Hanspeter Esriel Killer

Architecture of arachnoid trabeculae, pillars, and septa in the subarachnoid space of the human optic nerve: anatomy and clinical considerations

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).

Lymphatic capillaries in the meninges of the human optic nerve.

OBJECTIVE Although many anatomical studies of the orbit and the optic nerve have been performed, lymphatic capillaries in the dura of the human optic nerve have never been reported. This study was performed to determine whether or not lymphatic capillaries are present in the dura of the human optic nerve. MATERIALS AND METHODS This postmortem study was carried out in seven subjects without ocular disease. The subjects were obtained no later than 6 hours after death, following qualified consent for autopsy. The dura of the human optic nerve was studied with light microscopy, scanning electron microscopy, and transmission electron microscopy. In some cases, india ink was injected into the subarachnoid space as a marker. RESULTS Lymphatic capillaries in the dura of the human optic nerve were morphologically demonstrated with histological criteria (fenestrated endothelium, lack of a basal membrane, and absence of blood cells in the lumen of the vessels). The highest concentration of lymphatic capillaries was found in the bulbar part of the dura behind the ocular globe. Using light microscopy and transmission electron microscopy, ink was seen within the lumen of the lymphatic capillaries. The dura itself was not stained with the marker. CONCLUSION The presence of lymphatic capillaries in the dura of the human optic nerve was demonstrated with light microscopy, transmission electron microscopy, and scanning electron microscopy.

Cerebrospinal fluid exchange in the optic nerve in normal-tension glaucoma

Aim To report on the cerebrospinal fluid (CSF) exchange between the intracranial spaces (ie, basal cisterns) and the subarachnoid space (SAS) of the optic nerve (ON) in subjects with normal-tension glaucoma (NTG) compared with control subjects without NTG or other forms of glaucoma. Methods CT cisternography of the brain and orbits was performed in 18 patients with NTG (7 women, 11 men; mean age 64.9±8.9 years) and in four patients without glaucoma or intracranial disease (4 women; mean age 62.8±18.4 years). The density of contrast-loaded cerebrospinal fluid (CLCSF) in the intracranial spaces and in the SAS surrounding the ONs was measured in Hounsfield units. Study design Unmasked, prospective series. Statistical analysis was performed using an independent two-tailed t test and the non-parametric Spearman correlation test. Results The density of CLCSF in the SAS surrounding the ONs in the NTG group was significantly reduced compared with its density in the intracranial CSF spaces and in the SAS of ONs measured in the control group (p=0.006). There were no significant differences between men and women within the NTG group (p>0.35). Conclusions 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.

Optic nerve sheath diameter in normal-tension glaucoma patients

Background To report on the optic nerve sheath diameter (ONSD) in patients with normal-tension glaucoma (NTG) compared with controls without known optic nerve (ON) or intracranial disease. Methods In 18 patients with NTG (mean age 64.9±8.9 years; 7 women and 11 men), CT of the orbit was performed. 17 age- and gender-matched patients without ON or intracranial disease, who underwent CT of the orbits for non-ophthalmological reasons, served as controls. The widest intraorbital ONSD in axial sections was measured using a standardised technique. Study design: unmasked. Statistical analysis was performed using an independent two-tailed t Test and the non-parametric Spearman correlation test. Results ONSD was significantly (p<0.001) increased in NTG patients (right side: mean 7.9±0.9 mm SD; left: 8.0±1.1 mm) compared with controls (right: 6.3±0.5 mm; left: 6.1±0.6 mm). Neither the NTG nor the control group had a significant difference in ONSD between males and females or between right and left sides. Conclusions An increased ONSD is generally associated with increased intracranial pressure; however, ONSDs in a group of NTG patients also were significantly increased compared with controls. ON sheath compartmentation and thinning of the ON sheath are two possible explanations for an increase in the ONSD in patients with NTG.

Optic disc edema in an astronaut after repeat long-duration space flight

Background: A number of ophthalmic findings including optic disc edema, globe flattening, and choroidal folds have been observed in several astronauts after long-duration space flights. The authors report the first astronaut with previously documented postflight ophthalmic abnormalities who developed new pathological changes after a repeat long-duration mission. Methods: A case study of an astronaut with 2 long-duration (6 months) exposures to microgravity. Before and after his first long-duration space flight, he underwent complete eye examination, including fundus photography. Before and after his second flight, 9 years later, he underwent fundus photography, optical coherence tomography, ocular ultrasonography, and brain magnetic resonance imaging, as well as in-flight fundus photography and ultrasound. Results: After his first long-duration mission, the astronaut was documented to have eye findings limited to unilateral choroidal folds and a single cotton wool spot. During a subsequent 6-month mission, he developed more widespread choroidal folds and new onset of optic disc edema in the same eye. Conclusion: Microgravity-induced anatomical changes that occurred during the first mission may have set the stage for recurrent or additional changes when the astronaut was subjected to physiological stress of repeat space flight.

A new glaucoma hypothesis: a role of glymphatic system dysfunction

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 dynamics between the basal cisterns and the subarachnoid space of the optic nerve in patients with papilloedema

Aims To determine cerebrospinal fluid (CSF) dynamics between intracranial CSF spaces and CSF in the subarachnoid space (SAS) of optic nerves (ONs) in 10 patients with papilloedema. Methods Prospective assessment of 10 patients with papilloedema and two control subjects using CT cisternography and analysis of CSF for the presence of lipocalin-like prostaglandin D synthase (betatrace protein). Results CT cisternography showed a progressively reduced influx of contrast-loaded CSF from intracranial CSF spaces into the SAS. The lowest concentration of contrast-loaded CSF was found in the region of the ON immediately behind the globe, where the ON sheath was widened (possibly by unfolding) in all patients compared with normal subjects. The concentration of lipocalin-like prostaglandin D synthase differed between the spinal CSF and the CSF in the SAS, with a markedly higher concentration in the SAS. Conclusion The results of this study suggest that CSF turnover in the SAS of the ON is reduced in patients with papilloedema from various causes and that the composition of CSF differs between spinal CSF and that surrounding the ON.

Intraoperative magnetic resonance imaging and early prognosis for vision after transsphenoidal surgery for sellar lesions

OBJECT Sellar lesions with suprasellar extension may cause loss of visual acuity and visual field damage due to compression of the optic chiasm. Using intraoperative MR (iMR) imaging to detect symptomatic lesion remnants adjacent to the optic chiasm (that may be resected in the same procedure) may positively affect the functional outcome of patients with these lesions. The aim of this study was to evaluate the correlation between visual improvement and optic nerve decompression detected by iMR imaging in patients undergoing transsphenoidal resection of pituitary lesions. METHODS A total of 32 patients (23 men and 9 women) who underwent transsphenoidal resection of sellar lesions causing visual impairment were included in this study. Tumor volume ranged from 0.9 cm(3) to 55.7 cm(3) (mean 9.8 ± 11.7 cm(3)). Preoperative assessment showed visual field damage in 31 patients (97%) and loss of visual acuity in 28 patients (88%). The latency period between the appearance of symptoms and transsphenoidal decompression was 14.9 ± 19.5 weeks. RESULTS Intraoperative MR imaging was performed after the resection was believed to be complete, or if further tumor removal was not safely possible due to changed conditions in the surgical field. Complete resection was detected on these initial scans in 17 patients (53%). Partial resection was achieved in 9 patients (28%) and tumor debulking in 6 (19%). Additional resection was possible in 8 (53%) of these 15 patients. Four (50%) of these 8 cases had suprasellar remnants and the optic chiasm was subsequently decompressed. In 5 cases optimal decompression of the optic chiasm was not possible. On early follow-up within 1 month after surgery, overall improvement of visual field damage was observed in 27 patients (87%). In 23 patients (74%), the Goldmann perimetry demonstrated complete recovery. Improvement of visual acuity was noted in 24 patients (86%). Eighteen patients (64%) regained full visual acuity. Identification of a decompressed optic chiasm on iMR imaging was significantly correlated with visual field improvement (p = 0.0007; positive predictive value 0.96, 95% CI 0.81-0.99) and relief of visual acuity deficits (p = 0.0002; positive predictive value 0.96, 95% CI 0.79-0.99). Two patients needed transcranial procedures for symptomatic tumor remnants detected on iMR imaging. CONCLUSIONS Intraoperative MR imaging findings correlate with prognosis of visual deficits after transsphenoidal decompression of the anterior optic pathways. The use of iMR imaging may prevent revision surgery for unexpected symptomatic remnants.

Is open-angle glaucoma caused by impaired cerebrospinal fluid circulation: Around the optic nerve?

Chronic open‐angle glaucoma is the most frequent type of glaucoma and a leading cause for blindness. The role of intraocular pressure (IOP) in the pathogenesis of open‐angle glaucoma has been challenged by patients with typical glaucomatous optic disc changes and visual field loss in whom the IOP never exceeded normal values (normal‐tension glaucoma), as well as by patients with persistently elevated IOP who do not develop glaucomatous disc or field changes. Recent research has demonstrated that the cerebrospinal fluid (CSF) is not evenly distributed in all CSF spaces and that the subarachnoid space of the optic nerve can turn into a CSF compartment on its own. The biochemical components in this optic nerve compartment can differ markedly from normal CSF and some of its components (such as L‐PGDS) may produce a toxic effect on the optic nerve and may therefore play an important role in the pathophysiology of open‐angle glaucoma.

Cerebrospinal fluid segregation optic neuropathy: an experimental model and a hypothesis

Aim To describe the histological changes in the optic nerve (ON) after experimental segregation of cerebrospinal fluid (CSF). Methods In seven sheep, a silicone band was placed around one ON to compress the subarachnoid space (SAS) surrounding the nerve, thus blocking the flow of CSF without compressing the ON itself. After 4 or 21 days, both the ligated and untouched ONs were removed and evaluated histologically. Results All treated ONs showed marked loss of axons, destruction of myelin and swelling of meningoepithelial cells, most pronounced in the proximal ON adjacent to the globe at the location most distant to the ligature. There was no significant difference in histological findings between the ONs that were ligated for 4 days and those with 21 days of ligature. Conclusion CSF segregation in the ON by blocking the SAS leads within 4 days to severe nerve damage. The increasing severity of these changes with increasing distance from the site of the ligature argues against simple pressure- or microperfusion-dependent effects and supports the hypothesis that interruption of CSF flow in the SAS of the ON can produce damage due to a change of CSF flow and content.