Aims: To describe the anatomy and the arrangement of the arachnoid trabeculae, pillars, and septa in the subarachnoid space of the human optic nerve and to consider their possible clinical relevance for cerebrospinal fluid dynamics and fluid pressure in the subarachnoid space of the human optic nerve. Methods: Postmortem study with a total of 12 optic nerves harvested from nine subjects without ocular disease. All optic nerves used in this study were obtained no later than 7 hours after death, following qualified consent for necropsy. The study was performed with transmission (TEM) and scanning electron microscopy (SEM). Results: The subarachnoid space of the human optic nerve contains a variety of trabeculae, septa, and stout pillars that are arranged between the arachnoid and the pia layers of the meninges of the nerve. They display a considerable numeric and structural variability depending on their location within the different portions of the optic nerve. In the bulbar segment (ampulla), adjacent to the globe, a dense and highly ramified meshwork of delicate trabeculae is arranged in a reticular fashion. Between the arachnoid trabeculae, interconnecting velum-like processes are observed. In the mid-orbital segment of the orbital portion, the subarachnoid space is subdivided, and can appear even loosely chambered by broad trabeculae and velum-like septa at some locations. In the intracanalicular segment additionally, few stout pillars and single round trabeculae are observed. Conclusion: The subarachnoid space of the human optic nerve is not a homogeneous and anatomically empty chamber filled with cerebrospinal fluid, but it contains a complex system of arachnoid trabeculae and septa that divide the subarachnoid space. The trabeculae, septa, and pillars, as well as their arrangement described in this study, may have a role in the cerebrospinal fluid dynamics between the subarachnoid space of the optic nerve and the chiasmal cistern and may contribute to the understanding of the pathophysiology of asymmetric and unilateral papilloedema. All the structures described are of such delicate character that they can not even be visualised with high resolution magnetic resonance imaging (MRI).T he optic nerve is a white matter tract of the central nervous system that extents through the optic canal into the orbit. It is enveloped by the meninges and is surrounded by cerebrospinal fluid that enters the subarachnoid space via the chiasmal cistern.Anatomically the nerve can be divided into orbital and intracanalicular portions. The widest part of the orbital portion is adjacent to the ocular globe and is called the bulbar segment. It is followed by the mid-orbital segment (Fig 1).Although many studies on the cranial meninges are available, relatively few deal exclusively with the meninges of the optic nerve and the structures, such as trabeculae and septa, within its subarachnoid space. Anderson described arachnoid trabeculae stretching between the arachnoid layer and the pia layer in the subarachnoid space in the optic...

CSF is thought to flow continuously from the site of production in the ventricles into interconnected spaces; i.e. cisterns and subarachnoid spaces (SASs). Since the SAS of the optic nerve is defined by a cul-de-sac anatomy, it is not evident how local CSF might recycle from that region to the general SAS. The concept of free communication of CSF has recently been challenged by the description of a concentration gradient of beta-trace protein, a lipocalin-like prostaglandin d-synthase (L-PGDS), between the spinal CSF and that in the SAS of the optic nerve, indicating diminished local clearance or local overproduction of L-PGDS here. In fact, computed cisternography with a contrast agent in three patients with idiopathic intracranial hypertension and asymmetric papilloedema demonstrate a lack of contrast-loaded CSF in the SAS of the optic nerve despite it being present in the intracranial SAS, thus suggesting compartmentation of the SAS of the optic nerve. The concept of an optic nerve compartment syndrome is further supported by a concentration gradient of brain-derived L-PGDS between the spinal CSF and the CSF from the optic nerve SAS in the same patients.

In a recent review article titled “A new look at cerebrospinal fluid circulation”, Brinker et al. comprehensively described novel insights from molecular and cellular biology as well as neuroimaging research, which indicate that cerebrospinal fluid (CSF) physiology is much more complex than previously believed. The glymphatic system is a recently defined brain-wide paravascular pathway for CSF and interstitial fluid exchange that facilitates efficient clearance of interstitial solutes, including amyloid-β, from the brain. Although further studies are needed to substantiate the functional significance of the glymphatic concept, one implication is that glymphatic pathway dysfunction may contribute to the deficient amyloid-β clearance in Alzheimer’s disease. In this paper, we review several lines of evidence suggesting that the glymphatic system may also have potential clinical relevance for the understanding of glaucoma. As a clinically acceptable MRI-based approach to evaluate glymphatic pathway function in humans has recently been developed, a unique opportunity now exists to investigate whether suppression of the glymphatic system contributes to the development of glaucoma. The observation of a dysfunctional glymphatic system in patients with glaucoma would provide support for the hypothesis recently proposed by our group that CSF circulatory dysfunction may play a contributory role in the pathogenesis of glaucomatous damage. This would suggest a new hypothesis for glaucoma, which, just like Alzheimer’s disease, might be considered then as an imbalance between production and clearance of neurotoxins, including amyloid-β.

Cerebrospinal fluid (CSF) pressure and composition are generally thought to be homogeneous within small limits throughout all CSF compartments. CSF sampled during lumbar puncture therefore should be representative for all CSF compartments. On the basis of clinical findings, histology and biochemical markers, we present for the first time strong evidence that the subarachnoid spaces (SAS) of the optic nerve (ON) can become separated from other CSF compartments in certain ON disorders, thus leading to an ON sheath compartment syndrome. This may result in an abnormal concentration gradient of CSF molecular markers determined in locally sampled CSF compared with CSF taken during lumbar puncture.

The finding of a difference in the concentration gradients between the CLCSF within the intracranial spaces and the SAS of the ONs in this group of NTG patients compared with control subjects supports the hypothesis of a disturbed CSF exchange between the CSF in the intracranial spaces and the CSF in the SAS surrounding the ONs. The disturbance of CSF dynamics in this specific CSF pathway can be explained by ON compartmentation. The clinical importance of this finding warrants further investigation.