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Visual Pathway Axonal Loss in Benign Multiple Sclerosis: A Longitudinal Study

Galetta, Kristin M. MS; Graves, Jennifer MD, PhD; Talman, Lauren S. BA; Lile, Deacon J. BA; Frohman, Elliot M. MD, PhD; Calabresi, Peter A. MD; Galetta, Steven L. MD; Balcer, Laura J. MD, MSCE

Journal of Neuro-Ophthalmology: June 2012 - Volume 32 - Issue 2 - p 116–123
doi: 10.1097/WNO.0b013e318240204d
Original Contribution
Japanese Abstract

Background: Benign multiple sclerosis (MS), traditionally defined as Expanded Disability Status Scale (EDSS) score ≤3 and ≥15-year disease duration, is thought to follow a milder clinical course. We determined the extent of visual pathway axonal loss by optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness in a benign MS cohort and examined the relation to vision and quality of life (QOL).

Methods: In this longitudinal study of vision in MS at 3 academic centers, a subset of patients with EDSS, visual function, OCT, and QOL assessments was analyzed. Low- and high-contrast letter acuity was performed to assess visual function. RNFL thickness was determined using time-domain OCT. QOL scales included the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and Short Form-36 Health Survey.

Results: Among 68 patients (135 eyes) studied longitudinally, 13 (26 eyes) had benign MS using criteria of EDSS score ≤3 and ≥15-year disease duration. Benign MS eyes had as much RNFL thinning (−3.6 μm, P = 0.0008 vs baseline, paired t test) as typical MS eyes (−3.3 μm, P < 0.0001). Both groups had significant low-contrast acuity loss. History of optic neuritis (ON) was more frequent in benign MS (69% vs 33% of eyes). History of ON distinguished benign vs typical MS (P = 0.002) and correlated with RNFL thickness at baseline (P = 0.002) and disease duration (P = 0.03) but not EDSS (P = 0.32, logistic regression). NEI-VFQ-25 scores were also worse for benign MS, accounting for age (75 ± 21 vs 88 ± 11, P = 0.005).

Conclusion: Patients with benign MS have RNFL axonal loss that is as marked as that of typical MS and have reduced vision and QOL. While overall neurologic impairment is mild, visual dysfunction, not well captured by the EDSS, accounts for a substantial degree of disability in benign MS.

Departments of Neurology (KMG, JG, LST, DJL, SLG, LJB), Ophthalmology (SLG, LJB), and Epidemiology (LJB), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Department of Neurology (EMF), University of Texas Southwestern Medical Center at Dallas, Dallas, Texas; and Department of Neurology (PAC), Johns Hopkins University School of Medicine, Baltimore, Maryland.

Address correspondence to Laura J. Balcer, MD, MSCE, University of Pennsylvania School of Medicine, 3 E. Gates Building, 3400 Spruce Street, Philadelphia, PA 19104; E-mail:

Supported by National Institutes of Health R01 EY 014993 and K24 EY 018136; National Multiple Sclerosis Society RG 4212-A-4 and TR 3760-A-3; DADs Foundation; and McNeill Foundation.

Dr E. M. Frohman has received speaking and consulting honoraria from Biogen Idec, Novartis, Teva, and Acorda. Dr P. A. Calabresi has received personal compensation for consulting and serving on scientific advisory boards from Biogen Idec, Teva, and Novartis and has received research funding from companies Biogen Idec, Teva, EMD Serono, Vertex, Genentech, Abbott, and Bayer. Dr S. L. Galetta has received speaking and consulting honoraria from Biogen Idec, Novartis, and Teva. Dr L. J. Balcer has received speaking and consulting honoraria from Biogen Idec, Bayer, and Novartis.

© 2012 Lippincott Williams & Wilkins, Inc.