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.

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.

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.

OBJECTIVE: To examine the relation between low contrast letter acuity, a new visual function test for multiple sclerosis (MS) trials, and vision targeted health related quality of life (HRQOL). METHODS: Patients in this cross sectional study were part of an ongoing investigation of visual function in MS. Patients were tested binocularly using low contrast letter acuity and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) charts. The 25 Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), 10 Item Neuro-Ophthalmic Supplement to the NEI-VFQ-25, Impact of Visual Impairment Scale and Short Form 36 Health Survey (SF-36) were administered. RESULTS: Among 167 patients, mean age was 48 (10) years, with median Expanded Disability Status Scale (EDSS) 2.0 (range 1.0-7.5), and median binocular Snellen acuity equivalent (ETDRS charts) 20/16 (range 20/12.5 to 20/100). Reductions in vision specific HRQOL were associated with lower (worse) scores for low contrast letter acuity and VA (p<0.001, linear regression, accounting for age). Two line differences in visual function were associated, on average, with >4 point (6.7-10.9 point) worsening in the NEI-VFQ-25 composite score, reductions that are considered clinically meaningful. Scores for the 10 Item Neuro-Ophthalmic Supplement to the NEI-VFQ-25 also correlated well with visual function. Associations between reduced low contrast acuity and worse vision targeted HRQOL remained significant in models accounting for high contrast VA, EDSS and history of acute optic neuritis. CONCLUSIONS: Low contrast letter acuity scores correlate well with HRQOL in MS. Two line differences in scores for low contrast acuity and VA reflect clinically meaningful differences in vision targeted HRQOL. Low contrast acuity testing provides information on patient reported aspects of vision, supporting use of these measures in MS clinical trials.

BACKGROUND: Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNbeta) in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNbeta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNbeta. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri, Biogen Idec, Inc., Cambridge, MA) plus IM IFNbeta-1a (Avonex, Biogen Idec, Inc.) 30 microg compared with placebo plus IM IFNbeta-1a 30 microg. Clinical and MRI outcomes in patients treated with IM IFNbeta-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNbeta-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40). RESULTS: No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes. CONCLUSIONS: Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment.