Retrograde trans-synaptic degeneration (rTSD) of the visual pathway has been described in people with MS (pwMS) and is characterized by hemi macular retinal ganglion cell degeneration in connection with posterior visual pathway lesions. Longitudinal studies examining the rate of rTSD in pwMS and its association with clinical characteristics and visual outcomes are lacking.

In this single center longitudinal study, pwMS underwent clinical assessments, OCT imaging, and perimetry evaluation at baseline and 1 year follow up rTSD index values were analyzed from OCT data and mean visual hemifield defect differences corresponding to the rTSD index values were calculated. Predictors of longitudinal changes in rTSD index were assessed using multivariate linear regression. The association between longitudinal mean hemifield defect and rTSD index changes over time were assessed using multivariate linear regression adjusting for baseline age and stratified by history of optic neuritis (ON).

A total of 30 pwMS were included (mean age 46.2 ±14; 63% females; 26 RRMS and 4 progressive MS). An increase in absolute rTSD index, indicating worsening retinal trans-synaptic neurodegeneration, was significantly associated with female sex (β =1.36, p=0.001), progressive MS (β =0.94, p=0.01), and dyslipidemia history (β =1.45, p=0.001) . On average, mean hemifield defects worsened by 0.41 dB for each unit increase in rTSD index after adjusting for baseline age in pwMS without ON history (Beta=0.41,p=0.019), but was not significant in pwMS with ON history.

Longitudinal worsening of rTSD of the visual pathway in pwMS can be quantified using rTSD index values and is associated with progressive MS subtype, and worsening visual deficits in the corresponding hemifield.