Supplementary Material for: Digital Color Vision Testing Reveals Widespread Cone Dysfunction in Multiple Sclerosis Independent of Optic Neuritis

Introduction: To investigate the prevalence and pattern of color vision deficiency (CVD) in relapsing-remitting multiple sclerosis (RRMS) patients, with or without a history of optic neuritis (ON), and to assess its potential as a marker of subclinical optic pathway dysfunction. Methods: Color vision was assessed in a large cohort of 345 RRMS patients using the Waggoner Computerized Color Vision Test (WCCVT), screening for protan, deutan, tritan, and composite color deficiencies, with severity grading based on score thresholds. Statistical differences between eyes with a history of ON, fellow eyes without ON, and eyes from MS patients with no history of ON were analyzed using multivariable logistic regression, controlled for age, gender, disease duration, Expanded Disability Status Scale, and treatment status. Results: Out of the 676 eyes analyzed, CVD was observed in 76.0% of ON-affected eyes, 65.1% of fellow eyes without ON, and 62.3% of eyes from patients without ON. Multivariable logistic regression showed ON-affected eyes had significantly higher odds of severe CVD compared to fellow eyes (OR=2.48, p=0.020), which in turn had higher odds of moderate CVD compared to the no-ON group (OR=2.27, p=0.010). Conversely, the no-ON group had higher odds of mild CVD compared to fellow eyes without ON (OR=2.01, p=0.003). Composite CVD was the most frequent type (57.7%), with tritan deficiencies being the most common pure type (39.9%). Fellow eyes demonstrated higher odds of composite CVD compared to the no-ON group (OR=1.97, p=0.016). Conclusions: CVD is highly prevalent in MS even without clinical ON, indicating diffuse, subclinical optic pathway damage.