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Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis

From the Departments of Neurology and Radiology (E.G.-L., D.S.R., M.P., P.A.C.), Johns Hopkins School of Medicine, Baltimore; Kennedy Krieger Institute (B.C., S.A.S.), F.M. Kirby Research Center, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania, Philadelphia; Department of Neurology (E.M.F.), University of Texas Southwestern, Dallas; and Department of Biostatistics (G.C.), University of Alabama, Birmingham.

Address correspondence and reprint requests to Dr. Peter A. Calabresi, 600 N. Wolfe St., Pathology 627, Baltimore, MD 21287 calabresi{at}jhmi.edu

Objective: Optical coherence tomography (OCT) noninvasively quantifies retinal nerve fiber layer (RNFL) thickness. Studies show RNFL thinning in multiple sclerosis (MS), and we assessed its association with brain atrophy.

Methods: RNFL thickness was measured in 40 patients with MS and 15 controls. Brain parenchymal fraction (BPF) and partial brain volumes were estimated from cranial MRI scans using SIENA-X. Multiple linear regression modeling assessed the association between OCT and MRI measures of atrophy.

Results: Minimum RNFL thickness and subject age together predict 21% (p = 0.005) of the variance in BPF in all patients with MS and 43% (p = 0.003) of the variance in BPF in the subgroup with relapsing remitting MS (RRMS; n = 20). The partial correlation coefficient between BPF and minimum RNFL thickness, controlling for age, is 0.46 (p = 0.003) in all patients with MS and 0.69 (p = 0.001) in patients with RRMS. These associations are driven by CSF volume but not by gray or white matter volume. There is no significant association of these variables among controls.

Conclusions: In multiple sclerosis (MS), retinal nerve fiber layer thickness is associated with brain parenchymal fraction and CSF volume. These data suggest that quantification of axonal thickness in the retina by optical coherence tomography (OCT) provides concurrent information about MRI brain abnormality in MS. OCT should be examined in longitudinal studies to determine if it could be used as an outcome measure in clinical trials of neuroprotective drugs.

GLOSSARY: BPF = brain parenchymal fraction; EDSS = Expanded Disability Status Scale; KKI = Kennedy Krieger Institute; MNI = Montreal Neurological Institute; MPRAGE = magnetization-prepared rapid gradient echo; MS = multiple sclerosis; OCT = optical coherence tomography; PPMS = primary progressive MS; RNFL = retinal nerve fiber layer; RRMS = relapsing remitting MS; SPMS = secondary progressive MS; TMV = total macular volume.

Editorial, see page 1562

Supported by The Nancy Davis Center and NMSS TR-3760-A-3.

Disclosure: The authors report no conflicts of interest.

Received March 20, 2007. Accepted in final form April 20, 2007.

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