Memantine for axonal loss of optic neuritis

  • Mohammad Riazi Esfahani
  • Zahra Alami Harandi
  • Morteza Movasat
  • Mojgan Nikdel
  • Mohsen Adelpour
  • Arezo Momeni
  • Hamid Merat
  • Masoud Aghsaei Fard



To determine the effect of memantine on axonal loss and visual function during the course of optic neuritis (ON).


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.


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).


Memantine was effective in reduction of RNFL thinning, although this structural difference was not associated with improved visual function.


Optic neuritis Optical coherence tomography Retinal nerve fiber layer Memantine 

Supplementary material

417_2011_1894_MOESM1_ESM.docx (38 kb)
Appendices A (1)Baseline characteristic of all patients (VA: visual acuity; RNFL: retinal nerve fiber layer). (DOCX 37 kb)
417_2011_1894_MOESM2_ESM.docx (34 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)


  1. 1.
    Smith CH (2005) Optic neuritis. In: Miller NR, Newman NJ (eds) Walsh and Hoyt’s clinical neuro-ophthalmology. Lippincott Williams & Wilkins, Baltimore, pp 293–349Google Scholar
  2. 2.
    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 59:963–969PubMedCrossRefGoogle Scholar
  3. 3.
    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 64:325–331PubMedCrossRefGoogle Scholar
  4. 4.
    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 58:383–391PubMedCrossRefGoogle Scholar
  5. 5.
    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 133:2592–2602PubMedCrossRefGoogle Scholar
  6. 6.
    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 14:893–905PubMedCrossRefGoogle Scholar
  7. 7.
    Lamirel C, Newman NJ, Biousse V (2010) Optical coherence tomography in optic neuritis and MS. Rev Neurol (Paris) 166:978–986CrossRefGoogle Scholar
  8. 8.
    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 348:1333–1341PubMedCrossRefGoogle Scholar
  9. 9.
    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 329:1764–1769PubMedCrossRefGoogle Scholar
  10. 10.
    Odom JV, Bach M, Barber C, Brigell M, Marmor MF, Tormene AP, Holder GE, Vaegan (2004) Visual evoked potentials standard. Doc Ophthalmol 108:115–123PubMedCrossRefGoogle Scholar
  11. 11.
    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 58:840–846PubMedCrossRefGoogle Scholar
  12. 12.
    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 118:1532–1543PubMedCrossRefGoogle Scholar
  13. 13.
    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 68:1488–1494PubMedCrossRefGoogle Scholar
  14. 14.
    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 147:847–858PubMedCrossRefGoogle Scholar
  15. 15.
    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 73:46–52PubMedCrossRefGoogle Scholar
  16. 16.
    Danesh-Meyer HV, Levin LA (2009) Neuroprotection: extrapolating from neurologic diseases to the eye. Am J Ophthalmol 148:186–191PubMedCrossRefGoogle Scholar
  17. 17.
    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 45:2625–2639PubMedCrossRefGoogle Scholar
  18. 18.
    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 124:217–225PubMedCrossRefGoogle Scholar
  19. 19.
    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 137:89–96PubMedCrossRefGoogle Scholar
  20. 20.
    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 302:50–57PubMedCrossRefGoogle Scholar
  21. 21.
    Pitt D, Werner P, Raine CS (2000) Glutamate excitotoxicity in a model of multiple sclerosis. Nat Med 6:67–70PubMedCrossRefGoogle Scholar
  22. 22.
    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 94:8830–8835PubMedCrossRefGoogle Scholar
  23. 23.
    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 112:647–652PubMedCrossRefGoogle Scholar
  24. 24.
    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 67:749–760PubMedGoogle Scholar
  25. 25.
    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 47:4827–4835CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Mohammad Riazi Esfahani
    • 1
  • Zahra Alami Harandi
    • 1
  • Morteza Movasat
    • 1
  • Mojgan Nikdel
    • 1
  • Mohsen Adelpour
    • 1
  • Arezo Momeni
    • 1
  • Hamid Merat
    • 2
  • Masoud Aghsaei Fard
    • 1
  1. 1.Farabi Eye Research Center, Department of OphthalmologyTehran University of Medical SciencesTehranIran
  2. 2.Qazvin University of Medical ScienceQazvinIran

Personalised recommendations