J Clin Neurol.  2015 Jul;11(3):241-247. 10.3988/jcn.2015.11.3.241.

Benign Multiple Sclerosis is Associated with Reduced Thinning of the Retinal Nerve Fiber and Ganglion Cell Layers in Non-Optic-Neuritis Eyes

Affiliations
  • 1Division of Neurology, Department of Clinical and Experimental Medicine, Linkoping University Hospital, Linkoping, Sweden. yumin.link@ regionostergotland.se
  • 2Department of Occupational and Environmental Medicine and Linkoping Academic Research Center (LARC), Linkoping University, Linkoping, Sweden.
  • 3Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.

Abstract

BACKGROUND AND PURPOSE
It is exceedingly difficult to differentiate benign multiple sclerosis (BMS) from relapsing-remitting multiple sclerosis (RRMS) based on clinical characteristics, neuroimaging, and cerebrospinal fluid tests. Optical coherence tomography (OCT) allows quantification of retinal structures, such as the retinal nerve fiber layer (RNFL) thickness, at the optic disc and the ganglion cell layer (GCL) at the macula, on a micrometer scale. It can also be used to trace minor alterations and the progression of neurodegeneration, help predict BMS, and influence the choice of therapy. To utilize OCT to detect the extent of changes of the optic disk and macular microstructure in patients with BMS and RRMS compared to healthy controls (HCs), with special focus on changes related to the presence/absence of optic neuritis (ON).
METHODS
Spectral-domain OCT was applied to examine eyes from 36 patients with multiple sclerosis (MS), comprising 11 with BMS and 25 with RRMS, and 34 HCs.
RESULTS
The RNFL and GCL were significantly thinner in eyes previously affected by ON, irrespective of the type of MS (i.e., BMS or RRMS), than in HCs. Significant thinning of the GCL was also observed in non-ON RRMS (and not non-ON BMS) compared to HCs. Correspondingly, a significant association between disease duration and thinning rates of the RNFL and GCL was observed only in non-ON RRMS (-0.54+/-0.24 and -0.43+/-0.21 microm/year, mean+/-SE; p<0.05 for both), and not in non-ON BMS (-0.11+/-0.27 and -0.24+/-0.24 microm/year).
CONCLUSIONS
The RNFL and GCL were thinner in both ON- and non-ON MS, but the change was more pronounced in ON MS, irrespective of the MS subtype studied herein. GCL thinning and the thinning rate of both the GCL and RNFL were less pronounced in non-ON BMS than in non-ON RRMS. These findings may help to predict the course of BMS.

Keyword

benign multiple sclerosis; optic neuritis; optical coherence tomography; retinal nerve fiber layer; macular ganglion cell layer

MeSH Terms

Cerebrospinal Fluid
Ganglion Cysts*
Humans
Multiple Sclerosis*
Multiple Sclerosis, Relapsing-Remitting
Nerve Fibers*
Neuroimaging
Optic Disk
Optic Neuritis
Retinaldehyde*
Tomography, Optical Coherence
Retinaldehyde

Figure

  • Fig. 1 Optical coherence tomography (OCT) measurements in a healthy subject. A: Peripapillary measures centered on the optic disc. B: Macular measures centered on the fovea. C: High-resolution OCT image of the retinal microstructure. ELM: external limiting membrane, GCL: ganglion cell layer, ILM: inner limiting membrane, INL: inner nuclear layer, IPL: inner plexiform layer, IS/OS: inner/outer photoreceptor segments, NFL: nerve fiber layer, ONL: outer nuclear layer, OPL: outer plexiform layer, RPE: retinal pigment epithelium.


Reference

1. Pittock SJ, McClelland RL, Mayr WT, Jorgensen NW, Weinshenker BG, Noseworthy J, et al. Clinical implications of benign multiple sclerosis: a 20-year population-based follow-up study. Ann Neurol. 2004; 56:303–306.
Article
2. Sayao AL, Devonshire V, Tremlett H. Longitudinal follow-up of "benign" multiple sclerosis at 20 years. Neurology. 2007; 68:496–500.
Article
3. Hirst C, Ingram G, Pickersgill T, Swingler R, Compston DA, Robertson NP. Increasing prevalence and incidence of multiple sclerosis in South East Wales. J Neurol Neurosurg Psychiatry. 2009; 80:386–391.
Article
4. Glad SB, Aarseth JH, Nyland H, Riise T, Myhr KM. Benign multiple sclerosis: a need for a consensus. Acta Neurol Scand Suppl. 2010; (190):44–50.
Article
5. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983; 33:1444–1452.
Article
6. Goodin DS, Frohman EM, Garmany GP Jr, Halper J, Likosky WH, Lublin FD, et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 2002; 58:169–178.
Article
7. Comi G. Clinically isolated syndrome: the rationale for early treatment. Nat Clin Pract Neurol. 2008; 4:234–235.
Article
8. Parisi V, Manni G, Spadaro M, Colacino G, Restuccia R, Marchi S, et al. Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest Ophthalmol Vis Sci. 1999; 40:2520–2527.
9. Costello F, Coupland S, Hodge W, Lorello GR, Koroluk J, Pan YI, et al. Quantifying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol. 2006; 59:963–969.
Article
10. Gallo A, Esposito F, Sacco R, Docimo R, Bisecco A, Della Corte M, et al. Visual resting-state network in relapsing-remitting MS with and without previous optic neuritis. Neurology. 2012; 79:1458–1465.
Article
11. Klistorner A, Garrick R, Barnett MH, Graham SL, Arvind H, Sriram P, et al. Axonal loss in non-optic neuritis eyes of patients with multiple sclerosis linked to delayed visual evoked potential. Neurology. 2013; 80:242–245.
Article
12. Sriram P, Wang C, Yiannikas C, Garrick R, Barnett M, Parratt J, et al. Relationship between optical coherence tomography and electrophysiology of the visual pathway in non-optic neuritis eyes of multiple sclerosis patients. PLoS One. 2014; 9:e102546.
Article
13. Oberwahrenbrock T, Ringelstein M, Jentschke S, Deuschle K, Klumbies K, Bellmann-Strobl J, et al. Retinal ganglion cell and inner plexiform layer thinning in clinically isolated syndrome. Mult Scler. 2013; 19:1887–1895.
Article
14. Oberwahrenbrock T, Schippling S, Ringelstein M, Kaufhold F, Zimmermann H, Keser N, et al. Retinal damage in multiple sclerosis disease subtypes measured by high-resolution optical coherence tomography. Mult Scler Int. 2012; 2012:530305.
Article
15. Ratchford JN, Saidha S, Sotirchos ES, Oh JA, Seigo MA, Eckstein C, et al. Active MS is associated with accelerated retinal ganglion cell/inner plexiform layer thinning. Neurology. 2013; 80:47–54.
Article
16. Nolan R, Gelfand JM, Green AJ. Fingolimod treatment in multiple sclerosis leads to increased macular volume. Neurology. 2013; 80:139–144.
Article
17. Winges KM, Werner JS, Harvey DJ, Cello KE, Durbin MK, Balcer LJ, et al. Baseline retinal nerve fiber layer thickness and macular volume quantified by OCT in the North American phase 3 fingolimod trial for relapsing-remitting multiple sclerosis. J Neuroophthalmol. 2013; 33:322–329.
Article
18. Dinkin M, Paul F. Higher macular volume in patients with MS receiving fingolimod: positive outcome or side effect? Neurology. 2013; 80:128–129.
Article
19. Galetta KM, Graves J, Talman LS, Lile DJ, Frohman EM, Calabresi PA, et al. Visual pathway axonal loss in benign multiple sclerosis: a longitudinal study. J Neuroophthalmol. 2012; 32:116–123.
20. Lange AP, Zhu F, Sayao AL, Sadjadi R, Alkabie S, Traboulsee AL, et al. Retinal nerve fiber layer thickness in benign multiple sclerosis. Mult Scler. 2013; 19:1275–1281.
Article
21. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005; 58:840–846.
Article
22. Link H, Huang YM. Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness. J Neuroimmunol. 2006; 180:17–28.
Article
23. Walter SD, Ishikawa H, Galetta KM, Sakai RE, Feller DJ, Henderson SB, et al. Ganglion cell loss in relation to visual disability in multiple sclerosis. Ophthalmology. 2012; 119:1250–1257.
Article
24. Prasad S, Galetta SL. Anatomy and physiology of the afferent visual system. Handb Clin Neurol. 2011; 102:3–19.
Article
25. Fisher JB, Jacobs DA, Markowitz CE, Galetta SL, Volpe NJ, Nano-Schiavi ML, et al. Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology. 2006; 113:324–332.
Article
26. Saidha S, Sotirchos ES, Oh J, Syc SB, Seigo MA, Shiee N, et al. Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis. JAMA Neurol. 2013; 70:34–43.
Article
27. Syc SB, Saidha S, Newsome SD, Ratchford JN, Levy M, Ford E, et al. Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis. Brain. 2012; 135(Pt 2):521–533.
Article
28. Martínez-Lapiscina EH, Ortiz-Pérez S, Fraga-Pumar E, Martínez-Heras E, Gabilondo I, Llufriu S, et al. Colour vision impairment is associated with disease severity in multiple sclerosis. Mult Scler. 2014; 20:1207–1216.
Article
29. Keller J, Sánchez-Dalmau BF, Villoslada P. Lesions in the posterior visual pathway promote trans-synaptic degeneration of retinal ganglion cells. PLoS One. 2014; 9:e97444.
Article
30. Harwerth RS, Wheat JL, Rangaswamy NV. Age-related losses of retinal ganglion cells and axons. Invest Ophthalmol Vis Sci. 2008; 49:4437–4443.
Article
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