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Yuyi You, Stuart L Graham, Alexander Klistorner; Chronic demyelination contributes to accelerated retinal ganglion cell fibre loss in multiple sclerosis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2290.
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It has been well established that there is retinal ganglion cell (RGC) loss in patients with multiple sclerosis (MS), but the underlying mechanisms remain unknown. Both primary and transsynaptic neurodegeneration have been thought to be contributing factors. On the other hand, basic studies have demonstrated a neuron-glial interaction in the brain and loss of myelin can eventually lead to neuronal damage. Therefore, myelin deficits could be an additional cause of axonal loss in MS. This study was to examine whether chronic demyelination in the optic nerve is associated with progressive RGC loss.
100 MS patients (40.2±10.3yrs, 77F) and 25 age- and sex- matched healthy subjects (38.8±10.7yrs, 18 F) were enrolled. Both eyes were included in the study and underwent regular ocular examinations, OCT scans and multifocal visual evoked potential (mfVEP) recordings. MS patients were examined at least once a year at the Save Sight Institute and were followed-up for a median of 4.1 years. Temporal retinal nerve fibre layer (tRNFL) loss was analysed using the generalized estimating equation (GEE) model.
There were 49 patients with a positive medical history of unilateral optic neuritis (ON). In those patients, both ON (-1.6% per year; 95%CI:-1.9~-1.3) and non-ON eyes (-1.1% per year; 95%CI:-1.4~-0.8) showed a trend of faster progressive tRNFL loss compared to normal controls (-0.3% per year, 95%CI:-0.7~0.1; p<0.001 vs ON, p=0.01 vs NON). The comparison between ON and non-ON eyes also reached statistical significance (p=0.03). We then separated the patients into two groups based on the level of demyelination in the optic nerve, determined by VEP latency asymmetry (≥10ms, n=26; <10ms, n=23; brain pathology would effect on both eyes). In the advanced demyelination group, progressive tRNFL loss was significantly faster in ON eyes (p=0.02). By contrast, no intrasubject difference in tRNFL progression was observed between ON and non-ON eyes in the latency asymmetry< 10 ms group (p=0.32). In addition, we found that asymmetry of tRNFL progression between ON and non-ON eyes was associated with the level of VEP latency delay (p=0.006).
This study provides the first in vivo evidence that chronic demyelination leads to axonal loss in the central nervous system. The findings may have implications in not only MS, but also the pathogenesis of other neurological disorders.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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