Istradefylline Improves Impaired Smooth Pursuit Eye Movements in Parkinson’s Disease

INTRODUCTION: Patients with Parkinson’s disease (PD) exhibit alterations in eye movement control, primarily diverse oculomotor deficits which include hypometric saccade and impaired smooth pursuit with reduced pursuit-gain necessitating catch-up saccades. The effects of dopaminergic treatment of PD on eye movements are controversial. Previous studies suggest that smooth pursuit eye movements (SPEMs) are not directly influenced by the dopaminergic system. The nondopaminergic drug istradefylline, a selective adenosine A2A receptor antagonist, reduces the OFF time and improves somatomotor function in levodopa-treated PD. Here, we investigated whether istradefylline improves SPEMs in PD, and determined whether oculomotor performance is associated with somatomotor performance. METHODS: Using an infrared video eye tracking system, we quantified horizontal SPEMs in six patients with PD before and 4–8 weeks after initiation of istradefylline administration. A further five patients with PD were tested before and after a 4-week interval without istradefylline to control for practice effects. We evaluated smooth pursuit gain (eye velocity/target velocity), accuracy of smooth pursuit velocity, and saccade rate during pursuit before and after istradefylline administration during the ON state. RESULTS: Patients received istradefylline by single daily oral administration at 20 to 40 mg. Eye tracking data were obtained 4–8 weeks after initiation of istradefylline administration. Istradefylline increased smooth pursuit gain and the accuracy of smooth pursuit velocity, and tended to decrease saccade rates during pursuit. CONCLUSIONS: Istradefylline ameliorated the oculomotor deficit in SPEM of patients with PD, although differences in somatomotor performance before and after istradefylline treatment were not significant during ON periods. The discrepancy observed between the oculomotor and somatomotor responses to istradefylline supports previous findings that SPEM is at least partially under nondopaminergic control.