Transorbital sonography reveals retrobulbar optic nerve neuroaxonal changes in multiple sclerosis

Background: The optic nerve (ON), as an extension of the central nervous system, reflects multiple sclerosis (MS) pathological processes. Transorbital sonography (TOS) is emerging as a novel technique to detect ON changes. Our aim was to investigate retrobulbar ON morphometric changes in MS and their relationship with prior history of optic neuritis. Methods: 122 MS subjects were enrolled, 68 with and 54 without history of optic neuritis. ON diameters without and with sheath were measured at 3 mm (OND3 and ONSD3) and 5 mm (ONSD5) posterior to the optic disc; myelination index (MI=ONSD3/ONSD5) was calculated. To account for intrasubject dependencies, linear mixed models (LMMs) for repeated measures were employed, adjusting for age at onset and body mass index. Results: ONs with history of inflammation (I-ON) exhibited significantly reduced diameters versus companion nerves in both measurements with and without sheath (OND3: p = 0.002; ONSD3: p = 0.010; ONSD5: p = 0.046). All ONs diameters progressively decreased with increasing neuritis frequency, demonstrating a dose-response effect. Significant measurement reductions in OND and ONSD3 were observed in I-ON of patients with Expanded Disability Status Scale >3, whereas no significant differences emerged for progression index (PI) > 0.20 among ONs with and without history of optic neuritis. Conclusions: TOS reliably captures ON morphometric changes related to inflammatory history and chronic neuroaxonal injury in MS, supporting its role as a promising biomarker of disability burden and progression independent of relapse activity (PIRA).