Evaluating associations of RNFL thickness and multifocal VEP with cognitive assessment and brain MRI volumes in older adults: Optic nerve decline and cognitive change (ONDCC) initiative.

To examine the relationships of retinal structural (optical coherence tomography) and visual functional (multifocal visual evoked potentials, mfVEP) indices with neuropsychological and brain structural measurements in healthy older subjects. 95 participants (mean (SD) age 68.1 (9.0)) years were recruited in the Optic Nerve Decline and Cognitive Change (ONDCC) study in this observational clinical investigation. OCT was conducted for retinal nerve fibre layer (RNFL) and mfVEP for amplitude and latency measurements. Participants undertook neuropsychological tests for cognitive performance and MRI for volumetric evaluation of various brain regions. Generalised estimating equation models were used for association analysis (p < 0.05). The brain volumetric measures including total grey matter (GM), cortex, thalamus, hippocampal and fourth ventricular volumes were significantly associated with global and sectoral RNFL. RNFL thickness correlated with delayed recalls of California verbal learning test (CVLT) and Rey complex figure test (RCFT). The mfVEP amplitudes associated with cerebral white matter (WM) and cingulate GM volumes in MRI and CVLT, RCFT and trail making test outcomes. A significant association of mfVEP latency with logical memory delayed recall and thalamus volume was also observed. Our results suggested significant association of specific RNFL and mfVEP measures with distinctive brain region volumes and cognitive tests reflecting performance in memory, visuospatial and executive functional domains. These findings indicate that the mfVEP and RNFL measurements may parallel brain structural and neuropsychological measures in the older population.

The electrophysiological assessment of visual function in Multiple Sclerosis.

The assessment of vision is integral to the diagnosis and monitoring of patients with multiple sclerosis (MS). Visual electrophysiology, previously a critical investigation in patients with suspected MS, has in large part been supplanted by magnetic resonance imaging in clinical routine. However, the development of multi-focal visual evoked potentials and the advent of putative re-myelinating therapies that can be monitored with these techniques has led to a resurgence of interest in the field. Here, we review the clinical applications, technical considerations and limitations of visual evoked potentials in the management of patients with MS.

Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential.

BACKGROUND: Multifocal visual evoked potential (MF-VEP) assesses a wider visual field than full-field VEP (FF-VEP) and potentially offers a more precise analysis of optic nerve injury and repair following optic neuritis. MF-VEP may offer advantages over FF-VEP as an endpoint in clinical trials of remyelinating therapies. OBJECTIVE: MF-VEP testing was used to study changes in visual pathways in 48% of RENEW [phase II, opicinumab (anti-LINGO-1; BIIB033) vs. placebo after first acute unilateral optic neuritis] participants. METHODS: This exploratory MF-VEP RENEW substudy compared mean outcomes at weeks 24 and 32 among participants in the intent-to-treat (ITT; n = 39; 72% female; mean age: 32.3 years) and per-protocol (PP; n = 31; 71% female; mean age: 32.2 years) populations in affected and fellow eye latency from fellow eye baseline latency and affected and fellow eye amplitude from their own baselines. Treatment differences were evaluated using analysis of covariance (week 24) and a mixed-effect model of repeated measures (week 32). Last observation carried forward was used to impute missing data at week 24. RESULTS: A trend for improvement in affected eye MF-VEP latency with opicinumab versus placebo was seen in the ITT and PP populations at weeks 24 and 32. Both treatment groups in the ITT population experienced partial recovery of amplitude in the affected eye at week 32. Notably, the mean change in fellow eye amplitude at weeks 24 and 32 was - 17.57 and - 31.41 nanovolts (nV) in placebo but only - 0.59 and 1.93 nV in the opicinumab group [differences at weeks 24 and 32: 16.98 nV (p = 0.050) and 33.33 nV (p < 0.01), respectively]. CONCLUSION: Results from this substudy showed advantages of MF-VEP over FF-VEP in multicenter studies of central nervous system reparative therapies and provide novel evidence that fellow eye visual pathway amplitude loss occurs after optic neuritis but can potentially be prevented by opicinumab treatment. REGISTRATION: ClinicalTrials.gov identifier NCT01721161.

Multifocal VEP assessment of optic neuritis evolution.

OBJECTIVE: To evaluate multifocal visual evoked potentials (mfVEP) changes in optic neuritis (ON) and fellow eyes during first year after the attack. METHODS: Eighty-seven patients and twenty-five controls were examined. Patients were classified as multiple sclerosis (MS) group, high risk (HR) or low risk (LR) groups for conversion to MS. mfVEP recordings and retinal nerve fiber layer (RNFL) thickness were analyzed. RESULTS: Recovery of amplitude and shortening of latency was fastest within the first 3months. The largest amplitude reduction and longest latency delay of the ON eye were recorded in the MS group. This was accompanied by deterioration of both parameters in fellow eyes (p<0.03). mfVEP remained stable in fellow eyes of the LR group. Inter-eye asymmetry showed similar amount of amplitude reduction and latency delay in all three groups. RNFL thickness strongly correlated with mfVEP amplitude as early as 3 months after ON (R(2)=0.6, p=0.001). CONCLUSION: mfVEP amplitude is an early predictor of post-ON axonal loss. The apparent more severe involvement of ON eyes in the MS subgroup may be due to subclinical inflammation along the visual pathway. SIGNIFICANCE: Severity of amplitude reduction and latency delay after episode of ON is not MS-related. Retro-chiasmal demyelination is a possible factor contributing to amplitude and latency differences between MS and non-MS patients.