Visual Pathway Axonal Loss in Benign Multiple Sclerosis

Abstract

Background Benign MS, traditionally defined as EDSS ≤3 and ≥15 years’ disease duration, is thought to follow a milder course. We determined the extent of visual pathway axonal loss by optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness in a benign MS cohort, and examined the relation to vision and quality of life (QOL). Methods In this longitudinal study of vision in MS at three academic centers, a subset of patients with EDSS, visual function, OCT, and QOL assessments was analyzed. Low- and high-contrast letter acuity were performed to assess visual function. RNFL thickness was determined using OCT-3. QOL scales included the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and SF-36. Results Among 68 patients (135 eyes) studied longitudinally, 13 (26 eyes) had benign MS using criteria of EDSS ≤3 and ≥15 years disease duration. Benign MS eyes had as much RNFL thinning (-3.6 μm, P=0.0008 vs. baseline, paired t-test) as typical MS eyes (-3.3 μm, P<0.0001). Both groups had significant low-contrast acuity loss. Prior history of optic neuritis (ON) was more frequent in benign MS (69% vs. 33% of eyes). History of ON distinguished benign vs. typical MS (P=0.002) and correlated with RNFL thickness at baseline (P=0.002) and disease duration (P=0.03), but not EDSS (P=0.32, logistic regression). NEI-VFQ-25 scores were also worse for benign MS, accounting for age (75±21 vs. 88±11, P=0.005). Conclusions Patients with benign MS have RNFL axonal loss that is as marked as that of typical MS, and have reduced vision and QOL. While overall neurologic impairment is mild, visual dysfunction, not well-captured by the EDSS, accounts for a substantial degree of disability in benign MS.

Current and Future Potential of Retinal Optical Coherence Tomography in Multiple Sclerosis with and Without Optic Neuritis

“…Galetta et al and Sakai et al reported no difference in RNFL thickness between BMS and typical MS. The authors even suggested consistent trends of greater worsening for benign patients [38,61]. A more recent study, however, including all retinal layers stated that the macular GCC and the peripapillary RNFL and inner nuclear layer (INL) showed significantly more thinning in typical MS, compared with BMS.…”

Remaining Visual Field and Preserved Subjective Visual Functioning Prevent Mental Distress in Patients with Visual Field Defects

“…Designed for the assessment of ophthalmologic diseases (Mangione et al, 2001) the NEI-VFQ is a valid and reliable instrument which was frequently used in studies focusing on the impact of visual field defects on subjective vrQoL after central visual pathway lesions (Cole et al, 2000; Beck et al, 2004; Raphael et al, 2006; Papageorgiou et al, 2007; Gall et al, 2009, 2010; Wagenbreth et al, 2011; Galetta et al, 2012; Walter et al, 2012; Jasse et al, 2013). It was demonstrated that diminished vrQoL was significantly related to the size of the visual field defect (e.g., Gall et al, 2009).…”

Neuro-ophthalmology Annual Review

“…The authors concluded that patients with ''benign MS'' have similar and perhaps even greater degrees of visual pathway involvement. 56 To evaluate the retinal neurodegeneration in patients with MS, measurement of the retinal nerve fiber layer (RNFL) thickness using optical coherence tomography (OCT) has been proposed as a potential biomarker of axonal damage in MS. A cross-sectional, case-control study of 39 patients with MS circumpapillary RNFL thickness in affected eyes was decreased compared with nonaffected eyes. The thickness of the macular ganglion cell complex (GCC) had the highest sensitivity and specificity in detecting axonal loss independent of ON.…”