Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis
ABSTRACT To examine the relation of visual function to retinal nerve fiber layer (RNFL) thickness as a structural biomarker for axonal loss in multiple sclerosis (MS), and to compare RNFL thickness among MS eyes with a history of acute optic neuritis (MS ON eyes), MS eyes without an optic neuritis history (MS non-ON eyes), and disease-free control eyes.
Patients with MS (n = 90; 180 eyes) and disease-free controls (n = 36; 72 eyes).
Retinal never fiber layer thickness was measured using optical coherence tomography (OCT; fast RNFL thickness software protocol). Vision testing was performed for each eye and binocularly before OCT scanning using measures previously shown to capture dysfunction in MS patients: (1) low-contrast letter acuity (Sloan charts, 2.5% and 1.25% contrast levels at 2 m) and (2) contrast sensitivity (Pelli-Robson chart at 1 m). Visual acuity (retroilluminated Early Treatment Diabetic Retinopathy charts at 3.2 m) was also measured, and protocol refractions were performed.
Retinal nerve fiber layer thickness measured by OCT, and visual function test results.
Although median Snellen acuity equivalents were better than 20/20 in both groups, RNFL thickness was reduced significantly among eyes of MS patients (92 mum) versus controls (105 mum) (P<0.001) and particularly was reduced in MS ON eyes (85 mum; P<0.001; accounting for age and adjusting for within-patient intereye correlations). Lower visual function scores were associated with reduced average overall RNFL thickness in MS eyes; for every 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 mum.
Scores for low-contrast letter acuity and contrast sensitivity correlate well with RNFL thickness as a structural biomarker, supporting validity for these visual function tests as secondary clinical outcome measures for MS trials. These results also suggest a role for ocular imaging techniques such as OCT in trials that examine neuroprotective and other disease-modifying therapies. Although eyes with a history of acute optic neuritis demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes have less RNFL thickness than controls, suggesting the occurrence of chronic axonal loss separate from acute attacks in MS patients.
- SourceAvailable from: Raed Alroughani
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- "Diminished low-contrast visual acuity correlates significantly with loss of retinal nerve fibre layer thickness in MS (Fisher et al., 2006). Low-contrast visual acuity testing is particularly suited for use in MS, as subtle disturbances of visual function may not be apparent with high-contrast letter charts (Balcer and Frohman, 2010). "
ABSTRACT: For decades, the Expanded Disability Status Scale (EDSS) has been the principal measure of disability in clinical trials in patients with multiple sclerosis (MS) and in clinical practice. However, this test is dominated by effects on ambulation. Composite endpoints may provide a more sensitive measure of MS-related disability through the measurement of additional neurological functions. The MS Functional Composite (MSFC) includes a walking test (25-ft walk) plus tests of upper extremity dexterity (9-hole peg test) and cognitive function (Paced Auditory serial Addition test [PASAT]). Replacing PASAT with the Symbol Digit Modality test, a more sensitive test preferred by patients, may improve the clinical utility of the MSFC. In addition, disease-specific measures of QoL may be used alongside the MSFC (which does not include measurement of QoL). Clinical data suggest that disease-modifying therapies may delay or prevent relapse, and better composite measures will be valuable in the assessment of disease activity-free status in people with MS. Copyright © 2015 Elsevier B.V. All rights reserved.03/2015; 4(3). DOI:10.1016/j.msard.2015.03.004
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- "Brain damage and brain atrophy reflect axonal loss and are correlated with cognitive outcome in multiple sclerosis  . Recently, measures of retinal nerve fiber layer thickness (RNFL) by optical coherence tomography (OCT) showed to be a potentially reliable predictor outcome in MS and optic neuritis   . Some studies have demonstrated correlation between optical nerve atrophy measured by RNFL and the degree of brain atrophy in patients with MS . "
ABSTRACT: OBJECTIVE: To investigate cognitive impairment, to assess optical nerve axonal loss, and to determinate whether there is correlation between optical nerve axonal loss and cognition impairment in Clinically Isolated Syndrome (CIS). METHODS: Fifteen CIS patients and 15 controls were submitted to Wechsler memory scale, Rey Auditory Verbal Learning, Rey Complex Figure, Paced Auditory Serial Addition, Digit Span, verbal fluency, stroop color, D2, and Digit Symbol tests. CIS patients were evaluated by optical coherence tomography (OCT) (23 eyes). RESULTS: CIS patients had worse performance in Paced Auditory Serial Addition Test (PASAT) 2 seconds (P=0.009) and fluency tests (P=0.0038). Optical nerve axonal loss was found more frequently in eyes with previous optic neuritis (ON) (85.7%) than in those without previous ON (21.7%) (P=0.0146). There were no significant correlations between optical nerve axonal loss and cognitive findings. CONCLUSIONS: CIS patients had worse cognitive performance than controls. OCT can detect axonal loss resulting from optical neuritis and subclinical axonal loss in eyes without previous optical neuritis. Optical nerve axonal loss was not correlated with cognition.Clinical neurology and neurosurgery 11/2012; 115(7). DOI:10.1016/j.clineuro.2012.10.025 · 1.25 Impact Factor
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- "inflammation of the optic nerve, is the first diagnosed sign in approximately 20% of patients with MS and as many as 50% of patients with ON eventually develop the disease. Electroretinogram (ERG) studies, which assess retinal function and visual-evoked potential (VEP) data to determine optic nerve abnormalities, have demonstrated that visual function is impaired in MS patients and in animals with EAE (Kornek et al. 2000; Meyer et al. 2001; Fisher et al. 2006). MS and EAE are caused by an immune attack on the CNS by autoreactive T cells and activated macrophages. "
ABSTRACT: Optic neuritis (ON), which is an acute inflammatory autoimmune demyelinating disease of the central nervous system (CNS), often occurs in multiple sclerosis (MS). ON is an early diagnostic sign in most MS patients caused by damage to the optic nerve leading to visual dysfunction. Various features of both MS and ON can be studied following induction of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in Lewis rats. Inflammation and cell death in the optic nerve, with subsequent damage to the retinal ganglion cells in the retina, are thought to correlate with visual dysfunction. Thus, characterizing the pathophysiological changes that lead to visual dysfunction in EAE animals may help develop novel targets for therapeutic intervention. We treated EAE animals with and without the calpain inhibitor calpeptin (CP). Our studies demonstrated that the Ca(2+) -activated neutral protease calpain was upregulated in the optic nerve following induction of EAE at the onset of clinical signs (OCS) of the disease and these changes were attenuated following treatment with CP. These reductions correlated with decreases in inflammation (cytokines, iNOS, COX-2, NF-κB), and microgliosis (i.e. activated microglia). We observed that calpain inhibition reduced astrogliosis (reactive astroglia) and expression of aquaporin 4 (AQP4). The balance of Th1/Th2 cytokine production and also expression of the Th1-related CCR5 and CXCR3 chemokine receptors influence many pathological processes and play both causative and protective roles in neuron damage. Our data indicated that CP suppressed cytokine imbalances. Also, Bax:Bcl-2 ratio, production of tBid, PARP-1, expression and activities of calpain and caspases, and internucleosomal DNA fragmentation were attenuated after treatment with CP. Our results demonstrated that CP decreased demyelination [loss of myelin basic protein (MBP)] and axonal damage [increase in dephosphorylated neurofilament protein (de-NFP), and also promoted intracellular neuroprotective pathways in optic nerve in EAE rats. Thus, these data suggest that calpain is involved in inflammatory as well as in neurodegenerative aspects of the disease and may be a promising target for treating ON in EAE and MS. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry, J. Neurochem. (2012) 10.1111/jnc.12064.Journal of Neurochemistry 10/2012; DOI:10.1111/jnc.12064 · 4.24 Impact Factor