PURPOSE: To identify baseline clinical predictors of visual outcomes 6 months after acute optic neuritis using data from our completed clinical neuroprotection trial: Treatment of Optic Neuritis with Erythropoietin (TONE). DESIGN: Secondary analysis of data from the TONE study cohort (NCT01962571). PARTICIPANTS: A total of 103 patients presenting within 10 days of a first episode of acute unilateral optic neuritis as a clinically isolated syndrome with baseline high-contrast visual acuity (HCVA) ≤20/40 Snellen (logarithm of the minimum angle of resolution 0.3). Patients were recruited from 12 German university hospitals between November 25, 2014, and October 9, 2017. METHODS: We selected potential predictors based on literature research and experience, and then computed initial linear regression models that each included 1 predictor together with the baseline value of the outcome of interest. We used a forward-selection approach to build a multiple regression model for each outcome. Because the trial medication of the TONE study (erythropoietin) had no effect on the visual system, we used pooled (treatment-agnostic) data for all analyses. MAIN OUTCOME MEASURES: Independent predictors of HCVA, low-contrast letter acuity, visual-evoked potential (VEP) P100 peak times, macular ganglion cell and inner plexiform layer thickness, and peripapillary retinal nerve fiber layer thickness at 6 months. RESULTS: On multiple regression, the most consistent predictors were higher baseline HCVA, which was associated with better outcomes across all measures except VEP conduction time
male sex, which predicted worse outcomes for all measures except HCVA
and older age, which was linked to poorer functional outcomes. CONCLUSIONS: Patients who are older, are male, and present with worse initial visual function may be at risk for worse clinical outcomes in acute optic neuritis. This knowledge may inform individual patient counseling, facilitate patient selection for time-sensitive and invasive immunomodulatory treatments, and can be used to ensure balanced risk characteristics in clinical neuroprotection trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.