Normal tension glaucoma (NTG) is an exception in the "glaucoma family" where the major risk factor, increased intraocular pressure, is missing. If not increased intraocular pressure, then what other causes can then lead to glaucomatous optic disc change and visual field loss in NTG? Several possibilities will be discussed. Among them a higher sensitivity to normal pressure, vascular dysregulation, an abnormally high translaminar pressure gradient and a neurodegenerative process due to impaired cerebrospinal fluid dynamics in the optic nerve sheath compartment. There are many excellent review papers published on normal tension glaucoma (NTG). The aim of this paper is therefore not to add another extensive review on NTG but rather to focus on and to discuss some possible mechanisms that are thought to be involved in the pathophysiology of NTG and to discuss the stronger and weaker aspects of each concept. The fact that several concepts exist suggests that NTG is still not very well understood and that no single mechanism on its own might adequately explain NTG.

This study did not confirm either a lower lumbar CSF-p or increased TLP compared to previous retrospective and prospective studies. As cerebrospinal fluid (CSF) flow is not homogenous throughout all CSF spaces and CSF-p and IOP fluctuate, the current view on TLP needs modifications to improve its validity.

PurposeTo report on the optic canal cross-sectional area (OCA) in Caucasian patients with normal-tension glaucoma (NTG) compared with Caucasian control subjects without known optic nerve (ON) diseases.MethodsRetrospective analysis of computed tomographic images of the cranium and orbits in 56 NTG patients (30 females and 26 males; 99 of 112 eyes; mean age 67.7 ± 11.1 years). Fifty-six age- and gender-matched subjects (mean age: 68.0 ± 11.2 years) without known ON diseases served as controls. The OCA at the orbital opening was measured in square millimeters by using the tool “freehand.” Statistical analysis was performed by using the independent two-tailed t-test.ResultsThe mean orbital opening OCA in NTGs measured 14.5 ± 3.5 mm2 (right OCA: 14.4 ± 3.6 mm2, left OCA: 14.5 ± 3.4 mm2) and in controls measured 18.3 ± 2.6 mm2 (right OCA: 18.5 ± 2.7 mm2, left OCA: 18.1 ± 2.5 mm2). The difference between NTG and controls was statistically significant (p < 0.000 for the right OCA, p < 0.000 for the left OCA).ConclusionThis study demonstrates narrower OCAs in Caucasian NTG patients compared with Caucasian control subjects without known ON diseases. Narrower OCAs might contribute to a discontinuity of the cerebrospinal fluid flow between the intracranial and orbital subarachnoid space in NTG patients. This might have an influence onto the pathophysiology in NTG.

Purpose: To examine the cerebrospinal fluid (CSF) dynamics along the entire optic nerve in patients with idiopathic intracranial hypertension (IIH) and papilledema by computed tomographic (CT) cisternography.Methods: Retrospective analysis of CT cisternographies in 16 patients with a history of IIH and papilledema (14 females and 2 males, mean age: 49 ± 16 years). Contrast loaded CSF (CLCSF) was measured in Hounsfield Units (HU) at three defined regions of interest (ROI) along the optic nerve (orbital optic nerve portion: bulbar and mid-orbital segment, intracranial optic nerve portion) and additionally in the basal cistern. The density measurements in ROI 1, ROI 2, and ROI 3 consist of measurements of the optic nerve complex: optic nerve sheath, CLCSF filled SAS and optic nerve tissue. As controls served a group of patients (mean age: 60 ± 19 years) without elevated intracranial pressure and without papilledema.Results: In IIH patients the mean CLCSF density in the bulbar segment measured 65 ± 53 HU on the right and 63 ± 35 HU on the left side, in the mid-orbital segment 68 ± 37 HU right and 60 ± 21 HU left. In the intracranial optic nerve portion 303 ± 137 HU right and 323 ± 169 HU left and in the basal cistern 623 ± 188 HU. Within the optic nerve the difference of CLCSF density showed a highly statistical difference (p < 0.001) between the intracranial optic nerve portion and the mid-orbital segment. CLCSF density was statistically significantly (p < 0.001) reduced in both intraorbital optic nerve segments in patients with IIH compared to controls.Conclusions: The current study demonstrates reduced CLCSF density within the orbital optic nerve segments in patients with IIH and papilledema compared to 12 controls without elevated intracranial pressure and without papilledema. Impaired CSF dynamics could be involved in the pathophysiology of optic nerve damage in PE in IIH.

Diffusion-weighted imaging provides a method to evaluate CSF flow within the subarachnoid space of the optic nerve in a non-invasive manner. Compared to healthy controls, patients with normal tension glaucoma measure a significantly lower flow-range ratio. This finding suggests a possible role of impaired CSF dynamics in the pathophysiology in normal tension glaucoma.

This study demonstrates a gradual reduction in CLCSF towards the retrobulbar segment in NTG, while in controls without NTG, no reduction in CLCSF was measured within the orbital segments. Impaired CSF dynamics along the ON may contribute to the pathophysiology of NTG.

PurposeTo investigate on the relationship between the optic nerve sheath diameter (ONSD) and the lumbar cerebrospinal fluid pressure (CSF-p) in Caucasian patients with normal tension glaucoma (NTG).Patients and methodsRetrospective analysis of medical records of patients with open-angle glaucoma in the period from 2005 to 2015 from the Ophthalmology Department, Cantonal Hospital Aarau, Switzerland was performed. A total of 38 patients (mean age 68.6±11.3 years, 21 females and 17 males) fulfilled the diagnostic criteria of NTG and underwent computed tomography (CT) of the orbit and lumbar puncture (LP). In total, 38 age- and gender-matched Caucasian subjects (mean age: 68.9±10.9 years) without known ON diseases served as controls for ONSD measurements. ONSDs were measured at a distance of 3 mm from the posterior globe and lumbar CSF-p was related to the measurements. Statistical analysis was performed by using the independent two-tailed t-test and the non-parametric Spearman's correlation test.ResultsThe mean ONSD in NTGs measured 6.4±0.9 mm and in controls 5.4±0.6 mm. The difference between NTGs and controls showed statistical significance (t-test: P<0.000). The mean CSF-p in NTG was 11.6±3.7 mm Hg. There was no statistical significant correlation between ONSD and CSF-p (Spearman's correlation coefficient ρ=0.06, P=0.72).ConclusionsThis study demonstrates enlarged ONSDs and normal lumbar CSF-p in 38 Caucasian NTG patients. As enlarged ONSDs generally are associated with increased intracranial CSF-p, these results can be explained by a disturbed communication of CSF-p between the intracranial and intraorbital subarachnoid spaces.

Importance Optic nerve (ON) dysfunction is a common feature of different diseases. The pathophysiology is not yet fully understood. Background This study describes five patients with ON sheath (ONS) compartment syndrome (ONSCS) and contributes to the hypothesis that impaired cerebrospinal fluid (CSF) flow can play a role in the development of ON dysfunction. Design Retrospective case series. Participants Five patients with ONSCS were included in the study. Methods Elaboration of medical histories and clinical and diagnostic findings over a long time period was carried out by analysing medical records and by a detailed medical consultation. Main Outcome Measures The main outcome measures include clinical history; visual acuity; field, intraocular and CSF pressures; and contrast‐loaded computed tomographic (CT) cisternography. Results Compartmentation of the ONS demonstrated by contrast‐loaded CT cisternography was the consistent finding in all five patients who demonstrated findings of ON dysfunction. The aetiologies varied and included meningitis, papilloedema, sphenoid wing meningioma, disc herniation and normal‐tension glaucoma. Conclusion and Relevance Compartmentation of the ONS with consecutively impaired CSF dynamics within the ON subarachnoid space can lead to ON dysfunction. Different aetiologies can cause the development of ONSCS.