Faculty Bibliography

OBJECTIVE:To evaluate the performance of the EyeTribe compared to the EyeLink for eye movement recordings during a rapid number naming test in healthy control participants. BACKGROUND:With the increasing accessibility of portable, economical, video-based eye trackers such as the EyeTribe, there is growing interest in these devices for eye movement recordings, particularly in the domain of sports-related concussion. However, prior to implementation there is a primary need to establish the validity of these devices. One current limitation of portable eye trackers is their sampling rate (30-60 samples per second, or Hz), which is typically well below the benchmarks achieved by their research-grade counterparts (e.g., the EyeLink, which samples at 500-2000 Hz). METHODS:We compared video-oculographic measurements made using the EyeTribe with those of the EyeLink during a digitized rapid number naming task (the King-Devick test) in a convenience sample of 30 controls. RESULTS:EyeTribe had loss of signal during recording, and failed to reproduce the typical shape of saccadic main sequence relationships. In addition, EyeTribe data yielded significantly fewer detectable saccades and displayed greater variance of inter-saccadic intervals than the EyeLink system. CONCLUSION/CONCLUSIONS:Caution is advised prior to implementation of low-resolution eye trackers for objective saccade assessment and sideline concussion screening.

OBJECTIVE:To determine if native English speakers (NES) perform differently compared to non-native English speakers (NNES) on a sideline-focused rapid number naming task. A secondary aim was to characterize objective differences in eye movement behaviour between cohorts. BACKGROUND:The King-Devick (KD) test is a rapid number-naming task in which numbers are read from left-to-right. This performance measure adds vision-based assessment to sideline concussion testing. Reading strategies differ by language. Concussion may also impact language and attention. Both factors may affect test performance. METHODS:Twenty-seven healthy  NNES and healthy NES performed a computerized KD test under high-resolution video-oculography.  NNES also performed a Bilingual Dominance Scale (BDS) questionnaire to weight linguistic preferences (i.e., reliance on non-English language(s)). RESULTS:Inter-saccadic intervals were significantly longer in  NNES (346.3 ± 78.3 ms vs. 286.1 ± 49.7 ms, p = 0.001), as were KD test times (54.4 ± 15.1 s vs. 43.8 ± 8.6 s, p = 0.002). Higher BDS scores, reflecting higher native language dominance, were associated with longer inter-saccadic intervals in  NNES. CONCLUSION/CONCLUSIONS:These findings have direct implications for the assessment of athlete performance on vision-based and other verbal sideline concussion tests; these results are particularly important given the international scope of sport. Pre-season baseline scores are essential to evaluation in the event of concussion, and performance of sideline tests in the athlete's native language should be considered to optimize both baseline and post-injury test accuracy.

Background/UNASSIGNED:The retinal microcirculation has been studied in various diseases including multiple sclerosis (MS). However, inter-eye correlations and potential differences of the retinal blood flow velocity (BFV) remain largely unstudied but may be important in guiding eye selection as well as the design and interpretation of studies assessing or utilizing retinal BFV. The primary aim of this study was to determine inter-eye correlations in BFVs in healthy controls (HCs). Since prior studies raise the possibility of reduced BFV in MS eyes, a secondary aim was to compare retinal BFVs between MS eyes, grouped based on optic neuritis (ON) history and HC eyes. Methods/UNASSIGNED:Macular arteriole and venule BFVs were determined using a retinal function imager (RFI) in both eyes of 20 HCs. One eye from a total of 38 MS patients comprising 13 eyes with ON (MSON) and 25 eyes without ON (MSNON) history were similarly imaged with RFI. Results/UNASSIGNED: = 0.48, respectively). Conclusions/UNASSIGNED:Inter-eye arteriolar and venular BFVs do not differ significantly in HCs and are strongly correlated. Our findings support prior observations that arteriolar and venular BFVs may be reduced in MS eyes. Moreover, this seems to be the case in both MS eyes with and without a history of ON, raising the possibility of global blood flow alterations in MS. Future larger studies are needed to assess differences in BFVs between MSON and MSNON eyes.

Visual symptoms, such as photophobia and blurred vision, are common in patients with concussion. Such symptoms may be accompanied by abnormalities of specific eye movements, such as saccades and convergence, or accommodation deficits. The high frequency of visual involvement in concussion is not surprising, since more than half of the brain's pathways are dedicated to vision and eye movement control. These areas include many that are most vulnerable to head trauma, including the frontal and temporal lobes. Vision and eye movement testing is important at the bedside and on the sidelines of athletic events, where brief performance measures that require eye movements, such as rapid number naming, are reliable and sensitive measures for concussion detection. Tests of vision and eye movements are also being explored clinically to identify and monitor patients with symptoms of both sport- and nonsport-related concussion. Evaluation of vision and eye movements can assist in making important decisions after concussion, including the prognosis for symptom recovery, and to direct further visual rehabilitation as necessary.

Background/UNASSIGNED:Sports concussion has an annual incidence of approximately 3.8 million. Over half go unreported and a substantial number may be asymptomatic. A rapid, cost-effective, and reliable tool that facilitates diagnosis of concussion is needed. The King-Devick (K-D) test is a vision-based tool of rapid number naming for assessment of concussion. In this study, we evaluated the utility of the K-D test in real time for identification of symptomatic concussion in youth athletes and to determine if similar impairment (subclinical concussion) exists in youth athletes without an obvious head injury or symptoms. Methods/UNASSIGNED:Youth hockey players underwent K-D testing preseason, postseason, and immediately after suspected concussion. Additional testing was performed in a subgroup of nonconcussed athletes immediately before and after a game to determine effects of fatigue on K-D scores. Results/UNASSIGNED:< 0.05) and 51 nonconcussed players assessed before and after a game revealed no significant time change as a result of fatigue. Conclusions/UNASSIGNED:Rapid number naming using the K-D test accurately identifies real-time, symptomatic concussion in youth athletes. Scores in concussed players may remain abnormal over time. Athletes should undergo preseason and postseason K-D testing, with additional evaluation real time to inform the assessment of suspected concussion. Classification of Evidence/UNASSIGNED:This study provides Class III evidence that the K-D test accurately identifies real-time concussions in youth athletes.

BACKGROUND: Given that post-traumatic headache is one of the most prevalent and long-lasting post-concussion sequelae, causes significant morbidity, and might be associated with slower neurocognitive recovery, we sought to evaluate the use of concussion screening scores in a concussion clinic population to assess for post-traumatic headache. METHODS: This is a retrospective cross-sectional study of 254 concussion patients from the New York University (NYU) Concussion Registry. Data on the headache characteristics, concussion mechanism, concussion screening scores were collected and analyzed. RESULTS: 72% of the patients had post-traumatic headache. About half (56.3%) were women. The mean age was 35 (SD 16.2). 90 (35%) patients suffered from sport-related concussions (SRC). Daily post-traumatic headache patients had higher Sport Concussion Assessment Tool (SCAT)-3 symptom severity scores than the non-daily post-traumatic headache and the headache-free patients (50.2 [SD 28.2] vs. 33.1 [SD 27.5] vs. 21.6 SD23], p < 0.001). Patients with SRC had lower headache intensity (4.47 [SD 2.5] vs. 6.24 [SD 2.28], p < 0.001) and SCAT symptom severity scores (33.9 [SD 27.4] vs. 51.4 [SD 27.7], p < 0.001) than the other patients, but there were no differences in post-traumatic headache prevalence, frequency, and Standardized Assessment of Concussion (SAC) scores. CONCLUSION: The presence and frequency of post-traumatic headache are associated with the SCAT-3 symptom severity score, which is the most important predictor for post-concussion recovery. The SCAT-3 symptom severity score might be a useful tool to help characterize patients' post-traumatic headache.

BACKGROUND: Morphologic macular abnormalities (MMAs) are frequently seen on macular optical coherence tomography (OCT) imaging in neuroimmunology practice, yet studies pragmatically assessing prevalence and risk factors of MMAs to date are limited. OBJECTIVE: To describe the characteristics of MMAs in a neuroimmunology-based academic practice. METHODS: Cross-sectional study of 1450 patients (2900 eyes) who underwent spectral-domain macular OCT between June 2010 and June 2012. The association between MMAs and demographic variables was analyzed using mixed-effects logistic regression. Odds ratios (ORs) were calculated per 5-year age increments. RESULTS: MMAs were observed in 338/2872 eyes (11.7%) of 232/1445 participants (16.1%). The most common abnormalities identified, included drusen (6.0%), epiretinal membrane (ERM; 5.5%), and microcystoid macular pathology (MMP; 1.9%). Overall, patients with MMAs were older (OR: 1.79, p = 5 x 10-5) and more likely to be males (OR: 2.45, p = 0.014). In particular, advancing age was associated with higher risk of drusen and ERM (OR: 1.80 and 4.26, p = 2 x 10-5 and 7 x 10-3, respectively). MMP prevalence declined with age (OR: 0.73, p = 0.015) and was associated with African-American ethnicity (OR: 15.0, p = 5 x 10-5). CONCLUSION: Unexpected or incidental MMAs are common in patients assessed with OCT in neuroimmunology practice, emphasizing the importance of comprehensive OCT image review for risk stratification and appropriate ophthalmology referral.

Background: Retinal imaging by optical coherence tomography (OCT) has gained increasing attention in multiple sclerosis and other neuroinflammatory and neurodegenerative disorders. Ambiguous and incomplete reporting of methodology and OCT-derived data have limited the ability to compare data and to apply and generalize findings in the past. To improve this situation, the Advised Protocol for Optical coherence tomography Study Terminology and Elements (APOSTEL) recommendations have been developed to outline core information to be provided when reporting quantitative OCT studies with help of a 9-point checklist (Cruz-Herranz and Balk et al., Neurology 2016). The APOSTEL recommendations currently have the evidence level of an expert opinion (Class IV). Objective: To advance the APOSTEL recommendations for OCT reporting in a formalized procedure towards evidence-based guidelines. Methods: Studies reporting quantitative OCT results published within the last 24 months have been identified by a Pubmed search. The corresponding authors of these 1472 articles will be contacted and asked to participate in an online survey to evaluate and give feedback on the initial APOSTEL recommendations. The feedback obtained will be anonymized and distributed to a panel of international experts for evaluation and revision of the recommendations. After the initial round the corresponding authors who gave feedback will be informed about the intermediate results and asked to participate in the survey for a second time. This procedure will be repeated if necessary following the consensus-building procedure of a DELPHI process. To this end, for each round the feedback obtained as well as any revisions made to the APOSTEL recommendations will be summarized and questionnaires will be used for evaluation in order to reach consensus and to develop evidencebased guidelines for prospective OCT studies. Results: The degree of consensus of the survey's participants will be reported for the initial and the revised versions of the recommendations as well as the revisions made to the initial version. Conclusion: Formal guidelines for the reporting of quantitative OCT studies will be presented as well as the process of how they were developed

Introduction: The optic nerve and visual pathway are frequent sites for involvement in multiple sclerosis (MS). Optical coherence tomography (OCT) detects retinal nerve fiber layer (RNFL) thinning in eyes of patients with MS or in the case of clinically-or radiologically-isolated syndromes. Current diagnostic criteria do not include the optic nerve as an imaging lesion site despite a high prevalence of acute optic neuritis (ON) among early MS and clinically isolated syndrome (CIS) patients. We sought to determine optimal thresholds for inter-eye difference in RNFL thickness that are most predictive of an optic nerve lesion. Methods: Spectral-domain (SD-)OCT data from an ongoing collaborative study of visual outcomes in MS were analyzed for a single site. Median values for inter-eye difference in RNFL thickness were also calculated from the RENEW trial cohort at the 6-month endpoint. RENEW was a randomized, placebo-controlled trial of opicinumab in subjects with a first episode of acute unilateral ON, and represents the most well-characterized cohort of CIS patients with ON incorporating modern tests of visual structure and function. RENEW utilized SD-OCT with a centralized reading center. Results: Among healthy volunteer control participants in the collaborative investigation (convenience sample, n=31), the 95th percentile value for inter-eye difference (upper boundary of expected for normals) was 6.0 microns. This value, as well as median intereye differences from the RENEW cohort (8.5 microns for placebo, n=41; 13.0 microns for opicinumab, n=41), were applied to convenience sample group of MS patients (n=136) as a validation cohort. Positive predictive value, sensitivity and specificity for identifying MS patients with a history of unilateral ON were greatest for the 6-micron value compared to the RENEW medians in a 2x2 table analysis (p< 0.0001, chi-square). The 6-micron threshold was also predictive of worse binocular low-contrast acuity at 2.5% (p=0.02) and 1.25% (p=0.002, linear regression). ROC curve analysis demonstrated an optimal inter-eye difference threshold of 5 microns for identifying unilateral ON in the MS cohort. Conclusion: Inter-eye differences of 5-6 microns in RNFL thickness are thus far optimal for predicting a unilateral optic nerve lesion in MS. Larger international collaborative investigations involving 20 or more MS validation cohort sites are underway to maximize precision and generalizability for these OCT-based thresholds

BACKGROUND: Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the introduction of spectral domain optical coherence tomography (SD-OCT), supervised automated segmentation of individual retinal layers is possible. We aimed to investigate which retinal layers show atrophy associated with neurodegeneration in multiple sclerosis when measured with SD-OCT. METHODS: In this systematic review and meta-analysis, we searched for studies in which SD-OCT was used to look at the retina in people with multiple sclerosis with or without optic neuritis in PubMed, Web of Science, and Google Scholar between Nov 22, 1991, and April 19, 2016. Data were taken from cross-sectional cohorts and from one timepoint from longitudinal studies (at least 3 months after onset in studies of optic neuritis). We classified data on eyes into healthy controls, multiple-sclerosis-associated optic neuritis (MSON), and multiple sclerosis without optic neuritis (MSNON). We assessed thickness of the retinal layers and we rated individual layer segmentation performance by random effects meta-analysis for MSON eyes versus control eyes, MSNON eyes versus control eyes, and MSNON eyes versus MSON eyes. We excluded relevant sources of bias by funnel plots. FINDINGS: Of 25 497 records identified, 110 articles were eligible and 40 reported data (in total 5776 eyes from patients with multiple sclerosis [1667 MSON eyes and 4109 MSNON eyes] and 1697 eyes from healthy controls) that met published OCT quality control criteria and were suitable for meta-analysis. Compared with control eyes, the peripapillary retinal nerve fibre layer (RNFL) showed thinning in MSON eyes (mean difference -20.10 mum, 95% CI -22.76 to -17.44; p<0.0001) and in MSNON eyes (-7.41 mum, -8.98 to -5.83; p<0.0001). The macula showed RNFL thinning of -6.18 mum (-8.07 to -4.28; p<0.0001) in MSON eyes and -2.15 mum (-3.15 to -1.15; p<0.0001) in MSNON eyes compared with control eyes. Atrophy of the macular ganglion cell layer and inner plexiform layer (GCIPL) was -16.42 mum (-19.23 to -13.60; p<0.0001) for MSON eyes and -6.31 mum (-7.75 to -4.87; p<0.0001) for MSNON eyes compared with control eyes. A small degree of inner nuclear layer (INL) thickening occurred in MSON eyes compared with control eyes (0.77 mum, 0.25 to 1.28; p=0.003). We found no statistical difference in the thickness of the combined outer nuclear layer and outer plexiform layer when we compared MSNON or MSON eyes with control eyes, but we found a small degree of thickening of the combined layer when we compared MSON eyes with MSNON eyes (1.21 mum, 0.24 to 2.19; p=0.01). INTERPRETATION: The largest and most robust differences between the eyes of people with multiple sclerosis and control eyes were found in the peripapillary RNFL and macular GCIPL. Inflammatory disease activity might be captured by the INL. Because of the consistency, robustness, and large effect size, we recommend inclusion of the peripapillary RNFL and macular GCIPL for diagnosis, monitoring, and research. FUNDING: None.