DOI: 10.1002/mds.70412 ISSN: 0885-3185

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

Joey W.Y. Chan, Bei Huang, Siyi Gong, Yuhua Yang, Shi Tang, Steven Wai‐ho Chau, Ngan Yin Chan, Tim Man‐ho Li, Yaping Liu, Anne Y.Y. Chan, Karen K.Y. Ma, Shirley X. Li, Joshua Tsoh, Kelvin K.L. Chong, Kathryn A. Roecklein, Vincent C.T. Mok, Yun Kwok Wing

Abstract

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.

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