Digital measurement of ocular microtremor in Parkinson’s Disease: Analytical and clinical validation

Abstract Background: Ocular microtremor (OMT) is an involuntary fixational eye movement linked to brainstem activity. OMT has been shown to have a mean frequency range of 70 to 90 Hz in healthy adults and previous research suggests OMT may be reduced in neurological diseases, such as people with Parkinson’s Disease (PwPD). Historically, OMT has been measured invasively in specialist laboratories using lengthy and expensive protocols. Developments now allow for OMT measurement quickly, comfortably,and non-invasively using hand-held technology (i.e., iTremor ONE|). This pilot study aimed to examine the analytical and clinical validation of OMT measurement via the iTremor ONE in PwPD. Methods: A total of 33 PwPD and 31 age matched healthy controls participated in this study. For analytical validation, 22 PwPD completed a test re-test reliability and feasibility assessment of OMT measurement, with interclass correlation coefficients (ICC) used to assess reliability. For clinical validation, OMT frequency in PwPD (n=22) was compared to controls and correlations were explored with demographics and clinical scales.Additionally, 24 PwPD were tested ‘OFF’ (12hr withdrawal) and ‘ON’ their anti-Parkinson’s (dopaminergic) medication to compare OMT response to a known intervention. Results: The iTremor ONE reliably measured OMT frequency in PwPD, with excellent agreement (ICC >0.9). OMT frequency had good (AUC 0.75-0.77) ability to differentiate between PwPD and controls and related to age in both groups. However, no change was seen in OMT frequency in response to dopaminergic medication in PwPD. Conclusion: This is the first study to demonstrate that a non-invasive hand-held technology can reliably measure OMT in PwPD and presents OMT analytical and clinical validation evidence. Further research is required to understand the neural mechanisms underpinning OMT in PwPD.