Faculty Bibliography

OBJECTIVE: Concussion is a major public health problem and considerable efforts are focused on sideline-based diagnostic testing to guide return-to-play decision-making and clinical care. The King-Devick (K-D) test, a sensitive sideline performance measure for concussion detection, reveals slowed reading times in acutely concussed subjects, as compared to healthy controls; however, the normal behavior of eye movements during the task and deficits underlying the slowing have not been defined. METHODS: Twelve healthy control subjects underwent quantitative eye tracking during digitized K-D testing. RESULTS: The total K-D reading time was 51.24 (+/-9.7) seconds. A total of 145 saccades (+/-15) per subject were generated, with average peak velocity 299.5 degrees /s and average amplitude 8.2 degrees . The average inter-saccadic interval was 248.4ms. Task-specific horizontal and oblique saccades per subject numbered, respectively, 102 (+/-10) and 17 (+/-4). Subjects with the fewest saccades tended to blink more, resulting in a larger amount of missing data; whereas, subjects with the most saccades tended to make extra saccades during line transitions. CONCLUSIONS: Establishment of normal and objective ocular motor behavior during the K-D test is a critical first step towards defining the range of deficits underlying abnormal testing in concussion. Further, it sets the groundwork for exploration of K-D correlations with cognitive dysfunction and saccadic paradigms that may reflect specific neuroanatomic deficits in the concussed brain.

Mild head injury such as concussions and subconcussive repetitive impact may lead to subtle changes in brain function and it is imperative to find sensitive and reliable tests to detect such changes. Tests involving the visual system, in particular eye movements, can incorporate higher cortical functioning and involve diffuse pathways in the brain, including many areas susceptible to head impact. With concussions, the clinical neuro-ophthalmic exam is important for detecting abnormalities in vergence, saccades, pursuit, and visual fixation. On the sidelines, the King-Devick test has been used as a visual performance measure that incorporates eye movements and increases the sensitivity in detecting possible concussions in conjunction with standard sideline tests of cognition, symptom checklists, and balance. Much promise lies in the eye movement laboratory to quantitate changes in saccades and pursuit with concussions using video-oculography. A combination of eye movement tasks coupled with neuroimaging techniques and other objective biomarkers may lead to a better understanding of the anatomical and physiological consequences of concussion and to better understand the natural history of this condition.

We report four patients with monocular visual loss for whom optical coherence tomography (OCT) was helpful in distinguishing the sequelae of retinal artery occlusion from those of primary optic neuropathy. Determinations of the peripapillary retinal nerve fiber layer (RNFL) thickness as well as macular retinal layer thicknesses and architecture were used. The major findings in our patients show that changes in the inner retinal layers (including ganglion cell and inner plexiform layer) with disruption of normal macular architecture supports a diagnosis of retinal artery occlusion. Our results support the use of OCT imaging for patients with monocular visual loss of uncertain etiology; macular imaging as well as peripapillary RNFL thickness measurement can be helpful in differentiating primary retinal disease or ischemia from primary disorders of the optic nerve.

PURPOSE OF REVIEW: Idiopathic intracranial hypertension (IIH) is a potentially blinding disorder of unknown cause, characterized by elevated intracranial pressure in the absence of a mass lesion, venous sinus thrombosis, or meningitis. This review summarizes recent developments and insights from leading treatment trials, emerging treatment options, and evolving ways to evaluate IIH. RECENT FINDINGS: The Idiopathic Intracranial Hypertension Treatment Trial is the first large-scale, randomized, prospective study to evaluate medical treatment of patients with mild vision loss. These data have facilitated our understanding of baseline clinical manifestations, including impact on quality of life and treatment outcomes. Recent hypotheses and studies evaluating the role of cerebral venous sinus stenosis and stenting are discussed. Technological advances in optical coherence tomography are emerging to provide novel ways of evaluating and tracking optic disc swelling in IIH. SUMMARY: Recent changes in defining IIH, understanding the impact and treatment of mild visual loss, and the roles that cerebral venous stenting and optical coherence tomography might have in clinical practice provide the framework to better treat patients with IIH.

BACKGROUND: Retinal nerve fiber and ganglion cell+inner plexiform (GCIP) layer thinning following multiple sclerosis-related acute optic neuritis (AON) is well described. However, whether AON results in changes in the inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL) and/or photoreceptor segment (PS) layers remains undetermined. OBJECTIVES: The objective of this paper is to determine if INL+OPL and/or ONL+PS changes occur following AON. METHODS: Thirty-three AON patients underwent serial optical coherence tomography (OCT) and visual function testing (mean follow-up: 25 months). Longitudinal changes in retinal layer thickness were analyzed using mixed-effects linear regression. RESULTS: Four months following AON, the mean decrease in GCIP thickness relative to baseline was 11.4% (p < 0.001). At four months, a concomitant 3.4% increase in average ONL+PS thickness was observed (p < 0.001). The percentage decrease in GCIP thickness and increase in ONL+PS thickness were strongly correlated (r = -0.70; p < 0.001). Between months 4 to 12, ONL+PS thickness declined and, at 12 months, was no longer significantly different from baseline (mean change: 0.5%; p = 0.37). Similar, albeit less robust, changes in the INL+OPL were observed. CONCLUSIONS: Following AON, dynamic changes occur in the deep retinal layers, which are proportional to GCIP thinning. These novel findings help further our understanding of the biological and/or anatomical sequelae resulting from AON.

We examined the King-Devick (K-D) test, a vision-based test of rapid number naming, as a complement to components of the Sport Concussion Assessment Tool, 3rd edition (SCAT3) for diagnosis of concussion. Baseline and postconcussion data for the University of Florida men's football, women's soccer, and women's lacrosse teams were collected, including the K-D test, Standardized Assessment of Concussion (SAC), and Balance Error Scoring System (BESS). Among 30 athletes with first concussion during their athletic season (n = 217 total), differences from baseline to postinjury showed worsening of K-D time scores in 79%, while SAC showed a ≥2-point worsening in 52%. Combining K-D and SAC captured abnormalities in 89%; adding the BESS identified 100% of concussions. Adding a vision-based test may enhance the detection of athletes with concussion.

Background: Anti-LINGO-1 is a monoclonal antibody antagonist of LINGO-1, an oligodendrocyte differentiation and myelination suppressor. Objective: To determine the efficacy/safety of anti-LINGO-1 for CNS remyelination. Methods: Subjects with a first unilateral acute optic neuritis episode were treated with high-dose steroids and randomized to 100mg/kg anti-LINGO-1 IV or placebo every 4 weeks (NCT01721161). Subject and IRB approval were obtained. Nerve conduction latency recovery using full-field visual evoked potential (FF-VEP) in the affected eye over time versus unaffected eye at baseline assessed remyelination (pre-specified primary endpoint). Between-treatment comparisons were evaluated by ANCOVA and mixed-effect model repeated measure (MMRM) in subjects who completed the study and did not miss >1 study dose or receive MS modifying therapy (prespecified per-protocol population). Safety/tolerability was evaluated in those who received >1 study dose and included adverse event (AE) and clinical laboratory result assessments. Results: Anti-LINGO-1-treated subjects (n =33) showed improved latency recovery versus placebo (n=36): mean (95% confidence interval) -7.55ms (-15.12 to 0.01) at Week 24 (P=0.05); -9.13ms (-16.11 to -2.14; P=0.01) at Week 32. 54% of anti-LINGO-1 subjects had no/mild latency delay at Week 24 (affected eye FF-VEP latency <10% worse than baseline fellow eye) versus 27% of the placebo group (P=0.036). Additional subgroup analyses will be presented. 34/41 in each group experienced any AE, serious AEs occurred in 2 placebo and 5 anti-LINGO-1 subjects, and there were 3 treatment-related serious AEs. Conclusions: Improvement in FF-VEP latency is consistent with the first evidence of remyelination in a Phase 2 trial. Anti-LINGO-1 was generally well tolerated