Original Article

Longitudinal study of vision and retinal nerve fiber layer thickness in multiple sclerosis

  1. Lauren S. Talman BA1,
  2. Esther R. Bisker MD1,
  3. David J. Sackel BS1,
  4. David A. Long Jr. BS1,
  5. Kristin M. Galetta MS1,
  6. John N. Ratchford MD2,
  7. Deacon J. Lile BA1,
  8. Sheena K. Farrell BS2,
  9. Michael J. Loguidice BA1,
  10. Gina Remington BSN, RN3,
  11. Amy Conger COA3,
  12. Teresa C. Frohman BS3,
  13. Dina A. Jacobs MD1,
  14. Clyde E. Markowitz MD1,
  15. Gary R. Cutter PhD4,
  16. Gui-Shuang Ying PhD5,6,
  17. Yang Dai PhD5,6,
  18. Maureen G. Maguire PhD5,6,
  19. Steven L. Galetta MD1,5,
  20. Elliot M. Frohman MD, PhD3,
  21. Peter A. Calabresi MD2,
  22. Laura J. Balcer MD, MSCE1,5,7,*

Article first published online: 19 FEB 2010

DOI: 10.1002/ana.22005

Issue

Annals of Neurology

Annals of Neurology

Volume 67, Issue 6, pages 749–760, June 2010

Additional Information

How to Cite

Talman, L. S., Bisker, E. R., Sackel, D. J., Long, D. A., Galetta, K. M., Ratchford, J. N., Lile, D. J., Farrell, S. K., Loguidice, M. J., Remington, G., Conger, A., Frohman, T. C., Jacobs, D. A., Markowitz, C. E., Cutter, G. R., Ying, G.-S., Dai, Y., Maguire, M. G., Galetta, S. L., Frohman, E. M., Calabresi, P. A. and Balcer, L. J. (2010), Longitudinal study of vision and retinal nerve fiber layer thickness in multiple sclerosis. Ann Neurol., 67: 749–760. doi: 10.1002/ana.22005

Author Information

  1. 1

    Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA

  2. 2

    Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD

  3. 3

    Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX

  4. 4

    Department of Biostatistics, University of Alabama, Birmingham, AL

  5. 5

    Department of Ophthalmology, University of Pennsylvania School of Medicine, Philadelphia, PA

  6. 6

    Department of Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA

  7. 7

    Department of Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA

*Department of Neurology, 3 E. Gates, 3400 Spruce Street, Philadelphia, PA 19104

Publication History

  1. Issue published online: 25 MAY 2010
  2. Article first published online: 19 FEB 2010
  3. Accepted manuscript online: 19 FEB 2010 12:00AM EST
  4. Manuscript Accepted: 29 JAN 2010
  5. Manuscript Revised: 10 DEC 2009
  6. Manuscript Received: 10 SEP 2009

Funded by

  • National Multiple Sclerosis Society. Grant Number: PP1115
  • National Multiple Sclerosis Society Tissue Repair Partnership. Grant Number: TR 3760-A-3
  • NIH/ National Eye Institute. Grant Number: K24 EY 014136
  • DAD's Foundation
  • McNeill Foundation

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Abstract

Objective

Cross-sectional studies of optical coherence tomography (OCT) show that retinal nerve fiber layer (RNFL) thickness is reduced in multiple sclerosis (MS) and correlates with visual function. We determined how longitudinal changes in RNFL thickness relate to visual loss. We also examined patterns of RNFL thinning over time in MS eyes with and without a prior history of acute optic neuritis (ON).

Methods

Patients underwent OCT measurement of RNFL thickness at baseline and at 6-month intervals during a mean follow-up of 18 months at 3 centers. Low-contrast letter acuity (2.5%, 1.25% contrast) and visual acuity (VA) were assessed.

Results

Among 299 patients (593 eyes) with ≥6 months follow-up, eyes with visual loss showed greater RNFL thinning compared to eyes with stable vision (low-contrast acuity, 2.5%: p < 0.001; VA: p = 0.005). RNFL thinning increased over time, with average losses of 2.9μm at 2 to 3 years and 6.1μm at 3 to 4.5 years (p < 0.001 vs 0.5–1-year follow-up interval). These patterns were observed for eyes with or without prior history of ON. Proportions of eyes with RNFL loss greater than test-retest variability (≥6.6μm) increased from 11% at 0 to 1 year to 44% at 3 to 4.5 years (p < 0.001).

Interpretation

Progressive RNFL thinning occurs as a function of time in some patients with MS, even in the absence of ON, and is associated with clinically significant visual loss. These findings are consistent with subclinical axonal loss in the anterior visual pathway in MS, and support the use of OCT and low-contrast acuity as methods to evaluate the effectiveness of putative neuroprotection protocols. ANN NEUROL 2010;67:749–760

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