Variable abnormality of the melanopsin-derived portion of the pupillary light reflex (PLR) in patients with Parkinson’s disease (PD) and parkinsonism features

Abstract

Objectives Ascertain and quantify abnormality of the melanopsin-derived portion of the pupillary light reflex (PLR) in patients with Parkinson's disease (PD) and parkinsonism features based on a statistical predictive modeling strategy for PLR classification. Methods Exploratory cohort analysis of pupillary kinetics in non-disease controls, PD subjects, and subjects with parkinsonism features using chromatic pupillometry. Receiver operating characteristic (ROC) curve interpretation of pupillary changes consistent with abnormality of intrinsically photosensitive retinal ganglion cells (ipRGCs) was employed using a thresholding algorithm to discriminate pupillary abnormality between study groups. Results Twenty-eight subjects were enrolled, including 17 PD subjects (age range 64-85, mean 70.65) and nine controls (age range 48-95, mean 63.89). Two subjects were described as demonstrating parkinsonism symptoms due to presumed Lewy body dementia and motor system atrophy (MSA) respectively. On aggregate analysis, PD subjects demonstrated abnormal but variable pupillary dynamics suggestive of ipRGC abnormality. Subjects with parkinsonism features did not demonstrate pupillary changes consistent with ipRGC abnormality. There was no relationship between levodopa equivalent dosage or PD severity and ipRGC abnormality. The pupillary test sensitivity in predicting PD was 0.75 and likelihood ratio was 1.2. Conclusions ipRGC deficit is demonstrated in PD subjects; however, the degree and constancy of abnormality appear variable.

Chromatic pupillometry for evaluating melanopsin retinal ganglion cell function in Alzheimer’s disease and other neurodegenerative disorders: a review

“…In all, 17 PD subjects, 9 controls, and 2 subjects with parkinsonism presumed to have Lewy body dementia and multiple system atrophy were compared. Subjects with PD variably demonstrated altered PIPR with short-wavelength high irradiance stimuli, consistent with mRGC dysfunction, and abnormal pupil latency at both short- and long-wavelength stimuli, while subjects with parkinsonism did not show any pupillary changes ( Gaynes et al, 2022 ).…”

“…Furthermore, chromatic pupillometry to assess melanopsin retinal ganglion cell (mRGC) function has also been applied to other neurodegenerative disorders, such as Parkinson’s disease (PD) and its prodromal stage, idiopathic/isolated rapid eye movement sleep behavior disorder (iRBD) ( Joyce et al, 2018 ; Feigl et al, 2020 ; Tabashum et al, 2021 ; Gaynes et al, 2022 ; La Morgia et al, 2022 ; Steiner et al, 2022 ).…”

“…In particular, the PIPR magnitude measured after 1.7 s (s) from offset of the light stimulus is considered a specific measure of mRGC function ( Adhikari et al, 2015 , 2016 ). In this context, chromatic pupillometry has been used to evaluate this cellular system in several clinical settings, including blinding disorders such as hereditary optic neuropathies ( Kawasaki et al, 2010 ; Moura et al, 2013 ; Kawasaki et al, 2014 ; Munch et al, 2015 ; Nissen et al, 2015 ; Ba-Ali and Lund-Andersen, 2017 ; Loo et al, 2017 ), glaucoma ( Kankipati et al, 2011 ; Rukmini et al, 2015 ; Kelbsch et al, 2016 ; Najjar et al, 2018 , 2023 ) and neurodegenerative disorders such as Parkinson’s disease (PD) ( Joyce et al, 2018 ; Feigl et al, 2020 ; Tabashum et al, 2021 ; Gaynes et al, 2022 ), idiopathic/isolated rapid eye movement sleep behavior disorder (iRBD) ( La Morgia et al, 2022 ; Steiner et al, 2022 ), and Alzheimer’s disease (AD) ( Oh et al, 2019 ; Romagnoli et al, 2020 ; La Morgia et al, 2023 ).…”