Faculty Bibliography

BACKGROUND: The decision between conservative management and invasive treatment of juxtaorbital intracranial vascular anomalies can be challenging. Whereas arteriovenous malformations (AVMs) can lead to vision loss and are potentially life threatening if they rupture, invasive endovascular and surgical procedures also carry risks. CASE DESCRIPTIONS: Two patients developed blinding orbital congestion soon after successful treatment of cerebral vascular anomalies. The first patient, a 36 year-old man, underwent partial embolization followed by resection of a congenital frontal lobe AVM. The second patient, a 62 year-old woman, underwent embolization of a peri-orbital/skull base dural arteriovenous malformation. Following intervention, both patients developed unilateral vision loss proptosis, chemosis, complete ophthalmoplegia, and elevated intraocular pressure. The first patient suffered from acute orbital compartment syndrome in the absence of any acute localized hemorrhage or thrombosis. The second patient experienced refractory acute glaucoma from orbital congestion, secondary hyphema and angle closure due to superior ophthalmic vein and cavernous sinus thromboses. CONCULSIONS: These cases highlight the potential orbital congestion to worsen acutely after invasive treatment of juxtaorbital cerebral vascular anomalies, and suggest diverse mechanisms of resultant visual and orbital compromise. The first case represents the first report of orbital compartment syndrome following resection of a congenital AVM.

Purpose: The King-Devick (K-D) test, a rapid number naming test, captures impaired eye movements and saccades, findings correlated with suboptimal brain function. This test has been used to screen athletes for concussions, with worse time scores in athletes following concussion, consistent with widely distributed visual pathways. We examined the K-D test as a measure of vision and eye movements in multiple sclerosis (MS) and determined the relation of K-D scores to visual function, vision-specific quality of life (QoL), work disability, and history of optic neuritis (ON).
Method(s): Patients with MS and disease-free controls completed the test at a single visit. Scores represent time needed to read single-digit numbers on 3 test cards. Patients had testing of monocular and binocular low-contrast acuity (2.5%, 1.25%), high-contrast acuity (VA), spectral-domain OCT, NEI-VFQ-25, 10-Item Neuro-Ophthalmic Supplement, and MS Functional Composite.
Result(s): In the MS cohort (n=81), K-D scores were worse compared to controls (54.7+/-15.7 vs. 41.2+/-7.2 seconds, p=0.003, least squares means, adjusting for age). Higher scores in MS were associated with worse scores for vision-specific QoL (p<0.001 for NEI-VFQ-25, p<0.001 for 10-Item Supplement), binocular low-contrast acuity at 2.5%, 1.25% (p<0.001), binocular VA (p=0.003), timed 25-foot walk (p<0.001), 9-hole peg test (p=0.001), and 3- second PASAT3 (p=0.03, linear regression). Patients with history of acute ON (p=0.003) or binocular low-contrast acuities below the control group average (p=0.009 for 2.5%, logistic regression) had worse K-D scores. Correspondingly, monocular vision (p=0.001-0.009) and RNFL thickness (p=0.001) were reduced in eyes of patients with worse K-D (adjusting for age and within-patient, inter-eye correlations). Disabled patients (receiving disability pension) did worse on the K-D test compared to those working full-time, accounting for age (p<0.001).
Conclusion(s): The K-D test captures visual dysfunction, vision-specific quality of life and neurologic impairment in MS. Scores reffect work disability as well as structural changes as measured by OCT. History of ON and abnormal binocular acuities were associated with worse scores, suggesting that the K-D captures both a0erent and e0erent components of vision. The K-D test should be considered for future MS trials as a rapid global visual performance measure

Over the past decade, the visual pathway in multiple sclerosis (MS) has become an important system for assessing both patient function and disease burden. Abnormalities of low-contrast acuity, long recognized as important correlates of driving, facial recognition, and other activities of daily living, are now noted to be common among patients with MS, even among those with no history of acute optic neuritis (ON). Low-contrast letter acuity scores correlate well with brain MRI lesion burden, visual-evoked potential (VEP) amplitudes, health-related quality of life (QOL), and retinal nerve fiber layer (RNFL) axonal and neuronal loss as measured by optical coherence tomography (OCT). Axonal and neuronal degeneration in MS is likely to be an important cause of visual impairment and disability, particularly among patients with progressive MS subtypes. With the advent of OCT and the use of low-contrast letter acuity charts in MS research and clinical trials, the structure-function correlations afforded by the anterior visual pathway can be assessed and potentially harnessed as a model for testing new therapies. Recent advances in OCT, such as high resolution spectral-domain techniques and computerized algorithms for image analysis, have allowed for measurement of specific retinal layers, including the ganglion cell (GCL) neuronal layer and its intimately associated, thin layer of interneurons, the inner plexiform layer (IPL). Longitudinal collaborative studies of GCL+IPL thinning and RNFL axonal loss are providing an in vivo view into neuroretinal pathology, and are providing new insights into how the visual pathway may reflect overall mechanisms of disease in MS.

BACKGROUND: Low-contrast letter acuity and optical coherence tomography (OCT) capture visual dysfunction and axonal loss in adult-onset multiple sclerosis (MS), and have been proposed as secondary outcome metrics for therapeutic trials. Clinical trials will soon be launched in pediatric MS, but such outcome metrics have not been well-validated in this population. OBJECTIVES: To determine whether MS onset during childhood and adolescence is associated with measurable loss of visual acuity and thinning of the retinal nerve fiber layer (RNFL), whether such features are noted only in the context of clinical optic nerve inflammation (optic neuritis, ON) or are a feature of MS even in the absence of optic nerve relapses, and to define the optimal methods for such detection. STUDY DESIGN: Cross-sectional study. METHODS: Monocular and binocular high- and low-contrast letter acuity and contrast sensitivity were assessed in a cross-sectional cohort of children (ages 5 to 17 years) with MS (N=22 patients, 44 eyes; 8 patients with a history of ON) and disease-free controls (N=29 patients; 58 eyes) from three academic centers. Binocular summation was determined by calculating the number of letters correctly identified using the binocular score minus the better eye score for each visual test. RNFL thickness was measured using OCT (Stratus OCT-3). Results were analyzed in terms of "eyes" as: MS ON+, MS ON-, and control eyes. Generalized estimating equation (GEE) regression models were used to compare patients to controls. RESULTS: Traditional high-contrast visual acuity scores did not differ between MS ON+, MS ON-, and controls eyes. MS ON+ eyes had decreased monocular (p<0.001) and decreased binocular (p=0.007) low-contrast letter acuity (Sloan 1.25% contrast charts) scores. Monocular visual acuity did not differ when comparing MS ON- and control eyes. The magnitude of binocular summation using low-contrast charts was similar for pediatric MS participants and controls and was not diminished in children with a history of ON. While the mean RNFL thickness for all MS eyes (103+/-17 mum) trended lower when compared to corresponding measures in control eyes (109+/-9 mum, p=0.085), we confirmed a highly significant reduction in mean RNFL thickness in MS eyes with a history of ON (86+/-22 mum, p<0.001). RNFL thickness of MS ON- eyes in pediatric MS patients (109+/-11 mum) did not differ from controls (p=0.994). CONCLUSIONS: Low-contrast letter acuity detects subtle visual loss in MS patients with prior ON, consistent with incomplete recovery, a finding further supported by RNFL loss in ON affected eyes. In MS patients with prior unilateral ON, binocular acuity is decreased; however, the magnitude of binocular summation is preserved, unlike adult-onset MS who exhibit a reduced capacity for visual compensation in the context of unilateral injury. Also unlike findings in adult-onset MS, we did not demonstrate RNFL thinning in ON- eyes of children and adolescents with MS. Further validation is required to confirm whether neurodegeneration of visual pathways occurs in the absence of relapse, and thus whether OCT will serve as a sensitive metric for such pathology in the pediatric and adolescent MS context.

BACKGROUND:: Patients with multiple sclerosis (MS) demonstrate thinning of peripapillary retinal nerve fiber layer (RNFL) and decreased macular volume as measured by optical coherence tomography (OCT). To our knowledge, there are no previous reports from a large MS OCT database with strict quality control measures that quantitate RNFL and macula in patients with relapsing-remitting multiple sclerosis. METHODS:: The University of California Davis OCT Reading Center gathered OCT data at baseline as part of the North American phase 3 trial of fingolimod (Gilenya). Average RNFL thickness (RNFLT) and macular volume (TMV) were measured using time domain OCT (TD-OCT). RNFL quadrants, clock hours, and macular subfields were included. With strict quality control and accounting for signal strength differences, scans were categorized as "reduced" or "not reduced" for each field, based on being less than 5th percentile for age-matched controls derived from the normative database in the scanner software. Patients were deemed "abnormal" if at least 1 eye had reduced values for a given parameter. Patients with abnormalities in corresponding RNFL and macular subfields were compared by cross-tabulation. RESULTS:: The TD-OCT data were prospectively collected from 939 of the 1,083 trial patients, 712 of whom met all final quality and data inclusion criteria. Of the final cohort, 242 (34.0%) demonstrated reduced (less than 5th percentile) average RNFLT in at least 1 eye. One hundred seventy-eight (25.0%) patients had reduced TMV. One hundred twenty-eight (18.0%) demonstrated both reduced TMV and RNFLT in the same eye, whereas 42 (5.8%) had reduced TMV and RNFLT in both eyes. Of the 242 patients with reduced average RNFL thickness, 128 (52.9%) also had reduced TMV. Fifty patients had reduced TMV in the absence of reduced RNFLT in at least 1 eye, a cohort prevalence of 7.0%. Quadrant and subfield analysis showed a predominance of temporal and inferior RNFL thinning, with inferior macular thinning corresponding best to RNFL thinning. CONCLUSION:: RNFL and macular thinning/volume loss is common at baseline in relapsing-remitting multiple sclerosis, as measured by TD-OCT. When the RNFL is thin, the macular volume is reduced in more than half of the patients. There is a population of reduced TMV without any reduction in RNFLT. Documenting the prevalence and distribution of these structural abnormalities supports recent reports and suggests new retinal areas to probe for functional vision changes in MS.

Studies suggest that a lack of standardized knowledge may lead to underreporting and undertreatment of sports-related concussion. However, there has been little work done to establish how this knowledge may affect athletes' behaviors toward reporting their concussions and removing themselves from play. We conducted an anonymous online survey to assess athletes' knowledge of signs and symptoms of concussion, and also sought to estimate the potential frequency of underreporting in a collegiate athlete cohort. Among 262 athletes who responded to the survey, 43% of those with a history of concussion reported that they had knowingly hidden symptoms of a concussion to stay in a game, and 22% of athletes overall indicated that they would be unlikely or very unlikely to report concussion symptoms to a coach or athletic trainer in the future. These data suggest that there may be a substantial degree of underreporting of concussion among collegiate athletes, despite most acknowledging that they have been formally educated about the risks of concussion.

The diagnosis of pseudotumor cerebri, or idiopathic intracranial hypertension (IIH), is most confidently established in the typical patient with evidence of papilledema, imaging that does not suggest a structural lesion, and a CSF examination that shows both normal composition and elevated intracranial pressure (ICP). Prompted by an increasing number of reports over the past decade, Friedman et al.1 propose a revised set of diagnostic criteria for IIH, taking into account the most recent observations from neuroimaging studies. Although the patient with IIH is often a young woman who is above ideal body weight or obese, it is well-recognized that the disorder may also occur in obese men and in children, who are less likely to be obese than their adult counterparts. Several advances in the field prompted the expert authors to provide new guidance. First, a large study of children has redefined normal CSF opening pressure for children.2 In the obese or sedated child, an opening pressure of 280 mm H2O has been suggested as the requirement to claim confidently that the ICP is increased. Otherwise, the diagnostic criteria for children and adults continue to rely on a CSF lumbar opening pressure of 250 mm H2O or greater.