The complex interaction between ocular perfusion pressure and ocular blood flow - relevance for glaucoma.

Glaucoma is an optic neuropathy of unknown origin. The most important risk factor for the disease is an increased intraocular pressure (IOP). Reducing IOP is associated with reduced progression in glaucoma. Several recent large scale trials have indicated that low ocular perfusion pressure (OPP) is a risk factor for the incidence, prevalence and progression of the disease. This is a strong indicator that vascular factors are involved in the pathogenesis of the disease, a hypothesis that was formulated 150 years ago. The relation between OPP and blood flow to the posterior pole of the eye is, however, complex, because of a phenomenon called autoregulation. Autoregulatory processes attempt to keep blood flow constant despite changes in OPP. Although autoregulation has been observed in many experiments in the ocular vasculature the mechanisms underlying the vasodilator and vasoconstrictor responses in face of changes in OPP remain largely unknown. There is, however, recent evidence that the human choroid regulates its blood flow better during changes in blood pressure induced by isometric exercise than during changes in IOP induced by a suction cup. This may have consequences for our understanding of glaucoma, because it indicates that blood flow regulation is strongly dependent not only on OPP, but also on the level of IOP itself. Indeed there is data indicating that reduction of IOP by pharmacological intervention improves optic nerve head blood flow regulation independently of an ocular vasodilator effect.

[1]  Paul P. Lee,et al.  Association between intraocular pressure variation and glaucoma progression: data from a United States chart review. , 2007, American journal of ophthalmology.

[2]  Lin Wang,et al.  Endothelin B receptor in human glaucoma and experimentally induced optic nerve damage. , 2006, Archives of ophthalmology.

[3]  L. Schmetterer,et al.  Inhaled carbon monoxide increases retinal and choroidal blood flow in healthy humans. , 2005, Investigative ophthalmology & visual science.

[4]  W. Bayliss On the local reactions of the arterial wall to changes of internal pressure , 1902, The Journal of physiology.

[5]  Larry Kagemann,et al.  Measuring and interpreting ocular blood flow and metabolism in glaucoma. , 2008, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.

[6]  Leopold Schmetterer,et al.  Bidirectional Doppler Fourier-domain optical coherence tomography for measurement of absolute flow velocities in human retinal vessels. , 2008, Optics letters.

[7]  Leopold Schmetterer,et al.  Ocular blood flow and systemic blood pressure in patients with primary open-angle glaucoma and ocular hypertension. , 2004, Investigative ophthalmology & visual science.

[8]  Klaus Ley,et al.  Handbook of physiology : microcirculation , 2008 .

[9]  J. Kiel,et al.  Ocular perfusion pressure and choroidal blood flow in the rabbit. , 1995, Investigative ophthalmology & visual science.

[10]  J I Hoffman,et al.  Blood flow measurements with radionuclide-labeled particles. , 1977, Progress in cardiovascular diseases.

[11]  M. J. Davis,et al.  Myogenic response gradient in an arteriolar network. , 1993, The American journal of physiology.

[12]  M. Koss Effect of nitric oxide synthesis inhibition on post-occlusive choroidal blood flow in rats. , 2000, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[13]  J. Izatt,et al.  Retinal blood flow measurement by circumpapillary Fourier domain Doppler optical coherence tomography. , 2008, Journal of biomedical optics.

[14]  M. Wolzt,et al.  Effect of inhalation of different mixtures of O2 and CO2 on retinal blood flow , 2002, The British journal of ophthalmology.

[15]  A. Ball,et al.  Effects of acute delivery of endothelin-1 on retinal ganglion cell loss in the rat. , 2006, Experimental eye research.

[16]  D. R. Anderson,et al.  Angiotensin II binding receptors in retinal and optic nerve head blood vessels. An autoradiographic approach. , 1991, Investigative ophthalmology & visual science.

[17]  Leopold Schmetterer,et al.  Use of laser speckle flowgraphy in ocular blood flow research , 2010, Acta ophthalmologica.

[18]  B. Petrig,et al.  Choroidal blood flow during isometric exercises. , 1997, Investigative ophthalmology & visual science.

[19]  Charles E. Riva,et al.  Autoregulation of human optic nerve head blood flow in response to acute changes in ocular perfusion pressure , 1997, Graefe's Archive for Clinical and Experimental Ophthalmology.

[20]  R. Panerai Assessment of cerebral pressure autoregulation in humans - a review of measurement methods , 1998, Physiological measurement.

[21]  R. Blantz,et al.  Blood pressure and cardiovascular risks: implications of the presence or absence of a nocturnal dip in blood pressure. , 2003, Current opinion in nephrology and hypertension.

[22]  L. Schmetterer,et al.  Short-term increase of intraocular pressure does not alter the response of retinal and optic nerve head blood flow to flicker stimulation. , 2005, Investigative ophthalmology & visual science.

[23]  O Findl,et al.  Evaluation of the Zeiss retinal vessel analyser , 2000, The British journal of ophthalmology.

[24]  D. Lu,et al.  Bilateral Superior Cervical Ganglionectomy Increases Choroidal Blood Flow in the Rabbit , 2000, Ophthalmologica.

[25]  T. Moore SYSTEMIC ACTION OF VITAMIN A. , 1964, Experimental eye research.

[26]  Leopold Schmetterer,et al.  How can blood flow be measured? , 2007, Survey of ophthalmology.

[27]  S. Nilsson,et al.  Characteristics of uveal vasodilation produced by facial nerve stimulation in monkeys, cats and rabbits. , 1985, Experimental eye research.

[28]  Leopold Schmetterer,et al.  Endothelial dysfunction in glaucoma , 2009, Acta ophthalmologica.

[29]  L. Schmetterer,et al.  Effect of dorzolamide and timolol on ocular blood flow in patients with primary open angle glaucoma and ocular hypertension , 2005, British Journal of Ophthalmology.

[30]  Paul A. Sidoti,et al.  Tissue Plasminogen Activator and Glaucoma Drainage Implants , 1995, Journal of glaucoma.

[31]  A. Coleman,et al.  Association of blood pressure status with the optic disk structure in non-glaucoma subjects: the Thessaloniki eye study. , 2006, American journal of ophthalmology.

[32]  A. Bill,et al.  Effects of raised intraocular pressure on retinal, prelaminar, laminar, and retrolaminar optic nerve blood flow in monkeys. , 1979, Investigative ophthalmology & visual science.

[33]  Martial Geiser,et al.  Ocular blood flow assessment using continuous laser Doppler flowmetry , 2010, Acta ophthalmologica.

[34]  C. Chiang,et al.  Aqueous humor nitric oxide levels differ in patients with different types of glaucoma. , 2000, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[35]  C. Doré,et al.  Autoregulation in the human retinal circulation: assessment using isometric exercise, laser Doppler velocimetry, and computer-assisted image analysis. , 1996, Microvascular research.

[36]  R. Funk The vessel architecture of the pars plana in the cynomolgus monkey, rat and rabbit eye. A scanning electron microscopic study of plastic corrosion casts. , 1993, Ophthalmic research.

[37]  R. Zawadzki,et al.  Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography. , 2003, Optics express.

[38]  Larry Kagemann,et al.  An update on retinal circulation assessment technologies , 2003, Current eye research.

[39]  A. Bill,et al.  Ocular effects of endothelin-1 in the cat. , 1992, Current eye research.

[40]  J. Briers,et al.  Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging. , 2001, Physiological measurement.

[41]  J. Izatt,et al.  In vivo imaging of human retinal flow dynamics by color Doppler optical coherence tomography. , 2003, Archives of ophthalmology.

[42]  J. Kiel,et al.  Endothelin modulation of choroidal blood flow in the rabbit. , 2000, Experimental eye research.

[43]  C E Riva,et al.  Rebreathing into a bag increases human retinal macular blood velocity. , 1995, The British journal of ophthalmology.

[44]  D. R. Anderson,et al.  Angiotensin binding sites in bovine and human retinal blood vessels. , 1987, Investigative ophthalmology & visual science.

[45]  M. Koss Role of nitric oxide in maintenance of basal anterior choroidal blood flow in rats. , 1998, Investigative ophthalmology & visual science.

[46]  J E Schwartz,et al.  Stroke Prognosis and Abnormal Nocturnal Blood Pressure Falls in Older Hypertensives , 2001, Hypertension.

[47]  Sue Ann Sisto,et al.  Dynamometry testing in spinal cord injury. , 2007, Journal of rehabilitation research and development.

[48]  J. Pierce,et al.  Increased ocular blood vessel numbers and sizes following chronic sympathectomy in rat. , 2002, Experimental eye research.

[49]  Lin Wang,et al.  Retinal and choroidal vasoreactivity to altered PaCO2 in rat measured with a modified microsphere technique. , 2008, Experimental eye research.

[50]  M. Grant,et al.  Myogenic tone and reactivity of the rat ophthalmic artery. , 2004, Investigative ophthalmology & visual science.

[51]  Toke Bek,et al.  Response of retinal arteriole diameter to increased blood pressure during acute hyperglycaemia. , 2006, Acta ophthalmologica Scandinavica.

[52]  M. Grant,et al.  Characteristics of myogenic tone in the rat ophthalmic artery. , 2007, American journal of physiology. Heart and circulatory physiology.

[53]  J. Fisher,et al.  Retinal arteriolar diameter, blood velocity, and blood flow response to an isocapnic hyperoxic provocation. , 2005, American journal of physiology. Heart and circulatory physiology.

[54]  A. Laties Central retinal artery innervation. Absence of adrenergic innervation to the intraocular branches. , 1967, Archives of ophthalmology.

[55]  M. Wolzt,et al.  Characterization of angiotensin-II effects on cerebral and ocular circulation by noninvasive methods. , 1997, British journal of clinical pharmacology.

[56]  L. Schmetterer,et al.  Effects of topical clonidine versus brimonidine on choroidal blood flow and intraocular pressure during squatting. , 2007, Investigative ophthalmology & visual science.

[57]  M. C. Leske,et al.  Predictors of long-term progression in the early manifest glaucoma trial. , 2007, Ophthalmology.

[58]  Grant Cull,et al.  Impact of systemic blood pressure on the relationship between intraocular pressure and blood flow in the optic nerve head of nonhuman primates. , 2009, Investigative ophthalmology & visual science.

[59]  H. Kuno,et al.  Microvasculature of the rat eye: scanning electron microscopy of vascular corrosion casts. , 2006, Veterinary ophthalmology.

[60]  L. Schmetterer,et al.  Response of retinal blood flow to systemic hyperoxia in smokers and nonsmokers , 2005, Graefe's Archive for Clinical and Experimental Ophthalmology.

[61]  H. Hara,et al.  Endothelin-1 impairs retrograde axonal transport and leads to axonal injury in rat optic nerve. , 2006, Current neurovascular research.

[62]  A. Deussen,et al.  L-arginine-derived nitric oxide: a major determinant of uveal blood flow. , 1993, Experimental eye research.

[63]  M. Maguire,et al.  Optic nerve blood flow in glaucoma: effect of systemic hypertension. , 1999, American journal of ophthalmology.

[64]  M. Kass,et al.  Plasma and Aqueous Humor Endothelin Levels in Primary Open‐Angle Glaucoma , 1997, Journal of glaucoma.

[65]  P. P. Scott,et al.  NUTRITIONAL BLINDNESS IN THE CAT. , 1964, Experimental eye research.

[66]  M. Wolzt,et al.  Propranolol and atropine do not alter choroidal blood flow regulation during isometric exercise in healthy humans. , 2003, Microvascular research.

[67]  A. Neufeld,et al.  Isoforms of nitric oxide synthase in the optic nerves of rat eyes with chronic moderately elevated intraocular pressure. , 1999, Investigative ophthalmology & visual science.

[68]  M. Wolzt,et al.  Effects of systemic NO synthase inhibition on choroidal and optic nerve head blood flow in healthy subjects. , 2000, Investigative ophthalmology & visual science.

[69]  F. Kellermann,et al.  Spatial Summation of Retinal Excitation as Obtained by the Scotopic VECP and the Sensory Threshold , 1973 .

[70]  L. Schmetterer,et al.  Flicker light-induced vasodilatation in the human retina: effect of lactate and changes in mean arterial pressure. , 2003, Investigative ophthalmology & visual science.

[71]  M. Wolzt,et al.  Effects of insulin on retinal and pulsatile choroidal blood flow in humans. , 2000, Archives of ophthalmology.

[72]  L. Schmetterer,et al.  Effect of noradrenaline on retinal blood flow in healthy subjects. , 2002, Ophthalmology.

[73]  W. Kamphuis,et al.  Elevation of nitric oxide production in human trabecular meshwork by increased pressure , 2003, Graefe's Archive for Clinical and Experimental Ophthalmology.

[74]  A. Coleman,et al.  Intraocular Pressure Fluctuation : A Risk Factor for Visual Field Progression at Low Intraocular Pressures in the Advanced Glaucoma Intervention Study , 2008 .

[75]  W. Feuer,et al.  Autoregulation of human optic nerve head circulation in response to increased intraocular pressure. , 1997, Experimental eye research.

[76]  A. Harris,et al.  Retinal hemodynamics during increased intraocular pressure. , 1996, German journal of ophthalmology.

[77]  M. Koss Effects of inhibition of nitric oxide synthase on basal anterior segment ocular blood flows and on potential autoregulatory mechanisms. , 2001, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[78]  L. Schmetterer,et al.  Effects of moderate changes in intraocular pressure on ocular hemodynamics in patients with primary open-angle glaucoma and healthy controls. , 2005, Ophthalmology.

[79]  C E Riva,et al.  Effect of acute increases in intraocular pressure on intravascular optic nerve head oxygen tension in cats. , 1992, Investigative ophthalmology & visual science.

[80]  J. Briers,et al.  Retinal blood-flow visualization by means of laser speckle photography. , 1982, Investigative ophthalmology & visual science.

[81]  W. Goto,et al.  Effects of adenosine on optic nerve head circulation in rabbits. , 2004, Experimental eye research.

[82]  R. Danis,et al.  Retinal blood flow during dynamic exercise , 1996, Graefe's Archive for Clinical and Experimental Ophthalmology.

[83]  B L Petrig,et al.  Blood velocity and volumetric flow rate in human retinal vessels. , 1985, Investigative ophthalmology & visual science.

[84]  L. Schmetterer,et al.  Response of Retinal Blood Flow to CO2-Breathing in Humans , 2002, European journal of ophthalmology.

[85]  A. Alm,et al.  Ocular and optic nerve blood flow at normal and increased intraocular pressures in monkeys (Macaca irus): a study with radioactively labelled microspheres including flow determinations in brain and some other tissues. , 1973, Experimental eye research.

[86]  A. Neufeld,et al.  Nitric oxide synthase-2 in human optic nerve head astrocytes induced by elevated pressure in vitro. , 2001, Archives of ophthalmology.

[87]  J. Lovasik,et al.  Effects of Transient Mild Systemic Hypoxia on the Pulsatile Choroidal Blood Flow in Healthy Young Human Adults , 2005, Current eye research.

[88]  L. Kagemann,et al.  Glaucoma patients demonstrate faulty autoregulation of ocular blood flow during posture change , 1999, The British journal of ophthalmology.

[89]  印牧 信行,et al.  ウサギの眼の微細血管系 : 血管樹脂鋳型標本の走査型電子顕微鏡による観察(実験動物学) , 2008 .

[90]  M. Wolzt,et al.  Endothelin-1 contributes to hyperoxia-induced vasoconstriction in the human retina. , 2000, Investigative ophthalmology & visual science.

[91]  C E Riva,et al.  Blue field entoptic phenomenon and blood velocity in the retinal capillaries. , 1980, Journal of the Optical Society of America.

[92]  M. Wolzt,et al.  Effects of endothelin-1 (ET-1) on ocular hemodynamics. , 1997, Current eye research.

[93]  J. Connell,et al.  Effects of ACTH and Cortisol Administration on Blood Pressure, Electrolyte Metabolism, Atrial Natriuretic Peptide and Renal Function in Normal Man , 1987, Journal of hypertension.

[94]  G Michelson,et al.  Effect of breathing 100% oxygen on retinal and optic nerve head capillary blood flow in smokers and non-smokers , 1997, The British journal of ophthalmology.

[95]  D. Brooks,et al.  Endothelin-1, nitric oxide, and glutamate in the normal and glaucomatous dog eye. , 2007, Veterinary ophthalmology.

[96]  M. Koss,et al.  Sympathetic vasodilation in the rat anterior choroid mediated by beta(1)-adrenoceptors. , 1999, European journal of pharmacology.

[97]  Ronney B Panerai,et al.  Cerebral Autoregulation: From Models to Clinical Applications , 2008, Cardiovascular engineering.

[98]  J. Jonas,et al.  Ocular perfusion pressure and glaucoma: the Beijing Eye Study , 2009, Eye.

[99]  J. Kiel,et al.  Choroidal myogenic autoregulation and intraocular pressure. , 1994, Experimental eye research.

[100]  J Flammer,et al.  Ocular blood flow alteration in glaucoma is related to systemic vascular dysregulation , 2004, British Journal of Ophthalmology.

[101]  T. Yatagai,et al.  Optical coherence angiography. , 2006, Optics express.

[102]  G. Cioffi,et al.  The Effect of Chronic Ischemia on the Primate Optic Nerve , 1999, European journal of ophthalmology.

[103]  R. Weinreb,et al.  Intraocular pressure measurements throughout the 24 h , 2009, Current opinion in ophthalmology.

[104]  A. Reiner,et al.  Control of choroidal blood flow by the nucleus of Edinger-Westphal in pigeons: a laser Doppler study. , 1990, Investigative ophthalmology & visual science.

[105]  M. Koss Adrenoceptor mechanisms in epinephrine-induced anterior choroidal vasoconstriction in cats. , 1994, Experimental eye research.

[106]  O. Mäepea,et al.  Pressures in the anterior ciliary arteries, choroidal veins and choriocapillaris. , 1992, Experimental eye research.

[107]  B. Petrig,et al.  Effect of decreased ocular perfusion pressure on blood flow and the flicker-induced flow response in the cat optic nerve head. , 1996, Microvascular research.

[108]  V. O'brien,et al.  Blood flow in the human eye , 1989, Acta ophthalmologica. Supplement.

[109]  A. Just,et al.  Mechanisms of renal blood flow autoregulation: dynamics and contributions. , 2007, American journal of physiology. Regulatory, integrative and comparative physiology.

[110]  R. Aaslid,et al.  Cerebral autoregulation dynamics in humans. , 1989, Stroke.

[111]  A. Bill,et al.  Vasomotor effects of facial nerve stimulation: noncholinergic vasodilation in the eye. , 1980, Acta physiologica Scandinavica.

[112]  L. Kagemann,et al.  Laser Doppler flowmetry measurement of changes in human optic nerve head blood flow in response to blood gas perturbations. , 1996, Journal of glaucoma.

[113]  G. Chiou,et al.  The potential role of adenosine in regulating blood flow in the eye. , 1988, Journal of ocular pharmacology.

[114]  B Becker,et al.  Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[115]  P. Reinach,et al.  Role of nitric oxide in mediating retinal blood flow regulation in cats. , 1999, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[116]  M. Glucksberg,et al.  Direct measurement of retinal microvascular pressures in the live, anesthetized cat. , 1993, Microvascular research.

[117]  A. P. Shepherd,et al.  Autoregulation of choroidal blood flow in the rabbit. , 1992, Investigative ophthalmology & visual science.

[118]  L. Schmetterer,et al.  RI in central retinal artery as assessed by CDI does not correspond to retinal vascular resistance. , 2001, American journal of physiology. Heart and circulatory physiology.

[119]  L. Kagemann,et al.  Regional differences in retinal vascular reactivity. , 1999, Investigative ophthalmology & visual science.

[120]  M. Koss Analysis of blood flow in the long posterior ciliary artery of the cat. , 1999, Investigative ophthalmology & visual science.

[121]  M. Wolzt,et al.  The effect of inhalation of different mixtures of O2 and CO2 on ocular fundus pulsations. , 1996, Experimental eye research.

[122]  S. Yun,et al.  Twenty-four hour ocular perfusion pressure fluctuation and risk of normal-tension glaucoma progression. , 2009, Investigative ophthalmology & visual science.

[123]  M. Wiederholt,et al.  Endothelin-like immunoreactivity in aqueous humor of patients with primary open-angle glaucoma and cataract , 1997, Graefe's Archive for Clinical and Experimental Ophthalmology.

[124]  B. Petrig,et al.  Retinal blood flow autoregulation in response to an acute increase in blood pressure. , 1986, Investigative ophthalmology & visual science.

[125]  L. Schmetterer,et al.  Assessment of optic disk blood flow in patients with open-angle glaucoma. , 2000, American journal of ophthalmology.

[126]  W. Vilser,et al.  Retinal Vessel Reaction to Short-Term IOP Elevation in Ocular Hypertensive and Glaucoma Patients , 2001, European journal of ophthalmology.

[127]  C. Riva,et al.  Autoregulation of the retinal circulation in response to decrease of intraocular pressure below normal. , 1982, Investigative ophthalmology & visual science.

[128]  Charles E. Riva,et al.  Regulation of retinal blood flow in health and disease , 2008, Progress in Retinal and Eye Research.

[129]  T. Inomata,et al.  Microvascular architecture of the rabbit eye: a scanning electron microscopic study of vascular corrosion casts. , 2008, The Journal of veterinary medical science.

[130]  Leopold Schmetterer,et al.  Use of the retinal vessel analyzer in ocular blood flow research , 2010, Acta ophthalmologica.

[131]  M. Reim,et al.  Video fluorescein angiography: Method and clinical application , 2005, Graefe's Archive for Clinical and Experimental Ophthalmology.

[132]  V. Marks,et al.  Prednisone or prednisolone for the treatment of chronic active hepatitis? A comparison of plasma availability. , 1978, British journal of clinical pharmacology.

[133]  R. Weinreb,et al.  Variation of 24-hour intraocular pressure in healthy individuals: right eye versus left eye. , 2005, Ophthalmology.

[134]  M. Wolzt,et al.  Noninvasive investigations of the normal ocular circulation in humans. , 1998, Investigative ophthalmology & visual science.

[135]  L. Schmetterer,et al.  Regulation of human retinal blood flow by endothelin-1. , 2003, Experimental eye research.

[136]  B. Petrig,et al.  Autoregulation of human retinal blood flow. An investigation with laser Doppler velocimetry. , 1986, Investigative ophthalmology & visual science.

[137]  A. Bill,et al.  Effects of NG‐nitro‐l‐arginine methyl ester on the cardiovascular system of the anaesthetized rabbit and on the cardiovascular response to thyrotropin‐releasing hormone , 1993, British journal of pharmacology.

[138]  P. Kaufman Nitric-oxide synthase and neurodegeneration/neuroprotection. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[139]  J. Gidday,et al.  Adenosine-mediated autoregulation of retinal arteriolar tone in the piglet. , 1993, Investigative Ophthalmology and Visual Science.

[140]  E. Kohner,et al.  Retinal vascular autoregulation in conditions of hyperoxia and hypoxia using the blue field entoptic phenomenon. , 1985, Ophthalmology.

[141]  J Linder,et al.  Sympathetic control of cerebral blood flow in acute arterial hypertension. , 1976, Acta physiologica Scandinavica.

[142]  J. Kiel,et al.  Effects of timolol and betaxolol on choroidal blood flow in the rabbit. , 1998, Experimental eye research.

[143]  S. Roth,et al.  The effects of enflurane on ocular blood flow. , 1994, Journal of ocular pharmacology.

[144]  P. Campochiaro,et al.  Adenosine and its agonists cause retinal vasodilation and hemorrhages. Implications for ischemic retinopathies. , 1989, Archives of ophthalmology.

[145]  C. Delaey,et al.  Pressure-induced myogenic responses in isolated bovine retinal arteries. , 2000, Investigative ophthalmology & visual science.

[146]  M. C. Leske,et al.  Ocular perfusion pressure and glaucoma: clinical trial and epidemiologic findings , 2009, Current opinion in ophthalmology.

[147]  T. Resink,et al.  Vasospasm, its Role in the Pathogenesis of Diseases with Particular Reference to the Eye , 2001, Progress in Retinal and Eye Research.

[148]  L. Schmetterer,et al.  Regulation of choroidal blood flow during combined changes in intraocular pressure and arterial blood pressure. , 2007, Investigative ophthalmology & visual science.

[149]  J. T. O'neill,et al.  Nitric oxide modulation of retinal, choroidal, and anterior uveal blood flow in newborn piglets. , 1998, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[150]  P. Fasching,et al.  Renal and Ocular Hemodynamic Effects of Insulin , 1997, Diabetes.

[151]  R. Tripathi,et al.  Degenerative Changes in a Soft Hydrophilic Contact Lens , 1972 .

[152]  D. Lu,et al.  Effect of Sympathetic Denervation on Rabbit Choroidal Blood Flow , 2002, Ophthalmologica.

[153]  L. Schmetterer,et al.  Diurnal fluctuation of ocular blood flow parameters in patients with primary open-angle glaucoma and healthy subjects , 2008, British Journal of Ophthalmology.

[154]  M. Wolzt,et al.  Effects of losartan on cerebral and ocular circulation in healthy subjects. , 2003, British journal of clinical pharmacology.

[155]  M. F. Armaly,et al.  Effect of ocular pressure on choroidal circulation in the cat and Rhesus monkey. , 1975, Investigative ophthalmology.

[156]  B. Petrig,et al.  Effects of adenosine on ocular blood flow. , 1995, Investigative ophthalmology & visual science.

[157]  J. Kiel,et al.  Effects of nitric oxide synthase inhibition on ciliary blood flow, aqueous production and intraocular pressure. , 2001, Experimental eye research.

[158]  B. Chauhan Endothelin and its potential role in glaucoma. , 2008, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.

[159]  Leopold Schmetterer,et al.  Comparison of the autoregulatory mechanisms between middle cerebral artery and ophthalmic artery after thigh cuff deflation in healthy subjects. , 2005, Investigative ophthalmology & visual science.

[160]  A. Bill Studies of the heated thermocouple principle for determinations of blood flow in tissues. , 1962, Acta physiologica Scandinavica.

[161]  J. Kiel,et al.  Adrenergic modulation of choroidal blood flow in the rabbit. , 1996, Investigative ophthalmology & visual science.

[162]  H. Kergoat,et al.  Effects of oxygen and carbogen breathing on choroidal hemodynamics in humans. , 1999, Investigative ophthalmology & visual science.

[163]  D. Buerk,et al.  Vasomotion and spontaneous low-frequency oscillations in blood flow and nitric oxide in cat optic nerve head. , 1998, Microvascular research.

[164]  A. Neufeld,et al.  Nitric oxide synthase in the human glaucomatous optic nerve head. , 1997, Archives of ophthalmology.

[165]  R N Weinreb Assessment of the optic nerve and nerve fiber layer in glaucoma. , 1993, Journal of glaucoma.

[166]  M. Olufsen,et al.  Dynamics of cerebral blood flow regulation explained using a lumped parameter model. , 2002, American journal of physiology. Regulatory, integrative and comparative physiology.

[167]  Jaewan Choi,et al.  Circadian fluctuation of mean ocular perfusion pressure is a consistent risk factor for normal-tension glaucoma. , 2007, Investigative ophthalmology & visual science.

[168]  M. Wolzt,et al.  Role of endothelin-1 in choroidal blood flow regulation during isometric exercise in healthy humans. , 2002, Investigative ophthalmology & visual science.

[169]  L. Kagemann,et al.  Ocular blood flow measurements and their importance in glaucoma and age-related macular degeneration. , 2001, The Israel Medical Association journal : IMAJ.

[170]  J. Flammer,et al.  Systemic blood pressure in glaucoma patients , 1993, Graefe's Archive for Clinical and Experimental Ophthalmology.

[171]  R. Weinreb,et al.  Correlation between office and peak nocturnal intraocular pressures in healthy subjects and glaucoma patients. , 2005, American journal of ophthalmology.

[172]  T. Lüscher,et al.  Local action of the renin angiotensin system in the porcine ophthalmic circulation: effects of ACE-inhibitors and angiotensin receptor antagonists. , 1995, Investigative ophthalmology & visual science.

[173]  M. C. Leske,et al.  Fluctuation of intraocular pressure and glaucoma progression in the early manifest glaucoma trial. , 2007, Ophthalmology.

[174]  R. Klein,et al.  The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER. , 2001, Archives of ophthalmology.

[175]  M. Koss,et al.  Sympathetic vasoconstriction in the rat anterior choroid is mediated by alpha1-adrenoceptors. , 1998, European journal of pharmacology.

[176]  T. Bek,et al.  Myogenic response in isolated porcine retinal arterioles , 2003, Current eye research.

[177]  A. Hamilton,et al.  The technique and indications for photocoagulation in diabetic retinopathy I. Principles of photocoagulation , 1978, International Ophthalmology.

[178]  Leopold Schmetterer,et al.  Twelve‐hour reproducibility of retinal and optic nerve blood flow parameters in healthy individuals , 2009, Acta ophthalmologica.

[179]  M. Wolzt,et al.  Reproducibility and sensitivity of scanning laser Doppler flowmetry during graded changes in Po 2 , 1997, The British journal of ophthalmology.

[180]  Josef Flammer,et al.  What is the link between vascular dysregulation and glaucoma? , 2007, Survey of ophthalmology.

[181]  Kuldev Singh,et al.  Intraocular pressure fluctuations: how much do they matter? , 2009, Current opinion in ophthalmology.

[182]  A. Harris,et al.  Effects of Exercise on Intraocular Pressure and Ocular Blood Flow: A Review , 2009, Journal of glaucoma.

[183]  A. Fercher,et al.  The effect of hyperoxia and hypercapnia on fundus pulsations in the macular and optic disc region in healthy young men. , 1995, Experimental eye research.

[184]  M. Iester,et al.  Retinal Blood Flow Autoregulation after Dynamic Exercise in Healthy Young Subjects , 2007, Ophthalmologica.

[185]  L. Schmetterer,et al.  Ocular hemodynamics during isometric exercise. , 2001, Microvascular research.

[186]  B. Folkow,et al.  A comparison between “red” and “white” muscle with respect to blood supply, capillary surface area and oxygen uptake during rest and exercise , 1968 .

[187]  D. R. Bacon,et al.  An Endothelin‐1‐Induced Model of Chronic Optic Nerve Ischemia in Rhesus Monkeys , 1996, Journal of glaucoma.

[188]  J. Kiel,et al.  Modulation of choroidal autoregulation in the rabbit. , 1999, Experimental eye research.

[189]  Jaewan Choi,et al.  Effect of nocturnal blood pressure reduction on circadian fluctuation of mean ocular perfusion pressure: a risk factor for normal tension glaucoma. , 2006, Investigative ophthalmology & visual science.

[190]  M. Polokoff,et al.  Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. , 1994, Pharmacological reviews.

[191]  A. Bill Quantitative determination of uveal blood flow in rabbits. , 1962, Acta physiologica Scandinavica.

[192]  E. Lütjen-Drecoll Choroidal innervation in primate eyes. , 2006, Experimental eye research.

[193]  K. Kashiwagi,et al.  Association between Nocturnal Blood Pressure Reduction and Progression of Visual Field Defect in Patients with Primary Open-Angle Glaucoma or Normal-Tension Glaucoma , 2004, Japanese Journal of Ophthalmology.

[194]  E. Stefánsson,et al.  The impact of ocular blood flow in glaucoma , 2002, Progress in Retinal and Eye Research.

[195]  M. C. Leske,et al.  Risk factors for incident open-angle glaucoma: the Barbados Eye Studies. , 2008, Ophthalmology.

[196]  W. Lieb Color Doppler ultrasonography of the eye and orbit. , 1993, Current opinion in ophthalmology.

[197]  S. Orgül,et al.  Relationship between ocular perfusion pressure and retrobulbar blood flow in patients with glaucoma with progressive damage. , 2000, American journal of ophthalmology.

[198]  B L Petrig,et al.  Laser Doppler flowmetry in the optic nerve. , 1992, Experimental eye research.

[199]  A. Remky,et al.  Prolonged retinal arteriovenous passage time is correlated to ocular perfusion pressure in normal tension glaucoma , 2008, Graefe's Archive for Clinical and Experimental Ophthalmology.

[200]  Ophthalmol Soc,et al.  ISCHEMIC MODEL OF OPTIC NERVE INJURY , 2005 .

[201]  Grant Cull,et al.  Microspheres method for ocular blood flow measurement in rats: size and dose optimization. , 2007, Experimental eye research.

[202]  H. Tran,et al.  Blood pressure and blood flow variation during postural change from sitting to standing: model development and validation. , 2005, Journal of applied physiology.

[203]  L. Schmetterer,et al.  Effect of dorzolamide and timolol on ocular pressure: blood flow relationship in patients with primary open-angle glaucoma and ocular hypertension. , 2010, Investigative ophthalmology & visual science.

[204]  J. Staessen,et al.  Night–day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension , 2009, Journal of Human Hypertension.

[205]  W Drexler,et al.  Ultrahigh resolution Fourier domain optical coherence tomography. , 2004, Optics express.

[206]  L. Schmetterer,et al.  Role of Nitric Oxide in the Control of Ocular Blood Flow , 2001, Progress in Retinal and Eye Research.

[207]  B. Petrig,et al.  Blood flow in the human optic nerve head during isometric exercise. , 1998, Experimental eye research.

[208]  W. Ulrich,et al.  Oculo-oscillo-dynamography: a diagnostic procedure for recording ocular pulses and measuring retinal and ciliary arterial blood pressures. , 1985, Ophthalmic research.

[209]  Tetsuya Sugiyama,et al.  Evidence that nitric oxide is involved in autoregulation in optic nerve head of rabbits. , 2002, Investigative ophthalmology & visual science.

[210]  M. Mulvany,et al.  The myogenic response: established facts and attractive hypotheses. , 1999, Clinical science.

[211]  R. Linsenmeier,et al.  Oxygen distribution and consumption in the cat retina at increased intraocular pressure. , 1989, Investigative ophthalmology & visual science.

[212]  S. Wu,et al.  Adler's Physiology of the Eye , 2002 .

[213]  T. Oshika,et al.  Postural Response of Intraocular Pressure and Visual Field Damage in Patients With Untreated Normal-tension Glaucoma , 2010, Journal of glaucoma.

[214]  L. Schmetterer,et al.  Effect of endothelin and BQ123 on ocular blood flow parameters in healthy subjects. , 2001, Investigative ophthalmology & visual science.

[215]  M. Wolzt,et al.  Effect of dual endothelin receptor blockade on ocular blood flow in patients with glaucoma and healthy subjects , 2008, BMC Pharmacology.

[216]  L. Schmetterer,et al.  Altered nitric oxide system in patients with open-angle glaucoma. , 2007, Archives of ophthalmology.

[217]  A. Alm,et al.  The oxygen supply to the retina. I. Effects of changes in intraocular and arterial blood pressures, and in arterial P O2 and P CO2 on the oxygen tension in the vitreous body of the cat. , 1972, Acta physiologica Scandinavica.

[218]  C. Riva Basic principles of laser Doppler flowmetry and application to the ocular circulation , 2004, International Ophthalmology.

[219]  J. Flanagan,et al.  Retinal arteriolar and capillary vascular reactivity in response to isoxic hypercapnia. , 2008, Experimental eye research.

[220]  Leopold Schmetterer,et al.  A comparison between laser interferometric measurement of fundus pulsation and pneumotonometric measurement of pulsatile ocular blood flow 1. Baseline considerations , 2000, Eye.

[221]  W. Dewé,et al.  Ambulatory blood pressure monitoring in glaucoma patients. The nocturnal systolic dip and its relationship with disease progression , 2004, International Ophthalmology.

[222]  M. Dashwood,et al.  Endothelinrole in vascular disease , 2008 .

[223]  H. Hara,et al.  Intravitreal injection of endothelin-1 caused optic nerve damage following to ocular hypoperfusion in rabbits. , 2006, Experimental eye research.

[224]  M. Wolzt,et al.  Role of NO in the O2 and CO2 responsiveness of cerebral and ocular circulation in humans. , 1997, American journal of physiology. Regulatory, integrative and comparative physiology.

[225]  A. H. van den Meiracker,et al.  Causes and consequences of a non-dipping blood pressure profile. , 2007, The Netherlands journal of medicine.

[226]  B. Petrig,et al.  Retinal autoregulation in open-angle glaucoma. , 1984, Ophthalmology.

[227]  J. Provis Development of the Primate Retinal Vasculature , 2001, Progress in Retinal and Eye Research.

[228]  L. Schmetterer,et al.  Effects of Atropine and Propranolol on Retinal Vessel Diameters during Isometric Exercise , 2001, Ophthalmic Research.

[229]  B L Petrig,et al.  Laser Doppler flowmetry and optic nerve head blood flow. , 1999, American journal of ophthalmology.

[230]  P. Smith,et al.  Regional regulation of choroidal blood flow by autonomic innervation in the rat. , 2000, American journal of physiology. Regulatory, integrative and comparative physiology.

[231]  M. Blum,et al.  Noninvasive measurement of the Bayliss effect in retinal autoregulation , 1999, Graefe's Archive for Clinical and Experimental Ophthalmology.

[232]  M. J. Davis,et al.  Signaling mechanisms underlying the vascular myogenic response. , 1999, Physiological reviews.

[233]  L. Schmetterer,et al.  Effects of adenosine on intraocular pressure, optic nerve head blood flow, and choroidal blood flow in healthy humans. , 2003, Investigative ophthalmology & visual science.

[234]  C E Riva,et al.  Laser Doppler Velocimetry study of the effect of pure oxygen breathing on retinal blood flow. , 1983, Investigative ophthalmology & visual science.

[235]  D. Kripke,et al.  Twenty-four-hour intraocular pressure pattern associated with early glaucomatous changes. , 2003, Investigative ophthalmology & visual science.

[236]  S. Roth The effects of halothane on retinal and choroidal blood flow in cats. , 1992, Anesthesiology.

[237]  M. Wolzt,et al.  Role of NO in choroidal blood flow regulation during isometric exercise in healthy humans. , 2003, Investigative ophthalmology & visual science.

[238]  M. Wolzt,et al.  Vasodilator effects of L-arginine are stereospecific and augmented by insulin in humans. , 2003, American journal of physiology. Endocrinology and metabolism.

[239]  L. Stone RETURN OF VISION IN LARVAL EYES EXCHANGED BETWEEN AMBLYSTOMA PUNCTATUM AND THE CAVE SALAMANDER, TRYPHLOTRITON SPELAEUS. , 1964, Investigative ophthalmology.

[240]  R. Grinker TUMORS OF THE OPTIC NERVE , 1930 .

[241]  L. Schmetterer,et al.  Microcirculation of the Ocular Fundus , 2011 .

[242]  Leopold Schmetterer,et al.  A comparison between laser interferometric measurement of fundus pulsation and pneumotonometric measurement of pulsatile ocular blood flow 2. Effects of changes in pCO2 and pO2 and of isoproterenol , 2000, Eye.

[243]  L. Schmetterer,et al.  Nitric oxide regulates retinal vascular tone in humans. , 2003, American journal of physiology. Heart and circulatory physiology.

[244]  T. Bek,et al.  Increased blood pressure induces a diameter response of retinal arterioles that increases with decreasing arteriolar diameter. , 2007, Investigative ophthalmology & visual science.

[245]  B. Petrig,et al.  Choroidal blood flow during exercise-induced changes in the ocular perfusion pressure. , 2003, Investigative ophthalmology & visual science.

[246]  Lin Wang,et al.  Chronic ischemia induces regional axonal damage in experimental primate optic neuropathy. , 2004, Archives of ophthalmology.

[247]  T. Malmfors The adrenergic innervation of the eye as demonstrated by fluorescence microscopy. , 1965, Acta physiologica Scandinavica.

[248]  J. Lovasik,et al.  Response of Parapapillary retinal Vessels to Exercise , 1995, Optometry and vision science : official publication of the American Academy of Optometry.

[249]  L. Pasquale,et al.  Retinal blood flow response to posture change in glaucoma patients compared with healthy subjects. , 2008, Ophthalmology.

[250]  G. Marchini,et al.  Vascular risk factors for primary open angle glaucoma: the Egna-Neumarkt Study. , 2000, Ophthalmology.

[251]  Dao-Yi Yu,et al.  Model of endothelin-1-induced chronic optic neuropathy in rat. , 2004, Investigative ophthalmology & visual science.

[252]  T. Yorio,et al.  Effects of endothelin-1 on components of anterograde axonal transport in optic nerve. , 2002, Investigative ophthalmology & visual science.

[253]  J. Flanagan,et al.  Relative change in diurnal mean ocular perfusion pressure: a risk factor for the diagnosis of primary open-angle glaucoma. , 2005, Investigative ophthalmology & visual science.

[254]  A. Fercher,et al.  The effect of systemic nitric oxide-synthase inhibition on ocular fundus pulsations in man. , 1997, Experimental eye research.

[255]  T. K. Goldstick,et al.  Retinal tissue oxygen tension in normoxic cats under enflurane anesthesia. , 1995, Investigative ophthalmology & visual science.

[256]  J. Kim,et al.  Expression of neuronal nitric oxide synthase in the retina of a rat model of chronic glaucoma , 2007, Vision Research.

[257]  D. R. Anderson,et al.  Effect of elevated intraocular pressure on blood flow. Occurrence in cat optic nerve head studied with iodoantipyrine I 125. , 1983, Archives of ophthalmology.

[258]  Lin Wang,et al.  Quantification of dynamic blood flow autoregulation in optic nerve head of rhesus monkeys. , 2010, Experimental eye research.

[259]  L. Schmetterer,et al.  Response of choroidal blood flow in the foveal region to hyperoxia and hyperoxia-hypercapnia. , 2000, Current eye research.

[260]  L. Schmetterer,et al.  ETa-receptor blockade, but not ACE inhibition, blunts retinal vessel response during isometric exercise. , 2006, American journal of physiology. Heart and circulatory physiology.

[261]  T. Inomata,et al.  Microvasculature of the hamster eye: scanning electron microscopy of vascular corrosion casts. , 2001, Veterinary ophthalmology.

[262]  M. Wolzt,et al.  Retinal blood flow during hyperoxia in humans revisited: concerted results using different measurement techniques. , 2002, Microvascular research.

[263]  P. Hoyng,et al.  Increase in ocular blood flow induced by isobutylmethylxanthine and epinephrine. , 1991, Experimental eye research.

[264]  M. Araie,et al.  Non-contact, two-dimensional measurement of tissue circulation in choroid and optic nerve head using laser speckle phenomenon. , 1995, Experimental eye research.

[265]  T. Sugiyama,et al.  Experimental optic cup enlargement caused by endothelin-1-induced chronic optic nerve head ischemia. , 1999, Survey of ophthalmology.

[266]  W. Sponsel,et al.  Retinal hemodynamic effects of carbon dioxide, hyperoxia, and mild hypoxia. , 1992, Investigative ophthalmology & visual science.

[267]  W. Vilser,et al.  Autoregulative behavior of retinal arteries and veins during changes of perfusion pressure: a clinical study , 2004, Graefe's Archive for Clinical and Experimental Ophthalmology.

[268]  Paul P. Lee,et al.  Understanding the importance of IOP variables in glaucoma: a systematic review. , 2009, Survey of ophthalmology.

[269]  P Schilder,et al.  Estimation of pulsatile ocular blood flow from intraocular pressure , 1989, Acta ophthalmologica. Supplement.

[270]  Angus M'Gillivray,et al.  The Ocular Circulation , 1904, Edinburgh Medical Journal.

[271]  D. Hill,et al.  Postural changes in perfusion pressure and retinal arteriolar calibre. , 1988, The British journal of ophthalmology.

[272]  B L Petrig,et al.  Choroidal blood flow in the foveal region of the human ocular fundus. , 1994, Investigative ophthalmology & visual science.

[273]  L. Schmetterer,et al.  Role of NO in the control of choroidal blood flow during a decrease in ocular perfusion pressure. , 2009, Investigative ophthalmology & visual science.

[274]  R. Stone,et al.  Nitric oxide and choroidal blood flow regulation. , 1995, Investigative ophthalmology & visual science.

[275]  L. Schmetterer,et al.  Response of choroidal blood flow to carbogen breathing in smokers and non-smokers , 2004, British Journal of Ophthalmology.

[276]  A. Reiner,et al.  Role of muscarinic cholinergic transmission in Edinger-Westphal nucleus-induced choroidal vasodilation in pigeon. , 2000, Experimental eye research.

[277]  C. E. Ferree,et al.  REFRACTION FOR THE PERIPHERAL FIELD OF VISION , 1931 .

[278]  K. Sung,et al.  Twenty-Four Hour Blood Pressure Pattern in Patients With Normal Tension Glaucoma in the Habitual Position , 2009, Korean journal of ophthalmology : KJO.