Faculty Bibliography

Background: Optical coherence tomography (OCT) derived measures of retinal layer thicknesses have been shown to correlate with visual function, grey matter volume and Expanded Disability Status Scale (EDSS) scores in multiple sclerosis (MS). However, the prognostic value of retinal measurements for predicting long term disability in MS patients is still being evaluated. Goal: To determine whether retinal thicknesses as assessed by OCT predict disability in MS 10 years later. Methods: A total of 89 MS patients who were scanned on Stratus OCT between 2006 and 2007 underwent formal, blinded EDSS determination during 2015-2016. Average peripapillary retinal nerve fibre layer (RNFL) thickness and total macular volume (TMV) were assessed by calculating the mean value of these measures for both eyes in each subject. Patients were categorised by baseline diagnosis as relapsing remitting (RRMS), secondary progressive (SPMS), or primary progressive MS (PPMS). Mixed effects linear regression models were used to investigate whether average TMV and RNFL thicknesses at baseline predict EDSS scores after 10 years. Results: The final analysis included 75 RRMS, 9 SPMS, and 5 PPMS patients. 14 of the 75 patients with a baseline diagnosis of RRMS transitioned to SPMS during follow-up period. Baseline analyses revealed that the RRMS cohort was significantly younger than the SPMS and PPMS cohorts (mean differences= 21.5 years and 11.7 years respectively; p< 0.001 for both) and that SPMS patients had a longer disease duration than RRMS and PPMS patients (mean differences=14.2 years and 13.2 years respectively; p< 0.001 for both). A history of optic neuritis (ON) was observed in the RRMS and SPMS cohorts (41% and 44%, respectively), but not in the PPMS cohorts (0%; p=0.253). Adjusting for age, sex, and a history of ON, the mean TMV values at baseline predicted EDSS scores after a median follow-up of 9.3 years. On average, a 1mm3 lower TMV value at baseline predicts a mean decrease of 2 in EDSS at follow-up (adjusted R²=0.20; p=0.012). Mean baseline RNFL values did not significantly predict EDSS scores (adjusted R²=0.18; p=0.069). Conclusions: As has been previously shown with brain atrophy and lesion volume, retinal measures can have predictive value for medium-term disability in MS. Our preliminary findings support the utility of OCT as a tool to predict neurodegeneration and disease progression over time in MS patients

Abducens nerve palsy is a common clinical finding in neurology practice. In many instances, the origin is obvious and management straightforward; however, the list of possible etiologies and mimics is vast and diverse and diagnostic decisions can be challenging and even controversial. This is especially true when the abducens nerve is affected in isolation, since in the current era of cost-effective medicine, it is critical to accurately diagnose etiologies that may lead to major morbidity or mortality with efficiency. Topics for highlighted updates in this review include management of isolated abducens nerve palsy with a high likelihood of a microvascular ischemic etiology; common imaging pitfalls and current state-of-the-art neuroimaging; and abducens palsy mimics.

OBJECTIVE: To develop consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results. METHODS: A panel of experienced OCT researchers (including 11 neurologists, 2 ophthalmologists, and 2 neuroscientists) discussed requirements for performing and reporting quantitative analyses of retinal morphology and developed a list of initial recommendations based on experience and previous studies. The list of recommendations was subsequently revised during several meetings of the coordinating group. RESULTS: We provide a 9-point checklist encompassing aspects deemed relevant when reporting quantitative OCT studies. The areas covered are study protocol, acquisition device, acquisition settings, scanning protocol, funduscopic imaging, postacquisition data selection, postacquisition data analysis, recommended nomenclature, and statistical analysis. CONCLUSIONS: The Advised Protocol for OCT Study Terminology and Elements recommendations include core items to standardize and improve quality of reporting in quantitative OCT studies. The recommendations will make reporting of quantitative OCT studies more consistent and in line with existing standards for reporting research in other biomedical areas. The recommendations originated from expert consensus and thus represent Class IV evidence. They will need to be regularly adjusted according to new insights and practices.

BACKGROUND: Most patients with multiple sclerosis without previous optic neuritis have thinner retinal layers than healthy controls. We assessed the role of peripapillary retinal nerve fibre layer (pRNFL) thickness and macular volume in eyes with no history of optic neuritis as a biomarker of disability worsening in a cohort of patients with multiple sclerosis who had at least one eye without optic neuritis available. METHODS: In this multicentre, cohort study, we collected data about patients (age >/=16 years old) with clinically isolated syndrome, relapsing-remitting multiple sclerosis, and progressive multiple sclerosis. Patients were recruited from centres in Spain, Italy, France, Germany, Czech Republic, Netherlands, Canada, and the USA, with the first cohort starting in 2008 and the latest cohort starting in 2013. We assessed disability worsening using the Expanded Disability Status Scale (EDSS). The pRNFL thickness and macular volume were assessed once at study entry (baseline) by optical coherence tomography (OCT) and was calculated as the mean value of both eyes without optic neuritis for patients without a history of optic neuritis or the value of the non-optic neuritis eye for patients with previous unilateral optic neuritis. Researchers who did the OCT at baseline were masked to EDSS results and the researchers assessing disability with EDSS were masked to OCT results. We estimated the association of pRNFL thickness or macular volume at baseline in eyes without optic neuritis with the risk of subsequent disability worsening by use of proportional hazards models that included OCT metrics and age, disease duration, disability, presence of previous unilateral optic neuritis, and use of disease-modifying therapies as covariates. FINDINGS: 879 patients with clinically isolated syndrome (n=74), relapsing-remitting multiple sclerosis (n=664), or progressive multiple sclerosis (n=141) were included in the primary analyses. Disability worsening occurred in 252 (29%) of 879 patients with multiple sclerosis after a median follow-up of 2.0 years (range 0.5-5 years). Patients with a pRNFL of less than or equal to 87 mum or less than or equal to 88 mum (measured with Spectralis or Cirrus OCT devices) had double the risk of disability worsening at any time after the first and up to the third years of follow-up (hazard ratio 2.06, 95% CI 1.36-3.11; p=0.001), and the risk was increased by nearly four times after the third and up to the fifth years of follow-up (3.81, 1.63-8.91; p=0.002). We did not identify meaningful associations for macular volume. INTERPRETATION: Our results provide evidence of the usefulness of monitoring pRNFL thickness by OCT for prediction of the risk of disability worsening with time in patients with multiple sclerosis. FUNDING: Instituto de Salud Carlos III.