Melanopsin retinal ganglion cell function in Alzheimer's vs. Parkinson's disease an exploratory meta-analysis and review of pupillometry protocols

Oliver Leopold Steiner; Jan de Zeeuw

doi:10.1016/j.parkreldis.2024.106063

Melanopsin retinal ganglion cell function in Alzheimer's vs. Parkinson's disease an exploratory meta-analysis and review of pupillometry protocols

Parkinsonism Relat Disord. 2024 Feb 27:106063. doi: 10.1016/j.parkreldis.2024.106063. Online ahead of print.

Authors

Oliver Leopold Steiner¹, Jan de Zeeuw²

Affiliations

¹ Department of Neurology, Motor and Cognition Group, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Germany; Institute of Psychology, Humboldt-Universität zu Berlin, Germany; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Germany. Electronic address: oliver.steiner@charite.de.
² Sleep Research & Clinical Chronobiology, Institute of Physiology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Germany; Clinic for Sleep & Chronomedicine, St. Hedwig-Hospital, Berlin, Germany.

PMID: 38443213
DOI: 10.1016/j.parkreldis.2024.106063

Abstract

Background: Neurodegenerative diseases share retinal abnormalities. Chromatic pupillometry allows in vivo assessment of photoreceptor functional integrity, including melanopsin-expressing retinal ganglion cells. This exploratory meta-analysis assesses retinal photoreceptor functionality in Alzheimer's vs. Parkinson's disease and conducts an in-depth review of applied pupillometric protocols.

Methods: Literature reviews on PubMed and Scopus from 1991 to August 2023 identified chromatic pupillometry studies on Alzheimer's disease (AD; n = 42 patients from 2 studies) and Parkinson's disease (PD; n = 66 from 3 studies). Additionally, a pre-AD study (n = 10) and an isolated REM Sleep Behavior Disorder study (iRBD; n = 10) were found, but their results were not included in the meta-analysis statistics.

Results: Melanopsin-mediated post-illumination pupil response to blue light was not significantly impaired in Alzheimer's (weighted mean difference = -1.54, 95% CI: 4.57 to 1.49, z = -1.00, p = 0.319) but was in Parkinson's (weighted mean difference = -9.14, 95% CI: 14.19 to -4.08, z = -3.54, p < 0.001). Other pupil light reflex metrics showed no significant differences compared to controls. Studies adhered to international standards of pupillometry with moderate to low bias. All studies used full-field stimulation. Alzheimer's studies used direct while Parkinson's studies used consensual measurement. Notably, studies did not control for circadian timing and Parkinson's patients were on dopaminergic treatment.

Conclusion and relevance: Results affirm chromatic pupillometry as a useful method to assess melanopsin-related retinal cell dysfunction in Parkinson's but not in Alzheimer's disease. While adhering to international standards, future studies may analyze the effects of local field stimulation, dopaminergic treatment, and longitudinal design to elucidate melanopsin dysfunction in Parkinson's disease.

Keywords: Alzheimer's disease; Circadian system; Melanopsin; Parkinson's disease; Pupillometry; mRGC.

Publication types

Review