Faculty Bibliography

BACKGROUND: Although patients with acute optic neuritis (ON) recover high-contrast visual acuity (HCVA) to 20/40 or better in 95% of affected eyes, patients with a history of ON continue to note subjective abnormalities of vision. Furthermore, substantial and permanent thinning of the retinal nerve fiber layer (RNFL) and the ganglion cell layer (GCL) is now known to occur early in the course of ON. We measured vision-specific quality of life (QOL) in patients with a history of acute ON and recovery of VA to 20/40 or better in their affected eyes to determine how these QOL scores relate to RNFL and GCL thickness and low-contrast letter acuity (LCLA) across the spectrum of visual recovery. METHODS: Data from an ongoing collaborative study of visual outcomes in multiple sclerosis and ON were analyzed for this cross-sectional observational cohort. Patients and disease-free control participants completed the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement to the NEI-VFQ-25, as well as VA and LCLA testing for each eye separately and binocularly. Optical coherence tomography measures for each eye included peripapillary RNFL thickness and macular GCL + inner plexiform layer (GCL + IPL) thickness. RESULTS: Patients with a history of acute ON and recovery to 20/40 or better VA (n = 113) had significantly reduced scores for the NEI-VFQ-25 (83.7 +/- 15.4) and 10-Item Neuro-Ophthalmic Supplement (74.6 +/- 17.4) compared with disease-free controls (98.2 +/- 2.1 and 96.4 +/- 5.2, P < 0.001, linear regression models, accounting for age and within-patient, intereye correlations). Most patients with 20/40 or better visual recovery (98/112, 88%) had monocular HCVA in their affected eye of 20/20 or better. Although patients with 20/50 or worse HCVA recovery demonstrated the worst performance on low-contrast acuity, affected eye RNFL and GCL + IPL thickness, and QOL scales, these measures were also significantly reduced among those with 20/40 or better HCVA recovery compared with controls. CONCLUSIONS: Patients with a history of ON and "good" visual recovery, defined in the literature as 20/40 or better HCVA, are left with clinically meaningful reductions in vision-specific QOL. Such patient-observed deficits reflect the underlying significant degrees of retinal axonal and neuronal loss and visual dysfunction that are now known to characterize ON even in the setting of maximal HCVA recovery. There remains an unmet therapeutic need for patients with ON.

BACKGROUND: Outcome measures to capture disability, such as the Multiple Sclerosis Functional Composite (MSFC), were developed to enhance outcome measurements for clinical trials in adults with multiple sclerosis (MS). The MSFC initially included three components: a timed 25-foot walk [T25FW], 9-hole peg test [9HPT], and the Paced Auditory Serial Addition Task [PASAT]. Modifications to the original MSFC, such as adding binocular low-contrast letter acuity (LCLA) or substituting the symbol digit modalities test (SDMT) for the PASAT, improved the capacity to capture neurologic impairment in adults. Similar outcome scales for pediatric MS have not yet been established. OBJECTIVE: To determine whether the three-component MSFC or a modified MSFC with LCLA and the SDMT better identifies neurological deficits in pediatric MS. METHODS: We evaluated 5 measures (T25FW, 9HPT, Children's PASAT [ChiPASAT], SDMT, and binocular LCLA [Sloan charts, 1.25% contrast]) in children with MS (disease onset <18 years) and healthy controls. To be able to compare measures whose scores have different scales, Z-scores were also created for each test based on the numbers of standard deviations from a control group mean, and these individual scale scores were combined to create composite scores. Logistic regression models, accounting for age, were used to determine whether the standard 3-component MSFC or modified versions (including 4 or 5 metrics) best distinguished children with MS from controls. RESULTS: Twenty pediatric-onset MS subjects, aged 6-21 years, and thirteen healthy controls, aged 6-19 years, were enrolled. MS subjects demonstrated worse scores on the 9HPT (p=0.004) and SDMT (p=0.001), but not the 25FTW (adjusted for height, p=0.63) or the ChiPASAT (p=0.10): all comparisons adjusted for age. Decreased (worse) binocular LCLA scores were associated with MS (vs. control status, p=0.03, logistic regression; p=0.08, accounting for age). The MSFC composite score for the traditional 3 components did not differ between the groups (p=0.28). Replacing the ChiPASAT with the SDMT (OR 0.72, p=0.05) better distinguished MS from controls. A modified MSFC-4 with the SDMT replacing the ChiPASAT and including binocular 1.25% LCLA had the greatest capacity to distinguish pediatric MS from controls (OR 0.89, p=0.04, logistic regression). Including all 5 metrics as a composite MSFC-5 did not improve the model (p=0.18). CONCLUSIONS: A modified MSFC (25FTW, 9HPT, SMDT, and binocular 1.25% LCLA) is more sensitive than the traditional MSFC or its components to capture the subtle impairments that characterize pediatric MS and should be validated in order to be considered for future pediatric MS trials.

OBJECTIVE: The King-Devick (KD) test, which is based on rapid number naming speed, is a performance measure that adds vision and eye movement assessments to sideline concussion testing. We performed a laboratory-based study to characterize ocular motor behavior during the KD test in a patient cohort with chronic concussion to identify features associated with prolonged KD reading times. METHODS: Twenty-five patients with a concussion history (mean age: 31) were compared to control participants with no concussion history (n = 42, mean age: 32). Participants performed a computerized KD test under infrared-based video-oculography. RESULTS: Average intersaccadic intervals for task-specific saccades were significantly longer among concussed patients compared to controls (324.4 +/- 85.6 msec vs. 286.1 +/- 49.7 msec, P = 0.027). Digitized KD reading times were prolonged in concussed participants versus controls (53.43 +/- 14.04 sec vs. 43.80 +/- 8.55 sec, P = 0.004) and were highly correlated with intersaccadic intervals. Concussion was also associated with a greater number of saccades during number reading and larger average deviations of saccade endpoint distances from the centers of the to-be-read numbers (1.22 +/- 0.29 degrees vs. 0.98 +/- 0.27 degrees , P = 0.002). There were no differences in saccade peak velocity, duration, or amplitude. INTERPRETATION: Prolonged intersaccadic intervals, greater numbers of saccades, and larger deviations of saccade endpoints underlie prolonged KD reading times in chronic concussion. The KD test relies upon a diffuse neurocognitive network that mediates the fine control of efferent visual function. One sequela of chronic concussion may be disruption of this system, which may produce deficits in spatial target selection and planning of eye movements.

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.