Relation of Visual Function to Retinal Nerve Fiber Layer Thickness in Multiple Sclerosis
Presented at: American Academy of Ophthalmology Annual Meeting, October, 2005; Chicago, Illinois.
Received 1 June 2005; accepted 20 October 2005. published online 09 January 2006.
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 μm) versus controls (105 μm) (P<0.001) and particularly was reduced in MS ON eyes (85 μm; 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 μm.
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.
1Division of Neuro-ophthalmology, Departments of Neurology, Ophthalmology, and Biostatistics, University of Pennsylvania School of Medicine, Scheie Eye Institute, Philadelphia, Pennsylvania.
2Department of Biostatistics, University of Alabama, Birmingham, Alabama.
3Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas.
4Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Correspondence and reprint requests to Laura J. Balcer, MD, MSCE, 3 East Gates Building, 3400 Spruce Street, Philadelphia, PA 19104.
Manuscript no. 2005-476.
Supported in part by the National Institutes of Health, Bethesda, Maryland (grant nos.: R01 EY 013273, R01 EY 014993) (LJB); National Multiple Sclerosis Society, New York, New York (grant nos.: RG 3208-A-1, RG 3428A2/1, PP1115) (LJB); McNeill Foundation, Philadelphia, Pennsylvania (LJB); and Doris Duke Foundation, New York, New York (JBF).
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