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Optical coherence tomography measures axonal loss in multiple sclerosis independently of optic neuritis
Multiple sclerosis (MS) is a chronic disabling disorder histopathologically characterized by inflammation, demyelination, and axonal loss. Optical Coherence Tomography (OCT) is a non-invasive imaging technique similar to ultrasound echography that has recently been used to assess axonal loss and damage associated with optic neuritis (ON). Interestingly, some authors also observed significant reductions of retinal nerve fiber layer thickness (RNFL) even in clinically unaffected eyes, which is in line with postmortem studies demonstrating that atrophy of the nerve fiber and ganglion cell layers is present in the majority of MS patients even without a clinical history of ON. Our objective was to use OCT to demonstrate axonal loss in patients with MS.
We examined the RNFL thickness of 11 control individuals and 24 MS patients (12 RRMS, 9 SPMS, 3 PPMS) clinically evaluated using EDSS. The median RNFL thickness of controls (103.4 uM, SD 10.96, n=11 eyes) was significantly different to that observed in RRMS patients (86.91, SD 21.51, n=24 eyes, P<0.05 ANOVA), SPMS patients (70.57 uM, SD 16.76, n=18, P<0.01 ANOVA) and PPMS patients (80.45 uM, SD 17.76, n=6, P<0.05 ANOVA). Controls were significantly younger than MS patients (34.27 SD 6.21 years vs. 41.82 SD 7.37, P<0.01 Mann-Whitney test) and age affects RNFL thickness. But this cannot account for the differences observed between relapsing-remitting and progressive disease, as these groups did not differ in regard to age (RR-MS 38.75 SD 9.25 years, SPMS 41.78 SD 7.14 and PPMS 43 SD 10). In contrast to previous results, we did not observe a statistically significant difference in RNFL thickness between eyes with and without ON history in our collective of MS-patients. However, RNFL thickness correlated significantly to EDSS only in eyes without ON history (no ON r2=0.175, P=0.05 Spearman two tailed; ON r2=0.13, P>0.05 Spearman), although a trend towards RNFL reduction with increasing EDSS is evident in both groups.
We conclude that RNFL thickness as measured by OCT correlates with a progressive course of disease and with the clinical burden of disease. Axonal loss is a pathological hallmark of progressive MS; we therefore hypothesize that axonal loss measured by OCT also correlates with neuronal degeneration in the brain, which seems to be masked by local changes induced in the optic nerve in the context of ON. Thus, OCT might be a useful surrogate marker to monitor axonal loss and neuronal degeneration in MS.