Researchers Develop Protocol for Identifying INO in Multiple Sclerosis

close up of man's eye
close up of man’s eye
Researchers have developed a diagnostic protocol for identifying INO in Patients With MS.

Researchers have developed a diagnostic protocol for identifying internuclear ophthalmoplegia (INO) in patients with multiple sclerosis (MS). The protocol calculates the versional dysconjugacy index (VDI) for peak velocity, peak acceleration, and peak velocity and divides these variables by amplitude and area under the curve (AUC) of the horizontal saccadic trajectory. Findings from this study were published in Neurology.

In this observational cross-sectional study, individuals with MS (n=210) and healthy controls (n=58) were recruited from an ongoing observational MS cohort investigation at Amsterdam University Medical Center in The Netherlands. The prosaccade task of the DEMoNS (Demonstrate Eye Movement Networks with Saccades), a standardized infrared oculography protocol developed and validated by the study’s research team, was used to quantify prosaccades in both groups of participants.

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Study investigators measured eye movements and calculated the versional dysconjugacy index (VDI), a ratio between the abducting and adducting eye. VDI values were determined for peak velocity, peak acceleration, peak velocity divided by saccadic amplitude, and the area under the curve (AUC) of the horizontal saccadic trajectory. Diagnostic accuracy for VDI parameters was compared between patients with MS and healthy controls. Further, vision-related quality of life was assessed in all patients using the National Eye Institute Visual Function Questionnaire-25.

For INO detection, the highest accuracy cutoff value for the VDI AUC15 (15° horizontal prosaccades) was 1.174, which separated patients with MS from healthy controls with a specificity of 98%. VDI AUC was used to divide patients with MS into INO and non-INO groups. Of the patients identified as having MS, INO was classified in 34% (bilateral [37%], to the right [30%], and to the left [34%]).

Investigators found a greater percentage of patients with MS in the INO group reported any complaints of double vision compared with the non-INO group (35.2% vs 18.4%, respectively; P =.010). Patients with MS and an INO also reported a lower overall vision-related quality of life vs patients with MS without INO (median, 89.9 [interquartile range (IQR), 12.8] vs 91.8 [IQR, 9.3], respectively; P =.011).

A limitation of the study, as identified by study investigators, was the small number of participants included. They also recognize the infrared oculography technique used as a limitation, due to its potential for being unreliable if patients were unable to “properly fixate the target during the calibration procedure.”

The researchers do conclude, however, that “[b]ecause of the ease of measurement and the shown response to therapy, INO is a promising model for testing remyelination strategies in MS clinical trials.”


Nij Bijvank JA, van Rijn LJ, Balk LJ, et al. Diagnosing and quantifying a common deficit in multiple sclerosis: Internuclear ophthalmoplegia [published online April 19, 2019]. Neurology. doi:10.1212/WNL.0000000000007499.