Beyond the optic disc: Investigating gender-based differences in optic neuritis

Abstract

Optic neuritis (ON) is a focal inflammatory demyelinating disorder of the optic nerve. Although classically regarded as a sentinel event for multiple sclerosis (MS), ON also occurs in antibody-mediated entities such as aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin-oligodendrocyte-glycoprotein-antibody disease. In all these settings biological sex is a pivotal determinant of susceptibility, clinical expression, treatment response and long-term outcome. Data synthesized from an extensive literature analysis utilizing PubMed, Scopus, and Web of Science in this review shows that women experience ON far more frequently – with female-to-male ratios ranging from 3:1 in MS to almost 9:1 in AQP4-NMOSD – yet men, when affected, tend to accumulate irreversible neuro-axonal loss more rapidly. Sex-specific patterns arise at every biological stratum: X-linked gene dosage, epigenetic regulation, hormonal cycles from puberty through menopause, metabolic co-modifiers such as obesity and vitamin-D status, and psychosocial forces that influence healthcare utilization. By weaving these elements into an expanded narrative, the present review provides a detailed resource for clinicians and investigators aiming at gender-tailored management of ON.

Keywords: Optic neuritis; Gender differences; Neuromyelitis optica spectrum disorder; Myelin oligodendrocyte glycoprotein antibody disease; Optic nerve

Core Tip: Optic neuritis (ON) is affected by sex at all levels, from molecular biology to clinical outcomes. Women are considerably more predisposed to developing ON, particularly in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder. Men frequently experience more severe long-term neuroaxonal damage. The interaction of genetic, hormonal, metabolic, and behavioral variables highlights the necessity for sex-specific strategies in the diagnosis, treatment, and research of ON. Comprehending these distinctions is crucial for enhancing individualized treatment in ON across various demyelinating conditions.