Faculty Bibliography

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.

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.

Background/UNASSIGNED:Vision encompasses a large component of the brain's pathways, yet is not represented in current sideline testing. Objectives/UNASSIGNED:We performed a meta-analysis of published data for a vision-based test of rapid number naming (King-Devick [K-D] test). Studies & methods/UNASSIGNED:Pooled and meta-analysis of 15 studies estimated preseason baseline K-D scores and sensitivity/specificity for identifying concussed versus nonconcussed control athletes. Result/UNASSIGNED:= 0.0%; p=0.85 - indicating very little heterogeneity). Sensitivity was 86% (96/112 concussed athletes had K-D worsening; 95% CI: 78%, 92%); specificity was 90% (181/202 controls had no worsening; 95% CI: 85%, 93%). Conclusion/UNASSIGNED:Rapid number naming adds to sideline assessment and contributes a critical dimension of vision to sports-related concussion testing.

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.

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.

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.

OBJECTIVE: To determine whether atrophy of specific retinal layers and brain substructures are associated over time, in order to further validate the utility of optical coherence tomography (OCT) as an indicator of neuronal tissue damage in patients with multiple sclerosis (MS). METHODS: Cirrus high definition OCT (including automated macular segmentation) was performed in 107 MS patients biannually (median follow-up: 46-months). Three-tesla magnetic resonance imaging brain scans (including brain-substructure volumetrics) were performed annually. Individual-specific rates of change in retinal and brain measures (estimated with linear regression) were correlated, adjusting for age, sex, disease duration, and optic neuritis (ON) history. RESULTS: Rates of ganglion cell + inner plexiform layer (GCIP) and whole-brain (r=0.45,p<0.001), gray matter (GM; r=0.37,p<0.001), white matter (WM; r=0.28,p=0.007) and thalamic (r=0.38,p<0.001) atrophy were associated. GCIP and whole-brain (as well as GM and WM) atrophy rates were more strongly associated in progressive MS (r=0.67,p<0.001) than relapsing-remitting MS (RRMS; r=0.33,p=0.007). However, correlation between rates of GCIP and whole-brain (and additionally GM and WM) atrophy in RRMS increased incrementally with step-wise refinement to exclude ON effects; excluding eyes and then patients (to account for a phenotype effect) the correlation increased to 0.45 and 0.60 respectively, consistent with effect modification. In RRMS, lesion accumulation rate was associated with GCIP (r=-0.30,p=0.02) and inner nuclear layer (r=-0.25,p=0.04) atrophy rates. INTERPRETATION: Over time GCIP atrophy appears to mirror whole-brain, and particularly GM atrophy, especially in progressive MS, thereby reflecting underlying disease progression. Our findings support OCT for clinical monitoring and as an outcome in investigative trials

OBJECTIVE: To educate physicians about appropriate acute migraine treatment guidelines by determining (1) where headache patients were first prescribed opioids and barbiturates, and (2) the characteristics of the patient population who had been prescribed opioids and barbiturates. BACKGROUND: Several specialty societies issued recommendations that caution against the indiscriminate use of opioids or barbiturate containing medications for the treatment of migraine. These medications are still being prescribed in various medical settings and could put headache specialists in a difficult position when patients request these agents. METHODS: Patients presenting to a headache center comprised of eight physicians were asked to complete a survey that assessed headache types, comorbid conditions, and whether they had ever been prescribed opioids or barbiturates. If they responded affirmatively to the latter question, they were asked about the prescribing doctor, medication effectiveness, and whether they were currently on the medication. Data collection took place over a one month period. RESULTS: Two hundred forty-four patients were given the survey and 218 of these patients completed it. The predominant diagnosis was migraine (83.9%). More than half of the patients reported having been prescribed an opioid (54.8%) or a barbiturate (56.7%). About one fifth were on opioids (19.4%) or barbiturates (20.7%) at the time of completing the survey. Most patients reported being on opioids for more than 2 years (24.6%) or less than one week (32.1%). The reasons most frequently cited for stopping opioids were that the medications did not help (30.9%) or that they saw a new doctor who would not prescribe them (29.4%). Among patients who had previously been on barbiturates, 32.2% had been on these for over 2 years. Most patients (61.8%) stopped barbiturates because they did not find the medication helpful, while 17.6% said they saw a new doctor who would not prescribe them. The physician specialty most frequently cited as being the first prescriber for opioids was emergency medicine (20.2%) with family doctors and general neurologists the next groups at 17.7% each. General neurologists were the most frequent (37.8%) first prescribers of barbiturates. CONCLUSIONS: Approximately 20% of patients presenting to a headache center reported current use of opioids and/or barbiturates. ED physicians were reported to be the most frequent first prescribers of opioids and general neurologists were the most frequent first prescribers of barbiturates. Taken as a whole, these data provide a useful snapshot of the wide variety of physician specialties that might benefit from additional education on the appropriate use of opioids and barbiturate-containing medications in patients with headaches.

Concussion may lead to subtle changes in brain function, and tests involving the visual system probe higher cortical functioning and increase our sensitivity in detecting these changes. Concussions are acutely and sometimes more persistently associated with abnormalities in balance, cognition, and vision. The visual system involves roughly half of the brain's circuits, including many regions susceptible to head impacts. After a concussion, the neuro-ophthalmologic exam commonly detects abnormalities in convergence, accommodation, the vestibulo-ocular reflex, ocular muscle balance, saccades, and pursuit. The King-Devick (K-D) test is a visual performance measure that may increase the sensitivity of detecting concussions on the sideline when used in combination with tests of cognition and balance that are part of the Sports Concussion Assessment Tool (3rd ed.; SCAT3). Portable eye movement trackers and pupillometry may in the future improve our neuro-ophthalmic assessment after concussions. Combining visual tasks with neuroimaging and neurophysiology has allowed subtle changes to be detected, may refine our ability to make appropriate return-to-play decisions, and could potentially determine susceptibility to long-term sequelae of concussion.