Analysis of Neurodegenerative Process Within Visual Ways In Multiple Sclerosis

Study Overview
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Brief Summary
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This study will interest in the pathophysiology of silent retinal axonal loss in multiple sclerosis. Recent studies have suggested that silent retinal axonal loss (no past history of optic neuritis [ON]) may be due to inflammatory lesions within the optic radiations and a transsynaptic degenerative process. The objective is to measure the exact role of silent optic nerve lesion in the occurrence of silent retinal axonal loss by performing OCT, brain and optic nerve MRI in a cohort of patients without recent disease activity.

Detailed Description
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This study will interest in the neurodegenerative process reported in multiple sclerosis within the visual ways. Symptomatic and asymptomatic retinal axonal loss in multiple sclerosis (MS) have largely been described. Many recent optical coherence tomography (OCT) studies have suggested that subclinical retinal axonal loss (no past history of optic neuritis [ON]) observed in MS mainly due to inflammatory and demyelinating lesions within the optic radiations and a retrograde transsynaptic degenerative process. None of these studies clearly tried to investigate the role of asymptomatic optic nerve lesion(s) in subclinical retinal axonal loss occurence. The main objective of the study is to measure the exact role of silent optic nerve lesion in the occurrence of silent retinal axonal loss by performing OCT, brain and optic nerve MRI. The study will focus on a cohort of patients without recent disease activity in order to exclude or minimize the risk of recent and old lesion occurence on the visual ways, which could be a bias in our analysis.

Official Title
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Study of the Link Between Retinal Atrophy and Demyelinating Inflammatory Processes on Visual Pathways in Relapsing Multiple Sclerosis in Magnetic Resonance Imaging and Optical Coherence Tomography

Conditions
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Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsing Remitting Multiple Sclerosis (RRMS) patients treated by natalizumab for more than 6 months JohnCunninghamVirus (JCV) index < 0.9 patients followed in our MS center from the beginning of the disease Exclusion Criteria: ophthalmologic diseases diabetes mellitus contra-indication to MRI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study of asymptomatic retinal atrophy in multiple sclerosis and asymptomatic optic nerve demyelinating lesion | The temporal peripapillary Retinal Nerve Fiber Layer thickness (pRNFL; quantitative data) measured on optical coherence tomography will evaluate asymptomatic retinal atrophy Presence of subclinical optic nerve lesion will be assessed on optic nerve MRI (3D-double inversion recovery sequence; Y/N; qualitative data) and according to clinical information (past history of optic neuritis [ON] or not). It will enable investigators to define 3 eyes' groups: eyes' group with symptomatic optic nerve lesion (ON eyes), eyes' group with asymptomatic optic nerve lesion (NON eyes with asymptomatic lesion) and eyes' group without symptomatic or asymptomatic lesion (NON eyes without lesion). Investigators will proceed to comparison of temporal pRNFL between NON eyes with asymptomatic lesion and NON eyes without lesion | Day 1 (cross-sectional study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the link between asymptomatic retinal atrophy in multiple sclerosis and intensity of demyelinating process all along the optic ways (from the retina to the visual cortex) | Within NON eyes, investigators will evaluate the imaging parameters on the optic ways which is/are significantly and independently associated to temporal pRNFL (multivariate analysis) MRI parameters parameters included will be: length of asymptomatic optic nerve lesion; presence of lesion on chiasma, presence of lesion on optic tracts, T2 lesion burden on optic radiations, fractional anisotropy in optic radiations, volume of primary visual cortex | Day 1 (cross-sectional study) | 
| Evaluation of the link between symptomatic retinal atrophy in multiple sclerosis and intensity of demyelinating process all along the optic ways (from the retina to the visual cortex) | Within ON eyes, investigators will evaluate the imaging parameters on the optic ways which is/are significantly and independently associated to temporal pRNFL (multivariate analysis) MRI parameters parameters included will be: length of subclinical optic nerve lesion; presence of lesion on chiasma, presence of lesion on optic tracts, T2 lesion burden on optic radiations, fractional anisotropy in optic radiations, volume of primary visual cortex | Day 1 (cross-sectional study) | 
| Evaluation of the link between retinal atrophy and visual connectivity | Within all eyes (ON eyes + NON eyes with asymptomatic optic nerve lesion + NON eyes without asymptomatic lesion), investigators will evaluate the link between the mean temporal pRNFL of both eyes (pRNFL; quantitative data) and the strength of visual connectivity (seed based approach on resting state sequence) | Day 1 (cross-sectional study) | 
| Evaluation of the link between visual disability and MRI parameters measuring intensity of demyelinating process all along the optic ways (from the retina to the visual cortex) | Within all eyes (ON eyes + NON eyes with asymptomatic optic nerve lesion + NON eyes without asymptomatic lesion), investigators will evaluate the MRI parameters significantly and independently associated to visual disability. Visual disability will be measured by low contrast vision acuity (2.5%; unit LogMar) MRI parameters will be length of subclinical optic nerve lesion; presence of lesion on chiasma, presence of lesion on optic tracts, T2 lesion burden on optic radiations, fractional anisotropy in optic radiations, volume of primary visual cortex | Day 1 (cross-sectional study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, axonal loss, MS, OCT