Virtual reality-based oculography detects internuclear ophthalmoplegia in multiple sclerosis and other neurological...

Clinical-neurological examination may underestimate internuclear ophthalmoplegia (INO). We investigated immersive virtual reality (VR)-based eye-tracking in patients with multiple sclerosis (MS), other neurological disorders (ND), and healthy controls (HC) to detect INO.

In this prospective monocentric study, 471 participants (243 MS, 104 ND, 124 HC) underwent horizontal prosaccade testing (± 10°, ± 20°) using VR-based oculography. INO was determined in a blinded manner based on software-generated reports comparing adduction and abduction velocities. VR-based and clinical assessments were compared using Cohen's kappa (κ). Associations with demographic and clinical variables were analyzed using logistic regression.

VR-based assessment identified 43 cases of INO (40 ND, 3 HC). Agreement between VR-based and clinical assessment was moderate (κ = 0.42; 92.5% observer agreement; n = 414). Three cases were identified clinically only, whereas 28 were detected by VR-based assessment only. Within MS, agreement was similar (κ = 0.45; 89.1% agreement; n = 238), with 23 cases detected by VR only and three clinically only. In MS, VR-based INO was associated with male sex (p = 0.035), higher expanded disability status scale (EDSS) and brainstem functional system scores (p < 0.001), longer disease duration and older age (p = 0.002), and visual complaints (p = 0.007). In multivariable analysis, disease duration (OR 1.12, 95% CI 1.01-1.24), brainstem involvement (OR 21.59, 1.30-358.07), and clinical INO (OR 8.18, 1.43-46.96) were associated with VR-based INO.

VR-based eye-tracking showed moderate agreement with clinical assessment and identified additional cases of INO associated with markers of disease burden. These findings support further evaluation of VR-derived measures as complementary digital biomarkers of brainstem dysfunction.