Internuclear Ophthalmoparesis in Multiple Sclerosis: What’s the Prevalence?

Illustration of a nerve cell (neuron) with a damaged myelin sheath (yellow) around its axon.
Researchers sought to characterize the prevalence and clinical features of individuals with both MS and INO in a population-based cohort of patients with MS.

In patients with multiple sclerosis (MS), the presence of internuclear ophthalmoparesis (INO) is associated with worse cognition, arm function, and disability, according to a cross-sectional study published in the journal Multiple Sclerosis and Related Disorders.

INO is a common eye movement disorder among individuals with MS, which can be detected reliably with the use of infrared oculography eye-tracking techniques. The condition is reported in between 15% and 52% of patients with MS. INO is characterized by “slowed movement of the adducting eye relative to the abducting eye in horizontal saccades.”

The researchers sought to characterize INO prevalence and the clinical features of individuals with both MS and INO in a population-based cohort of patients with MS who were born in 1966 from Project Y — an observational cohort study carried out at the Amsterdam University Medical Center in The Netherlands.

Thresholds for the versional dysconjugacy index (VDI), evaluated with the use of standardized infrared oculography, were utilized to diagnose INO among participants from Project Y. The VDI is the ratio between the abducting eye and the adducting eye with respect to the parameters of area under the curve (AUC) and peak velocity divided by saccadic amplitude (PV/Am). Patients with MS and INO were compared with those with MS without INO with respect to clinical characteristics, visual functioning, and visual complaints.

The current study enrolled a total of 220 patients with MS and 110 healthy control individuals. VDI values that exceeded the threshold for INO were revealed in 24% (53 of 220) of participants with MS. The INO was leftward in 34% (18 of 53) of these individuals, rightward in 30% (16 of 53) of these patients, and bilateral in 36% (19 of 53) of these participants. VDI values that exceeded the threshold for INO were detected in 17% (19 of 110) of the control individuals.

Overall, in patients with MS and INO, 43 of the 72 INOs were diagnosed with the use of both the VDI-AUC and the VDI-PV/Am criteria, whereas 17 were diagnosed with the VDI-AUC criterion only and 12 were diagnosed with the VDI-PV/Am criterion only. The median VDI-AUC of an INO was 1.258 (range, 1.183 to 1.467); the median VDI-PV/Am of an INO was 1.243 (range, 1.182 to 1.6740). Among healthy control individuals, 12 of the participants surpassed the VDI-AUC threshold, 7 individuals surpassed the VDI-PV/Am threshold, and 3 participants surpassed both thresholds.

The median VDIs above the INO threshold in the control arm were 1.194 (range, 1.144 to 1.226) for VDI-AUC and 1.176 (range, 1.120 to 1.205) for VDI-PV/Am. These VDI values were significantly lower than those for INOs in individuals in the MS-plus-INO arm for both VDI-AUC (P =.003) and VDI-PV/Am (P <.001).

INO was linked to male sex, worse cognition, greater disability, and worse arm function among individuals with MS. No association was reported between INO and disease duration, visual functioning, or visual complaints.

Possible limitations of the current study include its cross-sectional design, as it remains unknown how oculographic features and visual complaints of INO develop over time. Further, not all of the individuals in Project Y received oculography.

The researchers concluded that additional validation studies are warranted, to ensure “the robustness of the currently used VDI thresholds in individuals with MS with varying demographic characteristics.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Hof SN, Loonstra FC, de Ruiter LRJ, et al. The prevalence of internuclear ophthalmoparesis in a population-based cohort of individuals with multiple sclerosis. Mult Scler Relat Disord. Published online April 25, 2022. doi:10.1016/j.msard.2022.103824