Quadrant Field Pupillometry Detects Melanopsin Dysfunction in Glaucoma Suspects and Early Glaucoma.

Prakash Adhikari,Ravi Thomas,Beatrix Feigl,Andrew J Zele

doi:10.1038/srep33373

Abstract

It is difficult to detect visual function deficits in patients at risk for glaucoma (glaucoma suspects) and at early disease stages with conventional ophthalmic tests such as perimetry. To this end, we introduce a novel quadrant field measure of the melanopsin retinal ganglion cell mediated pupil light response corresponding with typical glaucomatous arcuate visual field defects. The melanopsin-mediated post-illumination pupil response (PIPR) was measured in 46 patients with different stages of glaucoma including glaucoma suspects and compared to a healthy group of 21 participants with no disease. We demonstrate that the superonasal quadrant PIPR differentiated glaucoma suspects and early glaucoma patients from controls with fair (AUC = 0.74) and excellent (AUC = 0.94) diagnostic accuracy, respectively. The superonasal PIPR provides a linear functional correlate of structural retinal nerve fibre thinning in glaucoma suspects and early glaucoma patients. This first report that quadrant PIPR stimulation detects melanopsin dysfunction in patients with early glaucoma and at pre-perimetric stages may have future implications in treatment decisions of glaucoma suspects.

Highlights

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness[1]
The averaged pupil response traces to the blue stimulus with high melanopsin excitation for the controls, glaucoma suspects, early glaucoma and late glaucoma participants (Fig. 2) show that the mean peak pupil constriction and the postillumination pupil response (PIPR) amplitudes differed between the groups; detailed results follow
Our results show that selective superonasal quadrant field stimulation can be used to detect melanopsin expressing intrinsically photosensitive Retinal Ganglion Cell dysfunction in glaucoma suspects in the absence of perimetric deficits (Fig. 7)

Summary

Introduction

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness[1]. It causes a progressive and chronic loss of Retinal Ganglion Cells (RGCs) and their axons, leading to optic nerve atrophy[2]. The main subtype of interest for this study is the M1 ipRGC which pre-dominantly innervates the olivary pretectal nucleus shell for pupil control[38] These inner retinal photoreceptors entirely drive the post-illumination pupil response (PIPR)[21,28,39]. Based on typical glaucomatous arcuate deficits[51,52] and RNFL defects[8,11], and evidence that regional visual field deficits can be mapped to sectoral optic disc abnormalities in glaucoma[7,9,53,54], we introduce a quadrant field stimulation paradigm using optimised pupillometry protocols[39] in order to differentiate melanopsin function in glaucoma suspects and manifest glaucoma at different severity stages from healthy eyes by measuring the PLR and PIPR. Based on evidence that melanopsin dysfunction is related to sleep disorders in late glaucoma patients[26] and reports that melanopsin gene (OPN4) variants modulate the pupil response and sleep behaviour[55,56,57,58], a secondary aim was to investigate if the established OPN4 variants could affect the PIPR or sleep, independent of the different stages of glaucoma

Objectives

Methods

Results

Conclusion