Clinical predictors in acute optic neuritis: Analysis based on clinical trial data.

Purpose: To identify baseline clinical predictors of visual outcomes six months after acute optic neuritis using data from our completed clinical neuroprotection trial (TONE study).

Design: Secondary analysis of data from the TONE study cohort (NCT01962571).

Subjects: 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 (logMAR 0.3). Patients were recruited from 12 German university hospitals between November 25, 2014, and October 9th, 2017.

Methods: We selected potential predictors based on literature research and experience, then computed initial linear regression models that each included one 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. Since 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 potentials (VEP) P100 peak times, macular ganglion cell and inner plexiform layer thickness, and peripapillary retinal nerve fiber layer thickness at six 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, 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 counselling, facilitate patient selection for time-sensitive and invasive immunomodulatory treatments, and can be used to ensure balanced risk characteristics in clinical neuroprotection trials.