Survey of Ophthalmology
Volume 46, Issue 1 , Pages 59-80 , July 2001

Retinal Microvascular Abnormalities and their Relationship with Hypertension, Cardiovascular Disease, and Mortality

  • Tien Yin Wong, FRCS, MPH

      Affiliations

    • Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA
    • Singapore National Eye Center and Department of Ophthalmology, National University of Singapore, Singapore
    • Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD, USA
    • Corresponding Author InformationReprint address: Tien Yin Wong, MD, MPH, Department of Ophthalmology and Visual Science, University of Wisconsin–Madison, 610 North Walnut Street, 460 WARF, Madison, WI 53705-2397.
  • ,
  • Ronald Klein, MD, MPH

      Affiliations

    • Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA
  • ,
  • Barbara E.K Klein, MD, MPH

      Affiliations

    • Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA
  • ,
  • James M Tielsch, PhD

      Affiliations

    • Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD, USA
    • Department of International Health, Johns Hopkins University School of Public Health, Baltimore, MD, USA
  • ,
  • Larry Hubbard, MAT

      Affiliations

    • Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA
  • ,
  • F.Javier Nieto, MD, PhD

      Affiliations

    • Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD, USA

References 

  1. Akinkugbe OO. The rarity of hypertensive retinopathy in the African. Am J Med. 1968;45:401–404
  2. Akman A, Kadayifcilar S, Aydin P. Effects of hypertension on the retinal vein width at the retinal arterio-venous crossings. Eur J Ophthalmol. 1998;8:71–75
  3. Altus P. Hypertensive retinopathy in renovascular hypertension. N Engl J Med. 1980;302:867
  4. Aoki N. Epidemiological evaluation of funduscopic findings in cerebrovascular diseases. II. A multivariate analysis of funduscopic findings. Jpn Circ J. 1975;39:271–282
  5. Aoki N. Epidemiological evaluation of funduscopic findings in cerebrovascular diseases. I. Fundoscopic findings as risk factors for cerebrovascular diseases. Jpn Circ J. 1975;39:257–269
  6. Aoki N, Horibe H, Ohno Y, et al.  Epidemiological evaluation of funduscopic findings in cerebrovascular diseases. III. Observer variability and reproducibility for funduscopic findings. Jpn Circ J. 1977;41:11–17
  7. Apple DJ, Naumann GO. Retina. In:  Naumann GO,  Apple DJ editor. Pathology of the Eye. New York: Springer-Verlag; 1986;p. 580–583
  8. Arai H. Secular trend of retinal findings in changing environment. Jpn J Hyg. 1983;38:103–105
  9. Arzabe CW, Jalkh AE, Fariza E, et al.  A simple device to standardize measurements of retinal structures in fundus photographs and retinal angiograms. Am J Ophthalmol. 1990;109:107–108
  10. Ashton N. The eye in malignant hypertension. Trans Am Acad Ophthalmol Otolaryngol. 1972;76:17–40
  11. Ashton N, Harry J. The pathology of cotton-wool spots and cytoid bodies in hypertensive retinopathy and other diseases. Trans Ophthalmol Soc UK. 1963;83:91–114
  12. Ashton N, Peltier S, Garner A. Experimental hypertensive retinopathy in the monkey. Trans Ophthalmol Soc UK. 1969;88:167–186
  13. Aurell E, Tibblin G. Hypertensive eye-ground changes in a Swedish population of middle-aged men. Acta Ophthalmol Scand. 1965;43:355–361
  14. Behrendt T. Scanning densitometer for photographic fundus measurements. Am J Ophthalmol. 1966;62:689–693
  15. Behrendt T. A retinographic survey of fundus changes. Am J Ophthalmol. 1960;50:314–324
  16. Benfante R, Reed D. Is elevated serum cholesterol a risk factor for coronary disease in the elderly?. JAMA. 1990;263:393–396
  17. Biesenbach G, Zazgornik J. High prevalence of hypertensive retinopathy and coronary heart disease in hypertensive patients with persistent microalbuminuria under short intensive antihypertensive therapy. Clin Nephrol. 1994;41:211–218
  18. Biousse V. Carotid disease and the eye. Curr Opin Ophthalmol. 1997;8:16–26
  19. Bock KD. Regression of retinal vascular changes by antihypertensive therapy. Hypertension. 1984;6:158–162
  20. Boyd TAS, de Margerie J. Caliber of retinal arterioles in hypertension. Trans Canad Ophthalmol Soc. 1960;23:65–76
  21. Bracher D, Dozzi M, Lotmar W. Measurement of vessel width on fundus photographs. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1979;211:35–48
  22. Breckenridge A, Dollery CT, Parry EH. Prognosis of treated hypertension. Changes in life expectancy and causes of death between 1952 and 1967. Q J Med. 1970;39:411–429
  23. Breslin DJ, Gifford RW, Fairbairn JF. Essential hypertension. A twenty-year follow-up study. Circulation. 1966;33:87–97
  24. Breslin DJ, Gifford RW, Fairbairn JF, Kearns TP. Prognostic importance of ophthalmoscopic findings in essential hypertension. JAMA. 1966;195:335–338
  25. Brinchmann-Hansen O. The light reflex on retinal arteries and veins. A theoretical study and a new technique for measuring width and intensity profiles across retinal vessels. Acta Ophthalmol. 1986;179(Suppl):1–53
  26. Brinchmann-Hansen O, Christensen CC, Myhre K. The response of the light reflex of retinal vessels to reduced blood pressure in hypertensive patients. Acta Ophthalmol (Copenh). 1990;68:155–161
  27. Brinchmann-Hansen O, Myhre K, Sandvik L. The light reflex in retinal vessels and its relation to age and systemic blood pressure. Acta Ophthalmol (Copenh). 1987;65:206–212
  28. Brinchmann-Hansen O, Sandvik L. The width of the light reflex on retinal arteries and veins. Acta Ophthalmol (Copenh). 1986;64:433–438
  29. Burgess AM. Objective measurements of the retinal vessels. Ann Intern Med. 1967;67:1346–1347
  30. Chen HC, Patel V, Wiek J, et al.  Vessel diameter changes during the cardiac cycle. Eye. 1994;8:97–103
  31. Cogan DG. Development and senescence of the human retinal vasculature. Trans Ophthalmol Soc UK. 1963;83:475–489
  32. Cohen M. Lesions of the fundus in essential hypertension and in arterial and renal diseases. Arch Ophthalmol. 1937;17:994–1007
  33. Conlan MG, Folsom AR, Finch A. Associations of factor VIII and von Willebrand factor with age, race, sex, and risk factors for atherosclerosis. Thromb Haemost. 1993;70:380–385
  34. Cunha-Vaz JG, Lima JJ. Studies on retinal blood flow. I. Estimation of human retinal blood flow by slit-lamp fluorophotometry. Arch Ophthalmol. 1978;96:893–897
  35. Curb JD, Abbott RD, MacLean CJ, et al.  Age-related changes in stroke risk in men with hypertension and normal blood pressure. Stroke. 1996;27:819–824
  36. Dahlof B, Stenkula S, Hansson L. Hypertensive retinal vascular changes (relationship to left ventricular hypertrophy and arteriolar changes before and after treatment). Blood Press. 1992;1:35–44
  37. Davis BA, Crook JE, Vestal RE, Oates JA. Prevalence of renovascular hypertension in patients with grade III or IV hypertensive retinopathy. N Engl J Med. 1979;301:1273–1276
  38. Dawber TR. The Framingham study (the epidemiology of atherosclerotic disease). Cambridge, MA: Harvard University Press; 1980;
  39. Delori FC, Fitch KA, Feke GT, et al.  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
  40. Diabetic Retinopathy Study Research Group . Report (a modification of the Airlie House classification of diabetic retinopathy). Invest Ophthalmol Vis Sci. 1981;21:210–226
  41. Dimmitt SB, West JN, Eames SM, et al.  Usefulness of ophthalmoscopy in mild to moderate hypertension. Lancet. 1989;1:1103–1106
  42. Dodson PM, Lip GY, Eames SM, et al.  Hypertensive retinopathy (a review of existing classification systems and a suggestion for a simplified grading system). J Hum Hypertens. 1996;10:93–98
  43. Dollery CT, Ramalho PS, Patterson JW. Retinal vascular alterations in hypertension. In:  Gross F editors. Antihypertensive therapy; principles and practice, an international symposium. New York: Springer; 1966;p. 152
  44. Dozono K, Ishii N, Nishihara Y, Horie A. An autopsy study of the incidence of lacunes in relation to age, hypertension, and arteriosclerosis. Stroke. 1991;22:993–996
  45. Dumskyj MJ, Aldington SJ, Dore CJ, Kohner EM. The accurate assessment of changes in retinal vessel diameter using multiple frame electrocardiograph synchronised fundus photography. Curr Eye Res. 1996;15:625–632
  46. Early Treatment Diabetic Retinopathy Study Research Group . Grading retinopathy from stereoscopic color fundus photographs (an extension of the modified Airlie House classification: ETDRS report No. 10). Ophthalmology. 1986;98:786–806
  47. Eaton AM, Hatchell DL. Measurement of retinal blood vessel width using computerized image analysis. Invest Ophthalmol Vis Sci. 1988;29:1258–1264
  48. Epstein FH. Cardiovascular disease epidemiology (a journey from the past into the future). Circulation. 1996;93:1755–1764
  49. Epstein FH. Contributions of epidemiology to understanding coronary heart disease. In:  Marmot M,  Elliott P editor. Coronary heart disease epidemiology (from etiology to public health). New York: Oxford University Press; 1992;p. 20–32
  50. Evelyn KA, Nicholls JV, Turnbull W. A method of grading and recording the retinal changes in essential hypertension. Am J Ophthalmol. 1958;4:165–179
  51. Feke GT, Schwartz B, Takamoto T, et al.  Optic nerve head circulation in untreated ocular hypertension. Br J Ophthalmol. 1995;79:1088–1092
  52. Frant R, Groen J. Prognosis of vascular hypertension (A nine year follow-up study of four hundred and eighteen cases). Arch Int Med. 1950;85:727
  53. Friedenwald H. The Doyne Memorial Lecture (pathological changes in the retinal blood-vessels in arteriosclerosis and hypertension). Trans Ophthalmol Soc UK. 1930;50:452–531
  54. Friedman AH. The retinal lesions of the acquired immune deficiency syndrome. Trans Am Ophthalmol Soc. 1984;82:447–491
  55. Friendenwald JS, Wilder HC, Maumenee AE, et al.  In: Ophthalmic pathology. An Atlas and Textbook. Philadelphia: WB Saunders Company; 1952;p. 310–324
  56. Friendenwald JS. Retinal arteriosclerosis. In:  Cowdry EV editors. Arteriosclerosis. A Survey of the Problem. New York: MacMillan Co; 1993;p. 363–395Chapter 13,
  57. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–454
  58. Gao XW, Bharath A, Stanton A, et al.  Quantification and characterisation of arteries in retinal images. Comput Methods Programs Biomed. 2000;63:133–134
  59. Garner A, Ashton N. Pathogenesis of hypertensive retinopathy (a review). JR Soc Med. 1979;72:362–365
  60. Garner A, Ashton N, Tripathi R, et al.  Pathogenesis of hypertensive retinopathy. An experimental study in the monkey. Br J Ophthalmol. 1975;59:3–44
  61. George GS, Wolbarsht ML, Landers MB. Reproducible estimation of retinal vessel width by computerized microdensitometry. Int Ophthalmol. 1990;14:89–95
  62. Gillum RF. Retinal arteriolar findings and coronary heart disease. Am Heart J. 1991;122:262–263
  63. Goto I, Katsuki S, Ikui H, et al.  Pathological studies on the intracerebral and retinal arteries in cerebrovascular and noncerebrovascular diseases. Stroke. 1975;6:263–269
  64. Griffiths JD, Hill DW, Young S. Measurement of apparent vessel width in fluorescein angiography of the fundus oculi. Ophthalmic Res. 1974;6:1–5
  65. Gunn RM. On ophthalmoscopic evidence of general arterial disease. Trans Ophthalmol Soc UK. 1898;18:356–381
  66. Gunn RM. Opthalmocsopic evidence of (1) arterial changes associated with chronic renal diseases and (2) of increased arterial tension. Trans Ophthalmol Soc UK. 1892;12:124–125
  67. Hague S, Hill DW. Postural changes in perfusion pressure and retinal arteriolar calibre. Br J Ophthalmol. 1988;72:253–257
  68. Hamada Y. Ophthalmological study of the M-strain stroke-prone spontaneously hypertensive rats (2). Retinal arteriolar changes in fluorescein angiogram. Nippon Ganka Gakkai Zasshi. 1993;97:690–697
  69. Harjai KJ. Potential new cardiovascular risk factors (left ventricular hypertrophy, homocysteine, lipoprotein(a), triglycerides, oxidative stress, and fibrinogen). Ann Intern Med. 1999;131:376–386
  70. Hayreh SS. Classification of hypertensive fundus changes and their order of appearance. Ophthalmologica. 1989;198:247–260
  71. Hayreh SS, Servais GE. Retinal hemorrhages in malignant arterial hypertension. Int Ophthalmol. 1988;12:137–145
  72. Hayreh SS, Servais GE, Virdi PS. Retinal arteriolar changes in malignant arterial hypertension. Ophthalmologica. 1989;198:178–196
  73. Heier H, Brinchmann-Hansen O. Reliable measurements from fundus photographs in the presence of focusing errors. Invest Ophthalmol Vis Sci. 1989;30:674–677
  74. Hill DW, Griffiths JD, Young S. Retinal blood flow measured by fluorescence angiography. Trans Ophthalmol Soc UK. 1973;93:325–332
  75. Hodge JV, Parr JC, Spears GF. Comparison of methods of measuring vessel widths on retinal photographs and the effect of fluorescein injection on apparent retinal vessel calibers. Am J Ophthalmol. 1969;68:1060–1068
  76. Hollenhorst RW. Ocular manifestations of insufficiency or thrombosis of the internal carotid artery. Trans Am Ophthalmol Soc. 1958;56:474–506
  77. Hoover A, Kouznetsova V, Goldbaum M: Locating blood vessels in retinal images by piece-wise threshold probing of a matched filter response. Proc AMIA Symp 931–5, 1998
  78. Houben AJ, Canoy MC, Paling HA, et al.  Quantitative analysis of retinal vascular changes in essential and renovascular hypertension. J Hypertens. 1995;13:1729–1733
  79. Hubbard LD, Brothers RJ, King WN, et al.  Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study. Ophthalmology. 1999;106:2269–2280
  80. Hubbard LD, Ehrhardt B, Klein R. The association between generalized retinal arteriolar narrowing and blood pressure. Invest Ophthalmol Vis Sci. 1992;33(Suppl):804
  81. Jain P, Gupta A, Sharma BK. A correlative study of ophthalmoscopy and fluorescein angiography in systemic hypertension. Indian J Ophthalmol. 1990;38:169–174
  82. Johnston RL, Brucker AJ, Steinmann W, et al.  Risk factors of branch retinal vein occlusion. Arch Ophthalmol. 1985;103:1831–1832
  83. Jonas JB, Nguyen XN, Naumann GO. Parapapillary retinal vessel diameter in normal and glaucoma eyes. I. Morphometric data. Invest Ophthalmol Vis Sci. 1989;30:1599–1603
  84. Kadiri S, Olutade BO. The clinical presentation of malignant hypertension in Nigerians. J Hum Hypertens. 1991;5:339–343
  85. Kagan A, Aurell E, Dobree J. A note of signs in the fundus oculi and arterial hypertension (conventional assessment and significance). Bull World Health Organ. 1966;34:955–960
  86. Kagan A, Aurell E, Tibblin G, et al.  Signs of fundus oculi and arterial hypertension; unconventional assessment and significance. Bull World Health Organ. 1967;36:2231–2241
  87. Kearns TP, Hollenhorst RW. Venous-stasis retinopathy of occlusive disease of the carotid artery. Mayo Clin Proc. 1963;38:304–312
  88. Keith NM, Wagener HP, Barker NW. Some different types of essential hypertension (their course and prognosis). Am J Med Sci. 1939;197:332–343
  89. Kessler L, Wiesel ML, Attali P, et al.  Von Willebrand factor in diabetic angiopathy. Diabetes Metab. 1998;24:327–336
  90. Khaw KT, Barrett-Connor E, Suarez L, Criqui MH. Predictors of stroke-associated mortality in the elderly. Stroke. 1984;15:244–248
  91. King LA, Stanton AV, Sever PS, et al.  Arteriolar length-diameter (L:D) ratio (a geometric parameter of the retinal vasculature diagnostic of hypertension). J Hum Hypertens. 1996;10:417–418
  92. Klein BE, Davis MD, Segal P, et al.  Diabetic retinopathy. Assessment of severity and progression. Ophthalmology. 1984;91:10–17
  93. Klein R. Retinopathy in a population-based study. Trans Am Ophthalmol Soc. 1992;90:561–594
  94. Klein R, Klein BE, Moss SE. The relation of systemic hypertension to changes in the retinal vasculature (the Beaver Dam Eye Study). Trans Am Ophthalmol Soc. 1997;95:329–348discussion 348–50
  95. Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of diabetic retinopathy. XIV. Ten- year incidence and progression of diabetic retinopathy. Arch Ophthalmol. 1994;112:1217–1228
  96. Klein R, Klein BE, Moss SE, et al.  The Wisconsin Epidemiologic Study of Diabetic Retinopathy. IX. Four- year incidence and progression of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol. 1989;107:237–243
  97. Klein R, Klein BE, Neider MW, et al.  Diabetic retinopathy as detected using ophthalmoscopy, a nonmydriatic camera and a standard fundus camera. Ophthalmology. 1985;92:485–491
  98. Klein R, Klein BE, Magli YL, et al.  An alternative method of grading diabetic retinopathy. Ophthalmology. 1986;93:1183–1187
  99. Klein R, Klein BE, Moss SE, et al.  The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol. 1984;102:520–526
  100. Klein R, Klein BE, Moss SE, Wang Q. Hypertension and retinopathy, arteriolar narrowing, and arteriovenous nicking in a population. Arch Ophthalmol. 1994;112:92–98
  101. Klein R, Klein BE, Moss SE, Wang Q. Blood pressure, hypertension and retinopathy in a population. Trans Am Ophthalmol Soc. 1993;91:207–222discussion 222–6
  102. Klein R, Sharrett AR, Klein BE, et al.  Are retinal arteriolar abnormalities related to atherosclerosis? The Atherosclerosis Risk in Communities Study. Arterioscler Thromb Vasc Biol. 2000;20:1644–1650
  103. Kobayashi S, Okada K, Koide H, et al.  Subcortical silent brain infarction as a risk factor for clinical stroke. Stroke. 1997;28:1932–1939
  104. Kohner EM, Patel V, Rassam SM. Role of blood flow and impaired autoregulation in the pathogenesis of diabetic retinopathy. Diabetes. 1995;44:603–607
  105. Kuller L, Borhani N, Furberg C, et al.  Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study. Am J Epidemiol. 1994;139:1164–1179
  106. Kuller LH, Shemanski L, Psaty BM, et al.  Subclinical disease as an independent risk factor for cardiovascular disease. Circulation. 1995;92:720–726
  107. Ladipo GO. Hypertensive retinopathy in Nigerians. A prospective clinical study of 350 cases. Trop Geogr Med. 1981;33:311–316
  108. Lafaut BA, De Vriese AS, Stulting AA. Fundus fluorescein angiography of patients with severe hypertensive nephropathy. Graefes Arch Clin Exp Ophthalmol. 1997;235:749–754
  109. Landau WM. Is cholesterol a risk factor for stroke?. No. Arch Neurol. 1999;56:1521–1524
  110. Langer RD, Ganiats TG, Barrett-Connor E. Paradoxical survival of elderly men with high blood pressure. BMJ. 1989;298:1356–1357
  111. Lanigan LP, Clark CV, Hill DW. Retinal circulation responses to systemic autonomic nerve stimulation. Eye. 1988;2:412–417
  112. Leibowitz HM, Krueger DE, Maunder LR, et al.  The Framingham Eye Study monograph (An ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and visual acuity in a general population of 2631 adults, 1973–1975). Surv Ophthalmol. 1980;24(Suppl):335–610
  113. Leishman R. The eye in general vascular diseases (hypertension and arteriolsclerosis). Br J Ophthalmol. 1957;41:641–701
  114. Lowenthal MN, Zimlichman R. Resolution of hypertensive retinopathy despite persistent high diastolic pressure. South Med J. 1993;86:190–193
  115. MacMahon S. Blood pressure and the risk of cardiovascular disease. N Engl J Med. 2000;342:50–52
  116. Majewska K, Czechowicz-Janicka K, Przadka L, et al.  Computer data processing in the examination of retinal vessels in essential hypertension and atherosclerosis. Ophthalmologica. 1976;172:445–448
  117. Manfroi WC, Lavinski J, Ferreira Rd, et al: [Comparative study of the extension of coronary arteriosclerosis with risk factors and changes in the retinal artery]. Arq Bras Cardiol 63:185–9, 1994
  118. Mannucci PM. von Willebrand factor (a marker of endothelial damage?). Arterioscler Thromb Vasc Biol. 1998;18:1359–1362
  119. Matsui M, Matsumoto K, Yamamoto S, Yokouchi T: [A study on automatic and quantitative diagnosis of fundus photographs. II. Precise detection of contour line of retinal blood vessel images on color fundus photography (authors transl)]. Nippon Ganka Gakkai Zasshi 78:758–65, 1974
  120. McDonough JR, Garrison GE, Hames CG. Blood pressure and hypertensive disease among negroes and whites. A study in Evans County, Georgia. Ann Intern Med. 1964;61:208–228
  121. Meehan RT, Taylor GR, Rock P, et al.  An automated method of quantifying retinal vascular responses during exposure to novel environmental conditions. Ophthalmology. 1990;97:875–881
  122. Meltzer JI. Hypertensive retinopathy in renovascular hypertension. N Engl J Med. 1980;302:867
  123. Menotti A, Blackburn H, Kromhout D, et al.  The inverse relation of average population blood pressure and stroke mortality rates in the seven countries study (a paradox). Eur J Epidemiol. 1997;13:379–386
  124. Menotti A, Jacobs DR, Blackburn H, et al.  Twenty-five-year prediction of stroke deaths in the seven countries study (the role of blood pressure and its changes). Stroke. 1996;27:381–387
  125. Michaelson IC, Eliakim M, Avshalom A. An approach to the investigation of the vascular changes in the fundus of the eye in hypertension and arteriosclerosis. Excerpta Medica International Congr. 1966;146:207–219
  126. Michelson EL, Morganroth J, Nichols CW, MacVaugh H. Retinal arteriolar changes as an indicator of coronary artery disease. Arch Intern Med. 1979;139:1139–1141
  127. Mikuni M: [Measurement of ocular fundus, especially by means of fundus photograph]. Nippon Ganka Gakkai Zasshi 74:1328–57, 1970
  128. Moss SE, Klein R, Kessler SD. Comparison between ophthalmoscopy and fundus photography in determining severity of diabetic retinopathy. Ophthalmology. 1985;92:62–67
  129. Munch K, Vilser W, Senff I. Adaptive algorithm for automatic measurement of retinal vascular diameter. Biomed Tech (Berl). 1995;40:322–325
  130. Nagel E, Vilser W, Lindloh C, Klein S: [Measuring retinal vascular diameter using the scanning laser ophthalmoscope and computer. Initial results]. Ophthalmologe 89:432–6, 1992
  131. Nakayama T, Date C, Yokoyama T, et al.  A 15.5-year follow-up study of stroke in a Japanese provincial city. The Shibata Study. Stroke. 1997;28:45–52
  132. Nanba K: [Measurement of caliber of retinal blood vessels using fundus photograph. I. A method of measurement by Nikon profile projector, especially on magnification]. Nippon Ganka Gakkai Zasshi 75:1118–26, 1971
  133. National Heart Lung and Blood Institute . Morbidity and mortality (1998 chartbook on cardiovascular, lung and blood diseases). Rockville, MD: US Department of Health and Human Services, National Institutes of Health; 1998;
  134. Newsom RS, Rassam SM, Kohner EM. The effect of beta blockers on retinal blood flow in diabetic patients. Eur J Ophthalmol. 1991;1:131–136
  135. Newsom RS, Sullivan PM, Rassam SM, et al.  Retinal vessel measurement (comparison between observer and computer driven methods). Graefes Arch Clin Exp Ophthalmol. 1992;230:221–225
  136. O'Hare JP, Walker WG. Arteriosclerosis and hypertension. Arch Int Med. 1924;33:343–349
  137. Okada H, Horibe H, Yoshiyuki O, et al.  A prospective study of cerebrovascular disease in Japanese rural communities, Akabane and Asahi. Part 1 (evaluation of risk factors in the occurrence of cerebral hemorrhage and thrombosis). Stroke. 1976;7:599–607
  138. Oparil S, Oberman A. Nontraditional cardiovascular risk factors. Am J Med Sci. 1999;317:193–207
  139. OSullivan P, Hickey N, Maurer B, et al.  Retinal artery changes correlated with other hypertensive parameters in a coronary heart disease case-history study. Br Heart J. 1968;30:556–562
  140. Pahor M, Elam MB, Garrison RJ, et al.  Emerging noninvasive biochemical measures to predict cardiovascular risk. Arch Intern Med. 1999;159:237–245
  141. Palatini P, Penzo M, Bongiovi S, et al: [Role of ophthalmoscopy in arterial hypertension: a problem revisited]. Cardiologia 36:713–22, 1991
  142. Palmer RS, Loofbourow D, Doering CR. Prognosis in essential hypertension (Eight-year follow-up study of 430 patients on conventional medical treatment). N Engl Med J. 1948;239:990
  143. Parati G, Pomidossi G, Albini F, et al.  Relationship of 24-hour blood pressure mean and variability to severity of target-organ damage in hypertension. J Hypertens. 1987;5:93–98
  144. Parr JC. Hypertensive generalised narrowing of retinal arteries. Trans Ophthalmol Soc NZ. 1974;26:55–60
  145. Parr JC, Spears GF. General caliber of the retinal arteries expressed as the equivalent width of the central retinal artery. Am J Ophthalmol. 1974;77:472–477
  146. Parr JC, Spears GFS. Mathematic relationships between the width of a retinal artery and the widths of its branches. Am J Ophthalmol. 1974;77:478–483
  147. Patel V, Rassam S, Newsom R, et al.  Retinal blood flow in diabetic retinopathy. Br Med J. 1992;305:678–683
  148. Paul O, Lepper MH, Phelan WH. a longitudinal study of coronary heart disease. Circulation. 1963;28:20–31
  149. Pekkanen J, Tervahauta M, Nissinen A, Karvonen MJ. Does the predictive value of baseline coronary risk factors change over a 30-year follow-up?. Cardiology. 1993;82:181–190
  150. Peli E, Lahav M. Drusen measurement from fundus photographs using computer image analysis. Ophthalmology. 1986;93:1575–1580
  151. Penn JS, Gay CA. Computerized digital image analysis of retinal vessel density (application to normoxic and hyperoxic rearing of the newborn rat). Exp Eye Res. 1992;54:329–336
  152. Pontremoli R, Cheli V, Sofia A, et al.  Prevalence of micro- and macroalbuminuria and their relationship with other cardiovascular risk factors in essential hypertension. Nephrol Dial Transplant. 1995;10(Suppl 6):6–9
  153. Pose Reino A, Gonzalez-Juanatey JR, Castroviejo M. Relation between left ventricular hypertrophy and retinal vascular changes in mild hypertension. J Med Clin (Barc). 1997;108:281–285
  154. Preussner PR, Richard G, Darrelmann O, et al.  Quantitative measurement of retinal blood flow in human beings by application of digital image-processing methods to television fluorescein angiograms. Graefes Arch Clin Exp Ophthalmol. 1983;221:110–112
  155. Prospective Studies Collaboration . Cholesterol, diastolic blood pressure, and stroke (13 000 strokes in 450 000 people in 45 prospective cohorts). Lancet. 1995;346:1647–1653
  156. Ralph RA. Prediction of cardiovascular status from arteriovenous crossing phenomena. Ann Ophthalmol. 1974;6:323–326
  157. Ramalho PS, Dollery CT. Hypertensive retinopathy (calibre changes in retinal blood vessels following blood-pressure reduction and inhalation of oxygen). Circulation. 1968;37:580–588
  158. Rassam SM, Patel V, Brinchmann-Hansen O, et al.  Accurate vessel width measurement from fundus photographs (a new concept). Br J Ophthalmol. 1994;78:24–29
  159. 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
  160. Remky A, Arend O, Beausencourt E, et al.  Retinal vessels before and after photocoagulation in diabetic retinopathy. Determining the diameter using digitized color fundus slides. Klin Monatsbl Augenheilkd. 1996;209:79–83
  161. Ross R. Atherosclerosi—An inflammatory disease. N Eng J Med. 1999;340:115–126
  162. Saine PJ, Bovino JA, Marcus DF, Nelsen PT. Timing of color fundus photographs and intravenous fluorescein angiography. Am J Ophthalmol. 1984;97:783–785
  163. Saitoh M, Matsuo K, Nomoto S, et al.  Relationship between left ventricular hypertrophy and renal and retinal damage in untreated patients with essential hypertension. Intern Med. 1998;37:576–580
  164. Salus R. Diagnosis of arteriosclerosis and hypertension. Am J Ophthalmol. 1958;45:81–92
  165. Sandor T, Rhie FH, Soeldner JS, et al.  Reproducibility of the densitometric analysis of fluorescein angiograms. Int J Biomed Comput. 1981;12:401–418
  166. Sankai T, Iso H, Shimamoto T, et al: [A nested case-control study of risk factors for intracerebral hemorrhage and cerebral infarction classified by computed tomographic findings]. Nippon Koshu Eisei Zasshi 39:410–20, 1992
  167. Sano T, Arai H, Ogawa Y: [Relationship of fundus oculi changes to declines in mental and physical health conditions among elderly living in a rural community]. Nippon Koshu Eisei Zasshi 41:219–29, 1994
  168. Schack B, Vilser W, Putsche P, et al.  A new approach for detecting the position of retinal vessels and calculating their diameter on the basis of dynamic spectral analysis. Medinfo. 1995;8(Pt 1):701–705
  169. Scheie HG. Evaluation of ophthalmoscopic changes of hypertension and arteriolar sclerosis. Arch Ophthalmol. 1953;49:117–138
  170. Schouten EG, Vandenbroucke JP, van der Heide-Wessel C, van der Heide RM. Retinopathy as an independent indicator of all-causes mortality. Int J Epidemiol. 1986;15:234–236
  171. Schubert HD. Ocular manifestations of systemic hypertension. Curr Opin Ophthalmol. 1998;9:69–72
  172. Schwartz B, Takamoto T, Lavin P. Increase of retinal vessel width in ocular hypertensives with timolol therapy. Acta Ophthalmol Scand. 1995;215(Suppl):41–53
  173. Sechi LA, Kronenberg F, De Carli S, et al.  Association of serum lipoprotein(a) levels and apolipoprotein(a) size polymorphism with target-organ damage in arterial hypertension. JAMA. 1997;277:1689–1695
  174. Sharp PS, Chaturvedi N, Wormald R, et al.  Hypertensive retinopathy in Afro-Caribbeans and Europeans. Prevalence and risk factor relationships. Hypertension. 1995;25:1322–1325
  175. Sharrett AR, Hubbard LD, Cooper LS, et al.  Retinal arteriolar diameters and elevated blood pressure (the Atherosclerosis Risk in Communities Study). Am J Epidemiol. 1999;150:263–270
  176. Shelburne SA. The retina in hypertensive diseases. Ann Intern Med. 1957;47:1154–1164
  177. Shelburne SA. Retinal arteriovenous nicking. A long-term study of the development of arteriovenous nicking in hypertensive patients. Arch Intern Med. 1949;83:377–381
  178. Shelburne SA, Hawley J, McGee A. Retinal arteriovenous nicking. Relation to enlargement of the heart in ambulatory patients with hypertension. Arch Intern Med. 1942;69:213–221
  179. Shimamoto T, Komachi Y, Inada H, et al.  Trends for coronary heart disease and stroke and their risk factors in Japan. Circulation. 1989;79:503–515
  180. Simon J, Svojgrova M, Simecek K, et al.  Quantitative assessment of retinal vessels in relation to blood pressure. Hum Biol. 1974;46:605–611
  181. Simpson FO, Gilchrist AR. Prognosis in untreated hypertensive vascular disease. Scott Med J. 1958;3:1
  182. Sinthanayothin C, Boyce JF, Cook HL, Williamson TH. Automated localisation of the optic disc, fovea, and retinal blood vessels from digital colour fundus images. Br J Ophthalmol. 1999;83:902–910
  183. Stamler J: Established major coronary risk factors, in Marmot M, Elliott P (eds): Coronary Heart Disease Epidemiology: From Etiology to Public Health. New York: Oxford University Press, 1992 pp 35–66
  184. Stamler J, Dyer AR, Shekelle RB, et al.  Relationship of baseline major risk factors to coronary and all-cause mortality, and to longevity (findings from long-term follow-up of Chicago cohorts). Cardiology. 1993;82:191–222
  185. Stanton AV, Mullaney P, Mee F, et al.  A method of quantifying retinal microvascular alterations associated with blood pressure and age. J Hypertens. 1995;13:41–48
  186. Stanton AV, Wasan B, Cerutti A, et al.  Vascular network changes in the retina with age and hypertension. J Hypertens. 1995;13:1724–1728
  187. Stokoe NL, Turner RW. Normal retinal vascular pattern. Arteriovenous ratio as a measure of arterial calibre. Br J Ophthalmol. 1966;50:21–40
  188. Stolk RP, Vingerling JR, de Jong PT. Retinopathy, glucose, and insulin in an elderly population (the Rotterdam Study). Diabetes. 1995;44:11–15
  189. Stromland K, Hellstrom A, Gustavsson T. Morphometry of the optic nerve and retinal vessels in children by computer-assisted image analysis of fundus photographs. Graefes Arch Clin Exp Ophthalmol. 1995;233:150–153
  190. Sugiyama T, Schwartz B, Takamoto T, Azuma I. Evaluation of the circulation in the retina, peripapillary choroid and optic disk in normal-tension glaucoma. Ophthalmic Res. 2000;32:79–86
  191. Suzuki Y. Direct measurement of retinal vessel diameter (comparison with microdensitometric methods based on fundus photographs). Surv Ophthalmol. 1995;39(Suppl 1):S57–S65
  192. Suzuki Y, Yoshisuji M: [Retinal blood vessel measurement using a line sensor]. Nippon Ganka Gakkai Zasshi 98:92–7, 1994
  193. Svardsudd K, Wedel H, Aurell E, Tibblin G. Hypertensive eye ground changes. Prevalence, relation to blood pressure and prognostic importance. The study of men born in. 1978;1913.(Acta Med Scand 204):159–167
  194. Takahashi S, Kawaguchi K, Yamanobe R: [Hypertension and fundus change with special reference to narrowing of the retinal arteries]. Ganka 9:921–31, 1967
  195. Tanaka H, Hayashi M, Date C, et al.  Epidemiologic studies of stroke in Shibata, a Japanese provincial city (preliminary report on risk factors for cerebral infarction). Stroke. 1985;16:773–780
  196. Tanaka H, Ueda Y, Hayashi M, et al.  Risk factors for cerebral hemorrhage and cerebral infarction in a Japanese rural community. Stroke. 1982;13:62–73
  197. Tibblin G. High blood pressure in men aged 50—a population study of men born in 1913. Acta Med Scand. 1967;470(Suppl):1–84
  198. Tolias YA, Panas SM. A fuzzy vessel tracking algorithm for retinal images based on fuzzy clustering. IEEE Trans Med Imaging. 1998;17:263–273
  199. Tomikawa S, Mezawa M, Yoshida Y, et al: [Lipoprotein (a) and sclerotic changes in retinal arterioles]. Nippon Ganka Gakkai Zasshi 97:967–74, 1993
  200. Tso MO, Jampol LM. Pathophysiology of hypertensive retinopathy. Ophthalmology. 1982;89:1132–1145
  201. Tso MOM, Abrams GW, Jampol LM. Hypertensive retinopathy, choroidopathy, and optic neuropathy (a clinical and pathophysiological approach to classification). In:  Singerman LJ,  Jampol LM editor. Retinal and Choroidal Manifestations of Systemic Disease. Baltimore: Williams and Wilkins; 1991;p. 79–127
  202. van Buchem FSP, van der Heuvel-Aghina J, ven der Heuvel J. Hypertension and changes of the fundus oculi. Acta Med Scand. 1964;176:539–548
  203. van den Hoogen PC, Feskens EJ, Nagelkerke NJ, et al.  The relation between blood pressure and mortality due to coronary heart disease among men in different parts of the world. Seven Countries Study Research Group. N Engl J Med. 2000;342:1–8
  204. van Meurs JC, Schwoerer J, Schwartz B, et al.  Retinal vessel autoregulation in sickle cell patients. Graefes Arch Clin Exp Ophthalmol. 1992;230:442–445
  205. Vogelius H, Bechgaard P. The ophthalmoscopical appearance of the fundus oculi in elderly persons with arteriosclerosis and normal blood pressures. Br J Ophthalmol. 1950;34:404–408
  206. Wagener HP, Clay GE, Gipner JF. Classification of retinal lesions in the presence of vascular hypertension. Trans Am Ophthalmol Soc. 1947;45:57–73
  207. Wagener HP, Keith NM. Diffuse arteriolar disease with hypertension and the associated retinal lesions. Medicine. 1939;18:317–430
  208. Walsh JB. Hypertensive retinopathy. Description, classification, and prognosis. Ophthalmology. 1982;89:1127–1131
  209. Ward NP, Tomlinson S, Taylor CJ. Image analysis of fundus photographs. The detection and measurement of exudates associated with diabetic retinopathy. Ophthalmology. 1989;96:80–86
  210. Wells RE, Herman M, Gorlin R. Microvascular changes in coronary artery disease. Circulation. 1966;33–34:237
  211. Wendland JP. Retinal arteriolosclerosis in age, essential hypertension, and diabetes mellitus. Trans Am Ophthalmol Soc. 1966;64:735–761
  212. Wertheim AR, Deming QB. Management of the patient with primary (essential) hypertension. J Chronic Dis. 1955;1:574–588
  213. Whisnant JP, Wiebers DO, OFallon WM, et al.  A population-based model of risk factors for ischemic stroke (Rochester, Minnesota). Neurology. 1996;47:1420–1428
  214. Wiggins RL, Vaughan KD, Friedmann GB. Fundus camera holography of retinal microvasculature. Arch Ophthalmol. 1972;88:75–79
  215. Wilson TM, Constable IJ, Cooper RL, Alder VA. Image splitting—a technique for measuring retinal vascular reactivity. Br J Ophthalmol. 1981;65:291–293
  216. Wise GN, Dollery CT, Henkind P. In: The Retinal Circulation. New York: Harper and Row; 1971;p. 325
  217. Wolf PA, DAgostino RB, Belanger AJ, Kannel WB. Probability of stroke (a risk profile from the Framingham Study). Stroke. 1991;22:312–318
  218. Wolf PA, DAgostino RB, Kannel WB, et al.  Cigarette smoking as a risk factor for stroke. The Framingham Study. JAMA. 1988;259:1025–1029
  219. Wu DC, Schwartz B, Schwoerer J, Banwatt R. Retinal blood vessel width measured on color fundus photographs by image analysis. Acta Ophthalmol Scand. 1995;215(Suppl):33–40
  220. You R, McNeil JJ, OMalley HM, et al.  Risk factors for lacunar infarction syndromes. Neurology. 1995;45:1483–1487
  221. Yu T, Mitchell P, Berry G, et al.  Retinopathy in older persons without diabetes and its relationship to hypertension. Arch Ophthalmol. 1998;116:83–89

PII: S0039-6257(01)00234-X

Survey of Ophthalmology
Volume 46, Issue 1 , Pages 59-80 , July 2001