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Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis.

Background: Low-contrast vision is thought to be reduced in Parkinson's disease (PD). This may have a direct impact on quality of life such as driving, using tools, finding objects, and mobility in low-light condition. Low-contrast letter acuity testing has been successful in assessing low-contrast vision in multiple sclerosis. We report the use of a new iPad application to measure low-contrast acuity in patients with PD. Objective: To evaluate low- and high-contrast letter acuity in PD patients and controls using a variable contrast acuity eye chart developed for the Apple iPad. Methods: Thirty-two PD and 71 control subjects were studied. Subjects viewed the Variable Contrast Acuity Chart on an iPad with both eyes open at two distances (40 cm and 2 m) and at high contrast (black and white visual acuity) and 2.5% low contrast. Acuity scores for the two groups were compared. Results: PD patients had significantly lower scores (indicating worse vision) for 2.5% low contrast at both distances and for high contrast at 2 m (p < 0.003) compared to controls. No significant difference was found between the two groups for high contrast at 40 cm (p = 0.12). Conclusions: Parkinson's disease patients have reduced low and high contrast acuity compared to controls. An iPad app, as used in this study, could serve as a quick screening tool to complement more formal testing of patients with PD and other neurologic disorders.

OBJECTIVE: To evaluate the efficacy and safety of subcutaneous peginterferon beta-1a over 2 years in patients with relapsing-remitting multiple sclerosis in the ADVANCE study. METHODS: Patients were randomized to placebo or 125 microg peginterferon beta-1a every 2 or 4 weeks. For Year 2 (Y2), patients originally randomized to placebo were re-randomized to peginterferon beta-1a every 2 weeks or every 4 weeks. Patients randomized to peginterferon beta-1a in Year 1 (Y1) remained on the same dosing regimen in Y2. RESULTS: Compared with Y1, annualized relapse rate (ARR) was further reduced in Y2 with every 2 week dosing (Y1: 0.230 [95% CI 0.183-0.291], Y2: 0.178 [0.136-0.233]) and maintained with every 4 week dosing (Y1: 0.286 [0.231-0.355], Y2: 0.291 [0.231-0.368]). Patients starting peginterferon beta-1a from Y1 displayed improved efficacy versus patients initially assigned placebo, with reductions in ARR (every 2 weeks: 37%, p<0.0001; every 4 weeks: 17%, p=0.0906), risk of relapse (every 2 weeks: 39%, p<0.0001; every 4 weeks: 19%, p=0.0465), 12-week disability progression (every 2 weeks: 33%, p=0.0257; every 4 weeks: 25%, p=0.0960), and 24-week disability progression (every 2 weeks: 41%, p=0.0137; every 4 weeks: 9%, p=0.6243). Over 2 years, greater reductions were observed with every 2 week versus every 4 week dosing for all endpoints and peginterferon beta-1a was well tolerated. CONCLUSIONS: Peginterferon beta-1a efficacy is maintained beyond 1 year, with greater effects observed with every 2 week versus every 4 week dosing, and a similar safety profile to Y1. Clinicaltrials.gov Registration Number: NCT00906399.

Objective: To determine whether African-American (AA) multiple sclerosis (MS) patients exhibit more retinal damage and visual impairment compared to Caucasian-American (CA) MS patients. Methods: 687 MS patients (81 AA) and 110 healthy control (HC) subjects (14 AA) were recruited at three academic hospitals between 2008 and 2012. Using mixed effects regression models, we compared high and low contrast visual acuity (HCVA and LCVA) and high-definition spectral-domain optical coherence tomography (Cirrus-OCT) measures of retinal architecture between MS patients of self-identified AA and CA ancestry. Results: In HC, baseline peripapillary retinal nerve fiber layer thickness (RNFL) was 6.1 mum greater in AA (p = 0.047), while ganglion cell / inner plexiform layer (GCIP) thickness did not differ by race. In MS patients, baseline RNFL did not differ by race, and GCIP was 3.98 microm thinner in AA (p = 0.004). AA had faster RNFL and GCIP thinning rates compared to CA (p = 0.004 and p= 0.046, respectively). AA MS patients had lower baseline HCVA (p = 0.02) and worse LCVA per year of disease duration (p= 0.039). Among patients with an acute optic neuritis (AON) history, AA had greater loss of HCVA than CA patients (p = 0.012). Interpretation: This multicenter investigation provides objective evidence that AA MS patients exhibit accelerated retinal damage compared to CA MS patients. Self-identified AA ancestry is associated with worse MS-related visual disability, particularly in the context of an AON history, suggesting a more aggressive inflammatory disease course among AA MS patients or a subpopulation therein. ANN NEUROL 2014. (c) 2014 American Neurological Association.

BACKGROUND:: Low-contrast visual acuity (LCVA), a sensitive measure of visual function in multiple sclerosis (MS), demonstrated treatment effects as a secondary outcome measure in the Phase 3 trial of natalizumab, AFFIRM. In these posttrial analyses, we studied the relation of visual function to quality of life (QOL), magnetic resonance imaging (MRI) measures, and Expanded Disability Status Scale (EDSS) scores. METHODS:: At baseline and at 52 and 104 weeks in AFFIRM, patients underwent binocular testing of LCVA (1.25% and 2.5% contrast) and high-contrast visual acuity (HCVA). Vision-specific QOL was assessed by the Impact of Visual Impairment Scale (IVIS), whereas the SF-36 Health Survey and Visual Analog Scale were administered as generic QOL measures and the EDSS as a measure of neurologic impairment. RESULTS:: Among QOL measures, IVIS scores showed the most significant correlations with visual dysfunction at all time points in the trial (r= -0.25 to -0.45, P < 0.0001 for LCVA and HCVA). Higher MRI T1- and T2-lesion volumes were also associated with worse vision scores at all time points (P < 0.0001). Clinically meaningful worsening (progression) of LCVA was noted in substantial proportions of patients in AFFIRM and was prevalent even among those without EDSS progression over 2 years (21.9% with LCVA progression at 2.5% contrast; 26.2% at 1.25% contrast). HCVA worsened in only 3.7% of patients without EDSS progression. CONCLUSIONS:: Loss of visual function, particularly as measured by LCVA, was common in AFFIRM, occurring in >20% of patients. Both LCVA and HCVA scores reflect vision-specific aspects of QOL, but LCVA provides information about disability progression not entirely captured by the EDSS. Vision represents a key dimension of outcome assessment for MS and adds valuable information on disability and QOL that can be useful to clinicians.This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial-No derivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis. Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite 'normal' (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury. In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration. In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function.