Multimodal Characterization of Optic Neuritis in Demyelinating Disease: Clinical Phenotypes, Neuroimaging, and Visual Biomarkers

Abstract

Optic neuritis is a heterogeneous neuro-ophthalmological syndrome that may represent the first clinical manifestation of an underlying central nervous system demyelinating disease. This study analyzed the distinguishing characteristics of multiple sclerosis-associated optic neuritis, aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease through an integrated assessment of clinical phenotype, magnetic resonance imaging, optical coherence tomography, visual function, and serological biomarkers. The analysis identified partially overlapping but clinically meaningful patterns among the three disorders. Multiple sclerosis-associated optic neuritis was more frequently characterized by unilateral painful visual loss, shorter focal optic nerve lesions, comparatively less severe chronic retinal neuroaxonal damage, and generally favorable recovery of high-contrast visual acuity. AQP4-IgG-positive neuromyelitis optica spectrum disorder was associated with more severe visual impairment, recurrent attacks, posterior or chiasmal optic pathway involvement, greater retinal nerve fiber and ganglion cell loss, and a higher risk of persistent visual disability. MOG antibody-associated disease more commonly exhibited bilateral optic neuritis, marked optic disc edema, extensive anterior optic nerve involvement, and pronounced inflammatory changes, while substantial visual recovery could occur despite severe initial visual loss. Optical coherence tomography and visual evoked potentials demonstrated that structural and functional abnormalities may persist even after apparent recovery of conventional visual acuity. The findings support a multimodal diagnostic model in which clinical examination, neuroimaging, retinal structural assessment, functional visual testing, and disease-associated antibodies provide complementary rather than redundant information. Early integration of these domains may improve etiological classification, reduce diagnostic uncertainty, and facilitate neurological follow-up in patients presenting with a first episode of optic neuritis.