Faculty Bibliography

OBJECTIVE: The study purpose was to examine vision-specific and overall health-related quality of life (QOL) at baseline in Idiopathic Intracranial Hypertension Treatment Trial patients who were newly diagnosed and had mild visual loss. We also sought to determine the associations between vision-specific QOL scores and visual symptoms, visual function, pain, headache-related disability, and obesity. METHODS: We assessed QOL using the 36-Item Short Form Health Survey, National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25), and 10-Item NEI-VFQ-25 Neuro-Ophthalmic Supplement. We compared these results with those of previously reported idiopathic intracranial hypertension (IIH) QOL studies. We assessed relationships between QOL and other clinical characteristics. RESULTS: Among 165 participants with IIH (161 women and 4 men with a mean age +/- SD of 29.2 +/- 7.5 years), vision-specific QOL scores were reduced compared with published values for disease-free controls. Scores of participants were comparable to published results for patients with multiple sclerosis and a history of optic neuritis. A multiple linear regression model for the NEI-VFQ-25 composite score found that perimetric mean deviation in the best eye, visual acuity in the worst eye, visual symptoms, and pain symptoms (headache, neck pain), but not obesity, were independently associated with QOL. CONCLUSIONS: IIH affects QOL at time of diagnosis even in patients with mild visual impairment. Vision-specific QOL in patients with newly diagnosed IIH may be as decreased as that for patients with other neuro-ophthalmic disorders. IIH treatment should target visual loss and other symptoms of increased intracranial pressure associated with reduced QOL. Reduced QOL does not simply reflect obesity, an underlying IIH risk factor.

BACKGROUND: Treatment options for neuromyelitis optica (NMO) are currently based on small retrospective case series and open label studies, ranging from 10 to 103 patients. OBJECTIVE: To compare the efficacy and tolerability of azathioprine, cyclophosphamide, mycophenolate, and rituximab in patients with neuromyelitis optica. METHODS: This is a retrospective chart review and telephone follow-up study of 71 patients with NMO or NMO spectrum disorder, 54 of whom were treated with the study drugs. We compared adverse events, annualized relapse rates and expanded disability status scales before and after treatment. RESULTS: The median ARR decreased from 1.17 to 0.25 on rituximab (P<0.01), 0.92 to 0.56 on azathioprine (P=0.475), 1.06 to 0.39 on mycophenolate (P<0.05) and 1.30 to 0.92 on cyclophosphamide (P=0.746). When compared directly to azathioprine, rituximab significantly reduced relapse rates (P=0.021). The median EDSS decreased from 7 to 5 on rituximab (P<0.01) and 7 to 6 on azathioprine (P<0.01), and did not change significantly on mycophenolate (4 to 5; P=0.463) or cyclophosphamide (6.5 to 6.5; P=0.881). Twenty-five percent of patients noted adverse events on rituximab, 36% on azathioprine, 36% on mycophenolate, and 80% on cyclophosphamide. CONCLUSION: Rituximab significantly reduces relapse rates and improves disability while maintaining comparable tolerability to other immunosuppressive treatments for NMO.

PURPOSE: Sports-related concussion has received increasing attention as a result of neurologic sequelae seen among athletes, highlighting the need for a validated, rapid screening tool. The King-Devick (K-D) test requires vision, eye movements, language function and attention in order to perform and has been proposed as a promising tool for assessment of concussion. We investigated the K-D test as a sideline screening tool in a collegiate cohort to determine the effect of concussion. METHODS: Athletes (n=127, mean age 19.6+/-1.2 years) from the Wheaton College football and men's and women's basketball teams underwent baseline K-D testing at pre-season physicals for the 2012-2013 season. K-D testing was administered immediately on the sidelines for football players with suspected head injury during regular games and changes compared to baseline were determined. Post-season testing was also performed to compare non-concussed athletes' test performance. RESULTS: Concussed athletes (n=11) displayed sideline K-D scores that were significantly higher (worse) than baseline (36.5+/-5.6s vs. 31.3+/-4.5s, p<0.005, Wilcoxon signed-rank test). Post-season testing demonstrated improvement of scores and was consistent with known learning effects (35.1+/-5.2s vs. 34.4+/-5.0s, p<0.05, Wilcoxon signed-rank test). Test-retest reliability was analyzed between baseline and post-season administrations of the K-D test resulting in high levels of test-retest reliability (intraclass correlation coefficient (ICC)=0.95 [95% Confidence Interval 0.85-1.05]). CONCLUSIONS: The data show worsening of K-D test scores following concussion further supporting utility of the K-D test as an objective, reliable and effective sideline visual screening tool to help identify athletes with concussion.

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.

BACKGROUND: Concussion, particularly in relation to sports and combat activities, is increasingly recognized as a potential cause of both short- and long-term neurologic sequelae. This review will focus on the neuro-ophthalmologic findings associated with concussion, the current tests for concussion, and the potential for visual performance measures to improve our detection and assessment of concussions. EVIDENCE ACQUISITION: A PubMed search using the specific key words "concussion," "mild traumatic brain injury," "neuro-ophthalmological findings," and "diagnostic and management tests" was performed. An emphasis was placed on articles published during the past 5 years, but additional articles referenced within recent publications were obtained. RESULTS: Concussion is frequently associated with abnormalities of saccades, pursuit eye movements, convergence, accommodation, and the vestibular-ocular reflex. Current sideline testing for athletes includes the Sports Concussion Assessment Tool, Third Edition (SCAT3) incorporates cognitive and balance testing. The King-Devick (K-D) test is a rapid visual performance measures that can be used on sidelines by nonmedical personnel, including parents of youth athletes. The K-D test complements components of the SCAT3 and improves the detection of concussions. Other vision-based tools for diagnosing and for managing concussion include eye movement tracking devices, pupillary assessment, computerized testing, imaging modalities, and eletrophysiologic testing. Many of the imaging modalities and electrophysiological studies have been combined with vision-based tests. CONCLUSIONS: Concusssion is associated with many neuro-ophthalmologic signs and symptoms. Visual performance measures enhance the detection and management of concussion, and future studies are under way to further incorporate vision-based testing into sideline diagnosis and long-term clinical assessments.

OBJECTIVE: To assess relationships between spinal cord MRI (SC-MRI) and retinal measures, and to evaluate whether these measures independently relate to clinical disability in multiple sclerosis (MS). METHODS: One hundred two patients with MS and 11 healthy controls underwent 3-tesla brain and cervical SC-MRI, which included standard T1- and T2-based sequences and diffusion-tensor and magnetization-transfer imaging, and optical coherence tomography with automated segmentation. Clinical assessments included visual acuity (VA), Expanded Disability Status Scale, MS functional composite, vibration sensation threshold, and hip-flexion strength. Regions of interest circumscribing SC cross-sections at C3-4 were used to obtain cross-sectional area (CSA), fractional anisotropy (FA), perpendicular diffusivity (lambda perpendicular), and magnetization transfer ratio. Multivariable regression assessed group differences and SC, retinal, and clinical relationships. RESULTS: In MS, there were correlations between SC-CSA, SC-FA, SC-lambda perpendicular, and peripapillary retinal nerve fiber layer (pRNFL) (p = 0.01, p = 0.002, p = 0.001, respectively) after adjusting for age, sex, prior optic neuritis, and brain atrophy. In multivariable clinical models, when SC-CSA, pRNFL, and brain atrophy were included simultaneously, SC-CSA and pRNFL retained independent relationships with low-contrast VA (p = 0.04, p = 0.002, respectively), high-contrast VA (p = 0.06, p = 0.008), and vibration sensation threshold (p = 0.01, p = 0.05). SC-CSA alone retained independent relationships with Expanded Disability Status Scale (p = 0.001), hip-flexion strength (p = 0.001), and MS functional composite (p = 0.004). CONCLUSIONS: In this cross-sectional study of patients with MS, correlations exist between SC-MRI and retinal layers, and both exhibit independent relationships with clinical dysfunction. These findings suggest that the SC and optic nerve reflect ongoing global pathologic processes that supplement measures of whole-brain atrophy, highlighting the importance of combining measures from unique compartments to facilitate a thorough examination of regional and global disease processes that contribute to clinical disability in MS.