Cerebrospinal Fluid Pressure and Glaucoma

Author: John Berdahl, MD

Intracranial pressure may hold the key to understanding why IOP plays a major role in the development of glaucoma.

Glaucoma is not well understood. It is an optic neuropathy of unknown etiology that results in a characteristic pattern of visual field loss and changes to the optic nerve. Elevated IOP is a well-known risk factor for the development of glaucoma, but it is not always present, such as in cases of normal-tension glaucoma (NTG). Furthermore, an individual with high IOP may not develop glaucoma. For example, only a small percentage of people with ocular hypertension (OHT) ultimately develop glaucoma.1 The mechanism through which IOP contributes to optic nerve damage remains speculative despite immense research efforts.

In addition to IOP, the optic nerve is exposed to intracranial pressure (ICP) as it is surrounded by cerebrospinal fluid (CSF) in the subarachnoid space immediately posterior to the lamina cribrosa. Because the lamina cribrosa separates these two pressurized regions,2 the decrease in pressure that occurs across the lamina cribrosa (IOP - ICP) is known as the translaminar pressure difference. The average IOP is 16 mm Hg, and the average ICP is 12 mm Hg, resulting in a small, posteriorly directed pressure difference across the lamina.3 If this disparity became larger due either to an elevation in IOP or a reduction in ICP, the imbalance could result in glaucomatous changes.

Intracranial pressure may play significant role in glaucoma

Authors: Thomas W. Samuelson, MD, interviews John P. Berdahl, MD, the lead author of a study on the role of ICP in glaucoma.

In the May issue of Ophthalmology, Berdahl and colleagues published the results of their study pertaining to cerebrospinal fluid pressure and its relationship to primary open-angle glaucoma. In this retrospective study, the authors found a positive correlation between manifest glaucoma and an increased pressure differential across the lamina cribrosa. Although further study is needed, the pressure differential across the lamina cribrosa may be an underappreciated factor in patients with glaucoma.

This paper has received considerable attention in recent months. In addition to the article in Ophthalmology, the study was published in the August issue of Investigative Ophthalmology and Visual Science. Dr. Berdahl also presented his findings in September at the International Congress of Eye Research in Beijing.

Intraocular pressure correlates with optic nerve sheath diameter in patients with normal tension glaucoma

Authors: Abegão Pinto L, Vandewalle E, Pronk A, Stalmans I.

PURPOSE: 1. Identify differences in optic nerve sheath diameter (ONSD) as an indirect measure of intracranial pressure (ICP) in glaucoma patients and a healthy population. 2. Identify variables that may correlate with ONSD in primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) patients.

METHODS: Patients with NTG (n = 46) and POAG (n = 61), and healthy controls (n = 42) underwent B-scan ultrasound measurement of ONSD by an observer masked to the patient diagnosis. Intraocular pressure (IOP) was measured in all groups, with additional central corneal thickness (CCT) and visual field defect measurements in glaucomatous patients. Only one eye per patient was selected. Kruskal-Wallis or Mann-Whitney were used to compare the different variables between the diagnostic groups. Spearman correlations were used to explore relationships among these variables.

RESULTS: ONSD was not significantly different between healthy, NTG and POAG patients (6.09 ± 0.78, 6.03 ± 0.69, and 5.71 ± 0.83 respectively; p = 0.08). Visual field damage and CCT were not correlated with ONSD in either of the glaucoma groups (POAG, p = 0.31 and 0.44; NTG, p = 0.48 and 0.90 respectively). However, ONSD did correlate with IOP in NTG patients (r = 0.53, p < 0.001), while it did not in POAG patients and healthy controls (p = 0.86, p = 0.46 respectively). Patient's age did not relate to ONSD in any of the groups (p > 0.25 in all groups).

CONCLUSIONS: Indirect measurements of ICP by ultrasound assessment of the ONSD may provide further insights into the retrolaminar pressure component in glaucoma. The correlation of ONSD with IOP solely in NTG patients suggests that the translaminar pressure gradient may be of particular importance in this type of glaucoma.

Alzheimer's disease: cerebral glaucoma?

Authors: Wostyn P, Audenaert K, De Deyn PP.

In a 1994 Medical Hypotheses paper, it was speculated that high intracranial pressure (ICP) might increase the probability of developing Alzheimer's disease (AD). A study of cerebrospinal fluid pressure (CSFP) in normal volunteers showed interindividual variations in CSFP. Some normals had what would normally be considered elevated CSFP. The hypothesis postulated that this subgroup with a high characteristic individual ICP level might be more susceptible to developing AD. The Medical Hypotheses paper further speculated that in more advanced stages of AD, such pressure factor could already be missing due to the disease process. The present article discusses recent research findings regarding CSFP distribution in AD patients that could be interpreted as support for this hypothesis. Exposure of central nervous system tissue to high pressure stress is not unique to the ICP space. Indeed, a similar situation occurs in the intraocular pressure (IOP) space in eyes with glaucoma. Interestingly, recent research has revealed similarities in the process leading to retinal ganglion cell death in glaucoma and neuronal cell death in AD. In the present paper, we raise the question of whether AD could be a cerebral form of glaucoma. Indeed, the linking of glaucoma to mechanisms of AD could reflect the anatomical and functional similarities between the IOP space and the ICP space. Further studies are warranted, however, especially to determine the possible role of high ICP in at least some cases of AD.

Alzheimer's disease-related changes in diseases characterized by elevation of intracranial or intraocular pressure

Authors: Peter Wostyn a, Kurt Audenaert b and Peter Paul De Deyn c, d

In this review, we focus on the coexistence of Alzheimer's disease-related changes in brain diseases, such as normal pressure hydrocephalus and traumatic brain injury, and in glaucoma at the level of the retinal ganglion cells. This is a group of diseases that affect central nervous system tissue and are characterized by elevation of intracranial or intraocular pressure and/or local shear stress and strain. In considering possible mechanisms underlying Alzheimer-type changes in these diseases, we briefly summarize recent evidence indicating that caspase activation and abnormal processing of β-amyloid precursor protein, which are important events in Alzheimer's disease, may play a role both in glaucoma and following traumatic brain injury. With regard to normal pressure hydrocephalus, evidence suggests that changes in cerebrospinal fluid circulatory dynamics ultimately may result in reduced clearance of neurotoxins, such as β-amyloid peptides and tau protein, that play a role in the pathogenesis of Alzheimer's disease. Data presented in this review could be interpreted to suggest that Alzheimer-type changes in these diseases may result at least in part from exposure of central nervous system tissue to increased levels of mechanical stress. Evidence for such a relationship is of major importance because it may support an association between elevated mechanical load and the development of Alzheimer-type lesions. Further studies are warranted, however, especially to elucidate the role of elevated mechanical forces in Alzheimer's disease neuropathogenesis.

Are intracranial pressure fluctuations important in glaucoma?

Authors: Peter Wostyna, Veva De Grootb, Kurt Audenaertc and Peter Paul De Deynd, e

Glaucoma is one of the leading causes of irreversible blindness. Primary open-angle glaucoma (POAG), the most common type, is a progressive optic neuropathy with characteristic structural changes in the optic nerve head and functional changes in the visual field. Mechanical and vascular theories for the pathogenesis of glaucomatous optic neuropathy have been proposed. Elevated intraocular pressure (IOP) is a strong risk factor, although a subset of POAG patients has normal IOP and is designated normal tension glaucoma (NTG). Clearly, factors other than IOP are likely to be involved in retinal ganglion cell death in glaucoma. An intriguing finding of recent studies is that intracranial pressure (ICP) is lower in patients with POAG and NTG when compared with nonglaucomatous control subjects. It has been suggested that the relationship between IOP and ICP may play a fundamental role in the development of glaucoma. A decreased ICP could result in an increased trans-lamina cribrosa pressure difference (IOP minus ICP) and lead to glaucomatous damage. In the present paper, we raise the question of whether ICP fluctuations also may be important in glaucoma. The effect of ICP fluctuation might be comparable to that of IOP fluctuation, which has been recognized as an independent risk factor for glaucoma progression.


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