Faculty Bibliography

BACKGROUND: Inner (area adjacent to the fovea) and outer regions of the macula differ with respect to relative thicknesses of the ganglion cell layer (neurons) vs retinal nerve fiber layer (RNFL; axons). OBJECTIVE: To determine how inner vs outer macular volumes relate to peripapillary RNFL thickness and visual function in multiple sclerosis (MS) and to examine how these patterns differ among eyes with vs without a history of acute optic neuritis (ON). DESIGN: Study using cross-sectional optical coherence tomography. SETTING: Three academic tertiary care MS centers. PARTICIPANTS: Patients with MS, diagnosed by standard criteria, and disease-free control participants. MAIN OUTCOME MEASURES: Optical coherence tomography was used to measure macular volumes and RNFL thickness. Visual function was assessed using low-contrast letter acuity and high-contrast visual acuity (Early Treatment Diabetic Retinopathy Study charts). RESULTS: Among eyes of patients with MS (n = 1058 eyes of 530 patients), reduced macular volumes were associated with peripapillary RNFL thinning; 10-microm differences in RNFL thickness (9.6% of thickness in control participants without disease) corresponded to 0.20-mm(3) reductions in total macular volume (2.9% of volume in control participants without disease, P < .001). This relation was similar for eyes of MS patients with and without a history of ON. Although peripapillary RNFL thinning was more strongly associated with decrements in outer compared with inner macular volumes, correlations with inner macular volume were significant (r = 0.58, P < .001) and of slightly greater magnitude for eyes of MS patients with a history of ON vs eyes of MS patients without a history of ON (r = 0.61 vs r = 0.50). Lower (worse) visual function scores were associated with reduced total, inner, and outer macular volumes. However, accounting for peripapillary RNFL thickness, the relation between vision and inner macular volume remained significant and unchanged in magnitude, suggesting that this region contains retinal structures separate from RNFL axons that are important to vision. CONCLUSIONS: Analogous to studies of gray matter in MS, these data provide evidence that reductions of volume in the macula (approximately 34% neuronal cells by average thickness) accompany RNFL axonal loss. Peripapillary RNFL thinning and inner macular volume loss are less strongly linked in eyes of MS patients without a history of ON than in eyes of MS patients with a history of ON, suggesting alternative mechanisms for neuronal cell loss. Longitudinal studies with segmentation of retinal layers will further explore the relation and timing of ganglion cell degeneration and RNFL thinning in MS.

OBJECTIVE: To identify and describe patients with idiopathic intracranial hypertension (IIH) with concurrent functional visual loss (FVL). DESIGN: Observational, retrospective case series. PARTICIPANTS: Seventeen patients with IIH and FVL. METHODS: Clinical features were collected retrospectively. Data from 281 cases of IIH were analyzed for concurrence of FVL. MAIN OUTCOME MEASURES: Occurrence of FVL diagnosed at presentation or on subsequent follow-up. RESULTS: Seventeen patients had FVL and IIH. Of the 17 patients with FVL and IIH, 11 (65%) had FVL on presentation, with the remaining 6 patients developing FVL after initial presentation. Two patients in this cohort had documented recurrence of their IIH. There were several common patterns of FVL. All 17 patients had functional visual fields, with 82% having tubular fields and 71% exhibiting nonphysiologic constriction on perimetry testing. Seventy-six percent of patients had nerve/field mismatch showing no atrophic disc changes. Eighty-eight percent of patients had significant psychiatric, psychosocial, or other medical comorbidities. The majority of patients were managed surgically at some point in their clinical history, with 53% having nerve decompression, shunt, or both. Three patients had optic nerve sheath fenestrations after the diagnosis of FVL. CONCLUSIONS: Results suggest a high prevalence of FVL in IIH with a potential association with psychiatric illness and psychosocial stressors requiring careful consideration before surgical intervention. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

PURPOSE: To investigate the ability of a portable pupillometer, capable of 20-second binocular recordings of the swinging flashlight test (SFT), to detect relative afferent pupillary defects (rAPDs). METHODS: Pupillary response curves were recorded from both eyes in healthy volunteers (n = 22) with and without simulated rAPDs (using neutral density filters (NDFs)) and in abnormal patients (n = 24) with clinically graded rAPDs. The light stimulus (0.2 sec on and 1 sec off, or 2 sec on and 0.4 sec off) alternated between both eyes, simulating the SFT. Constriction amplitude (CA), constriction velocity (CV), and pupillary release were calculated by computer algorithm. In abnormal patients, NDFs were used to neutralize inter-eye differences. RESULTS: Significant correlation (Spearman's rho 0.71, 0.73) between NDF strength and absolute inter-eye differences was seen for CA and CV in simulated rAPDs. All abnormal patients (15/15) having rAPDs greater than 0.5 log units were distinguished from normals using either the upper bound of the one-sided 95% confidence interval (95% CI) value of CA or CV as determined from 22 healthy volunteers. Inter-eye variability in some normals prevented confident distinction of six abnormal patients with 0.3 log unit rAPDs. Using NDFs, subtle rAPDs were predicted in three patients having questionable rAPDs on clinical examination. CA and CV were more sensitive than pupillary release for all comparisons. CONCLUSIONS: This binocular pupillometer identified all of our patients with > 0.5 log unit rAPDs. Using NDFs, all of our abnormal patients were accurately identified and their rAPDs quantified. Variability in some normals makes them indistinguishable from patients with subtle rAPDs.

A mydriatic pupil has been infrequently reported as a manifestation of giant cell arteritis. We report a patient with acute, evolving pupil dilation who was diagnosed with biopsy-proven giant cell arteritis. We document the time course for the development of pupillary near-light dissociation and denervation hypersensitivity. We discuss the possible mechanisms leading to mydriasis, including 1) parasympathetic dysfunction due to ischemia of the ciliary ganglion and post-ganglionic parasympathetic fibers and 2) direct iris ischemia. Repeated episodes of pupil dilation in this patient suggested ongoing microvascular insufficiency.

The AFFIRM and SENTINEL studies showed that natalizumab was effective both as monotherapy and in combination with interferon beta (IFNbeta)-1a in patients with relapsing multiple sclerosis (MS). Further analyses of AFFIRM and SENTINEL data were conducted to determine the efficacy of natalizumab in prespecified patient subgroups according to baseline characteristics: relapse history 1 year before randomization (1, 2, > or = 3), Expanded Disability Status Scale score (< or = 3.5, > 3.5), number of T2 lesions (< 9, > or = 9), presence of gadolinium-enhancing (Gd+) lesions (0, > or = 1), age (< 40, > or = 40) and gender (male, female). A post hoc analysis was conducted to determine the efficacy of natalizumab in patients with highly active disease (i. e., > or = 2 relapses in the year before study entry and > or = 1 Gd+ lesion at study entry). In both AFFIRM and SENTINEL studies natalizumab reduced the annualized relapse rates across all subgroups (except the small subgroups with < 9 baseline T2 lesions) over 2 years. In AFFIRM, natalizumab significantly reduced the risk of sustained disability progression in most subgroups. In SENTINEL, natalizumab significantly reduced the risk of sustained disability progression in the following subgroups: > or = 9 T2 lesions at baseline, > or = 1 Gd+ lesions at baseline, female patients and patients < 40 years of age. Natalizumab reduced the risk of disability progression by 64 % and relapse rate by 81 % in treatment- naive patients with highly active disease and by 58 % and 76 %, respectively, in patients with highly active disease despite IFNbeta-1a treatment. These results indicate that natalizumab is effective in reducing disability progression and relapses in patients with relapsing MS, particularly in patients with highly active disease.

BACKGROUND: Trigeminal neuralgia is a syndrome of paroxysmal excruciating, lancinating unilateral facial pain. REVIEW SUMMARY: There are several clinical features that are characteristic of trigeminal neuralgia, but there may be red flags that should suggest alternative diagnoses. There is convincing evidence that the idiopathic form develops from focal demyelination at the trigeminal root entry zone with subsequent ephaptic cross-talk between axons. Vascular compression of the nerve root causes this demyelination in most patients. Medical management of this condition, using anticonvulsant therapy and other agents, aims to dampen the abnormal electrical signals and to ameliorate symptoms. In refractory cases, a number of surgical interventions can be considered, the most common of which is microvascular decompression of the trigeminal nerve. Gamma knife therapy is emerging as an alternative treatment for the patient with medically refractive trigeminal neuralgia, particularly in the elderly patient with comorbid conditions. CONCLUSION: Knowledge of the proper diagnosis and management of trigeminal neuralgia is essential to the successful management of these patients.

BACKGROUND: The efficacy of natalizumab on clinical and radiological measures in the phase III Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study has prompted the investigation of whether natalizumab can increase the proportion of patients with relapsing-remitting multiple sclerosis who do not have disease activity. METHODS: Post-hoc analyses of data from the AFFIRM study were done to determine the effects of natalizumab compared with placebo on the proportion of patients who were free of disease activity over 2 years. Absence of disease activity was defined as no activity on clinical measures (no relapses and no sustained disability progression), radiological measures (no gadolinium-enhancing lesions and no new or enlarging T2-hyperintense lesions on cranial MRI), or a composite of the two. FINDINGS: 383 (64%) of 596 patients taking natalizumab and 117 (39%) of 301 taking placebo were free of clinical disease activity (absolute difference 25.4%, 95% CI 18.7-32.1%, p<0.0001); 342 (58%) of 593 and 42 (14%) of 296 were free of radiological disease activity (43.5%, 37.9-49.1%, p<0.0001); and 220 (37%) of 600 and 22 (7%) of 304 were free of combined activity (29.5%, 24.7-34.3%, p<0.0001) over 2 years. The effect of natalizumab versus placebo was consistent across subgroups of patients with highly active or non-highly active disease at baseline. INTERPRETATION: Disease remission might become an increasingly attainable goal in multiple sclerosis treatment with the use of newer, more effective therapies.