An explanation for Terson syndrome at last: the glymphatic reflux theory

Abstract

Terson Syndrome (TS) describes the presence of intraocular hemorrhage in patients with intracranial hemorrhage, typically subarachnoid hemorrhage. Despite TS being a well-defined and frequently occurring phenomenon, its pathophysiology remains controversial. This review will present the current understanding of TS, with view to describing a contemporary and more plausible pathomechanism of TS, given recent advances in ophthalmic science and neurobiology. Previously proposed theories include a sudden rise in intracranial pressure (ICP) transmitted to the optic nerve sheath leading to rupture of retinal vessels; or intracranial blood extending to the orbit via the optic nerve sheath. The origin of blood in TS is uncertain, but retinal vessels appear to be an unlikely source. In addition, an anatomical pathway for blood to enter the eye from the intracranial space remains poorly defined. An ocular glymphatic system has recently been described, drainage of which from the globe into intracranial glymphatics is reliant on the pressure gradient between intraocular pressure and intracranial pressure. The glymphatic pathway is the only extravascular anatomical conduit between the subarachnoid space and the retina. We propose that subarachnoid blood in skull base cisterns near the optic nerve is the substrate of blood in TS. Raised ICP causes it to be refluxed through glymphatic channels into the globe, resulting in intraocular hemorrhage. We herewith present glymphatic reflux as an alternative theory to explain the phenomenon of Terson Syndrome. Response to Reviewers:Many thanks, please see the attached Word document which contains all responses to reviewer and editor comments in red. These are copied below as well.

Terson syndrome: Two case reports

“…But the last study by Ashwin Kumaria [4] reports the possibility of “the glymphatic reflux theory”. A new ocular glymphatic system has recently been described, the drainage of which from the globe into intracranial glymphatics is reliant on the pressure gradient between intraocular pressure and intracranial pressure.…”

“…A new ocular glymphatic system has recently been described, the drainage of which from the globe into intracranial glymphatics is reliant on the pressure gradient between intraocular pressure and intracranial pressure. The glymphatic pathway is the only extravascular anatomical conduit between the subarachnoid space and the retina [4] .…”

“…According to various studies, there are multiple causes and different clinical presentations are possible [4] , [5] , [8] . Terson Syndrome is often observed after rupturing of an aneurysm of the anterior circulation, especially of the anterior communicating artery or the internal carotid artery [9] , and this was the case in our first patient who presented with a ruptured aneurysm of the internal carotid artery at the level of its supraclinoid segment.…”

“…A rupture of the peripapillary and retinal capillaries secondary to an abrupt increase in intravascular pressure following a sudden intracranial hypertension event is often suggested [2] , [3] . The latest studies speak of a mechanism: the theory of glymphatic reflux [4] .…”

Multilayered macular hemorrhages as an unusual complication of transorbital neuroendoscopic surgery

“… 2 , 3 , 4 , 5 However, the origin of intraocular blood and the role of ICP fluctuation in the pathophysiology of Terson syndrome remains a matter of debate. 6 …”