Paramagnetic Rim Lesions Are Associated With Trans-Synaptic Degeneration of the Visual Pathway in Multiple Sclerosis

Retrograde trans-synaptic degeneration (rTSD) from posterior visual pathway lesions in multiple sclerosis (MS) is characterized by hemi-macular ganglion cell-inner plexiform layer (GCIPL) thinning and contralateral visual field loss. We investigated associations between rTSD, paramagnetic rim lesions (PRL), and longitudinal visual disability in people with MS (pwMS) using a novel optical coherence tomography (OCT) based biomarker of rTSD.

PwMS, non-MS neurological disease controls, and healthy controls underwent OCT, multiparametric brain MRI, and clinical assessments. A quantitative rTSD index was developed to capture hemispheric GCIPL asymmetry, with absolute values reflecting rTSD severity. Generalized linear models were used to investigate MRI and clinical predictors of rTSD. Longitudinal changes in rTSD were evaluated using mixed-effects linear regression models.

A total of 170 pwMS and 49 controls were included. PwMS had higher rTSD than healthy (p = 0.006) and non-MS controls (p = 0.009). African American race (p = 0.02) and longer disease duration (p = 0.005) were associated with higher baseline rTSD. PRL in the optic radiations (OR) was linked to a 4.5-fold increase in rTSD (p = 0.037; n = 37) and -1.18 dB reduction in hemifield sensitivity (p = 0.018). Longitudinally, each unit/year progression in rTSD was associated with a -0.07 dB/year decline in hemifield sensitivity (p = 0.005) and a 10.8-fold increase in the odds of expanded disability status scale score progression (p = 0.022). Higher body mass index was associated with faster rTSD progression longitudinally (p = 0.02).

PRL in the OR, African American race, disease duration, and higher BMI are associated with rTSD in pwMS. Longitudinal increase in rTSD is associated with worsening visual loss and clinical disability progression in MS.

ClinicalTrials.gov identifier: NCT05204459.