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 ¼ .000, P 120 minutes ¼ .000), lateral anterior eye chamber (P 20 minutes ¼ .001, P 120 minutes ¼ .005), and vitreous body with retina (P 20 minutes ¼ .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 ¼ .041) and vitreous body with retina (P 120 minutes ¼ .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. ABBREVIATIONS: AC ¼ anterior eye chamber; AEC ¼ anterior eye compartment; Gd ¼ gadolinium; GLOS ¼ gadolinium leakage in ocular structures; PEC ¼ posterior eye compartment; SI ¼ signal intensity; VB ¼ vitreous body with retina

Direct Visualization of Tracer Permeation into the Endolymph in Human Patients Using MR Imaging

“…38,39 Similarly, researches on the ocular glymphatic system and its relation to glaucoma are underway. 17,40,41 Regarding the inner ear, although the dynamics of drainage of the perilymph have been investigated by Yoshida et al, further research is needed on the drainage of the endolymph, which contains the sensory organs of the inner ear. 21 This study has set the stage for such research.…”

Human brain clearance imaging: Pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood

“…117,119 Furthermore, ocular Gd distribution following intravenous injection differed between pathologies of the anterior compared with the posterior eye segment, probably due to disruption of different parts of the blood-ocular barrier. 120…”

“…4 Signal enhancement after intravenous injection of Gd has been demonstrated in CSF spaces surrounding cranial nerves, such as the SAS surrounding the optic nerve, the Meckel's cave inhabiting the trigeminal ganglion, the internal auditory canal, as well as the cochlear perilymph surrounding the vestibulocochlear nerve with peak signal intensities within the first 4.5 h postinjection. 15,98,104,120,128 Furthermore, Varatharaj et al used the focal BBB breakdown in a MS brainstem lesion to simulate intraparenchymal administration of Gd. 129 After intravenous injection of the contrast agent, the proximal trigeminal nerve, which is devoid of a vascularized perineurium and epineurium, depicted an enhancement pattern similar to the brain parenchyma surrounding the MS lesion, while the signal enhancement within the peripheral part of the nerve resembled the vascular driven enhancement of the MS lesion.…”

“…For example, in children with retinoblastoma, enhancement of the anterior eye chamber predicted optic nerve infiltration 117,119 . Furthermore, ocular Gd distribution following intravenous injection differed between pathologies of the anterior compared with the posterior eye segment, probably due to disruption of different parts of the blood–ocular barrier 120 …”

“…Besides the optic and olfactory nerves, other cranial nerves have also attracted attention as possible CSF outflow routes 4 . Signal enhancement after intravenous injection of Gd has been demonstrated in CSF spaces surrounding cranial nerves, such as the SAS surrounding the optic nerve, the Meckel's cave inhabiting the trigeminal ganglion, the internal auditory canal, as well as the cochlear perilymph surrounding the vestibulocochlear nerve with peak signal intensities within the first 4.5 h postinjection 15,98,104,120,128 . Furthermore, Varatharaj et al used the focal BBB breakdown in a MS brainstem lesion to simulate intraparenchymal administration of Gd 129 .…”