Multiple Sclerosis
well with RNFL thickness in patients with MS: every one-line decrease in low-contrast letter acuity and contrast sensitivity test score was associated with an average 4µm thinning of the RNFL.44
Lower average RNFL thickness was correlated with patients with more active disease and greater Expanded Disability Status Scale (EDSS) at baseline and greater increase of EDSS over two years. The correlations are better in the temporal quadrant.46 Correlations have also been found between RNFL thickness and performance on some tests of cognitive function in MS patients, particularly the symbol digit modality test.45
Some correlations have been shown between RNLF thickness and disease characteristics. In one study RRMS patients who experienced relapses or a disability progression had a significantly thinner average RNLF compared with patients who remained relapse-free over a two-year period.45
Despite some conflicting
In patients with CIS who had no history of ON, our group in Lille failed to find significant differences in RNLF thickness, and changes did not increase the risk of conversion to MS after a six- month period of follow-up.48
results, longitudinal studies have shown a progressive thinning of RNLF thickness over time, with lower values in progressive MS than in RRMS.47
However, our analysis was not performed
using the latest technical methods. Since RNLF thickness may be associated with the degenerative component of MS, OCT measurements and atrophy of the brain, assessed using the brain parenchymal fraction (BPF), were compared. This identified a partial but significant correlation between BPF and minimum RNLF thickness, and the correlation was stronger in RRMS than in PPMS patients.49,50 Determination of axonal thickness in the retina by OCT can therefore provide concurrent information about MRI brain abnormality in MS.
The reliability of OCT in MS was demonstrated in a study in the US. A total of 396 patients with MS and 153 healthy controls were assessed using OCT at three different medical centres; the results showed excellent inter- and intra-rater reproducibility (intra-class correlation [ICC] 0.89 and 0.98, respectively).51
In addition, there was excellent
inter-visit correlation (ICC 0.91). These results indicated that OCT can be reliably performed at different centres to assess MS patients and can be performed by different operators at different times, with the results remaining comparable.
This study will involve a target 60 patients with clinically diagnosed MS with or without ON, and will also determine the mean change in RNFL in both eyes and other ophthalmological parameters. Another study is investigating the correlation between cognition and RNFL thickness determined by OCT in a group of 20 patients with MS who are receiving either natalizumab or an active
The feasibility of using OCT as an alternative to MRI scanning for monitoring the effects of glatiramer acetate versus placebo treatment on the condition of the optic nerve is being assessed in a study in The Netherlands.52
1. Confavreux C, Compston A, McAlpine Multiple Sclerosis: The natural history of multiple sclerosis, Elsevier, 2005;183–269.
2. 3. 4. 5. 6.
Ebers GC, Natural history of multiple sclerosis, J Neurol Neurosurg Psychiatry, 2001;71(Suppl. 2):ii16–19.
Pugliatti M, Rosati G, Carton H, et al., The epidemiology of multiple sclerosis in Europe, Eur J Neurol, 2006;13:700–722.
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Weinshenker BG, Bass B, Rice GP, et al., The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability, Brain, 1989;112(Pt 1):133–46. Koch M, Kingwell E, Rieckmann P, et al., The natural
9. 7. 8.
Patrick Vermersch is a Professor and Head of the Department of Neurology at the University of Lille, which deals with multiple sclerosis (MS) and other neuro- inflammatory diseases. The principal scientific interests of the department are neuroimmunology and markers of disease evolution. Professor Vermersch’s primary interests are clinical neurology, neuroimmunology and therapeutic research in MS, and he is the author or co-author of approximately 220 scientific or educational
papers. Professor Vermersch is President of the Scientific Committee of the Lille University Hospital and participates in many therapeutic protocols in MS. He was Vice President of the Regional Scientific Consultative Committee of INSERM (Institut National de la Santé et de la Recherche Medicale) from 1994 to 1996. He holds doctorates in medicine and cellular biology.
Olivier Outteryck is a Neurologist in the Department of Neurology at the University of Lille, dealing with multiple sclerosis (MS) and other neuro-inflammatory diseases. His research interests are neuro-ophthalmology and magnetic resonance imaging, mainly focused on MS. He has contributed to many therapeutic protocols in MS and is the author or co-author of several published scientific papers. Dr Outteryck graduated in neurology in 2007.
Axel Petzold is a Consultant Neurologist at the Free University Medical Centre in Amsterdam and an Honorary Senior Lecturer in the Department of Clinical Neurosciences at University College London (UCL) Institute of Neurology and the National Hospital for Neurology and Neurosurgery, UCL Hospitals NHS Foundation Trust. His primary clinical interests include axonal degeneration in multiple sclerosis and optic nerve disease and protein biomarkers for neurodegeneration.
His specific focus is the detection, quantification and monitoring of neuronal cell death and axonal degeneration in vivo and in vitro.
comparator.53
These small studies may provide additional evidence justifying the use of OCT as a lower-cost alternative for monitoring MS patients in both clinical trials and clinical practice.
Future Perspectives
Data from longitudinal and multicentre studies comparing OCT scans in patients with different MS subtypes and treatment regimens are limited. In addition, correlations of up-to-date OCT measurements with MRI and other clinical tests (physical evaluations, cognitive tests) have been mostly obtained in small patient populations assessed during short follow-up periods and correlated with single parameters.54
There
is consequently a need for more extensive studies that demonstrate the value of OCT in MS in larger populations than used to date. Future perspectives should therefore include: prospective and long-term studies including patients with different types of MS; confirmation of the relationship between MRI markers of disease activity, including RNLF, and clinical outcomes; and assessment of RNLF thickness in response to treatment. These studies need to be performed with the more advanced OCT instruments with facilities that include a realtime eye-tracking system. n
history of primary progressive multiple sclerosis, Neurology, 2009;73:1996–2002.
Miller DH, Leary SM, Primary-progressive multiple sclerosis, Lancet Neurol, 2007;6:903–12.
Benedict RH, Wahlig E, Bakshi R, et al., Predicting quality of life in multiple sclerosis: accounting for physical disability, fatigue, cognition, mood disorder, personality, and behavior change, J Neurol Sci, 2005;231:29–34.
Diamond BJ, Johnson SK, Kaufman M, et al., Relationships between information processing, depression, fatigue and cognition in multiple sclerosis, Arch Clin Neuropsychol, 2008;23:189–99.
10. Oken BS, Flegal K, Zajdel D, et al., Cognition and fatigue in multiple sclerosis: Potential effects of medications with central nervous system activity, J Rehabil Res Dev, 2006;43: 83–90.
11. Simioni S, Ruffieux C, Bruggimann L, et al., Cognition, mood and fatigue in patients in the early stage of multiple sclerosis, Swiss Med Wkly, 2007;137:496–501.
12. Grytten Torkildsen N, Lie SA, Aarseth JH, et al., Survival and cause of death in multiple sclerosis: results from a 50-year follow-up in Western Norway, Mult Scler, 2008;14: 1191–8.
13. Doggrell SA, Good results for early treatment of clinically
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