Disruption of pupil size modulation correlates with voluntary motor preparation deficits in Parkinson's disease

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, but it is often diagnosed after the majority of dopaminergic cells are already damaged. It is critical to develop biomarkers to identify the disease as early as possible for early intervention. PD patients appear to have an altered pupillary response consistent with an abnormality in photoreceptive retinal ganglion cells. Tracking the pupil size manually is a tedious process and offline automated systems can be prone to errors that may require intervention; for this reason in this work we describe a system for pupil size estimation with a user interface to allow rapid adjustment of parameters and extraction of pupil parameters of interest for the present study. We implemented a user-friendly system designed for clinicians to automate the process of tracking the pupil diameter to measure the post-illumination pupillary response (PIPR), permit manual corrections when needed, and continue automation after correction. Tracking was automated using a Kalman filter estimating the pupil center and diameter over time. The resulting system was tested on a PD classification task in which PD subjects are known to have similar responses for two wavelengths of light. The pupillary response is measured in the contralateral eye to two different light stimuli (470 and 610 nm) for 19 PD and 10 control subjects. The measured Net PIPR indicating different responsiveness to the wavelengths was 0.13 mm for PD subjects and 0.61 mm for control subjects, demonstrating a highly significant difference (p < 0.001). Net PIPR has the potential to be a biomarker for PD, suggesting further study to determine clinical validity.

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Fixation Duration and Pupil Size as Diagnostic Tools in Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202427 ◽

2021 ◽

pp. 1-11

Author(s):

Panagiota Tsitsi ◽

Mattias Nilsson Benfatto ◽

Gustaf Öqvist Seimyr ◽

Olof Larsson ◽

Prof Per Svenningsson ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Eye Movements ◽

Eye Tracking ◽

Eye Movement ◽

Pupil Size ◽

Clinical Investigation ◽

Sampling Rate ◽

Diagnostic Tools ◽

Eye Tracker

Background: Visual and oculomotor problems are very common in Parkinson’s disease (PD) and by using eye-tracking such problems could be characterized in more detail. However, eye-tracking is not part of the routine clinical investigation of parkinsonism. Objective: To evaluate gaze stability and pupil size in stable light conditions, as well as eye movements during sustained fixation in a population of PD patients and healthy controls (HC). Methods: In total, 50 PD patients (66% males) with unilateral to mild-to-moderate disease (Hoehn & Yahr 1– 3, Schwab and England 70– 90% ) and 43 HC (37% males) were included in the study. Eye movements were recorded with Tobii Pro Spectrum, a screen-based eye tracker with a sampling rate of 1200 Hz. Logistic regression analysis was applied to investigate the strength of association of eye-movement measures with diagnosis. Results: Median pupil size (OR 0.811; 95% CI 0.666– 0.987; p = 0.037) and longest fixation period (OR 0.798; 95% CI 0.691-0.921; p = 0.002), were the eye-movement parameters that were independently associated with diagnosis, after adjustment for sex (OR 4.35; 95% CI 1.516– 12.483; p = 0.006) and visuospatial/executive score in Montreal Cognitive Assessment (OR 0.422; 95% CI 0.233– 0.764; p = 0.004). The area under the ROC curve was determined to 0.817; 95% (CI) 0.732– 0.901. Conclusion: Eye-tracking based measurements of gaze fixation and pupil reaction may be useful biomarkers of PD diagnosis. However, larger studies of eye-tracking parameters integrated into the screening of patients with suspected PD are necessary, to further investigate and confirm their diagnostic value.

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