Melanopsin-Mediated Post-Illumination Pupillary Response in Idiopathic Rapid Eye Movement (REM) Sleep Behavior Disorder and Parkinson's Disease.

AIMS: To conduct a case-control study to investigate melanopsin-mediated post-illumination pupillary response (PIPR) in patients with Parkinson's disease (PD), video-polysomnography-confirmed isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD), and age-matched healthy controls (HC).

METHODS

PIPR was measured at 6 s after light offset (PIPR-6s). Net PIPR-6s was calculated by subtracting the red-light response from the blue-light response. Participants also underwent 1-week actigraphy, overnight urinary 6-sulfatoxymelatonin assessment, and cognitive testing using the Hong Kong Montreal Cognitive Assessment (HK-MoCA).

RESULTS

We recruited 135 participants (mean age 64.4 ± 5.7 years; 56% male), with 45 in each group. Net PIPR-6s was 23.8 ± 9.4% in HC, 18.6 ± 10.8% in iRBD, and 13.3 ± 9.6% in PD (P < 0.001; HC > iRBD > PD). Net PIPR-6s was positively associated with circadian rest-activity rhythm amplitude, mesor, and HK-MoCA score.

CONCLUSION

Attenuated PIPR may reflect early dysfunction in melanopsin-mediated phototransduction in the prodromal stage of synucleinopathy. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.