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.