Faculty Bibliography

OBJECTIVE: To retrospectively investigate whether disease-modifying therapies (DMTs) exert differential effects on rates of retinal atrophy in relapsing-remitting multiple sclerosis (RRMS), as assessed using optical coherence tomography (OCT). METHODS: A total of 402 patients with RRMS followed at the Johns Hopkins MS Center who underwent Cirrus-HD OCT were assessed for eligibility. Inclusion criteria included at least 1 year of OCT follow-up and adherence to a single DMT during the period of follow-up. Combined thickness of the ganglion cell + inner plexiform (GCIP) and other retinal layers was computed utilizing automated macular segmentation. Retinal thickness changes were analyzed using mixed-effects linear regression. RESULTS: The effects of glatiramer acetate (GA; n = 48), natalizumab (NAT; n = 46), and interferon-beta-1a subcutaneously (IFNSC; n = 35) and intramuscularly (IFNIM; n = 28) were assessed. Baseline analyses revealed no significant differences between groups in terms of age, sex, optic neuritis history, or follow-up duration. During follow-up, relative to NAT-treated patients, IFNSC- and GA-treated patients exhibited 0.37 mum/y (p < 0.001) and 0.14 mum/y (p = 0.035) faster rates of GCIP thinning, respectively, adjusting for the interval between initiation of DMT and OCT monitoring (gap time), age, sex, relapses, and disease duration. In the IFNSC group, GCIP thinning was 1.53 mum/y faster during the first year of therapy vs during the time interval afterwards (p < 0.001). CONCLUSIONS: Rates of GCIP atrophy in patients with RRMS vary according to DMT utilization. Our findings support OCT for monitoring neurodegenerative treatment effects in the retina, an easily accessible tissue, and as a practical outcome measure in RRMS clinical trials.

OBJECTIVE: This study introduces a rapid picture naming test, the Mobile Universal Lexicon Evaluation System (MULES), as a novel, vision-based performance measure for concussion screening. The MULES is a visual-verbal task that includes 54 original photographs of fruits, objects and animals. We piloted MULES in a cohort of volunteers to determine feasibility, ranges of picture naming responses, and the relation of MULES time scores to those of King-Devick (K-D), a rapid number naming test. METHODS: A convenience sample (n=20, age 34+/-10) underwent MULES and K-D (spiral bound, iPad versions). Administration order was randomized; MULES tests were audio-recorded to provide objective data on temporal variability and ranges of picture naming responses. RESULTS: Scores for the best of two trials for all tests were 40-50s; average times required to name each MULES picture (0.72+/-0.14s) was greater than those needed for each K-D number ((spiral: 0.33+/-0.05s, iPad: 0.36+/-0.06s, 120 numbers), p<0.0001, paired t-test). MULES scores showed the greatest degree of improvement between trials (9.4+/-4.8s, p<0.0001 for trials 1 vs. 2), compared to K-D (spiral 1.5+/-3.3s, iPad 1.8+/-3.4s). Shorter MULES times demonstrated moderate and significant correlations with shorter iPad but not spiral K-D times (r=0.49, p=0.03). CONCLUSION: The MULES test is a rapid picture naming task that may engage more extensive neural systems than more commonly used rapid number naming tasks. Rapid picture naming may require additional processing devoted to color perception, object identification, and categorization. Both tests rely on initiation and sequencing of saccadic eye movements.

BACKGROUND: Although patients with acute optic neuritis (ON) recover high-contrast visual acuity (HCVA) to 20/40 or better in 95% of affected eyes, patients with a history of ON continue to note subjective abnormalities of vision. Furthermore, substantial and permanent thinning of the retinal nerve fiber layer (RNFL) and the ganglion cell layer (GCL) is now known to occur early in the course of ON. We measured vision-specific quality of life (QOL) in patients with a history of acute ON and recovery of VA to 20/40 or better in their affected eyes to determine how these QOL scores relate to RNFL and GCL thickness and low-contrast letter acuity (LCLA) across the spectrum of visual recovery. METHODS: Data from an ongoing collaborative study of visual outcomes in multiple sclerosis and ON were analyzed for this cross-sectional observational cohort. Patients and disease-free control participants completed the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement to the NEI-VFQ-25, as well as VA and LCLA testing for each eye separately and binocularly. Optical coherence tomography measures for each eye included peripapillary RNFL thickness and macular GCL + inner plexiform layer (GCL + IPL) thickness. RESULTS: Patients with a history of acute ON and recovery to 20/40 or better VA (n = 113) had significantly reduced scores for the NEI-VFQ-25 (83.7 +/- 15.4) and 10-Item Neuro-Ophthalmic Supplement (74.6 +/- 17.4) compared with disease-free controls (98.2 +/- 2.1 and 96.4 +/- 5.2, P < 0.001, linear regression models, accounting for age and within-patient, intereye correlations). Most patients with 20/40 or better visual recovery (98/112, 88%) had monocular HCVA in their affected eye of 20/20 or better. Although patients with 20/50 or worse HCVA recovery demonstrated the worst performance on low-contrast acuity, affected eye RNFL and GCL + IPL thickness, and QOL scales, these measures were also significantly reduced among those with 20/40 or better HCVA recovery compared with controls. CONCLUSIONS: Patients with a history of ON and "good" visual recovery, defined in the literature as 20/40 or better HCVA, are left with clinically meaningful reductions in vision-specific QOL. Such patient-observed deficits reflect the underlying significant degrees of retinal axonal and neuronal loss and visual dysfunction that are now known to characterize ON even in the setting of maximal HCVA recovery. There remains an unmet therapeutic need for patients with ON.