Enhancing the diagnostic potential of electroretinography in Parkinson's disease: A review of protocol and cohort criteria

Electroretinography has emerged as a promising tool for identifying retinal functional anomalies in major psychiatric and neurodevelopmental disorders, such as schizophrenia, major depressive disorder, bipolar disorder, and autism spectrum disorder, positioning it as a potential biomarker of monoaminergic dysfunction. However, despite its potential, electroretinography studies in Parkinson's disease (PD) over the past decades have been inconsistent, largely due to variations in research methodologies. These limitations diminish its potential and hinder the association between retinal electrophysiological responses and PD neuropathology. To address this challenge, this review examines the most relevant sources of data variability and reduced reproducibility in electroretinography studies aimed at detecting a retinal functional signature characteristic of PD. We propose the consolidation of four key protocol factors and five cohort criteria to enhance the diagnostic accuracy of electroretinography in PD biomarker research. As electroretinography protocols are adapted from their clinical origins for research purposes, we argue that careful attention must be given to electrode type and placement, as well as to factors like age, sex, disease duration and severity, medication intake, psychiatric conditions, and comorbidities in cohort selection to ensure reproducible results. Suggesting that past inconsistencies in these areas may explain the variability in reported results and contribute to the lack of consensus on which electroretinography parameters comprise a disease signature in PD, we ultimately offer recommendations to improve the utility of electroretinography techniques as early biomarkers for PD.