CNS Drugs

, Volume 32, Issue 8, pp 763–770 | Cite as

The Effect of Glatiramer Acetate on Retinal Nerve Fiber Layer Thickness in Patients with Relapsing–Remitting Multiple Sclerosis: A Longitudinal Optical Coherence Tomography Study

  • Robert ZivadinovEmail author
  • Eleonora Tavazzi
  • Jesper Hagemeier
  • Ellen Carl
  • David Hojnacki
  • Channa Kolb
  • Bianca Weinstock-Guttman
Original Research Article



Optical coherence tomography (OCT) is a technique that allows for the assessment of retinal nerve fiber layer thickness (RNFLT) and total macular volume (TMV), which reflect neuroaxonal integrity within the retina. As such it has been used in multiple sclerosis (MS) to study neurodegeneration. Glatiramer acetate (GA) is a widely used treatment for MS, which is suggested to have a possible neuroprotective role.


The aim of this study was to assess RFNLT and TMV changes in relapsing–remitting MS (RRMS) patients who started treatment with GA and were followed for a 24-month period.


A cohort of 60 RRMS patients and 40 healthy controls (HCs) were imaged with OCT at baseline and follow-up. All subjects also underwent clinical and neurological examination. Measurements were compared between the RRMS patients and HCs as well as between optic neuritis (ON)-affected and ON-unaffected eyes.


At baseline, MS patients showed lower average RNFLT (p = 0.046) and TMV (p = 0.013) when compared with HCs. No significant differences in the evolution of OCT measures were detected over the follow-up between MS patients and HCs. MS patients with both affected and unaffected eyes showed significantly lower average RNFLT, temporal inferior RNFLT, and TMV at baseline, compared with HCs. No significant differences between ON-affected and ON-unaffected eyes in MS patients were detected over the follow-up, except for the nasal superior RNFLT (p = 0.019).


This study suggests a beneficial role of GA on retinal axonal degeneration in MS, and further confirms the utility of OCT to monitor the neuroprotective effect of disease-modifying treatment.



We acknowledge the contribution of Dejan Jakimovski for the technical part of the OCT protocol.

Compliance with Ethical Standards


This study was supported by an investigator-initiated grant from Teva Pharmaceuticals, Inc.

Conflict of interest

Robert Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Claret Medical, Celgene, and Novartis for speaking and consultant fees. He received financial support for research activities from Teva Pharmaceuticals, Biogen, Genzyme-Sanofi, Novartis, Claret Medical, Intekrin-Coherus, Protembis, and IMS Health. Eleonora Tavazzi, Jesper Hagemeier, and Ellen Carl have nothing to disclose. Channa Kolb has received speaker honoraria and consultant fees from EMD Serono, Teva Pharmaceuticals, Acorda, Novartis, Genzyme, and Biogen-Idec. David Hojnacki has received speaker honoraria and consultant fees from Biogen-Idec, Teva Pharmaceutical Industries Ltd., EMD Serono, Pfizer Inc., and Novartis. Bianca Weinstock- Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Sanofi Genzyme, Novartis, and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Sanofi Genzyme, Novartis, and Acorda.


  1. 1.
    Zivadinov R, et al. Clinical relevance of brain atrophy assessment in multiple sclerosis. Implications for its use in a clinical routine. Expert Rev Neurother. 2016;16(7):777–93.CrossRefGoogle Scholar
  2. 2.
    Johnson KP, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology. 1995;45(7):1268–76.CrossRefGoogle Scholar
  3. 3.
    Comi G, Filippi M, Wolinsky JS. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging–measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Glatiramer Acetate Study Group. Ann Neurol. 2001;49(3):290–7.CrossRefGoogle Scholar
  4. 4.
    Khan O, et al. Three times weekly glatiramer acetate in relapsing-remitting multiple sclerosis. Ann Neurol. 2013;73(6):705–13.CrossRefGoogle Scholar
  5. 5.
    Arnold DL, Narayanan S, Antel S. Neuroprotection with glatiramer acetate: evidence from the PreCISe trial. J Neurol. 2013;260(7):1901–6.CrossRefGoogle Scholar
  6. 6.
    Zivadinov R, et al. Glatiramer acetate recovers microscopic tissue damage in patients with multiple sclerosis. A case-control diffusion imaging study. Pathophysiology. 2011;18(1):61–8.CrossRefGoogle Scholar
  7. 7.
    Khan O, et al. Axonal metabolic recovery and potential neuroprotective effect of glatiramer acetate in relapsing-remitting multiple sclerosis. Mult Scler. 2005;11(6):646–51.CrossRefGoogle Scholar
  8. 8.
    Balk LJ, et al. Timing of retinal neuronal and axonal loss in MS: a longitudinal OCT study. J Neurol. 2016;263(7):1323–31.CrossRefGoogle Scholar
  9. 9.
    Brandt AU, et al. Monitoring the course of MS with optical coherence tomography. Curr Treat Options Neurol. 2017;19(4):15.CrossRefGoogle Scholar
  10. 10.
    Grazioli E, et al. Retinal nerve fiber layer thickness is associated with brain MRI outcomes in multiple sclerosis. J Neurol Sci. 2008;268(1–2):12–7.CrossRefGoogle Scholar
  11. 11.
    Gupta S, et al. Optical coherence tomography and neurodegeneration: are eyes the windows to the brain? Expert Rev Neurother. 2016;16(7):765–75.CrossRefGoogle Scholar
  12. 12.
    Button J, et al. Disease-modifying therapies modulate retinal atrophy in multiple sclerosis: a retrospective study. Neurology. 2017;88(6):525–32.CrossRefGoogle Scholar
  13. 13.
    Polman CH, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292–302.CrossRefGoogle Scholar
  14. 14.
    Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996;46(4):907–11.CrossRefGoogle Scholar
  15. 15.
    Zivadinov R, et al. Cerebral microbleeds in multiple sclerosis evaluated on susceptibility-weighted images and quantitative susceptibility maps: a case–control study. Radiology. 2016;281(3):884–95.CrossRefGoogle Scholar
  16. 16.
    Tewarie P, et al. The OSCAR-IB consensus criteria for retinal OCT quality assessment. PLoS One. 2012;7(4):e34823.CrossRefGoogle Scholar
  17. 17.
    Zivadinov R, et al. Retinal nerve fiber layer thickness and thalamus pathology in multiple sclerosis patients. Eur J Neurol. 2014;21(8):1137-e61.CrossRefGoogle Scholar
  18. 18.
    Syc SB, et al. Reproducibility of high-resolution optical coherence tomography in multiple sclerosis. Mult Scler. 2010;16(7):829–39.CrossRefGoogle Scholar
  19. 19.
    West B, Welch K, Galecki A. A practical guide using statistical software. London: Chapman & Hall/CRC; 2006. ISBN 978-1-584-88480-4.Google Scholar
  20. 20.
    Behbehani R, et al. Optical coherence tomography segmentation analysis in relapsing remitting versus progressive multiple sclerosis. PLoS One. 2017;12(2):e0172120.CrossRefGoogle Scholar
  21. 21.
    Garcia-Martin E, et al. Risk factors for progressive axonal degeneration of the retinal nerve fibre layer in multiple sclerosis patients. Br J Ophthalmol. 2011;95(11):1577–82.CrossRefGoogle Scholar
  22. 22.
    El Ayoubi NK, et al. Retinal measures correlate with cognitive and physical disability in early multiple sclerosis. J Neurol. 2016;263(11):2287–95.CrossRefGoogle Scholar
  23. 23.
    Green AJ, et al. Ocular pathology in multiple sclerosis: retinal atrophy and inflammation irrespective of disease duration. Brain. 2010;133(Pt 6):1591–601.CrossRefGoogle Scholar
  24. 24.
    Reich DS, et al. Damage to the optic radiation in multiple sclerosis is associated with retinal injury and visual disability. Arch Neurol. 2009;66(8):998–1006.CrossRefGoogle Scholar
  25. 25.
    Ratchford JN, et al. Active MS is associated with accelerated retinal ganglion cell/inner plexiform layer thinning. Neurology. 2013;80(1):47–54.CrossRefGoogle Scholar
  26. 26.
    Aharoni R. The mechanism of action of glatiramer acetate in multiple sclerosis and beyond. Autoimmun Rev. 2013;12(5):543–53.CrossRefGoogle Scholar
  27. 27.
    Spadaro M, et al. Biological activity of glatiramer acetate on Treg and anti-inflammatory monocytes persists for more than 10 years in responder multiple sclerosis patients. Clin Immunol. 2017;181:83–8.CrossRefGoogle Scholar
  28. 28.
    Arnon R, Aharoni R. Neurogenesis and neuroprotection in the CNS–fundamental elements in the effect of Glatiramer acetate on treatment of autoimmune neurological disorders. Mol Neurobiol. 2007;36(3):245–53.CrossRefGoogle Scholar
  29. 29.
    Toledo J, et al. Retinal nerve fiber layer atrophy is associated with physical and cognitive disability in multiple sclerosis. Mult Scler. 2008;14(7):906–12.CrossRefGoogle Scholar
  30. 30.
    Gordon-Lipkin E, et al. Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology. 2007;69(16):1603–9.CrossRefGoogle Scholar
  31. 31.
    Filippi M, Preziosa P, Rocca MA. Microstructural MR imaging techniques in multiple sclerosis. Neuroimaging Clin N Am. 2017;27(2):313–33.CrossRefGoogle Scholar
  32. 32.
    Barkhof F. MRI in multiple sclerosis: correlation with expanded disability status scale (EDSS). Mult Scler. 1999;5(4):283–6.CrossRefGoogle Scholar
  33. 33.
    Hackmack K, et al. Can we overcome the ‘clinico-radiological paradox’ in multiple sclerosis? J Neurol. 2012;259(10):2151–60.CrossRefGoogle Scholar
  34. 34.
    Saidha S, et al. Optical coherence tomography reflects brain atrophy in multiple sclerosis: a four-year study. Ann Neurol. 2015;78(5):801–13.CrossRefGoogle Scholar
  35. 35.
    Pisa M, et al. No evidence of disease activity is associated with reduced rate of axonal retinal atrophy in MS. Neurology. 2017;89:2469–75.CrossRefGoogle Scholar
  36. 36.
    Garcia-Martin E, et al. Effect of optic neuritis on progressive axonal damage in multiple sclerosis patients. Mult Scler. 2011;17(7):830–7.CrossRefGoogle Scholar
  37. 37.
    Petzold A, et al. Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol. 2017;16(10):797–812.CrossRefGoogle Scholar
  38. 38.
    Cruz-Herranz A, et al. The APOSTEL recommendations for reporting quantitative optical coherence tomography studies. Neurology. 2016;86(24):2303–9.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, Buffalo Neuroimaging Analysis CenterUniversity at Buffalo, State University of New YorkBuffaloUSA
  2. 2.Center for Biomedical Imaging at Clinical and Translational Science InstituteUniversity at Buffalo, State University of New YorkBuffaloUSA
  3. 3.Department of Neurology, School of Medicine and Biomedical Sciences, Jacobs Multiple Sclerosis CenterUniversity at Buffalo, State University of New YorkBuffaloUSA

Personalised recommendations