Neuro-Ophthalmic Adverse Events of COVID-19 Infection and Vaccines: A Nationwide Cohort Study

PURPOSE. To evaluate the association of COVID-19 infection and vaccination with neuro-ophthalmic adverse events. METHODS. In this nationwide population-based retrospective cohort study, 8,498,353 patients were classified into three groups: control, COVID-19 infection, and COVID-19 vaccination. We conducted separate analyses for the early phase (within 60 days) and late phases (61-180 days) to estimate the incidence rates and hazard ratio (HR) for each neuro-ophthalmic adverse event. The adverse events included in this analysis were optic neuritis, papilledema, ischemic optic neuropathy, third nerve palsy, fourth nerve palsy, sixth nerve palsy, facial palsy, nystagmus, ptosis, blepharospasm, anomalies of pupillary function, and Guillain-Barre syndrome/Miller Fisher syndrome (GBS/MFS). RESULTS. Neuro-ophthalmic adverse events other than ptosis and GBS/MFS exhibited no significant increase after COVID-19, and their incidence was extremely low. The incidence rate of ptosis in both phases was significantly higher in patients administered COVID-19 vaccination (HR = 1.65 in the early phase and HR = 2.02 in the late phase) than in the control group. Additionally, BNT162b2 conferred a lower ptosis risk than ChAdOx1. GBS/MFS had a significantly higher incidence rate in the early phase (HR = 5.97) in patients with COVID-19 infection than in the control group. CONCLUSIONS. Ptosis was associated with COVID-19 vaccination, particularly with the ChAdOx1 vaccine, while GBS/MFS was associated with COVID-19 infection. In contrast, no association was found between other neuro-ophthalmic adverse events and COVID-19 infection or vaccination. These results may provide helpful insights for diagnosing and treating the neuro-ophthalmological adverse events after COVID-19.