Eye Tracking Neurodegenerative Disease

Neurodegenerative diseases, such as Parkinson’s Disease (PD) and Multiple System Atrophy (MSA), present significant diagnostic challenges, particularly in their early and prodromal stages. Accurate and timely identification is crucial for effective treatment strategies aimed at delaying disease progression. This case study highlights the important role of eye tracking technology as a non-invasive, affordable, and sensitive diagnostic tool. 

The phenotypic similarities between early-stage PD and conditions like MSA complicate clinical differentiation, leading to potential delays in targeted interventions. Traditional diagnostic methods often rely on the manifestation of motor and cognitive symptoms, which may appear after significant neurodegeneration has already occurred. The research by Habibi et al. underscores the urgent need for reliable biomarkers that can identify individuals at risk, ideally during the prodromal stage, such as isolated REM Sleep Behavior Disorder (iRBD), which is a strong predictor for developing alpha-synucleinopathies – a group of neurodegenerative disorders characterized by abnormal accumulation of alpha-synuclein protein in neurons and glial cells.

Neurodegenerative Disease Eye Tracking Methodology

Eye tracking technology offers a unique window into the brain’s neurological health by allowing the precise measurement of eye movements, pupil size, and blinks. These oculomotor parameters are governed by complex neural circuits that can be subtly affected by neurodegenerative processes long before overt clinical symptoms emerge. In their recent research paper “Saccade, pupil, and blink abnormalities in prodromal and manifest alpha-synucleinopathies“, Habibi et al. (2025) used an EyeLink 1000 Plus eye tracker to record eye movements during an interleaved pro-/anti-saccade task (IPAST) on a cohort of patients with iRBD, PD, MSA, and healthy controls. This approach allowed for a detailed quantitative assessment of oculo-pupillo-motor parameters, providing valuable insights into the underlying neural circuitry affected by various disease processes.

Pupil Abnormalities Show Potential as Early Indicators of Disease

The research revealed critical distinctions across the groups:

• Pupil Abnormalities as Early Indicators: The most significant finding was the presence of abnormal pupil responses in iRBD patients, which were similar to those observed in PD and MSA. Specifically, iRBD patients exhibited reduced pupil dilation size and peak dilation velocity. This suggests that the premotor control circuits governing pupil function are impacted by iRBD disease processes before saccade control circuits are affected. 
• Intact Saccade and Blink Behavior in iRBD: In contrast to pupil abnormalities, horizontal saccade parameters and blink behavior were largely intact in iRBD patients, but abnormal in manifest PD and MSA. This indicates that saccadic impairments likely occur later in the disease course.
• Correlation with Disease Progression Markers: The extent of early alterations in pupillary parameters was found to be associated with a decline in Dopamine transporter imaging (DaTscan) results and the severity of hyposmia (reduced sense of smell), both known markers of alpha-synucleinopathies. This highlights the potential for pupil measurements to serve as predictive indicators for disease progression in iRBD.

The findings from this study underscore the power of eye tracking technology to detect subtle, yet pathological, alterations in oculomotor behavior. By identifying pupil abnormalities in the prodromal stage of alpha-synucleinopathies, eye tracking offers a non-invasive and accessible biomarker for early detection and monitoring.

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