Eye provides another possible window into the pressure changes in the intracranial compartment thanks to the fact that the space between the optic nerve and its sheath is a continuation of the subarachnoid space, and is consequently filled with cerebrospinal fluid whose pressure is equal to intracranial pressure. Intracranial hypertension will thus manifest in increased diameter of the optic nerve sheath, and will impede the blood flow through the central retinal vein that courses within the sheath, along and in part inside of the optical nerve. The impediment of venous return causes visible changes in the eye fundus (venous engorgement, and papilledema, i.e. swelling and elevation of the optic nerve disc) that can be observed with an ophthalmoscope and have therefore been used by clinicians for more than a century as signs of increased ICP. Quantitative assessment of ICP can be made noninvasively in two different ways: by measuring changes in diameter of the optic nerve sheath with an appropriate technique (ultrasound or MRI), or by usingophthalmodynamometry to determine the pressure in the central retinal vein, which is normally slightly higher (1- 2mmHg) than ICP. Intracranial hypertension also induces changes at the cellular or axonal level such as the swelling of the fibers of the optic nerve that form the innermost layer of the retina (so called nerve fiber layer – NFL). The information provided by the classic ophthalmoscopy is however only qualitative and may be inconclusive during early phases of intracranial hypertension since it usually takes between two and four hours from the onset of ICP elevation for a papilledema to develop.
A patented method that utilizes optical coherence tomography to measure the thickness of the nerve fiber layer and infers ICP from it laid claims of being able to detect theIH-induced thickening of the retina shortly after the onset of IH, but there has been no data that would support the claims or clarify the relationship between the NFL thickness and levels of ICP.
Optic Nerve Sheath Diameter. The use of optic nerve sheath diameter (ONSD) for the assessment of ICP dates back to 1987 when Cennamo and colleagues 1 demonstrated a linear relationship between ICP and the sheath diameter measured with a trans-orbital ultrasound probe in an A-scan mode (principally equivalent to the time-of-the-flight measurements of the cranium diameter). The original measurement method was technically difficult and unreliable because of the nearly coaxial alignment of the optic nerve and propagation axis of the ultrasound wave, but the precision was significantly improved with the use of B-scan (or planar) ultrasound which provided longitudinal cross-section images of the optic nerve and its sheath. Since then, the method has been successsfully validated in several relatively large studies that included patients with severe head trauma, hydrocephalus, intracranial hemorrhage or stroke, liver failure, and climbers with acute mountain sickness. While the ONSD can at any given point along the optic nerve be measured with a precision of <1mm, reliability of derived ICP levels is plagued by inter-individual variability and the dependance of ONSD magnitude on the point along the nerve at which the measurement was taken. Almost all validation studies so far have recommended that ONSD be used for identification of patients with intracranial hypertension that requires treatment (ICP>20mmHg, i.e. ONSD>5mmHg) rather than for a measurement of ICP.
Ophthalmodynamometry or the measurement of the retinal venous outflow pressure (VOP) is performed by applying external pressure on the sclera, for example with a spring plunger, while observing the retinal vessels through an ophthalmoscope. The pressure is gradually increased until the central retinal vein begins to pulsate, which happens at the point when the applied external pressure nears the VOP and is approximately equal to ICP. The original method was described in 1925 by Baurmann 2 and belongs to the public domain, but several modifications have been recently patented that combine the classic ophthalmodynamometry with reflectance oximetry of the retina 3 or ultrasound measurement of blood flow in the central retinal artery 4, or automate the method by adding a camera and an image processing software capable of recognizing venous pulsations from a sequence of images of the eye fundus 5 . Evaluation in patients confirmed a strong linear relationship and clinically negligible differences (2-3mmHg) between VOP and the invasively measured ICP. Ophthalmodynamometry requires dilated pupils, a skilled physician or medic and collaboration of the patient, which all hampers its applicability in the field. It cannot be applied in cases of ocular trauma or conditions that selectively affect the optic nerve, and gives erroneously high readings in the presence of a papilledema, which may persist long after ICP has returned to normal.
Neurolife Non-invasive Solutions Inc. developed technology based on Braxton‘s patent. They won Purdue University’s business plan competition in 2006, and were using the funds to develop iScan, its initial prototype. The approach worked on measuring ICP non-invasively by assessing changes in the retinal blood flow. However this is dependent on other factors apart from ICP, so it will be difficult to generate accuracy sufficient for clinical practice.
Third Eye Diagnostics, Inc. is developing the Cerepress™, a non-invasive intracranial pressure monitor that gathers information from the patient's eye. The Cerepress™ measures blood pressure in the eye’s central retinal vein (CRV) and blood velocity in the ophthalmic artery, which taken together highly correlate to intracranial pressure. To obtain CRV pressure, 3ED has developed a novel apparatus that simultaneously records images of the CRV and measures intraocular pressure (IOP) while pressure in the eye is increased. A medical technician aligns the system by easily centering the field of view to patient’s pupil eye. The system then contacts the patient’s cornea and simultaneously collects images of the cornea and the retinal fundus. The contact force increases the IOP and momentarily compresses the CRV. At the instant of complete CRV compression, the Cerepress™ records the eye pressure, which is equivalent to CRV pressure. CRV pressure is a known to be a good correlate to ICP.
1 Cennamo G, Gangemi M, Stella L. The correlation between endocranial pressure and optic nerve diameter: An ultrasonographic study. Ophthalmic Echography 1987; 7:603-606.
2 M. Über die Entstehung und klinische Bedeutung des Netzhautvenenpulses. Ber Zusammenkunft Dtsch Ophthalmol Ges 1925; 45: 53-59.
3 Denninghoff, K.R.: US20026390989 (2002).
4 Querfurth, H.W.: US20067122007 (2006).
5 Braxton, E.E.: US20060206037 (2006).