# Optic nerve and susceptibility imaging at asymptomatic stage of multiple sclerosis: impact and predictive value

## TL;DR

This study finds that optic nerve and paramagnetic rim lesions are common in asymptomatic multiple sclerosis and linked to retinal thinning and higher risk of disease progression.

## Contribution

The study is the first to evaluate optic nerve lesion frequency and their impact on retinal thickness in radiologically isolated syndrome.

## Key findings

- Optic nerve lesions were found in 21.9% of asymptomatic MS patients and were associated with retinal thinning.
- Patients with optic nerve or paramagnetic rim lesions had a higher risk of clinical conversion to MS.
- Silent optic nerve lesions appear to be the main cause of subclinical retinal neuro-axonal loss in early MS.

## Abstract

Optic nerve is now included as a fifth typical location in multiple sclerosis diagnosis criteria. The radiologically isolated syndrome represents the earliest stage of multiple sclerosis. Previous optical coherence tomography studies in this asymptomatic context reported no or slight retinal thickness difference compared to healthy subjects. Frequency of asymptomatic optic nerve lesions has never been evaluated at this stage of the disease. Susceptibility-weighted imaging findings on brain MRI are incorporated in the recent revised multiple sclerosis diagnostic criteria (2024) through the ‘central vein sign’ and ‘paramagnetic rim lesion’ parameters but for the diagnosis of asymptomatic form, ‘paramagnetic rim lesion’ are not included. In this study, we aim to measure the frequency of optic nerve lesions in radiologically isolated syndrome and to evaluate their impact on retinal thicknesses. Second, we aim to evaluate the association of optic nerve lesion and susceptibility-weighted imaging parameters with the disease course.

This retrospective cohort study collected data (August 2020 to December 2024) on patients with radiologically isolated syndrome at Lille (France). MRI was performed at baseline and every year. Optic nerves were studied using MRI and optical coherence tomography performed on the same day by measuring retinal thickness intereye difference. Clinical examination was performed every 6 months.

We included 32 untreated patients (63 eyes; one eye excluded due to the fortuitous discovery of an ocular melanoma). Nine optic nerves showed lesions on MRI in the orbital or canalicular part. These eyes had a thinner peripapillary retinal nerve fibre layer compared to eyes without optic nerve lesions on MRI (median = 87.4 µm versus 96.8 µm, P = 0.003). No association was found between peripapillary retinal nerve fibre layer thickness and quantitative MRI parameters as optic radiations T2 lesions or primary visual cortex volumes.

During follow-up (median: 22.1 months), three patients converted to relapsing multiple sclerosis and two patients to progressive multiple sclerosis. Among them, 60% had an optic nerve lesion (versus 25.9%) and 60% had at least one paramagnetic rim lesion (versus 25.9%). In total, 24 patients fulfilled dissemination in time and space according to the revised multiple sclerosis diagnostic criteria (2024).

As in clinically isolated syndrome and clinically definite MS, silent optic nerve lesions seem to be the main cause of subclinical retinal neuro-axonal loss at radiologically isolated syndrome stage. Our results suggest that patients with paramagnetic rim lesion or optic nerve lesion might present a higher risk of clinical conversion.

Lafontaine et al. report that optic nerve (21.9%) and paramagnetic rim (31.5%) lesions are frequently observed in patients with asymptomatic multiple sclerosis, particularly in those who will experience clinical conversion. Optic nerve lesions were associated with a significant retinal thinning, suggesting that this is the main cause of retinal axonal loss.

Graphical Abstract