Pupil autoregulation impairment as an early marker of glaucomatous damage

Glaucoma, a degenerative and progressive disease, leads to structural and functional changes in the optic nerve head and retinal ganglion cells (RGCs), while the vasculature of the iris stays intact.

The aim of this study was to determine whether the coherence level associated with pupil geometry and peripheral arterial pulsation can be the basis for differentiating glaucoma and glaucoma-suspected patients from a control group.

This is an investigator-initiated, single-center prospective cohort study. Patients with diagnosed glaucoma (glaucoma group - GG) or glaucoma suspects (glaucoma suspects group - GSG), as well as healthy participants (control group - CG), were prospectively enrolled in the study. Glaucoma-diagnosed patients and glaucoma suspects who converted to glaucoma within 5 years were included. All patients underwent a full ophthalmological examination that included measurements of the thicknesses of the retinal nerve fiber layer (RNFL) and the ganglion cell complex (GCC) along with other parameters. A custom-made pupilometer was synchronized with a pulsometer to simultaneously record an image of the pupil and the peripheral arterial pulsation signal. All readings were processed with a script developed by the researchers. The main indicator of an increased influence of the vascular structures of the iris on pupil geometry in the patients and CG were the coherence levels (levC) between parameters describing the pupillary shape and peripheral arterial pulsation.

Differences in the median value of the levCpS, levCpε and levCpθ parameters between the GG and GSG compared to the CG were found (p < 0.001). During the follow-up period, a larger decrease was observed in RNFL thickness and GCC thickness in the GSG than in the GG (p < 0.05). Strong correlations were found between levCpS and RNFL and GCC loss among the GSG group (p < 0.001), while in the GG this parameter correlated with RNFL and GCC thickness (p < 0.001).

This is the first attempt to relate changes in the neuronal signaling pathways in glaucoma to the vascular-dependent changes of pupil geometry. The findings presented herein suggest that this approach can be used to determine which glaucoma suspects have autonomic system impairment in the eye, increasing their probability of glaucoma conversion.