Exploring ocular glymphatics: The association between intraocular pressure, tear total-tau and MRI-visible perivascular spaces

Abstract

Purpose : Impaired cerebral waste clearance is a key feature of aging and various neurodegenerative conditions. In Alzheimer’s disease accumulation of the waste product total-tau is observed, a protein associated with neuronal damage. Cerebral waste removal operates through a network of perivascular spaces (PVS), where enlarged PVS are an indicator of impaired waste clearance. Recent research suggests the existence of a similar system in the eyes, the ocular glymphatic system. This system is theorized to be driven by the intraocular pressure (IOP), draining waste products from the eye along the optic nerve. This study aimed to gain more insights into the eye-brain connection by investigating the relation between MRI-visible PVS, tear total-tau, and IOP.

Methods : Tear fluid was collected from cognitively healthy elderly (N=30) using Schirmer’s strips and analyzed for total-tau using ELISA. IOP was measured in the majority of subjects (N=23) using non-contact tonometry. All participants underwent 7T MRI, with PVS visually rated in the basal ganglia (BG) and centrum semiovale (CSO) on T2-weighted images. Partial Spearman’s correlation coefficients were computed between the PVS scores and both tear total-tau and IOP, while adjusting for age, sex, tear-wetting length, and their respective hemispheric white matter or BG volumes.

Results : A higher level of tear total-tau was found to be moderately correlated to a higher CSO PVS score in both the left and right hemisphere (R_s=0.538, p=0.004; R_s=0.546, p=0.004, respectively). A lower IOP OD was moderately correlated with higher right hemispheric CSO PVS scores (R_s=-0.454, p=0.044), and a similar moderate correlation was found between the IOP OS and left hemispheric CSO PVS scores (R_s=-0.474, p=0.035).

Conclusions : Increased levels of tear total-tau were linked to enlarged PVS in the CSO in both hemispheres. Therefore, elevated tear total-tau may indicate compromised ocular waste clearance, which in turn could signify impaired cerebral waste clearance. Additionally, lower IOP was associated with more PVS in the ipsilateral CSO. In conclusion, while the findings suggest promising insights into the ocular glymphatic system, further research is essential for an understanding of the mechanisms and potential clinical implications.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.