Risk factors for disease generalization in acetylcholine receptor antibody-positive ocular myasthenia: a multicenter retrospective study

Objective – This study aimed to identify factors associated with secondary generalization in patients with ocular-onset myasthenia gravis (OoMG) who were positive for anti–acetylcholine receptor (AChR) antibodies. Early identification of patients at higher risk of progression to generalized myasthenia gravis (gMG) is clinically relevant to optimize therapeutic strategies and improve long-term outcomes. Methods – We conducted a multicenter retrospective cohort study including patients with anti-AChR–positive OoMG recruited from three Italian neurology centers. Demographic, clinical, electrophysiological, and serological data were collected. Univariable and multivariable Cox regression analyses were performed to identify factors associated with disease generalization. Results – Among 85 patients, 40 (47.1%) developed gMG during follow-up. In univariable Cox regression, higher anti-AChR antibody titers (HR 3.37, 95% CI 1.53–7.43; p = 0.002) and abnormal repetitive nerve stimulation of facial muscles (HR 2.49, 95% CI 1.16–5.34; p = 0.020) were significantly associated with secondary generalization. However, no independent predictors were identified in multivariable analysis. Conclusion – Higher anti-AChR antibody titers and abnormal facial repetitive nerve stimulation were associated with an increased risk of secondary generalization in seropositive OoMG. Although these factors did not independently predict generalization in multivariable analysis, their combined assessment may support early clinical risk stratification. Larger prospective studies are warranted to validate these findings and refine prognostic assessment.