Eye Tracking
Eye tracking as a measure of remyelination in people with multiple sclerosis
BACKGROUND
Visual outcome measures of remyelination have proven considerably important to capture remyelination in clinical trials. Visual evoked potentials (VEP) have been used effectively to demonstrate remyelination but capture an effect restricted to the visual pathway. Building on work pioneered in Cambridge, as well as our collaborators in Amsterdam, we are extending this framework to assess remyelination through the measurement of eye movements.
Saccadic eye movements are rapid, reflexive shifts of gaze and offer a unique window into visual and motor pathways, as well as the decision making apparatus of the nervous system. The speed and precision of saccades is believed to be sensitive to demyelination and neurodegeneration, and can be captured rapidly and non-invasively at the bedside. Unlike established structural and biochemical measures using MRI and blood tests, saccadometry yields a direct functional readout of neural integrity.
OUR METHODS
Our group uses two methodologies for the study of saccades. The first is a head-mounted saccadometer, which uses infra-red detectors to detect eye movements. The second is a video-based device which allows precision movements of the direction of gaze. In this way, we can present different visual stimuli to participants and capture the time taken to make an eye movement (latency) but also measure any differences between the movement of the two eyes (dysconjugacy). By presenting tasks of varying complexity, we can access the functioing of different parts of the nervous system. We have been deploying these measures in our most recent remyelination trials, while also validating our findings against established markers of disease including VEP latency, MRI and blood markers.
APPLICATION OF SACCADOMETRY TO CCMR TWO TRIAL
Our methods have been applied within the CCMR Two trial and yielded promising results: participants receiving the combination treatment of metformin and clemastine had a significant reduction in saccadic latency. Interestingly, we only saw the effect on reflex eye movements. Tasks requiring higher levels of cortical processing were unaffected by the treatment. This is an active area of research as we seek to understand how best to measure eye movements in future myelin repair trials.
THE DANIEL-MS STUDY
The DANIEL-MS (Demyelination Assessments of Nerves by Investigating Eye-movement Latencies) study was designed to systematically characterise saccadic performance in people with MS compared to healthy volunteers, and to validate these tests against established imaging and biomarker measures. This study recruited MS participants from across the CCMR2 trial and the ARMOUR-One observational study (IRAS 313164), alongside a healthy volunteer cohort.
So far, the DANIEL study has shown that saccadometry can differentiate MS patients from healthy controls, while also showing meaningful associations with currently used markers of both demyelination and neurodegeneration. We expect to demonstrate the complementary role of eye movement assessments in the measurement of remyelination and continue to apply these techniques in further research projects.