Abstract
Much of our basic knowledge of retinal blood flow regulation is based on data obtained from animal experiments through the use of invasive techniques. However, during the last decades, major developments in the field of optics and lasers have led to a variety of noninvasive techniques, which have been applied to the human eye for the investigation of retinal hemodynamics, and more specifically the regulation of retinal blood flow in response to a number of physiological and pharmacological stimuli. The Retinal Vessel Analyzer has markedly simplified the measurement of the diameter of retinal vessels, as well as the change in this diameter evoked by various physiological stimuli (dynamic measurements). Bidirectional laser Doppler velocimetry allows the measurement of absolute red blood cell centerline velocity, which, when combined with the diameter allows the calculation of retinal blood flow in the main retinal vessels. Laser Doppler flowmetry and laser speckle flowgraphy are techniques that measure the velocities of blood in discrete areas of the retinal tissue microcirculation. Adding a scanning capability, a spatial map of velocities across the retinal tissue is obtained. The blue-field simulation technique allows the quantification of the velocity, number and velocity pulsatility of leukocytes moving in the retinal capillaries of the macular region. With color Doppler imaging, the peak systolic and end-diastolic values of blood velocity in the ophthalmic and central retinal artery are measured, from which a resistivity index is obtained. These techniques may help better understand the role of altered retinal blood flow and its regulation in the pathogenesis of retinal diseases of vascular origin.
References
1.
Hickam JB, Frayser R: Studies of the retinal circulation in man: observation on vessel diameter, arteriovenous oxygen difference and mean circulation time. Circulation 1966;33:302–316.
2.
Murray CD: The physiological principle of minimum work. I. The vascular system and the cost of blood volume. Proc Natl Acad Sci USA 1926;12:207–214.
3.
LaBarbera M: The design of fluid transport systems: a comparative perspective; in Bevan JA, Kaley G, Rubanyi GM (eds): Flow-Dependent Regulation of Vascular Function. New York, Oxford University Press, 1995.
4.
Glucksberg MR, Dunn R: Direct measurement of retinal microvascular pressures in the live, anesthetized cat. Microvasc Res 1993;45:158–165.
5.
Stoltz JF, Donner M: New trends in clinical hemorheology: an introduction to the concept of the hemorheological profile. Schweiz Med Wochenschr Suppl 1991;43:41–49.
6.
Knabben HWS, Remky A, Schulte K, Arend O, Reim M: Retinal hemodynamics in patients with hyperviscosity syndrome. Klin Monatsbl Augenheilkd 1995;206:152–156.
7.
Delori FC, Fitch KA, Feke GT, Deupree DM, Weiter JJ: Evaluation of micrometric and microdensitometric methods for measuring the width of retinal vessel images on fundus photographs. Graefes Arch Clin Exp Ophthalmol 1988;226:393–399.
8.
Rassam SM, Patel V, Brinchmann-Hansen O, Engvold O, Kohner EM: Accurate vessel width measurement from fundus photographs: a new concept. Br J Ophthalmol 1994;78:24–29.
9.
Nagel E, Munch K, Vilser W: Measurement of the diameter of segments of retinal branch vessels in digital fundus images: an experimental study of the method and reproducibility. Klin Monatsbl Augenheilkd 2001;218:616–620.
10.
Pache M, Nagel E, Flammer J: Reproducibility of measurements with the retinal vessel analyzer under optimal conditions. Klin Monatsbl Augenheilkd 2002;219:523–527.
11.
Polak K, Dorner G, Kiss B, Polska E, Findl O, Rainer G, Eichler HG, Schmetterer L: Evaluation of the Zeiss retinal vessel analyser. Br J Ophthalmol 2000;84:1285–1290.
12.
Seifertl BU, Vilser W: Retinal Vessel Analyzer (RVA) – design and function. Biomed Tech (Berl) 2002;47(suppl 1):678–681.
13.
Formaz F, Riva CE, Geiser MH: Diffuse luminance flicker increases retinal vessel diameter in humans. Curr Eye Res 1997;16:1252–1257.
14.
Polak K, Schmetterer L, Riva CE: Influence of flicker frequency on flicker-induced changes of retinal vessel diameter. Invest Ophthalmol Vis Sci 2002;43:2721–2726.
15.
Riva CE, Logean E, Falsini B: Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina. Prog Retin Eye Res 2005;24:183–215.
16.
Wong TY, Mitchell P: The eye in hypertension. Lancet 2007;369:425–435.
17.
Wong TY, Klein R, Couper DJ, Cooper LS, Shahar E, Hubbard LD, Wofford MR, Sharrett AR: Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study. Lancet 2001;358:1134–1140.
18.
Wong TY, Klein R, Sharrett AR, Duncan BB, Couper DJ, Tielsch JM, Klein BE, Hubbard LD: Retinal arteriolar narrowing and risk of coronary heart disease in men and women. The Atherosclerosis Risk in Communities Study. JAMA 2002;287:1153–1159.
19.
Wang JJ, Liew G, Klein R, Rochtchina E, Knudtson MD, Klein BE, Wong TY, Burlutsky G, Mitchell P: Retinal vessel diameter and cardiovascular mortality: pooled data analysis from two older populations. Eur Heart J 2007;28:1984–1992.
20.
Mendrinos E, Mangioris G, Papadopoulou DN, Dosso AA, Pournaras CJ: Retinal vessel analyzer measurements of the effect of panretinal photocoagulation on the retinal arteriolar diameter in diabetic retinopathy. Retina 2010;30:555–561.
21.
Meier P, Zierler KL: On the theory of the indicator-dilution method for measurement of blood flow and volume. J Appl Physiol 1954;6:731–744.
22.
Gonzalez-Fernandez JM: Theory of the measurement of the dispersion of an indicator in indicator-dilution studies. Circ Res 1962;10:409–428.
23.
Riva CE, Feke GT, Ben-Sira I: Fluorescein dye-dilution technique and retinal circulation. Am J Physiol 1978;234:H315–H322.
24.
Riva CE, Alm A, Pournaras CJ: Ocular circulation; in Levin LA, Nilsson SFE, Ver- Hoeve J, Wu S, Kaufman PL, Alm A (eds): Adler’s Physiology of the Eye, ed 11. New York, Elsevier, 2011.
25.
Wolf S, Jung F, Kiesewetter H, Korber N, Reim M: Video fluorescein angiography: method and clinical application. Graefes Arch Clin Exp Ophthalmol 1989;227:145–151.
26.
Tomic L, Maepea O, Sperber GO, Alm A: Comparison of retinal transit times and retinal blood flow: a study in monkeys. Invest Ophthalmol Vis Sci 2001;42:752–755.
27.
Sperber GO, Alm A: Retinal mean transit time determined with an impulse-response analysis form video fluorescein angiograms. Acta Ophthalmol Scand 1997;75:532–536.
28.
Nishiwaki H, Ogura Y, Kimura H, Kiryu J, Honda Y: Quantitative evaluation of leukocyte dynamics in retinal microcirculation. Invest Ophthalmol Vis Sci 1995;36:123–130.
29.
Matsuda N, Ogura Y, Nishiwaki H, Miyamoto K, Matsubara T, Kiryu J, Honda Y: Visualization of leukocyte dynamics in the choroid with indocyanine green. Invest Ophthalmol Vis Sci 1996;37:2228–2233.
30.
Le Gargasson JF, Paques M, Guez JE, Boval B, Vicaut E, Hou X, Grall Y, Gaudric A: Scanning laser ophthalmoscope imaging of fluorescein-labelled blood cells. Graefes Arch Clin Exp Ophthalmol 1997;235:56–58.
31.
Yang Y, Kim S, Kim J: Fluorescent dots in fluorescein angiography and fluorescein leukocyte angiography using a scanning laser ophthalmoscope in humans. Ophthalmology 1997;104:1670–1676.
32.
Hossain P, Liversidge J, Cree MJ, Manivannan A, Vieira P, Sharp PF, Brown GC, Forrester JV: In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics. Invest Ophthalmol Vis Sci 1998;39:1879–1887.
33.
Riva CE, Petrig B: Blue field entoptic phenomenon and blood velocity in the retinal capillaries. J Opt Soc Am 1980;70:1234–1238.
34.
Riva CE, Petrig BL: Retinal blood flow: laser Doppler velocimetry and blue field simulation technique; in Masters BR (ed): Noninvasive Diagnostic Techniques in Ophthalmology. New York, Springer, 1990, pp 390–409.
35.
Fallon TJ, Maxwell D, Kohner EM: Measurement of autoregulation of retinal blood flow using the blue field entoptic phenomenon. Trans Ophthalmol Soc UK 1985;104:857–860.
36.
Robinson F, Petrig BL, Sinclair SH, Riva CE, Grunwald JE: Does topical phenylephrine, tropicamide, or proparacaine affect macular blood flow? Ophthalmology 1985;92:1130–1132.
37.
Lofti K, Grunwald JE: The effect of caffeine on the human macular circulation. Invest Ophthalmol Vis Sci 1991;32:3028–3032.
38.
Fuchsjager-Mayrl G, Malec M, Polska E, Jilma B, Wolzt M, Schmetterer L: Effects of granulocyte colony stimulating factor on retinal leukocyte and erythrocyte flux in the human retina. Invest Ophthalmol Vis Sci 2002;43:1520–1524.
39.
Loukovaara S, Harju M, Kaaja R, Immonen I: Retinal capillary blood flow in diabetic and nondiabetic women during pregnancy and postpartum period. Invest Ophthalmol Vis Sci 2003;44:1486–1491.
40.
Loebl M, Riva CE: Macular circulation and the flying corpuscles phenomenon. Ophthalmology 1978;85:911–917.
41.
Martin JA, Roorda A: Direct and noninvasive assessment of parafoveal capillary leukocyte velocity. Ophthalmology 2005;112:2219–2224.
42.
Riva CE, Petrig BL: Laser Doppler techniques in ophthalmology: principles and applications; in Fankhauser F, Kwasniewska S (eds): Lasers in Ophthalmology – Basic, Diagnostic and Surgical Aspects. The Hague, Kugler 2003, pp 51–59.
43.
Riva CE, Grunwald JE, Sinclair SH, O’Keefe K: Fundus camera based retinal LDV. Appl Opt 1981;20:117–120.
44.
Riva CE, Feke GT, Eberli B, Benary V: Bidirectional LDV system for absolute measurement of blood speed in retinal vessels. Appl Opt 1979;18:2301–2306.
45.
Yazdanfar S, Rollins AM, Izatt JA: Imaging and velocimetry of the human retinal circulation with color Doppler optical coherence tomography. Opt Lett 2000;25:1448–1450.
46.
Leitgeb RA, Schmetterer L, Drexler W, Fercher AF: Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography. Opt Express 2003;11:3116–3121.
47.
Logean E, Schmetterer L, Riva CE: Velocity profile of red blood cells in human retinal vessels using confocal scanning laser Doppler velocimetry. Laser Physics 2003;13:45–51.
48.
Yazdanfar S, Rollins AM, Izatt JA: In vivo imaging of human retinal flow dynamics by color Doppler optical coherence tomography. Arch Ophthalmol 2003;121:235–239.
49.
Zhong Z, Song H, Chui TY, Petrig BL, Burns SA: Noninvasive measurements and analysis of blood velocity profiles in human retinal vessels. Invest Ophthalmol Vis Sci 2011;52:4151–4157.
50.
Riva CE, Grunwald JE, Sinclair SH, Petrig BL: Blood velocity and volumetric flow rate in human retinal vessels. Invest Ophthalmol Vis Sci 1985;26:1124–1132.
51.
Feke GT, Goger DG, Tagawa H, Delori FC: Laser Doppler technique for absolute measurement of blood speed in retinal vessels. IEEE Trans Biomed Eng 1987;34:673–680.
52.
Grunwald JE, Riva CE, Baine J, Brucker AJ: Total retinal volumetric blood flow rate in diabetic patients with poor glycemic control. Invest Ophthalmol Vis Sci 1992;33:356–363.
53.
Khoobehi B, Peyman GA, Niesman MR, Oncel M: Measurement of retinal blood velocity and flow rate in primates using a liposome dye system. Ophthalmology 1989;96:905–912.
54.
Guran T, Zeimer RC, Shahidi M, Mori MT: Quantitative analysis of retinal hemodynamics using targeted dye delivery. Invest Ophthalmol Vis Sci 1990;31:2300–2306.
55.
Alm A: Ocular circulation; in Hart W (ed): Adler’s Physiology of the Eye. St Louis, Mosby-Year Book, 1992, pp 198–227.
56.
Wang Y, Lu A, Gil-Flamer J, Tan O, Izatt JA, Huang D: Measurement of total blood flow in the normal human retina using Doppler Fourier-domain optical coherence tomography. Br J Ophthalmol 2009;93:634–637.
57.
Feke GT, Tagawa H, Deupree DM, Goger DG, Sebag J, Weiter JJ: Blood flow in the normal human retina. Invest Ophthalmol Vis Sci 1989;30:58–65.
58.
Rassam SM, Patel V, Chen HC, Kohner EM: Regional retinal blood flow and vascular autoregulation. Eye 1996;10:331–337.
59.
Garcia JPS Jr, Garcia PT, Rosen RB: Retinal blood flow in the normal human eye using the canon laser blood flowmeter. Ophthalmic Res 2002;34:295–299.
60.
Kimura I, Shinoda K, Tanino T, Ohtake Y, Mashima Y, Oguchi Y: Scanning laser Doppler flowmeter study of retinal blood flow in macular area of healthy volunteers. Br J Ophthalmol 2003;87:1469–1473.
61.
Dorner GT, Garhoefer G, Zawinka C, Kiss B, Schmetterer L: Response of retinal blood flow to CO2-breathing in humans. Eur J Ophthalmol 2002;12:459–466.
62.
Wang Y, Bower BA, Izatt JA, Tan O, Huang D: Retinal blood flow measurement by circumpapillary Fourier domain Doppler optical coherence tomography. J Biomed Opt 2008;13:064003.
63.
Yoshida A, Feke GT, Ogasawara H, Goger DG, McMeel JW: Retinal hemodynamics in middle-aged normal subjects. Ophthalmic Res 1996;28:343–350.
64.
O’Day DM, Fish MB, Aronson SB, Pollycove M, Coon A: Ocular blood flow measurement by nuclide labeled microspheres. Arch Ophthalmol 1971;86:205–209.
65.
Alm A, Bill A: 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. Exp Eye Res 1973;15:15–29.
66.
Yoshida A, Feke GT, Mori F, Nagaoka T, Fujio N, Ogasawara H, Konno S, McMell JW: Reproducibility and clinical application of a newly developed stabilized retinal laser Doppler instrument. Am J Ophthalmol 2003;135:356–361.
67.
Deng Y, Wang M, Duan J: The modality of huoxue-huayu in treatment of retinal vein occlusion. Yen Ko Hsueh Pao 1995;11:57–60.
68.
Izatt JA, Kulkarni MD, Yazdanfar S, Barton JK, Welch AJ: In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography. Opt Lett 1997;22:1439–1441.
69.
White B, Pierce M, Nassif N, Cense B, Park B, Tearney G, Bouma B, Chen T, de Boer J: In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography. Opt Express 2003;11:3490–3497.
70.
Leitgeb RA, Schmetterer L, Hitzenberger CK, Fercher AF: Real-time measurement of in vitro flow by Fourier-domain color Doppler optical coherence tomography. Opt Lett 2004;2:171–173.
71.
Wang Y, Bower BA, Izatt JA, Tan O, Huang D: In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography. J Biomed Opt 2007;12:041215.
72.
Makita S, Fabritius T, Yasuno Y: Quantitative retinal-blood flow measurement with three-dimensional vessel geometry determination using ultrahigh-resolution Doppler optical coherence angiography. Opt Lett 2008;33:836–838.
73.
Riva CE, Harino S, Petrig BL, Shonat RD: Laser Doppler flowmetry in the optic nerve. Exp Eye Res 1992;55:499–506.
74.
Bonner R, Nossal R: Model for laser Doppler measurements of blood flow in tissue. Appl Opt 1981;20:2097–2107.
75.
Michelson G, Schmauss B, Langhans MJ, Harazny J, Groh MJM: Principle, validity, and reliability of scanning laser Doppler flowmetry. J Glaucoma 1996;5:99–105.
76.
Fercher AF, Briers JD: Flow visualization by means of single-exposure speckle photography. Opt Commun 1981;37:326–330.
77.
Briers JD, Fercher AF: Retinal blood-flow visualization by means of laser speckle photography. Invest Ophthalmol Vis Sci 1982;22:255–259.
78.
Tamaki Y, Araie M, Kawamoto E, Eguchi S, Fujii H: Non-contact, two-dimensional measurement of microcirculation in choroid and optic nerve using laser speckle phenomenon. Exp Eye Res 1995;60:373–384.
79.
Zinser G: Scanning laser Doppler flowmetry; in Pillunat LEH, Anderson A, Greve DR (eds): Current Concepts on Ocular Blood Flow in Glaucoma. The Hague, Kugler, 1999, pp 197–204.
80.
Petrig BL, Riva CE, Hayreh SS: Laser Doppler flowmetry and optic nerve head blood flow. Am J Ophthalmol 1999;127:413–425.
81.
Riva CE: Basic principles of laser Doppler flowmetry and application to the ocular circulation. Int Ophthalmol 2001;23:183–189.
82.
Harris A, Shoemaker JA, Cioffi GA: Assessment of human ocular hemodynamics. Surv Ophthalmol 1998;42:509–533.
83.
Lieb WE, Cohen SM, Merton DA, Shields JA, Mitchell DG, Goldberg BB: Color Doppler imaging of the eye and orbit: technique and normal vascular anatomy. Arch Ophthalmol 1991;109:527–531.
84.
Riva CE, Schmetterer L: Microcirculation of the ocular fundus; in Tuma RF, Duran WN, Ley K (eds): Handbook of Physiology: Microcirculation. Amsterdam, Academic Press, 2008, pp 735–765.
85.
Frangieh GT, Green WR, Barraquer-Somers E, Finkelstein D: Histopathologic study of nine branch retinal vein occlusions. Arch Ophthalmol 1982;100:1132–1140.
86.
Hayreh SS: Prevalent misconceptions about acute retinal vascular occlusive disorders. Prog Retin Eye Res 2005;24:493–519.
87.
Vilser W, Deufrains A, Dietze U, Seewald D, Büchner D, Königsdörffer E, Jütte A: Clinical interpretation of retinal circulatory measurements. IV. Photocoagulation in diabetic retinopathy and venous occlusive diseases (in German). Ophthalmologica 1986;193:108–125.
88.
Vilser W, Graser T, Leisner H, Deufrains A, Königsdörffer E, Seewald D, Friedrich R, Jütte A: Clinical interpretation of retinal circulatory measurements. III. Blood flow velocity and vessel diameter in normal persons and in patients with venous occlusive diseases (in German). Ophthalmologica 1986;193:97–107.
89.
Vilser W, Jütte A, Seewald D, Dietze U, Friedrich R, Königsdörffer E, Büchner D: Measurements of retinal microcirculation in retinal vessel occlusion before and after treatment. Graefes Arch Clin Exp Ophthalmol 1986;224:179–183.
90.
Rosen DA, Marshall J, Kohner EM, Hamilton AM, Dollery CT: Experimental retinal branch vein occlusion in rhesus monkeys. II. Retinal blood flow studies. Br J Ophthalmol 1979;63:388–392.
91.
Peyman GA, Khoobehi B, Moshfeghi A, Moshfeghi D: Reversal of blood flow in experimental branch retinal vein occlusion. Ophthalmic Surg Lasers 1998;29:595–597.
92.
Ben-nun J: Capillary blood flow in acute branch retinal vein occlusion. Retina 2001;21:509–512.
93.
Paques M, Naoun K, Garmyn V, Laurent P, Gaudric A: Circulatory consequences of retinal vein occlusions: advantages of dynamic angiography (in French). J Fr Ophtalmol 2002;25:898–902.
94.
Avila CP Jr, Bartsch DU, Bitner DG, Cheng L, Mueller AJ, Karavellas MP, Freeman WR: Retinal blood flow measurements in branch retinal vein occlusion using scanning laser Doppler flowmetry. Am J Ophthalmol 1998;126:683–690.
95.
Donati G, Pournaras CJ, Pizzolato GP, Tsacopoulos M: Decreased nitric oxide production accounts for secondary arteriolar constriction after retinal branch vein occlusion. Invest Ophthalmol Vis Sci 1997;38:1450–1457.
96.
Donati G, Pournaras CJ, Tsacopoulos M: Effect of nitroprusside on arteriolar constriction after retinal branch vein occlusion. Invest Ophthalmol Vis Sci 1998;39:1910–1917.
97.
Donati G, Pournaras CJ, Munoz JL, Poitry S, Poitry-Yamate CL, Tsacopoulos M: Nitric oxide controls arteriolar tone in the retina of the miniature pig. Invest Ophthalmol Vis Sci 1995;36:2228–2237.
98.
Attariwala R, Jensen PS, Glucksberg MR: The effect of acute experimental retinal vein occlusion on cat retinal vein pressures. Invest Ophthalmol Vis Sci 1997;38:2742–2749.
99.
Iannaccone A, Letizia C, Pazzaglia S, Vingolo EM, Clemente G, Pannarale MR: Plasma endothelin-1 concentrations in patients with retinal vein occlusions. Br J Ophthalmol 1998;82:498–503.
100.
Haufschild T, Prunte C, Messerli J, Flammer J: Increased endothelin-1 plasma level in young adults with retinal vascular occlusive diseases. Klin Monatsbl Augenheilkd 2004;221:357–359.
101.
Stangos AN, Petropoulos IK, Pournaras JA, Mendrinos E, Pournaras CJ: The vasodilatory effect of juxta-arteriolar microinjection of endothelin A receptor inhibitor in healthy and acute branch retinal vein occlusion minipig retinas. Invest Ophthalmol Vis Sci 2010;51:2185–2190.
102.
Kohner EM: Dynamic changes in the microcirculation of diabetics as related to diabetic microangiopathy. Acta Med Scand Suppl 1975;578:41–47.
103.
Pournaras CJ, Rungger-Brandle E, Riva CE, Hardarson SH, Stefansson E: Regulation of retinal blood flow in health and disease. Prog Retin Eye Res 2008;27:284–330.
104.
Schmetterer L, Wolzt M: Ocular blood flow and associated functional deviations in diabetic retinopathy. Diabetologia 1999;42:387–405.
105.
Grunwald JE, DuPont J, Riva CE: Retinal haemodynamics in patients with early diabetes mellitus. Br J Ophthalmol 1996;80:327–331.
106.
Feke GT, Buzney SM, Ogasawara H, Fujio N, Goger DG, Spack NP, Gabbay KH: Retinal circulatory abnormalities in type 1 diabetes. Invest Ophthalmol Vis Sci 1994;35:2968–2975.
107.
Gilmore ED, Hudson C, Nrusimhadevara RK, Harvey PT, Mandelcorn M, Lam WC, Devenyi RG: Retinal arteriolar diameter, blood velocity, and blood flow response to an isocapnic hyperoxic provocation in early sight-threatening diabetic retinopathy. Invest Ophthalmol Vis Sci 2007;48:1744–1750.
108.
Gilmore ED, Hudson C, Nrusimhadevara RK, Ridout R, Harvey PT, Mandelcorn M, Lam WC, Devenyi RG: Retinal arteriolar hemodynamic response to an acute hyperglycemic provocation in early and sight-threatening diabetic retinopathy. Microvasc Res 2007;73:191–197.
109.
Grunwald JE, Brucker AJ, Grunwald SE, Riva CE: Retinal hemodynamics in proliferative diabetic retinopathy. A laser Doppler velocimetry study. Invest Ophthalmol Vis Sci 1993;34:66–71.
110.
Fallon TJ, Maxwell DL, Kohner EM: Autoregulation of retinal blood flow in diabetic retinopathy measured by the blue-light entoptic technique. Ophthalmology 1987;94:1410–1415.
111.
Sieker HO, Hickam JB: Normal and impaired retinal vascular reactivity. Circulation 1953;7:79–83.
112.
Grunwald JE, Riva CE, Brucker AJ, Sinclair SH, Petrig BL: Altered retinal vascular response to 100% oxygen breathing in diabetes mellitus. Ophthalmology 1984;91:1447–1452.
113.
Takagi C, Bursell SE, Lin YW, Takagi H, Duh E, Jiang Z, Clermont AC, King GL: Regulation of retinal hemodynamics in diabetic rats by increased expression and action of endothelin-1. Invest Ophthalmol Vis Sci 1996;37:2504–2518.
114.
Blum M, Vollrath D, Bartke T, Bachmann K, Strobel J: Vasoconstriction of retinal arterioles with oxygen breathing in diabetic retinopathy (in German). Ophthalmologe 2003;100:306–309.
115.
Grunwald JE, Brucker AJ, Petrig BL, Riva CE: Retinal blood flow regulation and the clinical response to panretinal photocoagulation in proliferative diabetic retinopathy. Ophthalmology 1989;96:1518–1522.
116.
Morgado PB, Chen HC, Patel V, Herbert L, Kohner EM: The acute effect of smoking on retinal blood flow in subjects with and without diabetes. Ophthalmology 1994;101:1220–1226.
117.
Bertram B, Wolf S, Arend O, Schulte K, Reim M: Retinal circulation and current blood glucose value in diabetic retinopathy (in German). Klin Monatsbl Augenheilkd 1992;200:654–657.
118.
Bertram B, Wolf S, Fiehofer S, Schulte K, Arend O, Reim M: Retinal circulation times in diabetes mellitus type 1. Br J Ophthalmol 1991;75:462–465.
119.
Atherton A, Hill DW, Young S, Edwards EJ: The effect of acute hyperglycaemia on the retinal circulation of the normal cat. Diabetologia 1980;18:233–237.
120.
Ernest JT, Goldstick TK, Engerman RL: Hyperglycemia impairs retinal oxygen autoregulation in normal and diabetic dogs. Invest Ophthalmol Vis Sci 1983;24:985–989.
121.
Sullivan PM, Davies GE, Caldwell G, Morris AC, Kohner EM: Retinal blood flow during hyperglycemia. A laser Doppler velocimetry study. Invest Ophthalmol Vis Sci 1990;31:2041–2045.
122.
Williamson JR, Chang K, Frangos M, Hasan KS, Ido Y, Kawamura T, Nyengaard JR, Van den Enden M, Kilo C, Tilton RG: Perspectives in diabetes. Hyperglycemic pseudohypoxia and diabetic complications. Diabetes 1993;42:801–813.
123.
Tiedeman JS, Kirk SE, Srinivas S, Beach JM: Retinal oxygen consumption during hyperglycemia in patients with diabetes without retinopathy. Ophthalmology 1998;105:31–36.
124.
Fallon TJ, Sleightholm MA, Merrick C, Chahal P, Kohner EM: The effect of acute hyperglycemia on flow velocity in the macular capillaries. Invest Ophthalmol Vis Sci 1987;28:1027–1030.
125.
Sullivan PM, Parfitt VJ, Jagoe R, Newsom R, Kohner EM: Effect of meal on retinal blood flow in IDDM patients. Diabetes Care 1991;14:756–758.
126.
Waldhausl W, Freyler H, Bratusch-Marrain P, Vierhapper H, Bruneder H: Continuous subcutaneous insulin infusion: long-term treatment in an unselected group of insulin-dependent diabetics. Dtsch Med Wochenschr 1983;108:570–577.
127.
Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977.
128.
Frank RN: Diabetic retinopathy. Prog Retin Eye Res 1995;14:361–392.
129.
Grunwald JE, Riva CE, Petrig BL, Brucker AJ, Schwartz SS, Braunstein SN, DuPont J, Grunwald S: Strict control of glycaemia: effects on blood flow in the large retinal vessels and in the macular microcirculation. Br J Ophthalmol 1995;79:735–741.
130.
Grunwald JE, Brucker AJ, Schwartz SS, Braunstein SN, Baker L, Petrig BL, Riva CE: Diabetic glycemic control and retinal blood flow. Diabetes 1990;39:602–607.
131.
Grunwald JE, Brucker AJ, Braunstein SN, Schwartz SS, Baker L, Petrig BL, Riva CE: Strict metabolic control and retinal blood flow in diabetes mellitus. Br J Ophthalmol 1994;78:598–604.
132.
Fuchsjager-Mayrl G, Kautzky-Willer A, Kiss B, Roden M, Wagner O, Pleiner J, Wolzt M, Schmetterer L: Ocular hyperperfusion following onset of intensified insulin therapy is inversely correlated with plasma endothelin-1 in type I diabetes. Diabetologia 2002;45:883–889.
133.
Sinclair SH, Grunwald JE, Riva CE, Braunstein SN, Nichols CW, Schwartz SS: Retinal vascular autoregulation in diabetes mellitus. Ophthalmology 1982;89:748–750.
134.
Rassam SM, Patel V, Kohner EM: The effect of experimental hypertension on retinal vascular autoregulation in humans: a mechanism for the progression of diabetic retinopathy. Exp Physiol 1995;80:53–68.
135.
Dumskyj MJ, Eriksen JE, Dore CJ, Kohner EM: Autoregulation in the human retinal circulation: assessment using isometric exercise, laser Doppler velocimetry, and computer-assisted image analysis. Microvasc Res 1996;51:378–392.
136.
Dumskyj MJ, Kohner EM: Retinal blood flow regulation in diabetes mellitus: impaired autoregulation and no detectable effect of autonomic neuropathy using laser Doppler velocimetry, computer assisted image analysis, and isometric exercise. Microvasc Res 1999;57:353–356.
137.
Blum M, Pils C, Müller UA, Strobel J: The myogenic response of retinal arterioles in diabetic retinopathy (in German). Ophthalmologe 2006;103:209–213.
138.
Lanigan LP, Clark CV, Allawi J, Hill DW, Keen H: Responses of the retinal circulation to systemic autonomic stimulation in diabetes mellitus. Eye 1989;3:39–47.
139.
Garhofer G, Zawinka C, Resch H, Kothy P, Schmetterer L, Dorner GT: Reduced response of retinal vessel diameters to flicker stimulation in patients with diabetes. Br J Ophthalmol 2004;88:887–891.
140.
Pemp B, Garhofer G, Weigert G, Karl K, Resch H, Wolzt M, Schmetterer L: Reduced retinal vessel response to flicker stimulation but not to exogenous nitric oxide in type 1 diabetes. Invest Ophthalmol Vis Sci 2009;50:4029–4032.
141.
Mizutani M, Gerhardinger C, Lorenzi M: Muller cell changes in human diabetic retinopathy. Diabetes 1998;47:445–449.
142.
Dawczynski J, Mandecka A, Blum M, Muller UA, Ach T, Strobel J: Endothelial dysfunction of central retinal vessels: a prognostic parameter for diabetic retinopathy? (in German). Klin Monatsbl Augenheilkd 2007;224:827–831.
143.
Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, Kass MA: The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120:714–720; discussion 829–830.
144.
Leske MC, Wu SY, Hennis A, Honkanen R, Nemesure B: Risk factors for incident open-angle glaucoma: the Barbados Eye Studies. Ophthalmology 2008;115:85–93.
145.
Grunwald JE, Riva CE, Stone RA, Keates EU, Petrig BL: Retinal autoregulation in open-angle glaucoma. Ophthalmology 1984;91:1690–1694.
146.
Hafez AS, Bizzarro RL, Rivard M, Lesk MR: Changes in optic nerve head blood flow after therapeutic intraocular pressure reduction in glaucoma patients and ocular hypertensives. Ophthalmology 2003;110:201–210.
147.
Riva CE, Salgarello T, Logean E, Colotto A, Galan EM, Falsini B: Flicker-evoked response measured at the optic disc rim is reduced in ocular hypertension and early glaucoma. Invest Ophthalmol Vis Sci 2004;45:3662–3668.
148.
Garhofer G, Zawinka C, Resch H, Huemer KH, Schmetterer L, Dorner GT: Response of retinal vessel diameters to flicker stimulation in patients with early open angle glaucoma. J Glaucoma 2004;13:340–344.
© 2012 S. Karger AG, Basel
2012
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