The effect of levodopa on saccades - Oxford Quantification in Parkinsonism study

Objectives: The evaluation of novel disease modifying drugs requires biomarkers that are simultaneously sensitive to disease state but resistant to the effects of background symptomatic treatment. Saccadic eye movement parameters have been proposed as a neurophysiological biomarker for Parkinson's disease (PD) and so it is important to know how they are affected by dopaminergic medication. Studies to date are conflicting: some have concluded that medication prolongs saccadic latencies while others suggest they are shortened. We aimed to characterise the effects of antiparkinsonian medication on prosaccadic and antisaccadic parameters in a large cohort of PD patients and age matched healthy controls and to survey the current literature in comparison to the study findings. Methods: We studied saccades both off and on medication in 38 PD patients and 34 healthy controls (HC). Latencies, amplitudes, velocities, and directional errors were evaluated, using a published standardised protocol. We then combined this study and previously published literature in a meta-analysis of the effects of antiparkinsonian medication on prosaccadic latency (PSL). Results: PSL is significantly prolonged by dopaminergic medication in PD, from a mean of 222.7 ms in the OFF medication state to a mean of 236.0 ms in the ON medication state (p = 0.028). This effect size is comparable to the difference between PD OFF medication and healthy control values. There was no statistically significant change in any other saccadic parameter with medication. Of particular note, antisaccadic latency was almost exactly the same on and off medication (means of 414.9 ms and 417.2 ms respectively, p = 0.97), while being almost 20% longer in PD patients compared to healthy controls (HC mean 357.2 ms; PD ON vs HC p = 0.015; PD OFF vs HC p = 0.0066). Conclusion: PSL is significantly affected by dopaminergic medication which may complicate its use as a biomarker in drug trials. Antisaccadic latency is particularly interesting in this regard because it shows a large disease effect with no medication effect.