Background. Retinal nerve fiber layer thickness and total macular volume (TMV) represent markers of neuroaxonal degeneration within the anterior visual pathway that might correlate with ambulation in persons with multiple sclerosis (MS). Objective. This study examined the associations between and TMV with ambulatory parameters in MS. Methods. Fifty-eight MS patients underwent a neurological examination for generation of an expanded disability status scale (EDSS) score and measurement of and TMV using optical coherence tomography (OCT). Participants completed the 6-minute walk (6MW) and the timed 25-foot walk (T25FW). The associations were examined using generalized estimating equation models that accounted for within-patient, inter-eye correlations, and controlled for disease duration, EDSS score, and age. Results. was not significantly associated with 6MW or T25FW . TMV was significantly associated with 6MW and T25FW . The coefficients indicated that unit differences in 6MW (100 feet) and T25FW (1 second) were associated with 0.040 and ？0.048 unit differences in TMV (mm3), respectively. Conclusion. Integrity of the anterior visual pathway, particularly TMV, might represent a noninvasive measure of neuroaxonal degeneration that is correlated with ambulatory function in MS. 1. Introduction The anterior visual pathway (i.e., retina, optic nerves, chiasm, and optic tracts) represents a valuable model for understanding axonal and neuronal loss and clinical and functional correlates in persons with multiple sclerosis (MS) [1]. This pathway, particularly the optic nerve, is often affected by the MS pathological disease processes given its proximity with the vasculature around the ventricles of the brain [2]. The integrity of the anterior visual pathway can be noninvasively imaged using optical coherence tomography (OCT) of the retina. OCT provides metrics of retinal nerve fiber layer thickness (RNFLT) and total macular volume (TMV). RNFLT reflects the integrity of nonmyelinated axonal tissue, whereas TMV reflects the integrity of nonmyelinated axonal tissue as well as all retinal layers including cellular segments [3]. We further note that RNFLT and TMV have been associated with lesion volume and brain atrophy metrics from magnetic resonance imaging in persons with MS [4–6]. This is important as imaging the anterior visual pathway may provide a correlate of the clinical and functional consequences of axonal and neuronal loss in MS. The integrity of the anterior visual pathway might be associated with walking function in persons with MS. Visual and ambulatory
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