Blood Pressure, Perfusion Pressure, and Glaucoma

doi:10.1016/j.ajo.2010.01.018

American Journal of Ophthalmology

Volume 149, Issue 5, May 2010, Pages 704-712

https://doi.org/10.1016/j.ajo.2010.01.018 Get rights and content

Purpose

To provide a critical review of the relationships between blood pressure, ocular blood flow, and glaucoma and the potential for glaucoma treatment through modulation of ocular perfusion.

Design

Summaries of the pertinent literature and input from glaucoma researchers and specialists with relevant experience.

Methods

Review and interpretation of selected literature and the results of a 1-day group discussion involving glaucoma researchers and specialists with expertise in epidemiology, blood flow measurements, and cardiovascular physiology.

Results

Accurate, reproducible, and clinically relevant measurements of blood flow within the optic nerve head and associated capillary beds are not fully achievable with current methodology. Autoregulation of blood flow in the retina and optic nerve head occurs over a large range of intraocular pressures and blood pressures. Regulation of choroidal blood flow is provided by a mix of neurohumoral and local mechanisms. Vascular factors may be important in a subgroup of patients with primary open-angle glaucoma, and particularly in patients with normal-tension glaucoma and evidence of vasospasm. Low ocular perfusion pressure and low blood pressure are associated with an increased risk of glaucoma in population-based studies. The physiologic nocturnal dip in blood pressure is protective against systemic end-organ damage, but its effects on glaucoma are not well elaborated or understood. Large-scale longitudinal studies would be required to evaluate the risk of glaucomatous progression in non-dippers, dippers, and extreme nocturnal blood pressure dippers.

Conclusions

Decreases in perfusion pressure and blood pressure have been associated with glaucoma. However, there is no evidence to support the value of increasing a patient's blood pressure as therapy for glaucoma. Such recommendations are not currently warranted, since we lack crucial information about the microvascular beds in which perfusion is important in glaucoma, and the appropriate methods to evaluate their blood flow. There are also cardiovascular safety concerns associated with treatments designed to increase ocular perfusion pressure and blood flow by increasing blood pressure, especially in elderly patients. For these reasons and with present evidence it is unlikely that safe and effective glaucoma treatments based on altering optic nerve perfusion will soon be available.

Section snippets

Anatomy and Clinical Measurements of Ocular Blood Flow

The ocular circulation is composed of a complex arterial supply and an even more complex venous drainage system. The ophthalmic artery and its tributaries, the posterior ciliary arteries and the central retinal artery, provide arterial blood flow to the posterior segment. The short posterior ciliary arteries from the choroid mainly supply the prelaminar portion of the optic nerve, with a minor contribution to the surface of the disc from fine branches of the central retinal artery.³

A variety of

Physiology and Autoregulation of Ocular Blood Flow

The driving force for ocular blood flow is the ocular perfusion pressure (OPP), defined as the ocular arterial pressure minus the IOP. A relationship between OPP and ocular blood flow has been demonstrated in several animal models, where arterial pressure can be precisely controlled.13, 14 In this model, choroidal blood flow ceases when the OPP is zero, indicating the ear artery pressure is a reasonable estimate of the arterial pressure entering the choroid. However, in humans and other species

Ischemia and Glaucoma

Ocular nerve head cupping is a hallmark of glaucoma. Although multiple factors are likely to be involved in the etiology of glaucoma, IOP is the best recognized. Laminar cupping may result from the mechanical stress of IOP that causes deformation of the optic nerve head, while prelaminar cupping may result from retinal ganglion cell loss and changes in glial architecture.²² Other possible etiologic factors in glaucoma include vascular factors, genetic factors, autoimmunity, loss of normal

Clinical Evidence of Ischemic Pathophysiology in Glaucoma

In an early case-series study of 29 normal-tension glaucoma patients, 10 had a history of a severe hemodynamic crisis.²⁶ This led to concern that overtreatment of systemic hypertension might exacerbate glaucoma. Nine of these patients did not progress, however, so they may have been patients with ischemic damage rather than progressive glaucoma. Subsequent studies have found little or no relationship between glaucoma and either symptomatic hypotensive episodes or systemic antihypertensive

Systemic Cardiovascular Considerations

Despite the protection that high blood pressure may initially confer against glaucomatous damage, the resultant microangiopathy of long-term hypertension can produce harmful effects on the retina and optic nerve. High blood pressure must be treated because it is one of the most important risk factors for cardiovascular morbidity and mortality. The risk of cardiovascular mortality doubles with each 20 mm Hg rise in systolic blood pressure and each 10 mm Hg rise in diastolic blood pressure. The

Nocturnal Dips and Glaucoma Progression

The physiologic increase in OPP when an individual lies down has important implications regarding the extent to which a nocturnal dip in blood pressure might affect actual OPP and ocular blood flow (Figure). Since OPP increases by about 15 mm Hg when an individual lies down, blood pressure would have to decrease by more than 15 mm Hg before the resultant decrease of OPP could cause an ischemic insult. In the normal dipping pattern characterized by a 10% to 20% decrease in blood pressure during

Blood Pressure Measurements in Glaucoma

The recognition of low OPP and low systolic blood pressure as risk factors in glaucoma has led to a discussion concerning the role of blood pressure monitoring in glaucoma management. Is it necessary to take blood pressures along with IOP measurements? Are office measurements of blood pressure sufficient, or is home monitoring or ambulatory monitoring required? These questions have not been satisfactorily answered. Further, there is the question of whether care must be taken to avoid excessive

Prospects for Drug Development

Studies with various methods to assess ocular blood flow have suggested that optic nerve perfusion may be reduced in glaucoma,³⁹ but all of the techniques used clinically to evaluate blood flow have significant limitations. The extent to which blood flow may be reduced, as well as the accurate identification of the vascular beds affected, remains to be determined. Even if ocular blood flow in relevant vascular beds is reduced in glaucoma, the reduction may not be a cause of glaucomatous damage,

Conclusions

There is currently little evidence that measurements of ocular circulation or blood flow are useful in glaucoma management, or that vasoactive medications have any benefit in glaucoma patients. Significant challenges remain in the measurement and interpretation of ocular blood flow. The location of the microvascular beds that are most relevant to glaucomatous damage continues to be debated. The OPP estimated with current office measurements is only a surrogate for the physiologic OPP, and it

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PerspectiveBlood Pressure, Perfusion Pressure, and Glaucoma

Purpose

Design

Methods

Results

Conclusions

Section snippets

Anatomy and Clinical Measurements of Ocular Blood Flow

Physiology and Autoregulation of Ocular Blood Flow

Ischemia and Glaucoma

Clinical Evidence of Ischemic Pathophysiology in Glaucoma

Systemic Cardiovascular Considerations

Nocturnal Dips and Glaucoma Progression

Blood Pressure Measurements in Glaucoma

Prospects for Drug Development

Conclusions

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Blood Pressure, Perfusion Pressure, and Glaucoma