Transocular detection of premotor Parkinson’s disease via retinal neurovascular coupling through functional OCT angiography

The early detection of premotor Parkinson’s disease (PD) is important for initiating neuroprotective interventions prior to the widespread and irreversible loss of dopaminergic (DAergic) neurons. We propose a novel optical functional approach for detecting premotor PD from the retina by using functional OCT angiography (fOCTA) to measure PD-related changes in retinal neurovascular coupling (rNVC) at the capillary level, termed fOCTA-rNVC. We demonstrated that, likely due to the retinal DAergic degeneration, functional rNVC was attenuated and delayed in premotor PD mice, whereas no significant change in the retinal structure was found. Furthermore, the administration of levodopa reversed PD-related rNVC attenuation in premotor PD mice, whereas no recovery in ageing-related attenuation in aged mice without significant DAergic deficits was observed. On the basis of the levodopa recoverability of attenuated capillary rNVC, we achieved a remarkable accuracy of ∼100% in detecting premotor PD mice with ∼14.1% loss of midbrain DAergic neurons. These findings suggest that fOCTA-rNVC can be applied for the noninvasive and accurate detection of premotor PD, offering a cost-effective solution with improved accessibility and convenience for large-scale screening.