Noninvasive Estimation of Pulsatile and Static Intracranial Pressure by Optical Coherence Tomography.

Purpose: To explore the ability of optical coherence tomography (OCT) to noninvasively estimate pulsatile and static intracranial pressure (ICP). Methods: An OCT examination was performed in patients who underwent continuous overnight monitoring of the pulsatile and static ICP for diagnostic purpose. We included two patient groups, patients with idiopathic intracranial hypertension (IIH; n = 20) and patients with no verified cerebrospinal fluid disturbances (reference; n = 12). Several OCT parameters were acquired using spectral-domain OCT (RS-3000 Advance; NIDEK, Singapore). The ICP measurements were obtained using a parenchymal sensor (Codman ICP MicroSensor; Johnson & Johnson, Raynham, MA, USA). The pulsatile ICP was determined as the mean ICP wave amplitude (MWA), and the static ICP was determined as the mean ICP. Results: The peripapillary Bruch's membrane angle (pBA) and the optic nerve head height (ONHH) differed between the IIH and reference groups and correlated with both MWA and mean ICP. Both OCT parameters predicted elevated MWA. Area under the curve and cutoffs were 0.82 (95% confidence interval [CI], 0.66-0.98) and -0.65° (sensitivity/specificity; 0.75/0.92) for pBA and 0.84 (95% CI, 0.70-0.99) and 405 µm (0.88/0.67) for ONHH. Adjusting for age and body mass index resulted in nonsignificant predictive values for mean ICP, whereas the predictive value for MWA remained significant. Conclusions: This study provides evidence that the OCT parameters pBA and ONHH noninvasively can predict elevated pulsatile ICP, represented by the MWA. Translational Relevance: OCT shows promise as a method for noninvasive estimation of ICP.

In Vivo Evidence for Impaired Glymphatic Function in the Visual Pathway of Patients With Normal Pressure Hydrocephalus.

Purpose: Impaired ability to remove toxic metabolites from central nervous system may be an important link between cerebral and ophthalmic degenerative diseases. The aim of the present study was to compare the glymphatic function in the visual pathway in patients with idiopathic normal pressure hydrocephalus (iNPH), a neurodegenerative dementia subtype, with a reference group. Methods: We compared 31 subjects with Definite iNPH (i.e., shunt-responsive) with 13 references in a prospective and observational study. After intrathecal injection of the magnetic contrast agent gadobutrol (Gadovist, 0.5 mL, 1.0 mmol/mL, Bayer Pharma AG), serving as a tracer, consecutive magnetic resonance imaging (MRI) scans were obtained (next 24-48 hours). The normalized MRI T1 signal recorded in the cerebrospinal fluid (CSF) and along the visual pathway served as a semi-quantitative measure of tracer enrichment. Gadobutrol does not penetrate the blood-brain barrier and is thus confined to the extravascular space. Overnight measurements of pulsatile intracranial pressure were used as a surrogate marker for the intracranial compliance. Results: The tracer enriched the prechiasmatic cistern similarly in both groups, but clearance was delayed in the iNPH group. Moreover, both delayed enrichment and clearance of the tracer were observed in the visual pathway in the iNPH subjects. The enrichment in the visual pathway and the CSF correlated. Individuals with elevated pulsatile intracranial pressure showed reduced enrichment within the visual pathway. Conclusions: There was delayed enrichment and clearance of a tracer in the visual pathway of iNPH patients, which suggests impaired glymphatic function in the visual pathway in this disease.

The Human Visual Pathway Communicates Directly With the Subarachnoid Space.

Purpose: Explore in vivo whether there is direct communication between the cerebrospinal fluid (CSF) and extravascular compartment of human visual pathway structures. Methods: A prospective and observational study included 10 subjects who underwent intrathecal gadolinium-enhanced magnetic resonance imaging (MRI) for suspected CSF circulation disorder, but with a negative result and with no known ophthalmic diseases. After precontrast T1-weighted MRI, 0.5 mL of gadobutrol (Gadovist, 1.0 mmol/mL) was injected intrathecally. Gadobutrol distributes in the extravascular space, and served as a CSF tracer. Consecutive MRI scans were obtained throughout 24 to 48 hours. To assess gadobutrol contrast enrichment, regions of interest (ROIs) were placed at multiple locations along the visual pathway, from the primary visual cortex to the eye's vitreous body. CSF tracer dependent T1 signal was measured in each ROI. A linear mixed-model was used for statistical analyses. Results: CSF tracer enrichment was found within the optic nerve, optic chiasm, optic tract, and primary visual cortex (P < 0.001). Peak tracer enrichment in the visual pathway generally occurred after 24 hours and was preceded by peak enhancement in the prechiasmatic cistern after 4 to 6 hours. Conclusions: The results indicate direct communication between CSF of subarachnoid space and the extravascular space of the human visual pathway. Extravascular entry of the CSF tracer is a prerequisite for a glymphatic system, the present findings may suggest its presence. The existence of a glymphatic system in the human visual pathway could bring novel perspectives on the pathophysiology and treatment of ophthalmic diseases.