of the study (MN, MA, AM). Authors are grateful to Dr.Ebrahimi (University of Pharmacology) for his support in preparing the drugs. The study was carried out with the approval of the research ethics committee of Tehran University. Informed consent was obtained from all patients, and the study was conducted in accordance with declaration of Helsinki. Clinical Trials registration: Australian New Zealand Clinical Trial Registry, 12609000111279.
Author information
Authors and Affiliations
Corresponding author
Additional information
This study was supported by grants from Tehran University of Medical Science. The authors do not have any financial interests to disclose. The authors have full control of all primary data, and they agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data upon request. Clinical Trials registration: Australian New Zealand Clinical Trial Registry, 12609000111279.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Appendices A (1)
Baseline characteristic of all patients (VA: visual acuity; RNFL: retinal nerve fiber layer). (DOCX 37 kb)
Appendices A (2)
Patients’ data at 3 months. (VA: visual acuity; RNFL: retinal nerve fiber layer thickness (μm); MD: mean deviation of visual field; PSD: pattern standard deviation of visual field; P100: values of the time-to-peak of P100 (msec) of visual evoked potential) (DOCX 34 kb)
Rights and permissions
About this article
Cite this article
Esfahani, M.R., Harandi, Z.A., Movasat, M. et al. Memantine for axonal loss of optic neuritis. Graefes Arch Clin Exp Ophthalmol 250, 863–869 (2012). https://doi.org/10.1007/s00417-011-1894-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00417-011-1894-3