Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis

Ophthalmology. 2006 Feb;113(2):324-32. doi: 10.1016/j.ophtha.2005.10.040. Epub 2006 Jan 10.


Purpose: To examine the relation of visual function to retinal nerve fiber layer (RNFL) thickness as a structural biomarker for axonal loss in multiple sclerosis (MS), and to compare RNFL thickness among MS eyes with a history of acute optic neuritis (MS ON eyes), MS eyes without an optic neuritis history (MS non-ON eyes), and disease-free control eyes.

Design: Cross-sectional study.

Participants: Patients with MS (n = 90; 180 eyes) and disease-free controls (n = 36; 72 eyes).

Methods: Retinal never fiber layer thickness was measured using optical coherence tomography (OCT; fast RNFL thickness software protocol). Vision testing was performed for each eye and binocularly before OCT scanning using measures previously shown to capture dysfunction in MS patients: (1) low-contrast letter acuity (Sloan charts, 2.5% and 1.25% contrast levels at 2 m) and (2) contrast sensitivity (Pelli-Robson chart at 1 m). Visual acuity (retroilluminated Early Treatment Diabetic Retinopathy charts at 3.2 m) was also measured, and protocol refractions were performed.

Main outcome measures: Retinal nerve fiber layer thickness measured by OCT, and visual function test results.

Results: Although median Snellen acuity equivalents were better than 20/20 in both groups, RNFL thickness was reduced significantly among eyes of MS patients (92 mum) versus controls (105 mum) (P<0.001) and particularly was reduced in MS ON eyes (85 mum; P<0.001; accounting for age and adjusting for within-patient intereye correlations). Lower visual function scores were associated with reduced average overall RNFL thickness in MS eyes; for every 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 mum.

Conclusions: Scores for low-contrast letter acuity and contrast sensitivity correlate well with RNFL thickness as a structural biomarker, supporting validity for these visual function tests as secondary clinical outcome measures for MS trials. These results also suggest a role for ocular imaging techniques such as OCT in trials that examine neuroprotective and other disease-modifying therapies. Although eyes with a history of acute optic neuritis demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes have less RNFL thickness than controls, suggesting the occurrence of chronic axonal loss separate from acute attacks in MS patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Contrast Sensitivity / physiology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / physiopathology*
  • Nerve Fibers / pathology*
  • Optic Neuritis / physiopathology*
  • Retinal Ganglion Cells / pathology*
  • Tomography, Optical Coherence
  • Visual Acuity / physiology*