Early diagnosis, monitoring, and treatment of optic neuritis.
ABSTRACT About half of multiple sclerosis patients present with optic neuritis (ON) as a clinically isolated syndrome (CIS). In the Optic Neuritis Treatment Trial study, 28% of patients with ON and an abnormal brain magnetic resonance imaging (MRI) did not have a relapse at the end of 15 years. It is still difficult to predict which CIS patients will go on to develop clinically definite multiple sclerosis and which will have a benign course.
This review focuses on more advanced methods of detecting and quantifying ON in multiple sclerosis that have been developed in the past 15 years, especially on recent developments in optical coherence tomography measurement of the retinal nerve fiber layer and its role in monitoring axonal loss in the course of the disease. New clinical trial methods of measuring visual acuity include high-contrast visual acuity testing with the Early Treatment Diabetic Retinopathy Study charts, low-contrast letter acuity, and contrast sensitivity testing. More advanced neuroimaging techniques include magnetization transfer imaging and diffusion tensor imaging to quantify visual pathway lesions. Other tests of visual function, such as multifocal visual-evoked potentials and functional MRI, have been shown to be more sensitive than conventional visual-evoked potentials or MRI in detecting early, subtle visual impairment in ON and early recovery of visual function related to cortical plasticity. Newer agents are currently being investigated for CIS in ongoing clinical trials.
Better methods are being developed for the earlier diagnosis, monitoring, and treatment of ON. In the future, CIS patients may be stratified according to their risk of development of clinically definite multiple sclerosis and therefore, receive the appropriate treatment.
- SourceAvailable from: Per Soelberg Sorensen[show abstract] [hide abstract]
ABSTRACT: Interferon beta reduces activity in multiple sclerosis as measured clinically and by magnetic resonance imaging (MRI). We assessed the effect of interferon beta-1a on the occurrence of relapses in patients after first presentation with neurological events, who are at high risk of conversion to clinically definite multiple sclerosis. Eligible patients had had a first episode of neurological dysfunction suggesting multiple sclerosis within the previous 3 months and had strongly suggestive brain MRI findings. Patients were randomly assigned interferon beta-1a 22 microg or placebo subcutaneously once weekly for 2 years. Neurological and clinical assessments were done every 6 months and brain MRI every 12 months. Analyses excluded one patient assigned placebo who received no study injections. 241 (78%) of 308 randomised patients received study treatment for 2 years; 278 (90%) remained in the study until termination. 57 (85%) of 67 who stopped therapy did so after conversion to clinically definite multiple sclerosis. Fewer patients developed clinically definite multiple sclerosis in the interferon group than in the placebo group (52/154 [34%] vs 69/154 [45%]; p=0.047). The time at which 30% of patients had converted to clinically definite multiple sclerosis was 569 days in the interferon group and 252 in the placebo group (p=0.034). The annual relapse rates were 0.33 and 0.43 (p=0.045). The number of new T2-weighted MRI lesions and the increase in lesion burden were significantly lower with active treatment. Interferon beta-1a treatment at an early stage of multiple sclerosis had significant positive effects on clinical and MRI outcomes.The Lancet 06/2001; 357(9268):1576-82. · 39.06 Impact Factor
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ABSTRACT: Optical coherence tomography (OCT)--measured retinal nerve fiber layer (RNFL) values may represent a surrogate biomarker for axonal integrity in multiple sclerosis (MS). The purpose of this study was to determine whether RNFL measurements obtained within two years of an optic neuritis (ON) event distinguish patients at increased risk of developing clinically-definite MS (CDMS). Fifty consecutively sampled patients who experienced a single ON event were followed prospectively for a mean period of 34 months with OCT testing. Values of RNFL in clinically-affected and non-affected eyes were compared between patients who developed CDMS and those that did not develop MS after ON. Twenty-one patients (42%) developed CDMS during the course of the study, with a mean conversion time of 27 months. Mean RNFL values were thinner in the clinically-affected eyes of non-MS patients than CDMS eyes after one year (p = 0.0462) due to more severe ON events in the former. By year two, CDMS patients manifested more recurrent ON events and RNFL thinning than non-MS patients. Temporal RNFL values were thinner in the non-affected eyes of CDMS patients with a trend towards significance (p = 0.1302). Our results indicate that RNFL thickness does not reliably distinguish patients at higher risk of converting to CDMS after ON. The severity of ON has a greater effect on RNFL thickness than risk of CDMS at one year. The CDMS patients demonstrate progressive RNFL thinning likely due to recurrent sub-clinical ON events, which may help differentiate them from non-MS patients over time.The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 10/2008; 35(4):482-7. · 1.33 Impact Factor
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ABSTRACT: Visual dysfunction is one of the most common causes of disability in multiple sclerosis (MS). The Multiple Sclerosis Functional Composite (MSFC), a new clinical trial outcome measure, does not currently include a test of visual function. To examine contrast letter acuity as a candidate visual function test for the MSFC. Binocular contrast letter acuity testing (Sloan charts) was performed in a subgroup of participants from the International Multiple Sclerosis Secondary Progressive Avonex Controlled Trial (IMPACT Substudy) and in MS patients and disease-free control subjects from a cross-sectional study of visual outcome measures (Multiple Sclerosis Vision Prospective cohort [MVP cohort]). High-contrast visual acuity was measured in both studies; MVP cohort participants underwent additional binocular testing for contrast sensitivity (Pelli-Robson chart), color vision (D-15 desaturated test), and visual field (Esterman test, Humphrey Field Analyzer II). Contrast letter acuity (Sloan charts, p < 0.0001, receiver operating characteristic curve analysis) and contrast sensitivity (Pelli-Robson chart, p = 0.003) best distinguished MS patients from disease-free control subjects in the MVP cohort. Correlations of Sloan chart scores with MSFC and Expanded Disability Statue Scale (EDSS) scores in both studies were significant and moderate in magnitude, demonstrating that Sloan chart scores reflect visual and neurologic dysfunction not entirely captured by the EDSS or MSFC. Among clinical measures, contrast letter acuity (Sloan charts) and contrast sensitivity (Pelli-Robson chart) demonstrate the greatest capacity to identify binocular visual dysfunction in MS. Sloan chart testing also captures unique aspects of neurologic dysfunction not captured by current EDSS or MSFC components, making it a strong candidate visual function test for the MSFC.Neurology 12/2003; 61(10):1367-73. · 8.25 Impact Factor