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Pupil responses to melanopsin-isolating stimuli as a potential diagnostic biomarker for glaucoma

Year: 2025

Type: article

Abstract: PURPOSE: To test whether differences in pupil responses to melanopsin-isolating spectral stimuli in glaucoma may be useful as a diagnostic biomarker. METHODS: Spectral stimuli were presented to 20 glaucoma and 15 age-similar healthy control participants. Stimuli were pairs of silent-substitution spectra designed to provide (1) equal stimulation to cone photoreceptors but maximum (~325%) contrast to melanopsin or (2) equal stimulation to melanopsin but ~325% contrast to cones. Narrowband long-wavelength/red (657 nm) and short-wavelength/blue (471 nm) pulses were also presented from a dark background to 16 glaucoma and 12 control participants. Pulses lasted 3 seconds and pupil size was measured for 15 seconds. Pupil response metrics were compared by t-test and relationships with visual field and OCT summary indices were assessed by Spearman's rank correlation. Diagnostic accuracy was measured by area under the receiver operating characteristic curve (AUC). RESULTS: Pupil constriction was more persistent after pulse offset for the melanopsin-directed stimulus (2% mean paired difference 6s post-pulse offset, p < 0.001). All pupil parameters were similar between groups (p = 0.04-0.90) for all stimuli. Correlations between pupil response parameters and visual field summary indices and circumpapillary retinal nerve fibre layer thickness were weak (rho 0.02-0.57, all p > 0.05). Diagnostic accuracy for all pupil parameters was poor, with AUC 95% confidence intervals overlapping 0.5 for all but time to maximal constriction for the cone-directed stimulus. CONCLUSIONS: Pupil responses to melanopsin-isolating spectra were similar between glaucoma and control participants. Pupillary responses to melanopsin-isolating silent substitution spectra are unlikely to be useful as a diagnostic biomarker for glaucoma.

Source: PLoS ONE

DOI: 10.1371/journal.pone.0324373

Authors: Jonathan Denniss, Riccardo Cheloni, Joel T. Martin, Manuel Spitschan