August, 2022 Identification of Ocular Biomarkers for the Development of an Early Stage Diagnostic Tool for Neurodegenerative Disease Tarini Basireddy, Arnav Bhalla, Rushank Goyal, Emery Han, Sai Mattapalli, Tanmay Neema, Brian Zhou, Rohan Kalahasty* Authors listed in alphabetical order * denotes corresponding author Abstract Current methods of diagnosis for neurodegenerative diseases are almost purely qualitative and highly apparent only when extensive neuronal dystrophy and degeneration have occurred. Therefore, creating a clinically viable tool that leverages early biomarkers of neurodegenerative disease is necessary. Past research indicates that ocular biomarkers are a potential source of quantitative assessment for the early diagnosis of neurodegenerative disease. In this paper, we identify specific ocular biomarkers that could be used as a basis for the early detection of neurodegenerative disease, potentially using machine learning techniques. Furthermore, we outline data collection procedures that can be implemented for patients completing Pro-Saccade, Anti-Saccade, Express-Saccadic, and Smooth Pursuit tasks. We expect that the findings in this paper can be utilized to guide the future creation of tools and datasets for developing a gaze-based diagnostic tool. 1. Background Table 1: Six Basic Types of Eye Movement Vestibulo-ocular reflex Gaze stabilization, correcting for in- ertial differences during accelera- tion Optokinetic reflex Complements VOR at low frequen- cies Saccades Rapid movements of the eye be- tween points of fixation Smooth pursuit Used to keep a moving object’s im- age on the fovea Vergence Provide binocular alignment for changing object depths Fixation Keeps gaze fixed on the object of interest The cerebrum, brainstem, and cerebellum are key regions involved in ocular movements in the brain, the abnormality of which can serve as a supplemental indicator of neurode- generation. Alzheimer’s patients, for instance, exhibit lower fixation stability and more antisaccade errors, while Parkin- son’s patients show a consistent hypometria of voluntary eye movements; even presymptomatic Huntington’s cases dis- play an increase in saccade latency and its variability. Table 1 shows the latency and amplitude of saccades in vari- ous neurodegenerative diseases. The daggers and asterisks indicate a significant difference from normal controls before and after correction, respectively, for multiple comparisons. The three-lined band in the middle is the 95% confidence