To define subclinical optic pathway involvement in early multiple sclerosis (MS) and clinically isolated syndromes (CIS)

The role of asymptomatic optic nerve and retinal involvement early MS and CIS is still debated. Ganglion cell (GCIPL) loss is considered as a marker of neurodegeneration in MS but whether it only reflects subclinical optic neuritis (ON) in CIS needs further elucidation. Recently, inflammatory episodes have been associated with thickening of inner nuclear layer (INL) thickening, possibly in relation to swelling of Muller cells.

Consecutive patients with CIS (73) or early MS (78) underwent diagnostic assessement including: OCT, lumbar puncture, visual, somatosensory, motor evoked potentials (VEP, SSEP-MEP), brain MRI, visual acuity, EDSS.

In CIS subclinical VEP abnormalities were found in the 19.2% of patients; OCT inter-eye asymmetries (cut-off values: 5 um pRNFL or 4 um GCIPL) in 17.8%. Asymptomatic VEPs abnormalities were associated with higher brain T2 lesion load (p=0.01), abnormal MEP-SSEP (p=0.002), frequency of oligoclonal bands (p=0.005) and longer disease duration (p=0.02).

When correcting for the presence of subclinical evidence of VEP/OCT involvement, GCIPL thinning was still associated with higher disease burden measured as EDSS (p=0.038), EP score (p=0.027), oligoclonal bands (p=0.029) and disease duration (p=0.028).

INL was increased in the subacute phase after a relapse (1.1 to 3.7 months), particularly in the subgroup tested before steroid treatment, and correlated with CSF IL-7, MCP-1 and MIP-1b levels (R² 0.4; p<0.001). No correlation was found between INL and gadolinium enhancing lesions, CSF Link Index, serum neurofilaments.

Asymptomatic optic nerve involvement in CIS, revealed by OCT and VEP, is relatively frequent and associated with several markers of disease burden. While neuroretinal atrophy is associated with accumulation of disease burden, INL thickening reflects a transient response to inflammatory acute events, possibly owing to Muller cell responses to neuronal injury.