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

Ocular microtremor (OMT) is an involuntary fixational eye movement linked to brainstem activity. OMT is thought to have a mean frequency range of 70-90 Hz in healthy adults. Previous research suggests OMT may be reduced in neurological diseases like Parkinson's Disease. Historically, OMT has been measured invasively in specialist laboratories using lengthy and expensive protocols. Developments now allow for OMT measurement quickly 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 people with Parkinson's Disease (PwPD). 33 PwPD and 31 age matched healthy controls participated in this study. For analytical validation, 22 PwPD completed a test re-test reliability assessment of OMT measurement, assessed using interclass correlation coefficients (ICC). For clinical validation, OMT frequency in PwPD (n = 33) was compared to controls. 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. The iTremor ONE demonstrated excellent test-retest reliability (ICC > 0.9) for measuring OMT frequency in PwPD. Mean OMT frequency was significantly lower in PwPD (63.78 ± 4.82 Hz) compared to controls (69.44 ± 6.47 Hz, p < .001), with good discriminative ability (AUC 0.75-0.77). OMT frequency correlated with age in both groups and with specific motor features (speech, facial expression, gait) in PwPD. No significant differences in OMT frequency were observed between 'OFF' and 'ON' dopaminergic medication states. This is the first study to demonstrate that a non-invasive hand-held device can reliably measure OMT in PwPD and presents OMT analytical and clinical validation evidence. OMT frequency may provide a supporting measure for diagnosis or screening. Further research is required to understand the neural mechanisms underpinning OMT in PwPD and the role it could play in clinical practice.