Elsevier

Ophthalmology

Volume 113, Issue 2, February 2006, Pages 324-332
Ophthalmology

Original Article
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.
https://doi.org/10.1016/j.ophtha.2005.10.040Get rights and content

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.

Section snippets

Subjects

Patients and disease-free control subjects in the MS Vision Prospective Cohort Study,15 an ongoing investigation of visual outcome measures, were invited to participate. Multiple sclerosis was diagnosed by standard clinical and neuroimaging criteria.42 Disease duration, disease-specific therapies (e.g., immunomodulatory agents) and their duration, and MS disease phenotype (relapsing–remitting, secondary progressive, primary progressive) were ascertained for each MS patient. Patients with

Results

Ninety patients with MS (180 eyes) and 36 disease-free controls (72 eyes) underwent vision testing and OCT imaging. Demographic and clinical characteristics are presented in Table 1. Because patients and disease-free controls in this convenience sample differed with respect to age, statistical models used for analyses included age as a covariate. Multiple sclerosis patients in our cohort were similar to the United States MS population with regard to age, gender, and race (88% Caucasian). Eighty

Discussion

Results of these investigations demonstrate that low-contrast letter acuity and contrast sensitivity, the two most promising candidate visual outcome measures for MS, correlate well with RNFL thickness. Although eyes with a history of acute optic neuritis (MS ON eyes) demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes are also abnormal (including fellow eyes of MS patients with a history of unilateral optic neuritis), supporting the occurrence of anterior visual pathway

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    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).

    No conflicting relationships exist.

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