Glymphatic System in Ocular Diseases: Evaluation of MRI Findings

Abstract

Background and purpose: There is growing evidence of leakage of gadolinium in an impaired blood-retina barrier. We investigated gadolinium enhancement in different eye compartments and correlated the enhancement with specific ophthalmologic diseases.

Materials and methods: In a prospective clinical study (ClinicalTrials.gov Identifier: NCT05035251), 95 patients (63 with and 32 without ophthalmologic disease) were examined before and after gadolinium administration (20 and 120 minutes) with heavily T2-weighted FLAIR. The cohort was divided according to the location of pathology into anterior and posterior eye compartment groups. Relative signal intensity increase in the anterior eye chamber, vitreous body with retina, optic nerve sheath, and the Meckel cave was analyzed and correlated with the final clinical diagnosis.

Results: In patients with a disorder in the anterior eye compartment, significant signal intensity increases were found in the central anterior eye chamber (P 20 minutes = .000, P 120 minutes = .000), lateral anterior eye chamber (P 20 minutes = .001, P 120 minutes = .005), and vitreous body with retina (P 20 minutes = .02) compared with the control group. Patients with pathologies in the posterior eye compartment showed higher signal intensity levels in the central anterior eye compartment (P 20 minutes = .041) and vitreous body with retina (P 120 minutes = .006).

Conclusions: Increased gadolinium enhancement was found in the central and lateral anterior eye compartments and the vitreous body with retina in patients with anterior eye compartment disorders 20 and 120 minutes after contrast application, suggesting impairment of the blood-aqueous barrier. In patients with a disorder in the posterior eye compartment, pathologic enhancement indicated disruption of the blood-retinal barrier that allows gadolinium to diffuse into the vitreous body with retina from posterior to anterior, opposite to the known physiologic glymphatic pathway.

© 2022 by American Journal of Neuroradiology.

Figures

FIG 1.

Examples of ROIs in the lateral and central eye chamber and the VB (A), the optical nerve sheath (ONS) (B), the Meckel Cave (MC), and the basal cistern (C) and lateral ventricles (D). Min indicates minimum; Max, maximum.

FIG 2.

Image demonstrating contrast agent kinetics after injection of gadolinium in healthy patients: native scan (A), scan 20 minutes after Gd injection demonstrating the physiologic permeability of Gd in the lateral eye chamber (small arrow) (B), and physiologic, symmetric enhancement in the central eye chamber and the VB in the late scan after 120 minutes (C) (thick arrows).

FIG 3.

Example of a patient with a disorder in the AEC on the right; native scan (A), scan 20 minutes after gadolinium injection demonstrating a higher permeability of Gd in the lateral eye chamber (small arrow) and increased Gd enhancement in the in the central eye chamber on the right (thick arrow) (B), and the VB (arrowhead) in the late scan after 120 minutes in the right eye (C).

FIG 4.

Example of a patient with a disorder in the PEC (retinal). Native scan (A), 20 minutes after gadolinium injection demonstrating a pathologic permeability of Gd at the blood-retinal barrier (small arrows) (B), and accumulation of Gd in the VB after 120 minutes (arrowhead) demonstrating an opposite pathway of Gd (C). The physiologic enhancement in the anterior eye segment can also be seen in C, independent of the pathology of the posterior eye segment.

FIG 5.

Relative SI 20 minutes (white boxplot) and 120 minutes (gray boxplot) after contrast application in the AC central (AC_central_1 = 20 minutes, AC_central_2 = 120 minutes), AC lateral (AC_lateral_1 = 20 minutes, AC_lateral = 120 minutes), and VB (VB_1 = 20 minutes, VB_2 = 120 minutes) in the control group and in patients with disorders in the AECs and PECs.