P ERSPECTIVE Blood Pressure, Perfusion Pressure, and Glaucoma JOSEPH CAPRIOLI AND ANNE L. COLEMAN, ON BEHALF OF THE BLOOD FLOW IN GLAUCOMA DISCUSSION GROUP ● PURPOSE: To provide a critical review of the relation- ships 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 liter- ature and the results of a 1-day group discussion involv- ing glaucoma researchers and specialists with expertise in epidemiology, blood flow measurements, and cardiovas- cular physiology. ● RESULTS: Accurate, reproducible, and clinically rele- vant 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. Reg- ulation 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 popula- tion-based studies. The physiologic nocturnal dip in blood pressure is protective against systemic end-organ damage, but its effects on glaucoma are not well elabo- rated or understood. Large-scale longitudinal studies would be required to evaluate the risk of glaucomatous progression in non-dippers, dippers, and extreme noctur- nal blood pressure dippers. ● CONCLUSIONS: Decreases in perfusion pressure and blood pressure have been associated with glaucoma. How- ever, 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 appro- priate 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. (Am J Ophthalmol 2010;149:704 –712. © 2010 by Elsevier Inc. All rights reserved.) G LAUCOMA IS A FAMILY OF OPTIC NEUROPATHIES having in common a characteristic cupping of the optic nerve head and a distinctive pattern of visual field loss for which increased intraocular pressure (IOP) is an important risk factor. From the time of its earliest recognition, there has been a debate about its etiology and preferred treatment. Elevated IOP has long been thought to increase the risk of glaucoma by causing abnormalities of the optic nerve head at the level of the lamina cribrosa, affecting the intracellular transport within the retinal ganglion cell axons or by causing vascular abnormalities that lead to ischemic damage. When von Graefe introduced iridectomy as a suc- cessful treatment for acute glaucoma in the mid-1800s, he postulated that it was helpful because it reduced aqueous production and IOP, while Jaeger believed that it was helpful because it altered ocular blood flow to improve nutrition and decrease inflammation. The role of IOP as a risk factor for glaucoma is now well established, and current treatment of glaucoma aims to reduce IOP to a target pressure low enough to prevent or significantly slow progression. 1 The role of optic nerve and retinal blood flow and ischemia in glaucoma is not clear. 2 In the 1990s, Hayreh, Drance, and others raised the important issues of systemic hypotension and nocturnal blood pressure dips in the progression of glaucoma and the desirability of accurate clinical measurements of ocular blood flow. Interest in these topics has resurged in light of recent epidemiologic data concerning low blood pressure and low calculated “ocular perfusion pressure” as risk factors for the development and progression of glaucoma. The purpose of this Perspective is to critically evaluate the current evidence for reduced blood flow in the pathology of glaucoma, its measurement, and its iatrogenic perturbation as a means of treatment for glaucoma. Accepted for publication Jan 8, 2010. From the Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California. Inquiries to Joseph Caprioli, UCLA David Geffen School of Medicine, Department of Ophthalmology, 2-118 Jules Stein Eye Institute, Los Angeles, CA 90095; e-mail: Caprioli@ucla.edu © 2010 BY ELSEVIER INC.ALL RIGHTS RESERVED. 704 0002-9394/10/$36.00 doi:10.1016/j.ajo.2010.01.018