Project description:BackgroundOptic neuritis is an inflammatory disease of the optic nerve. It occurs more commonly in women than in men. Usually presenting with an abrupt loss of vision, recovery of vision is almost never complete. Closely linked in pathogenesis to multiple sclerosis, it may be the initial manifestation for this condition. In certain patients, no underlying cause can be found.ObjectivesTo assess the effects of corticosteroids on visual recovery of patients with acute optic neuritis.Search methodsWe searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 1), MEDLINE (January 1950 to February 2012), EMBASE (January 1980 to February 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to February 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 21 February 2012. We also searched reference lists of identified trial reports to find additional trials.Selection criteriaWe included randomized trials that evaluated corticosteroids, in any form, dose or route of administration, in people with acute optic neuritis.Data collection and analysisTwo authors independently extracted the data on methodological quality and outcomes for analysis.Main resultsWe included six randomized trials which included a total of 750 participants. Two trials evaluated low dose oral corticosteroids while one trial evaluated low dose intravenous corticosteroids across two treatment arms and two trials evaluated a higher dose of intravenous corticosteroids. One three-arm trial evaluated low-dose oral corticosteroids and high-dose intravenous corticosteroids against placebo. Trials evaluating oral corticosteroids compared varying doses of corticosteroids with placebo. Hence, we did not conduct a meta-analysis of such trials. In a meta-analysis of trials evaluating corticosteroids with total dose greater than 3000 mg administered intravenously, the relative risk of normal visual acuity with intravenous corticosteroids compared with placebo was 1.06 (95% confidence interval (CI) 0.89 to 1.27) at six months and 1.06 (95% CI 0.92 to 1.22) at one year. The risk ratio of normal contrast sensitivity for the same comparison was 1.10 (95% CI 0.92 to 1.32) at six months follow up. We did not conduct a meta-analysis for this outcome at one year follow up since there was substantial statistical heterogeneity. The risk ratio of normal visual field for this comparison was 1.08 (95% CI 0.96 to 1.22) at six months and 1.02 (95% CI 0.86 to 1.20) at one year. Quality of life was assessed and reported in one trial.Authors' conclusionsThere is no conclusive evidence of benefit in terms of recovery to normal visual acuity, visual field or contrast sensitivity with either intravenous or oral corticosteroids at the doses evaluated in trials included in this review.
Project description:Importance:Intravenous (IV) administration of corticosteroids is the standard of care in the treatment of acute optic neuritis. However, it is uncertain whether a bioequivalent dose of corticosteroid administered orally, which may be more cost-efficient and convenient for patients, is as effective as IV administration in the treatment of acute optic neuritis. Objective:To determine whether recovery of vision following treatment of acute optic neuritis with a high-dose IV corticosteroid is superior to that with a bioequivalent dose of an oral corticosteroid. Design, Setting, and Participants:This single-blind (participants unblinded) randomized clinical trial with 6-month follow-up was conducted at a single tertiary care center in London, Ontario, Canada. Participants were enrolled from March 2012 to May 2015, with the last participant's final visit occurring November 2015. Patients 18 to 64 years of age presenting within 14 days of acute optic neuritis onset, without any recovery at time of randomization and without history of optic neuritis in the same eye, were screened. Inclusion criteria included best-corrected visual acuity (BCVA) of 20/40 or worse and corticosteroids deemed required by treating physician. In total, 89 participants were screened; 64 were eligible, but 9 declined to participate. Thus, 55 participants were enrolled and randomized. Primary analysis was unadjusted and according to the intention-to-treat principle. Interventions:Participants were randomized 1:1 to the IV methylprednisolone sodium succinate (1000-mg) or oral prednisone (1250-mg) group. Main Outcomes and Measures:Primary outcome was recovery of the latency of the P100 component of the visual evoked potential at 6 months. Secondary outcomes were the P100 latency at 1 month and BCVA as assessed with Early Treatment Diabetic Retinopathy Study letter scores on the alphabet chart and scores on low-contrast letters at 1 and 6 months. Results:Of 55 randomized participants, the final analyzed cohort comprised 23 participants in the IV and 22 in the oral treatment groups. The mean (SD) age of the cohort was 34.6 (9.5) years, and there were 28 women (62.2%). At 6 months' recovery, P100 latency in the IV group improved by 62.9 milliseconds (from a mean [SD] of 181.9 [53.6] to 119.0 [16.5] milliseconds), and the oral group improved by 66.7 milliseconds (from a mean [SD] of 200.5 [67.2] to 133.8 [31.5] milliseconds), with no significant difference between groups (P?=?.07). Similarly, no significant group difference was found in the mean P100 latency recovery at 1 month. For BCVA, recovery between the groups did not reach statistical significance at 1 month or 6 months. In addition, improvements in low-contrast (1.25% and 2.5%) BCVA were not significantly different between treatment groups at 1 or 6 months' recovery. Conclusions and Relevance:This study finds that bioequivalent doses of oral corticosteroids may be used as an alternative to IV corticosteroids to treat acute optic neuritis. Trial Registration:clinicaltrials.gov Identifier: NCT01524250.
Project description:AIMS: The aim of this study is to provide a clinical update on optic neuritis (ON), its association with multiple sclerosis (MS), and neuromyelitis optica (NMO). METHODS: This study included a PubMed review of the literature written in the English language. RESULTS: ON in adults is typically idiopathic or demyelinating, and is characterised by unilateral, subacute, painful loss of vision that is not associated with any systemic or other neurological symptoms. Demyelinating ON is associated with MS, and we review the key studies of ON including the ON treatment trial and several other MS treatment trials and NMO. CONCLUSION: Acute demyelinating ON can occur in isolation or be associated with MS. Typical ON does not require additional evaluation other than cranial magnetic resonance imaging. NMO is likely a separate disorder from MS and the ON in NMO has a different treatment and prognosis. METHODOLOGY: The authors conducted an English language search using Pubmed from the years 1964 to 2010 using the search terms 'ON', 'MS' and 'NMO'. The authors included original articles, review articles, and case reports, which revealed new aspects as far as epidemiology, histopathology, clinical manifestations, imaging, genetics, and treatment of ON. Titles were reviewed for topicality and full references were obtained. Letters to the editor, unpublished work, and abstracts were not included in this review.
Project description:Neuromyelitis optica (NMO) is an autoimmune demyelinating disease associated with recurrent episodes of optic neuritis and transverse myelitis, often resulting in permanent blindness and/or paralysis. The discovery of autoantibodies (AQP4-IgG) that target aquaporin-4 (AQP4) has accelerated our understanding of the cellular mechanisms driving NMO pathogenesis. AQP4 is a bidirectional water channel expressed on the plasma membranes of astrocytes, retinal Müller cells, skeletal muscle, and some epithelial cells in kidney, lung and the gastrointestinal tract. AQP4 tetramers form regular supramolecular assemblies at the cell plasma membrane called orthogonal arrays of particles. The pathological features of NMO include perivascular deposition of immunoglobulin and activated complement, loss of astrocytic AQP4, inflammatory infiltration with granulocyte and macrophage accumulation, and demyelination with axon loss. Current evidence supports a causative role of AQP4-IgG in NMO, in which binding of AQP4-IgG to AQP4 orthogonal arrays on astrocytes initiates complement-dependent and antibody-dependent cell-mediated cytotoxicity and inflammation. Immunosuppression and plasma exchange are the mainstays of therapy for NMO optic neuritis. Novel therapeutics targeting specific steps in NMO pathogenesis are entering the development pipeline, including blockers of AQP4-IgG binding to AQP4 and inhibitors of granulocyte function. However, much work remains in understanding the unique susceptibility of the optic nerves in NMO, in developing animal models of NMO optic neuritis, and in improving therapies to preserve vision.
Project description:The clinical diagnosis and natural history of optic neuritis was established in the late 1880s by the ophthalmologists von Graefe and Nettleship. The earlier, accurate and insightful description of transient, bilateral visual loss of Esther, the main character in the Charles Dickens novel Bleak House (1852--1853), suggests optic neuritis as a Dickensian diagnosis. Remarkably, Dickens' observations, also preceding the earliest clinical description of multiple sclerosis by Charcot in 1868, described many clinical features such as a prodromal phase; a nadir; gradual recovery over weeks; glare disability; reduced contrast sensitivity; possibly Uhthoff's phenomenon; and visual fading. All this with an accuracy that, to quote Russell Brain, "would credit a trained physician."
Project description:Signs and symptoms of optic neuritis (ON), an autoimmune disorder of the central nervous system (CNS), differ between patients. Pain, which is commonly reported by ON patients, may be the major reason for some patients to visit the clinic. This article reviews the presence of pain related to ON with respect to underlying disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein associated disease (MOGAD). The aim of this review is to provide an overview of pain symptoms in accordance with the context of various pathophysiological explanations, assist in differential diagnosis of ON patients, especially at the onset of disease, and make recommendations to aid physicians make decisions for follow up diagnostic examinations.
Project description:Trans-synaptic degeneration could exacerbate neurodegeneration in multiple sclerosis (MS). We aimed to assess whether anterograde trans-synaptic degeneration could be identified in the primary visual pathway in vivo. Diffusion tensor imaging (DTI) was used to assess the optic radiations in 15 patients with previous optic nerve inflammation and 9 healthy volunteers. A probabilistic atlas of the optic radiations was created from healthy diffusion tractography data. Lengthwise profiles for DTI parameters (axial [?(||) ], radial [?(?) ] and mean diffusivity [MD], fractional anisotropy [FA] and the angle of deviation of the principal eigenvector [?]) were analyzed for patients and controls. Patients also underwent multifocal visual evoked potential (mfVEP) assessments to characterize the latency and amplitude of cortical potentials. Correlations were performed between mfVEP latency and amplitude in the left and right visual hemi-fields and DTI parameters in the contra-lateral optic radiations. Patients displayed a significant decrease in ?(||) within the body of both optic radiations, which significantly correlated with loss of mfVEP amplitude. Abnormal ?(?) and FA were detected bilaterally throughout the optic radiations in patients but the abnormality was not associated with amplitude reduction or latency prolongation of the mfVEP. An abnormal ? value was observed in the left optic radiations of patients, and the ? value in the body of the optic radiations also correlated with mfVEP amplitude loss. The assocation between bilateral DTI abnormalities within the optic radiations and loss of afferent electrical activity could indicate anterograde trans-synaptic degeneration occurs following optic neuritis.
Project description:IMPORTANCE Retrospective studies have demonstrated disparate outcomes following acute optic neuritis in individuals of African descent compared with individuals of white race/ethnicity. However, published analyses of the prospectively collected Optic Neuritis Treatment Trial (ONTT) data identified no association between worse visual outcomes and black race/ethnicity. OBJECTIVES To investigate the associations of age, sex, and race/ethnicity with visual outcomes following acute optic neuritis through application of longitudinal data analysis techniques to the ONTT data set. DESIGN Secondary analysis of the ONTT (a prospective randomized controlled trial) data set. Our models included effects of treatment (placebo, oral prednisone, or intravenous methylprednisolone), time, and treatment × time interaction, as well as demographic covariates of age, sex, and race/ethnicity. SETTING AND PARTICIPANTS The ONTT data were collected at multiple centers in the United States. Patients of black (n = 58) and white (n = 388) race/ethnicity with acute optic neuritis who enrolled in the ONTT within 8 days of symptom onset were included in analyses. MAIN OUTCOMES AND MEASURES The contrast sensitivity and visual acuity (logMAR) in the affected eye were modeled using 2-stage mixed-effects regression techniques. All available follow-up data from baseline to 15 to 18 years were included. RESULTS The data identified no relationship of age, sex, or treatment with contrast sensitivity or visual acuity outcomes. Race/ethnicity was significantly related to contrast sensitivity (P < .001) and visual acuity (P < .001) during a 15-year period following acute optic neuritis, with black race/ethnicity being associated with worse scores for both. CONCLUSIONS AND RELEVANCE Race/ethnicity seems to be associated with contrast sensitivity and visual acuity outcomes in affected eyes following acute optic neuritis. To our knowledge, this is the largest cohort of black race/ethnicity with acute optic neuritis to be studied and represents the first evidence from a prospectively collected data set to support a hypothesis of race/ethnicity-dependent visual outcomes of acute optic neuritis.