Primary Open Angle Glaucoma is Associated with MR Biomarkers of Cerebral Small Vessel Disease

Abstract

This prospective study tests the hypotheses that: 1) glaucoma is associated with evidence of cerebral small vessel disease; 2) that imaging biomarkers of cerebral small vessel disease in POAG and NTG will show different characteristics. 12 normal controls, 7 patients with primary open angle glaucoma (POAG) and 9 patients with normal tension glaucoma (NTG) were recruited. Ophthalmological clinical assessment and MR imaging of the brain were performed. MR imaging was used to quantify white matter lesion load, frequency of dilated perivascular spaces (PVS) and abnormalities in cerebral hydrodynamics. Patients with POAG had significantly greater white matter lesion load (p < 0.05), more PVS in the centrum semiovale (p < 0.05) and had higher overall PVS scores than controls (p < 0.05). In the POAG group, optic cup-to-disc ratio (CDR) was positively correlated with deep white matter hyperintensities (R2 = 0.928, p < 0.01). Mean deviation on the Humphrey visual field assessment was negatively correlated with deep white matter lesion load (R2 = −0.840, p < 0.01), total white matter lesion load (R2 = −0.928, p < 0.01) and total PVS (R2 = −0.820, p < 0.01). MR evidence of cerebral small vessel disease is strongly associated with a diagnosis of POAG and with the severity of abnormalities in CDR and visual field.

Dilated Virchow-Robin spaces in primary open-angle glaucoma: a biomarker of glymphatic waste clearance dysfunction?

“…Given that impairment of the arterial pulsation-driven ''perivascular pump'' may lead to CSF flux disturbance, and given that distension of the VRSs may be related to the fluid retention in and along the paravascular circulation (7), we postulate that dilated VRSs could occur in POAG in association with arterial stiffening or loss of arterial pulsatility. Interestingly, in accordance with this view, a very recent study showed significantly higher deep white matter lesion load and increased numbers of dilated VRSs in association with POAG suggesting the presence of significant cerebral small vessel disease (8). If dilation of VRSs may result from a disturbed interplay between the vascular and glymphatic system, then preventing arterial stiffness may protect against glaucoma, at least in part, by promoting solute clearance via the CSF.…”

“…Indeed, if CSF outflow is reduced as a consequence of either CSF flow obstruction or cerebral artery pulsatility inefficiency, or cerebrospinal venous insufficiency and lymphatic disorders, local perivascular CSF recirculation may be impaired and, consequently, the VRSs may dilate due to fluid retention ( 7 ). Interestingly, dilated VRSs are a known histological feature of cerebral small vessel disease and can be demonstrated on magnetic resonance imaging ( 8 ).…”

Validation of external and internal exposome of the findings associated to cerebral small vessel disease: A Mendelian randomization study

“…The constructed CSVD exposome revealed exposures suggestively associated with CSVD (Figure 3). It included some previously-reported relevant exposures, such as intraocular pressure 38 and depression. 39 But we didn’t notice suggestively significant results in other previously-reported exposures, like sleep quality 40 and chronic renal failure.…”

Neurodegenerative Disorders of the Eye and of the Brain: A Perspective on Their Fluid-Dynamical Connections and the Potential of Mechanism-Driven Modeling

“…In fact, lower levels of CSF pressure have been shown in both glaucomatous patients (Berdahl et al, 2008) and AD patients (Silverberg et al, 2006). Another indication of the cerebral involvement in the glaucomatous damage has been shown by Mercieca et al (2016), who found an increased number of cerebral small vessel disease assessed by magnetic resonance in patients with glaucoma, compared to healthy controls.…”