Chromatic Pupillometry Findings in Alzheimer's Disease

Martina Romagnoli; Michelangelo Stanzani Maserati; Maddalena De Matteis; Sabina Capellari; Michele Carbonelli; Giulia Amore; Gaetano Cantalupo; Corrado Zenesini; Rocco Liguori; Alfredo A Sadun; Valerio Carelli; Jason C Park; Chiara La Morgia

doi:10.3389/fnins.2020.00780

Chromatic Pupillometry Findings in Alzheimer's Disease

Front Neurosci. 2020 Aug 11:14:780. doi: 10.3389/fnins.2020.00780. eCollection 2020.

Authors

Martina Romagnoli¹, Michelangelo Stanzani Maserati¹, Maddalena De Matteis¹, Sabina Capellari^{1

2}, Michele Carbonelli¹, Giulia Amore², Gaetano Cantalupo³, Corrado Zenesini¹, Rocco Liguori^{1

2}, Alfredo A Sadun⁴, Valerio Carelli^{1

2}, Jason C Park⁵, Chiara La Morgia^{1

2}

Affiliations

¹ IRCCS Istituto Delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Ospedale Bellaria, Bologna, Italy.
² Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
³ Division of Child Neuropsychiatry, Department of Surgical Sciences, Dentistry, Gynaecology and Paediatrics, University of Verona, Verona, Italy.
⁴ Department of Ophthalmology, Doheny Eye Institute, University of California, Los Angeles, Los Angeles, CA, United States.
⁵ Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, United States.

Abstract

Intrinsically photosensitive melanopsin retinal ganglion cells (mRGCs) are crucial for non-image forming functions of the eye, including the photoentrainment of circadian rhythms and the regulation of the pupillary light reflex (PLR). Chromatic pupillometry, using light stimuli at different wavelengths, makes possible the isolation of the contribution of rods, cones, and mRGCs to the PLR. In particular, post-illumination pupil response (PIPR) is the most reliable pupil metric of mRGC function. We have previously described, in post-mortem investigations of AD retinas, a loss of mRGCs, and in the remaining mRGCs, we demonstrated extensive morphological abnormalities. We noted dendrite varicosities, patchy distribution of melanopsin, and reduced dendrite arborization. In this study, we evaluated, with chromatic pupillometry, the PLR in a cohort of mild-moderate AD patients compared to controls. AD and controls also underwent an extensive ophthalmological evaluation. In our AD cohort, PIPR did not significantly differ from controls, even though we observed a higher variability in the AD group and 5/26 showed PIPR values outside the 2 SD from the control mean values. Moreover, we found a significant difference between AD and controls in terms of rod-mediated transient PLR amplitude. These results suggest that in the early stage of AD there are PLR abnormalities that may reflect a pathology affecting mRGC dendrites before involving the mRGC cell body. Further studies, including AD cases with more severe and longer disease duration, are needed to further explore this hypothesis.

Keywords: Alzheimer’s disease; chromatic pupillometry; melanopsin retinal ganglion cells; post-illumination pupil response; pupil; pupillary light reflex.