Diabetic Macular Ischemia

  • Scott E. Pautler


Diabetic retinopathy encompasses many interrelated pathological changes that occur in the retina of diabetic patients. Retinal ischemia has received much attention as a primary risk factor for the development of proliferative diabetic retinopathy.1 Ischemia affecting the macula has received less attention in the literature likely due to difficulty in detection and lack of treatment options.2 Retinal capillary nonperfusion was first described by Ashton using India ink preparations of the diabetic retina (Fig. 1).3 Subsequent histological studies revealed acellular capillaries in zones of nonperfusion (Fig. 2).4–7


Vascular Endothelial Growth Factor Diabetic Retinopathy Macular Edema Fluorescein Angiography Diabetic Macular Edema 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Fluorescein angiographic risk factors for progression of diabetic retinopathy. 0TDRS report number 13. Early treatment diabetic retinopathy study research group. Ophthalmology. 1991;98:834–40.Google Scholar
  2. 2.
    Conrath J, Giorgi R, Ridings B, Raccah D. Metabolic factors and the foveal avascular zone of the retina in diabetes mellitus. Diabetes Metab. 2005;31:465–470.PubMedGoogle Scholar
  3. 3.
    Ashton N. Arteriolar involvement in diabetic retinopathy. Br J Ophthalmol. 1953;37:282–292.PubMedGoogle Scholar
  4. 4.
    Garner A. Histopathology of diabetic retinopathy in man. Eye. 1993;7(Pt 2):250–253.PubMedGoogle Scholar
  5. 5.
    Cogan DG, Toussant D, Kuwabara T. Retinal vascular patterns. IV. Diabetic retinopathy. Arch Ophthalmol. 1961;66:366–378.PubMedGoogle Scholar
  6. 6.
    Kuwabara T, Cogan DG. Retinal vascular patterns. VI. Mural cells of the retinal capillaries. Arch Ophthalmol. 1963;69:492–502.PubMedGoogle Scholar
  7. 7.
    Bresnick GH, Engerman R, Davis MD, et al. Patterns of ischemia in diabetic retinopathy. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol. 1976;81:OP694–OP709.PubMedGoogle Scholar
  8. 8.
    Classification of diabetic retinopathy from fluorescein angiograms. ETDRS report number 11. Early treatment diabetic retinopathy study research group. Ophthalmology. 1991;98:807–822.Google Scholar
  9. 9.
    Kohner EM, Henkind P. Correlation of fluorescein angiogram and retinal digest in diabetic retinopathy. Am J Ophthalmol. 1970;69:403–414.PubMedGoogle Scholar
  10. 10.
    UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317:703–713.Google Scholar
  11. 11.
    UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–853.Google Scholar
  12. 12.
    The Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. Arch Ophthalmol. 1995;113:36–51.Google Scholar
  13. 13.
    Conrath J, Giorgi R, Raccah D, Ridings B. Foveal avascular zone in diabetic retinopathy: quantitative vs. qualitative assessment3. Eye. 2005;19:322–326.PubMedGoogle Scholar
  14. 14.
    Golubovic-Arsovska M. Correlation of diabetic maculopathy and level of diabetic retinopathy. Prilozi. 2006;27:139–150.PubMedGoogle Scholar
  15. 15.
    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.PubMedGoogle Scholar
  16. 16.
    Klein R, Klein BE, Moss SE, et al. The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol. 1984;102:527–532.PubMedGoogle Scholar
  17. 17.
    Golubovic-Arsovska M. Correlation of diabetic maculopathy and level of diabetic retinopathy. Prilozi. 2006;27:139–150.PubMedGoogle Scholar
  18. 18.
    Flynn HW, Jr., Chew EY, Simons BD, et al. Pars plana vitrectomy in the early treatment diabetic retinopathy study. ETDRS report number 17. The early treatment diabetic retinopathy study research group. Ophthalmology. 1992;99:1351–1357.Google Scholar
  19. 19.
    Tsilibary EC. Microvascular basement membranes in diabetes mellitus. J Pathol. 2003;200:537–546.PubMedGoogle Scholar
  20. 20.
    Ljubimov AV, Burgeson RE, Butkowski RJ, et al. Basement membrane abnormalities in human eyes with diabetic retinopathy. J Histochem Cytochem. 1996;44:1469–1479.PubMedGoogle Scholar
  21. 21.
    Frank RN. Aldose reductase activity and basement membrane thickening. Metabolism. 1986;35:35–40.PubMedGoogle Scholar
  22. 22.
    Kuiper EJ, Hughes JM, Van Geest RJ, et al. Effect of VEGF-A on expression of profibrotic growth factor and extracellular matrix genes in the retina. Invest Ophthalmol Vis Sci. 2007;48:4267–4276.PubMedGoogle Scholar
  23. 23.
    Arjamaa O, Nikinmaa M. Oxygen-dependent diseases in the retina: role of hypoxia-inducible factors. Exp Eye Res. 2006;83:473–483.PubMedGoogle Scholar
  24. 24.
    Gardiner TA, Anderson HR, Stitt AW. Inhibition of advanced glycation end-products protects against retinal capillary basement membrane expansion during long-term diabetes. J Pathol. 2003;201:328–333.PubMedGoogle Scholar
  25. 25.
    Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004;25:581–611.PubMedGoogle Scholar
  26. 26.
    Glaser BM, Kalebic T, Garbisa S, et al. Degradation of basement membrane components by vascular endothelial cells: role in neovascularization. Ciba Found Symp. 1983;100:150–162.PubMedGoogle Scholar
  27. 27.
    Williamson JR, Kilo C. Basement-membrane thickening and diabetic microangiopathy. Diabetes. 1976;25:925–927.PubMedGoogle Scholar
  28. 28.
    Zarbin MA. Age-related macular degeneration: review of pathogenesis. Eur J Ophthalmol. 1998;8:199–206.PubMedGoogle Scholar
  29. 29.
    Wayland H. Permeability characteristics of microvascular walls. Biorheology. 1984;21:107–120.PubMedGoogle Scholar
  30. 30.
    Shepro D, Morel NM. Pericyte physiology. FASEB J. 1993;7:1031–1038.PubMedGoogle Scholar
  31. 31.
    Matsugi T, Chen Q, Anderson DR. Contractile responses of cultured bovine retinal pericytes to angiotensin II. Arch Ophthalmol. 1997;115:1281–1285.PubMedGoogle Scholar
  32. 32.
    Butryn RK, Ruan H, Hull CM, Frank RN. Vasoactive agonists do not change the caliber of retinal capillaries of the rat. Microvasc Res. 1995;50:80–93.PubMedGoogle Scholar
  33. 33.
    Nachman RL, Rafii S. Platelets, petechiae, and preservation of the vascular wall. N Engl J Med. 2008;359:1261–1270.PubMedGoogle Scholar
  34. 34.
    Mizutani M, Kern TS, Lorenzi M. Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy. J Clin Invest. 1996;97:2883–2890.PubMedGoogle Scholar
  35. 35.
    Pfister F, Feng Y, von Hagen F, et al. Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes. 2008;57:2495–2502.PubMedGoogle Scholar
  36. 36.
    Beltramo E, Buttiglieri S, Pomero F, et al. A study of capillary pericyte viability on extracellular matrix produced by endothelial cells in high glucose. Diabetologia. 2003;46:409–415.PubMedGoogle Scholar
  37. 37.
    Li W, Yanoff M, Liu X, Ye X. Retinal capillary pericyte apoptosis in early human diabetic retinopathy. Chin Med J (Engl). 1997;110:659–663.Google Scholar
  38. 38.
    Hammes HP, Lin J, Renner O, et al. Pericytes and the pathogenesis of diabetic retinopathy. Diabetes. 2002;51:3107–3112.PubMedGoogle Scholar
  39. 39.
    Nayak RC, Lynch K, Gustavsson C, et al. Circulating antipericyte autoantibodies: a novel modifier of risk of progression of diabetic retinopathy? Retina. 2007;27:211–215.PubMedGoogle Scholar
  40. 40.
    Nayak RC, Agardh E, Kwok MG, et al. Albuminuria and hypertension are independently associated with circulating antipericyte autoantibodies in type 2 diabetic patients. Metabolism. 2005;54:188–193.PubMedGoogle Scholar
  41. 41.
    Attawia MA, Nayak RC. Circulating antipericyte autoantibodies in diabetic retinopathy. Retina. 1999;19:390–400.PubMedGoogle Scholar
  42. 42.
    El-Osta A, Brasacchio D, Yao D, et al. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med. 2008;205:2409–2417.PubMedGoogle Scholar
  43. 43.
    Brownlee M, Cerami A. The biochemistry of the complications of diabetes mellitus. Annu Rev Biochem. 1981;50:385–432.PubMedGoogle Scholar
  44. 44.
    Brownlee M, Vlassara H, Cerami A. Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med. 1984;101:527–537.PubMedGoogle Scholar
  45. 45.
    Tesfamariam B. Free radicals in diabetic endothelial cell dysfunction. Free Radic Biol Med. 1994;16:383–391.PubMedGoogle Scholar
  46. 46.
    Kuroki M, Voest EE, Amano S, et al. Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo. J Clin Invest. 1996;98:1667–1675.PubMedGoogle Scholar
  47. 47.
    Du Y, Smith MA, Miller CM, Kern TS. Diabetes-induced nitrative stress in the retina, and correction by aminoguanidine. J Neurochem. 2002;80:771–779.PubMedGoogle Scholar
  48. 48.
    Adamis AP. Is diabetic retinopathy an inflammatory disease? Br J Ophthalmol. 2002;86:363–365.PubMedGoogle Scholar
  49. 49.
    Gabbay KH. The sorbitol pathway and the complications of diabetes. N Engl J Med. 1973;288:831–836.PubMedGoogle Scholar
  50. 50.
    Xia P, Inoguchi T, Kern TS, et al. Characterization of the mechanism for the chronic activation of diacylglycerol-protein kinase C pathway in diabetes and hypergalactosemia. Diabetes. 1994;43:1122–1129.PubMedGoogle Scholar
  51. 51.
    Grant MB, Afzal A, Spoerri P, et al. The role of growth factors in the pathogenesis of diabetic retinopathy. Expert Opin Invest Drugs. 2004;13:1275–1293.Google Scholar
  52. 52.
    Aiello LP. The potential role of PKC beta in diabetic retinopathy and macular edema. Surv Ophthalmol. 2002;47(Suppl 2):S263–S269.PubMedGoogle Scholar
  53. 53.
    Aiello LP, Wong JS. Role of vascular endothelial growth factor in diabetic vascular complications. Kidney Int Suppl. 2000;77:S113–S119.PubMedGoogle Scholar
  54. 54.
    Deinum J, Chaturvedi N. The Renin-Angiotensin system and vascular disease in diabetes. Semin Vasc Med. 2002;2:149–156.PubMedGoogle Scholar
  55. 55.
    Stellmach V, Crawford SE, Zhou W, Bouck N. Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor. Proc Natl Acad Sci USA. 2001;98:2593–2597.PubMedGoogle Scholar
  56. 56.
    Gupta K, Kshirsagar S, Li W, et al. VEGF prevents apoptosis of human microvascular endothelial cells via opposing effects on MAPK/ERK and SAPK/JNK signaling. Exp Cell Res. 1999;247:495–504.PubMedGoogle Scholar
  57. 57.
    Chibber R, Ben-Mahmud BM, Chibber S, Kohner EM. Leukocytes in diabetic retinopathy. Curr Diabetes Rev. 2007;3:3–14.PubMedGoogle Scholar
  58. 58.
    De La Cruz JP, Moreno A, Guerrero A, de la Cuesta FS. Antiplatelet effects of prostacyclin and nitric oxide in patients with type I diabetes and ischemic or edematous retinopathy. Platelets. 2001;12:210–217.Google Scholar
  59. 59.
    Joussen AM, Poulaki V, Mitsiades N, et al. Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. FASEB J. 2002;16:438–440.PubMedGoogle Scholar
  60. 60.
    Joussen AM, Murata T, Tsujikawa A, et al. Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am J Pathol. 2001;158:147–152.PubMedGoogle Scholar
  61. 61.
    Giusti C, Schiaffini R, Brufani C, et al. Coagulation pathways and diabetic retinopathy: abnormal modulation in a selected group of insulin dependent diabetic patients. Br J Ophthalmol. 2000;84:591–595.PubMedGoogle Scholar
  62. 62.
    McMillan DE. Development of vascular complications in diabetes. Vasc Med. 1997;2:132–142.PubMedGoogle Scholar
  63. 63.
    Nishijima K, Kiryu J, Tsujikawa A, et al. Platelets adhering to the vascular wall mediate postischemic leukocyte-endothelial cell interactions in retinal microcirculation. Invest Ophthalmol Vis Sci. 2004;45:977–984.PubMedGoogle Scholar
  64. 64.
    Yamashiro K, Tsujikawa A, Ishida S, et al. Platelets accumulate in the diabetic retinal vasculature following endothelial death and suppress blood-retinal barrier breakdown. Am J Pathol. 2003;163:253–259.PubMedGoogle Scholar
  65. 65.
    Wilson SH, Ljubimov AV, Morla AO, et al. Fibronectin fragments promote human retinal endothelial cell adhesion and proliferation and ERK activation through alpha5beta1 integrin and PI 3-kinase. Invest Ophthalmol Vis Sci. 2003;44:1704–1715.PubMedGoogle Scholar
  66. 66.
    Hofman P, van Blijswijk BC, Gaillard PJ, et al. Endothelial cell hypertrophy induced by vascular endothelial growth factor in the retina: new insights into the pathogenesis of capillary nonperfusion. Arch Ophthalmol. 2001;119:861–866.PubMedGoogle Scholar
  67. 67.
    Boeri D, Maiello M, Lorenzi M. Increased prevalence of microthromboses in retinal capillaries of diabetic individuals. Diabetes. 2001;50:1432–1439.PubMedGoogle Scholar
  68. 68.
    McLeod D. A chronic grey matter penumbra, lateral microvascular intussusception and venous peduncular avulsion underlie diabetic vitreous haemorrhage. Br J Ophthalmol. 2007;91:677–689.PubMedGoogle Scholar
  69. 69.
    Barouch FC, Miyamoto K, Allport JR, et al. Integrin-mediated neutrophil adhesion and retinal leukostasis in diabetes. Invest Ophthalmol Vis Sci. 2000;41:1153–1158.PubMedGoogle Scholar
  70. 70.
    Ogura Y. In vivo evaluation of leukocyte dynamics in the retinal and choroidal circulation. Jpn J Ophthalmol. 2000;44:322–323.PubMedGoogle Scholar
  71. 71.
    Lutty GA, Cao J, McLeod DS. Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid. Am J Pathol. 1997;151:707–714.PubMedGoogle Scholar
  72. 72.
    Bek T. Glial cell involvement in vascular occlusion of diabetic retinopathy. Acta Ophthalmol Scand. 1997;75:239–243.PubMedGoogle Scholar
  73. 73.
    Vinores SA, Youssri AI, Luna JD, et al. Upregulation of vascular endothelial growth factor in ischemic and non-ischemic human and experimental retinal disease. Histol Histopathol. 1997;12:99–109.PubMedGoogle Scholar
  74. 74.
    Petrovic MG, Korosec P, Kosnik M, et al. Local and genetic determinants of vascular endothelial growth factor expression in advanced proliferative diabetic retinopathy. Mol Vis. 2008;14:1382–1387.PubMedGoogle Scholar
  75. 75.
    Endo M, Yanagisawa K, Tsuchida K, et al. Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy. Horm Metab Res. 2001;33:317–322.PubMedGoogle Scholar
  76. 76.
    Deissler H, Deissler H, Lang S, Lang GE. VEGF-induced effects on proliferation, migration and tight junctions are restored by ranibizumab (Lucentis) in microvascular retinal endothelial cells. Br J Ophthalmol. 2008;92:839–843.PubMedGoogle Scholar
  77. 77.
    Nguyen QD, Tatlipinar S, Shah SM, et al. Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. Am J Ophthalmol. 2006;142:961–969.PubMedGoogle Scholar
  78. 78.
    Lange J, Yafai Y, Reichenbach A, et al. Regulation of pigment epithelium-derived factor production and release by retinal glial (Mueller) cells under hypoxia. Invest Ophthalmol Vis Sci. 2008;49:5161–5167.PubMedGoogle Scholar
  79. 79.
    Ramsay WJ, Ramsay RC, Purple RL, Knobloch WH. Involutional diabetic retinopathy. Am J Ophthalmol. 1977;84:851–858.PubMedGoogle Scholar
  80. 80.
    Nishijima K, Ng YS, Zhong L, et al. Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. Am J Pathol. 2007;171:53–67.PubMedGoogle Scholar
  81. 81.
    Chung EJ, Roh MI, Kwon OW, Koh HJ. Effects of macular ischemia on the outcome of intravitreal bevacizumab therapy for diabetic macular edema. Retina. 2008;28:957–963.PubMedGoogle Scholar
  82. 82.
    Chen E, Hsu J, Park CH. Acute visual acuity loss following intravitreal bevacizumab for diabetic macular edema. Ophthalmic Surg Lasers Imaging. 2009;40:68–70.PubMedGoogle Scholar
  83. 83.
    McDonald HR. Diagnostic and therapeutic challenges. Retina. 2009;28:1357–1360.Google Scholar
  84. 84.
    Kook D, Wolf A, Kreutzer T, et al. Long-term effect of intravitreal bevacizumab (avastin) in patients with chronic diffuse diabetic macular edema. Retina. 2008;28:1053–1060.PubMedGoogle Scholar
  85. 85.
    Bonini-Filho M, Costa RA, Calucci D, et al. Intravitreal Bevacizumab for diabetic macular edema associated with severe capillary loss: one-year results of a pilot study. Am J Ophthalmol. 2009; 147:1022–30.Google Scholar
  86. 86.
    Neubauer AS, Kook D, Haritoglou C, et al. Bevacizumab and retinal ischemia. Ophthalmology. 2007;114:2096.PubMedGoogle Scholar
  87. 87.
    Avery RL. Regression of retinal and iris neovascularization after intravitreal bevacizumab (Avastin) treatment. Retina. 2006;26:352–354.PubMedGoogle Scholar
  88. 88.
    Gardner TW, Antonetti DA, Barber AJ, et al. Diabetic retinopathy: more than meets the eye. Surv Ophthalmol. 2002;47(Suppl 2):S253–S262.PubMedGoogle Scholar
  89. 89.
    Fletcher EL, Phipps JA, Ward MM, et al. Neuronal and glial cell abnormality as predictors of progression of diabetic retinopathy. Curr Pharm Des. 2007;13:2699–2712.PubMedGoogle Scholar
  90. 90.
    Tzekov R, Arden GB. The electroretinogram in diabetic retinopathy. Surv Ophthalmol. 1999;44:53–60.PubMedGoogle Scholar
  91. 91.
    Yoshida A, Kojima M, Ogasawara H, Ishiko S. Oscillatory potentials and permeability of the blood-retinal barrier in noninsulin-dependent diabetic patients without retinopathy. Ophthalmology. 1991;98:1266–1271.PubMedGoogle Scholar
  92. 92.
    Li Q, Zemel E, Miller B, Perlman I. Early retinal damage in experimental diabetes: electroretinographical and morphological observations. Exp Eye Res. 2002;74:615–625.PubMedGoogle Scholar
  93. 93.
    Shimada Y, Li Y, Bearse MA Jr, et al. Assessment of early retinal changes in diabetes using a new multifocal ERG protocol. Br J Ophthalmol. 2001;85:414–419.PubMedGoogle Scholar
  94. 94.
    Ewing FM, Deary IJ, Strachan MW, Frier BM. Seeing beyond retinopathy in diabetes: electrophysiological and psychophysical abnormalities and alterations in vision. Endocr Rev. 1998;19:462–476.PubMedGoogle Scholar
  95. 95.
    Barton FB, Fong DS, Knatterud GL. Classification of Farnsworth-Munsell 100-hue test results in the early treatment diabetic retinopathy study. Am J Ophthalmol. 2004;138:119–124.PubMedGoogle Scholar
  96. 96.
    Ong GL, Ripley LG, Newsom RS, Casswell AG. Assessment of colour vision as a screening test for sight threatening diabetic retinopathy before loss of vision. Br J Ophthalmol. 2003;87:747–752.PubMedGoogle Scholar
  97. 97.
    Han Y, Adams AJ, Bearse MA Jr, Schneck ME. Multifocal electroretinogram and short-wavelength automated perimetry measures in diabetic eyes with little or no retinopathy. Arch Ophthalmol. 2004;122:1809–1815.PubMedGoogle Scholar
  98. 98.
    Arden GB, Wolf JE, Tsang Y. Does dark adaptation exacerbate diabetic retinopathy? Evidence and a linking hypothesis. Vision Res. 1998;38:1723–1729.PubMedGoogle Scholar
  99. 99.
    Kaneko M, Sugawara T, Tazawa Y. Electrical responses from the inner retina of rats with streptozotocin-induced early diabetes mellitus. Nippon Ganka Gakkai Zasshi. 2000;104:775–778.PubMedGoogle Scholar
  100. 100.
    Klemp K, Larsen M, Sander B, et al. Effect of short-term hyperglycemia on multifocal electroretinogram in diabetic patients without retinopathy. Invest Ophthalmol Vis Sci. 2004;45:3812–19.Google Scholar
  101. 101.
    Lonneville YH, Ozdek SC, Onol M, et al. The effect of blood glucose regulation on retinal nerve fiber layer thickness in diabetic patients. Ophthalmologica. 2003;217:347–350.PubMedGoogle Scholar
  102. 102.
    Zheng L, Gong B, Hatala DA, Kern TS. Retinal ischemia and reperfusion causes capillary degeneration: similarities to diabetes. Invest Ophthalmol Vis Sci. 2007;48:361–367.PubMedGoogle Scholar
  103. 103.
    Chavakis E, Dimmeler S. Regulation of endothelial cell survival and apoptosis during angiogenesis. Arterioscler Thromb Vasc Biol. 2002;22:887–893.PubMedGoogle Scholar
  104. 104.
    Amin RH, Frank RN, Kennedy A, et al. Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 1997;38:36–47.PubMedGoogle Scholar
  105. 105.
    Jin KL, Mao XO, Greenberg DA. Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia. Proc Natl Acad Sci USA. 2000;97:10242–10247.PubMedGoogle Scholar
  106. 106.
    Pulido JE, Pulido JS, Erie JC, et al. A role for excitatory amino acids in diabetic eye disease. Exp Diabetes Res. 2007;2007:36150.PubMedGoogle Scholar
  107. 107.
    Hardy P, Beauchamp M, Sennlaub F, et al. New insights into the retinal circulation: inflammatory lipid mediators in ischemic retinopathy. Prostaglandins Leukot Essent Fatty Acids. 2005;72:301–325.PubMedGoogle Scholar
  108. 108.
    Nao-i N, Fukiyama J, Sawada A. Retinitis pigmentosa with recurrent vitreous hemorrhage. Acta Ophthalmol Scand. 1996;74:509–512.PubMedGoogle Scholar
  109. 109.
    Catalani E, Cervia D, Martini D, et al. Changes in neuronal response to ischemia in retinas with genetic alterations of somatostatin receptor expression. Eur J Neurosci. 2007;25:1447–1459.PubMedGoogle Scholar
  110. 110.
    Mali RS, Cheng M, Chintala SK. Plasminogen activators promote excitotoxicity-induced retinal damage. FASEB J. 2005;19:1280–1289.PubMedGoogle Scholar
  111. 111.
    Puro DG. Diabetes-induced dysfunction of retinal Muller cells. Trans Am Ophthalmol Soc. 2002;100:339–352.PubMedGoogle Scholar
  112. 112.
    Fong DS, Strauber SF, Aiello LP, et al. Comparison of the modified early treatment diabetic retinopathy study and mild macular grid laser photocoagulation strategies for diabetic macular edema. Arch Ophthalmol. 2007;125:469–480.PubMedGoogle Scholar
  113. 113.
    Arend O, Wolf S, Jung F, et al. Retinal microcirculation in patients with diabetes mellitus: dynamic and morphological analysis of perifoveal capillary network. Br J Ophthalmol. 1991;75:514–518.PubMedGoogle Scholar
  114. 114.
    Focal photocoagulation treatment of diabetic macular edema. Relationship of treatment effect to fluorescein angiographic and other retinal characteristics at baseline: ETDRS report no. 19. early treatment diabetic retinopathy study research group. Arch Ophthalmol. 1995;113:1144–1155.Google Scholar
  115. 115.
    Mansour AM, Schachat A, Bodiford G, Haymond R. Foveal avascular zone in diabetes mellitus. Retina. 1993;13:125–128.PubMedGoogle Scholar
  116. 116.
    Sander B, Larsen M, Engler C, et al. Early changes in diabetic retinopathy: capillary loss and blood-retina barrier permeability in relation to metabolic control. Acta Ophthalmol (Copenh). 1994;72:553–559.Google Scholar
  117. 117.
    Scott IU, Amirikia A, Flynn HW, Jr. Improved retinal capillary perfusion following treatment of severe proliferative diabetic retinopathy. Ophthalmic Surg Lasers. 2000;31:148–150.PubMedGoogle Scholar
  118. 118.
    Takahashi K, Kishi S, Muraoka K, Shimizu K. Reperfusion of occluded capillary beds in diabetic retinopathy. Am J Ophthalmol. 1998;126:791–797.PubMedGoogle Scholar
  119. 119.
    Kohner EM. The evolution and natural history of diabetic retinopathy. Int Ophthalmol Clin. 1978;18:1–16.PubMedGoogle Scholar
  120. 120.
    de B, I, Kestenbaum B, Rue TC, et al. Insulin therapy, hyperglycemia, and hypertension in type 1 diabetes mellitus. Arch Intern Med. 2008;168:1867–1873.Google Scholar
  121. 121.
    Li HY, Wei JN, Sung FC, Chuang LM. Higher rate of obesity and hypertension in adolescents with type 2 diabetes than in those with type 1 diabetes. Diabetes Care. 2006;29:2326.PubMedGoogle Scholar
  122. 122.
    Eppens MC, Craig ME, Cusumano J, et al. Prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes. Diabetes Care. 2006;29:1300–1306.PubMedGoogle Scholar
  123. 123.
    Grading diabetic retinopathy from stereoscopic color fundus photographs–an extension of the modified Airlie House classification. ETDRS report number 10. early treatment diabetic retinopathy study research group. Ophthalmology. 1991;98:786–806.Google Scholar
  124. 124.
    Bresnick GH, de Venecia G, Myers FL, et al. Retinal ischemia in diabetic retinopathy. Arch Ophthalmol. 1975;93:1300–1310.PubMedGoogle Scholar
  125. 125.
    Goldbaum MH. Retinal depression sign indicating a small retinal infarct. Am J Ophthalmol. 1978;86:45–55.PubMedGoogle Scholar
  126. 126.
    Bresnick GH, Condit R, Syrjala S, et al. Abnormalities of the foveal avascular zone in diabetic retinopathy. Arch Ophthalmol. 1984;102:1286–1293.PubMedGoogle Scholar
  127. 127.
    Bligard E, de Venesia G, Wallow I, et al. Aging changes of the parafoveal vasculature. Invest Ophthalmol Vis Sci. 1982;22(suppl):8.Google Scholar
  128. 128.
    Laatikainen L, Larinkari J. Capillary-free area of the fovea with advancing age. Invest Ophthalmol Vis Sci. 1977;16:1154–1157.PubMedGoogle Scholar
  129. 129.
    Arend O, Wolf S, Harris A, Reim M. The relationship of macular microcirculation to visual acuity in diabetic patients. Arch Ophthalmol. 1995;113:610–614.PubMedGoogle Scholar
  130. 130.
    Parodi MB, Visintin F, Della RP, Ravalico G. Foveal avascular zone in macular branch retinal vein occlusion. Int Ophthalmol. 1995;19:25–28.PubMedGoogle Scholar
  131. 131.
    Bradley A, Applegate RA, Zeffren BS, van Heuven WA. Psychophysical measurement of the size and shape of the human foveal avascular zone. Ophthalmic Physiol Opt. 1992;12:18–23.PubMedGoogle Scholar
  132. 132.
    Goebel W, Kretzchmar-Gross T. Retinal thickness in diabetic retinopathy: a study using optical coherence tomography (OCT). Retina. 2002;22:759–767.PubMedGoogle Scholar
  133. 133.
    Mason JO, III, Colagross CT, Haleman T, et al. Visual outcome and risk factors for light perception and no light perception vision after vitrectomy for diabetic retinopathy. Am J Ophthalmol. 2005;140:231–235.PubMedGoogle Scholar
  134. 134.
    Pendergast SD, Hassan TS, Williams GA, et al. Vitrectomy for diffuse diabetic macular edema associated with a taut premacular posterior hyaloid. Am J Ophthalmol. 2000;130:178–186.PubMedGoogle Scholar
  135. 135.
    Jonas JB, Martus P, Degenring RF, et al. Predictive factors for visual acuity after intravitreal triamcinolone treatment for diabetic macular edema. Arch Ophthalmol. 2005;123:1338–1343.PubMedGoogle Scholar
  136. 136.
    Wilkinson CP, Ferris FL, III, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110:1677–1682.PubMedGoogle Scholar
  137. 137.
    McDonald HR, Williams GA, Scott IU, et al. Laser scanning imaging for macular disease: a report by the American academy of ophthalmology. Ophthalmology. 2007;114:1221–1228.Google Scholar
  138. 138.
    Nilsson M, von WG, Wanger P, Martin L. Early detection of macular changes in patients with diabetes using Rarebit Fovea Test and optical coherence tomography. Br J Ophthalmol. 2007;91:1596–1598.PubMedGoogle Scholar
  139. 139.
    Biallosterski C, van Velthoven ME, Michels RP, et al. Decreased optical coherence tomography-measured pericentral retinal thickness in patients with diabetes mellitus type 1 with minimal diabetic retinopathy. Br J Ophthalmol. 2007;91:1135–1138.PubMedGoogle Scholar
  140. 140.
    Oshitari T, Hanawa K, chi-Usami E. Changes of macular and RNFL thicknesses measured by Stratus OCT in patients with early stage diabetes. Eye. 2009;23:884–889.Google Scholar
  141. 141.
    Unoki N, Nishijima K, Sakamoto A, et al. Retinal sensitivity loss and structural disturbance in areas of capillary nonperfusion of eyes with diabetic retinopathy. Am J Ophthalmol. 2007;144:755–760.PubMedGoogle Scholar
  142. 142.
    Lang GE. Optical coherence tomography findings in diabetic retinopathy. Dev Ophthalmol. 2007;39:31–47.PubMedGoogle Scholar
  143. 143.
    Gupta P, Sadun AA, Sebag J. Multifocal retinal contraction in macular pucker analyzed by combined optical coherence tomography/scanning laser ophthalmoscopy. Retina. 2008;28:447–452.PubMedGoogle Scholar
  144. 144.
    Brasil OF, Smith SD, Galor A, et al. Predictive factors for short-term visual outcome after intravitreal triamcinolone acetonide injection for diabetic macular oedema: an optical coherence tomography study. Br J Ophthalmol. 2007;91:761–765.PubMedGoogle Scholar
  145. 145.
    Soliman W, Sander B, Jorgensen TM. Enhanced optical coherence patterns of diabetic macular oedema and their correlation with the pathophysiology. Acta Ophthalmol Scand. 2007;85:613–617.PubMedGoogle Scholar
  146. 146.
    Sakata K, Funatsu H, Harino S, et al. Relationship between macular microcirculation and progression of diabetic macular edema. Ophthalmology. 2006;113:1385–1391.PubMedGoogle Scholar
  147. 147.
    Bengtsson B, Heijl A, Agardh E. Visual fields correlate better than visual acuity to severity of diabetic retinopathy. Diabetologia. 2005;48:2494–2500.PubMedGoogle Scholar
  148. 148.
    Pahor D. Reduction of retinal light sensitivity in diabetic patients. Klin Monatsbl Augenheilkd. 2003;220:868–872.PubMedGoogle Scholar
  149. 149.
    Realini T, Lai MQ, Barber L. Impact of diabetes on glaucoma screening using frequency-doubling perimetry. Ophthalmology. 2004;111:2133–2136.PubMedGoogle Scholar
  150. 150.
    Verrotti A, Lobefalo L, Altobelli E, et al. Static perimetry and diabetic retinopathy: a long-term follow-up. Acta Diabetol. 2001;38:99–105.PubMedGoogle Scholar
  151. 151.
    Racette L, Sample PA. Short-wavelength automated perimetry. Ophthalmol Clin North Am. 2003;16:227-vii.Google Scholar
  152. 152.
    Bengtsson B, Hellgren KJ, Agardh E. Test-retest variability for standard automated perimetry and short-wavelength automated perimetry in diabetic patients. Acta Ophthalmol. 2008;86:170–176.PubMedGoogle Scholar
  153. 153.
    Federman JL, Lloyd J. Automated static perimetry to evaluate diabetic retinopathy. Trans Am Ophthalmol Soc. 1984;82:358–370.PubMedGoogle Scholar
  154. 154.
    Pahor D. Automated static perimetry as a screening method for evaluation of retinal perfusion in diabetic retinopathy. Int Ophthalmol. 1997;21:305–309.PubMedGoogle Scholar
  155. 155.
    Remky A, Arend O, Hendricks S. Short-wavelength automated perimetry and capillary density in early diabetic maculopathy. Invest Ophthalmol Vis Sci. 2000;41:274–281.PubMedGoogle Scholar
  156. 156.
    Agardh E, Stjernquist H, Heijl A, Bengtsson B. Visual acuity and perimetry as measures of visual function in diabetic macular oedema. Diabetologia. 2006;49:200–206.PubMedGoogle Scholar
  157. 157.
    Rohrschneider K, Bultmann S, Springer C. Use of fundus perimetry (microperimetry) to quantify macular sensitivity. Prog Retin Eye Res. 2008;27:536–548.PubMedGoogle Scholar
  158. 158.
    Takahashi H, Goto T, Shoji T, et al. Diabetes-associated retinal nerve fiber damage evaluated with scanning laser polarimetry. Am J Ophthalmol. 2006;142:88–94.PubMedGoogle Scholar
  159. 159.
    Lopes de Faria JM, Russ H, Costa VP. Retinal nerve fibre layer loss in patients with type 1 diabetes mellitus without retinopathy. Br J Ophthalmol. 2002;86:725–728.Google Scholar
  160. 160.
    Apaydin KC, Akar Y, Akar ME, et al. Menstrual cycle dependent changes in blue-on-yellow visual field analysis of young diabetic women with severe non-proliferative diabetic retinopathy. Clin Experiment Ophthalmol. 2004;32:265–269.PubMedGoogle Scholar
  161. 161.
    Fortune B, Schneck ME, Adams AJ. Multifocal electroretinogram delays reveal local retinal dysfunction in early diabetic retinopathy. Invest Ophthalmol Vis Sci. 1999;40:2638–2651.PubMedGoogle Scholar
  162. 162.
    Bronson-Castain KW, Bearse MA, Jr., Han Y, et al. Association between multifocal ERG implicit time delays and adaptation in patients with diabetes. Invest Ophthalmol Vis Sci. 2007;48:5250–5256.PubMedGoogle Scholar
  163. 163.
    Holm K, Larsson J, Lovestam-Adrian M. In diabetic retinopathy, foveal thickness of 300 mm seems to correlate with functionally significant loss of vision. Doc Ophthalmol. 2007;114:117–124.PubMedGoogle Scholar
  164. 164.
    Weiner A, Christopoulos VA, Gussler CH, et al. Foveal cone function in nonproliferative diabetic retinopathy and macular edema. Invest Ophthalmol Vis Sci. 1997;38:1443–1449.PubMedGoogle Scholar
  165. 165.
    Barton FB, Fong DS, Knatterud GL. Classification of Farnsworth-Munsell 100-hue test results in the early treatment diabetic retinopathy study. Am J Ophthalmol. 2004;138:119–124.PubMedGoogle Scholar
  166. 166.
    Barton FB, Fong DS, Knatterud GL. Classification of Farnsworth-Munsell 100-hue test results in the early treatment diabetic retinopathy study. Am J Ophthalmol. 2004;138:119–124.PubMedGoogle Scholar
  167. 167.
    Mortlock KE, Chiti Z, Drasdo N, et al. Silent substitution S-cone electroretinogram in subjects with diabetes mellitus. Ophthalmic Physiol Opt. 2005;25:392–399.PubMedGoogle Scholar
  168. 168.
    Cho NC, Poulsen GL, Ver Hoeve JN, Nork TM. Selective loss of S-cones in diabetic retinopathy. Arch Ophthalmol. 2000;118:1393–1400.PubMedGoogle Scholar
  169. 169.
    Barton FB, Fong DS, Knatterud GL. Classification of Farnsworth-Munsell 100-hue test results in the early treatment diabetic retinopathy study. Am J Ophthalmol. 2004;138:119–124.PubMedGoogle Scholar
  170. 170.
    Fong DS, Barton FB, Bresnick GH. Impaired color vision associated with diabetic retinopathy: early treatment diabetic retinopathy study report no. 15. Am J Ophthalmol. 1999;128:612–617.Google Scholar
  171. 171.
    Tregear SJ, Knowles PJ, Ripley LG, Casswell AG. Chromatic-contrast threshold impairment in diabetes. Eye. 1997;11(Pt 4):537–546.PubMedGoogle Scholar
  172. 172.
    Findl O, Dallinger S, Rami B, et al. Ocular haemodynamics and colour contrast sensitivity in patients with type 1 diabetes. Br J Ophthalmol. 2000;84:493–498.PubMedGoogle Scholar
  173. 173.
    Arend O, Remky A, Evans D, et al. Contrast sensitivity loss is coupled with capillary dropout in patients with diabetes. Invest Ophthalmol Vis Sci. 1997;38:1819–1824.PubMedGoogle Scholar
  174. 174.
    Talwar D, Sharma N, Pai A, et al. Contrast sensitivity following focal laser photocoagulation in clinically significant macular oedema due to diabetic retinopathy. Clin Exp Ophthalmol. 2001;29:17–21.Google Scholar
  175. 175.
    Verrotti A, Lobefalo L, Petitti MT, et al. Relationship between contrast sensitivity and metabolic control in diabetics with and without retinopathy. Ann Med. 1998;30:369–374.PubMedGoogle Scholar
  176. 176.
    Harris A, Arend O, Danis RP, et al. Hyperoxia improves contrast sensitivity in early diabetic retinopathy. Br J Ophthalmol. 1996;80:209–213.PubMedGoogle Scholar
  177. 177.
    Rimmer T, Fallon TJ, Kohner EM. Long-term follow-up of retinal blood flow in diabetes using the blue light entoptic phenomenon. Br J Ophthalmol. 1989;73:1–5.PubMedGoogle Scholar
  178. 178.
    Yap M, Gilchrist J, Weatherill J. Psychophysical measurement of the foveal avascular zone. Ophthalmic Physiol Opt. 1987;7:405–410.PubMedGoogle Scholar
  179. 179.
    Sinclair SH. Macular retinal capillary hemodynamics in diabetic patients. Ophthalmology. 1991;98:1580–1586.PubMedGoogle Scholar
  180. 180.
    Smith RT, Lee CM, Charles HC, et al. Quantification of diabetic macular edema. Arch Ophthalmol. 1987;105:218–222.PubMedGoogle Scholar
  181. 181.
    Fong DS, Ferris FL, III, Davis MD, Chew EY. Causes of severe visual loss in the early treatment diabetic retinopathy study: ETDRS report no. 24. Early treatment diabetic retinopathy study research group. Am J Ophthalmol. 1999;127:137–141.Google Scholar
  182. 182.
    Helbig H. Surgery for diabetic retinopathy. Ophthalmologica. 2007;221:103–111.PubMedGoogle Scholar
  183. 183.
    Shimizu K, Kobayashi Y, Muraoka K. Midperipheral fundus involvement in diabetic retinopathy. Ophthalmology. 1981;88:601–612.PubMedGoogle Scholar
  184. 184.
    Shukla D, Kolluru CM, Singh J, et al. Macular ischaemia as a marker for nephropathy in diabetic retinopathy. Indian J Ophthalmol. 2004;52:205–210.PubMedGoogle Scholar
  185. 185.
    Espiritu RB, Sy GT. Fluorescein angiographically evident diabetic maculopathy. Clin Hemorheol Microcirc. 2003;29:357–365.PubMedGoogle Scholar
  186. 186.
    Niki T, Muraoka K, Shimizu K. Distribution of capillary nonperfusion in early-stage diabetic retinopathy. Ophthalmology. 1984;91:1431–1439.PubMedGoogle Scholar
  187. 187.
    Ticho U, Patz A. The role of capillary perfusion in the management of diabetic macular edema. Am J Ophthalmol. 1973;76:880–886.PubMedGoogle Scholar
  188. 188.
    Photocoagulation for diabetic macular edema. Early treatment diabetic retinopathy study report number 1. Early treatment diabetic retinopathy study research group. Arch Ophthalmol. 1985;103:1796–1806.Google Scholar
  189. 189.
    Sakata K, Funatsu H, Harino S, et al. Relationship of macular microcirculation and retinal thickness with visual acuity in diabetic macular edema. Ophthalmology. 2007;114:2061–2069.PubMedGoogle Scholar
  190. 190.
    Cruess AF, Williams JC, Willan AR. Argon green and krypton red laser treatment of diabetic macular edema. Can J Ophthalmol 1988;23:262–266.PubMedGoogle Scholar
  191. 191.
    Gardner TW, Eller AW, Friberg TR. Reduction of severe macular edema in eyes with poor vision after panretinal photocoagulation for proliferative diabetic retinopathy. Graefe’s Arch Clin Exp Ophthalmol. 1991;229:323–328.Google Scholar
  192. 192.
    Olk RJ, Akduman L. Minimal intensity diode laser (810 nanometer) photocoagulation (MIP) for diffuse diabetic macular edema (DDME). Semin Ophthalmol. 2001;16:25–30.PubMedGoogle Scholar
  193. 193.
    Gastaud P, Negre F, Leguay JM. Surgical treatment of serous detachments of the macular neuroepithelium in diabetics. J Fr Ophthalmol. 1997;20:741–748.Google Scholar
  194. 194.
    Cunningham MA, Edelman JL, Kaushal S. Intravitreal steroids for macular edema: the past, the present, and the future. Surv Ophthalmol. 2008;53:139–149.PubMedGoogle Scholar
  195. 195.
    Mittra RA and Pollack JS, ASRS PAT Survey. 2008. Accessed November 15, 2008.
  196. 196.
    Lobo C, Bernardes R, Faria dA, Jr., Cunha-Vaz JG. Novel imaging techniques for diabetic macular edema. Doc Ophthalmol. 1999;97:341–347.PubMedGoogle Scholar
  197. 197.
    Lobo CL, Bernardes RC, Cunha-Vaz JG. Alterations of the blood-retinal barrier and retinal thickness in preclinical retinopathy in subjects with type 2 diabetes. Arch Ophthalmol. 2000;118:1364–1369.PubMedGoogle Scholar
  198. 198.
    Hayreh SS. Role of retinal hypoxia in diabetic macular edema: a new concept. Graefe’s Arch Clin Exp Ophthalmol. 2008;246:353–361.Google Scholar
  199. 199.
    Blair NP, Shahidi M, Lai WW, Zelkha R. Correlation between microaneurysms and retinal thickness in diabetic macular edema. Retina. 2008;28:1097–1103.PubMedGoogle Scholar
  200. 200.
    Averous K, Erginay A, Timsit J, et al. Resolution of diabetic macular oedema following high altitude exercise. Acta Ophthalmol Scand. 2006;84:830–831.PubMedGoogle Scholar
  201. 201.
    Daniele S, Daniele C. Aggravation of laser-treated diabetic cystoid macular edema after prolonged flight: a case report. Aviat Space Environ Med. 1995;66:440–442.Google Scholar
  202. 202.
    Lee M, Choi D, Choi MJ, et al. Hypoxia-inducible gene expression system using the erythropoietin enhancer and 3'-untranslated region for the VEGF gene therapy. J Control Release. 2006;115:113–119.PubMedGoogle Scholar
  203. 203.
    Browning DJ, Glassman AR, Aiello LP, et al. Relationship between optical coherence tomography-measured central retinal thickness and visual acuity in diabetic macular edema. Ophthalmology. 2007;114:525–536.PubMedGoogle Scholar
  204. 204.
    Srinivasan VJ, Wojtkowski M, Witkin AJ, et al. High-definition and 3-dimensional imaging of macular pathologies with high-speed ultrahigh-resolution optical coherence tomography. Ophthalmology. 2006;113:2054e1–14.Google Scholar
  205. 205.
    Lu M, Adamis AP. Vascular endothelial growth factor gene regulation and action in diabetic retinopathy. Ophthalmol Clin North Am. 2002;15:69–79.PubMedGoogle Scholar
  206. 206.
    El-Remessy AB, Bartoli M, Platt DH, et al. Oxidative stress inactivates VEGF survival signaling in retinal endothelial cells via PI 3-kinase tyrosine nitration. J Cell Sci. 2005;118:243–252.PubMedGoogle Scholar
  207. 207.
    Ring HG, Fujino T. Observations on the anatomy and pathology of the choroidal vasculature. Arch Ophthalmol. 1967;78:431–444.PubMedGoogle Scholar
  208. 208.
    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.PubMedGoogle Scholar
  209. 209.
    Yoneya S, Tso MO. Angioarchitecture of the human choroid. Arch Ophthalmol. 1987;105:681–687.PubMedGoogle Scholar
  210. 210.
    Schocket LS, Brucker AJ, Niknam RM, et al. Foveolar choroidal hemodynamics in proliferative diabetic retinopathy. Int Ophthalmol. 2004;25:89–94.PubMedGoogle Scholar
  211. 211.
    Nagaoka T, Kitaya N, Sugawara R, et al. Alteration of choroidal circulation in the foveal region in patients with type 2 diabetes. Br J Ophthalmol. 2004;88:1060–1063.PubMedGoogle Scholar
  212. 212.
    Shiragami C, Shiraga F, Matsuo T, et al. Risk factors for diabetic choroidopathy in patients with diabetic retinopathy. Graefe’s Arch Clin Exp Ophthalmol. 2002;240:436–442.Google Scholar
  213. 213.
    Dimitrova G, Kato S, Tamaki Y, et al. Choroidal circulation in diabetic patients. Eye. 2001;15:602–607.PubMedGoogle Scholar
  214. 214.
    Langham ME, Grebe R, Hopkins S, et al. Choroidal blood flow in diabetic retinopathy. Exp Eye Res. 1991;52:167–173.PubMedGoogle Scholar
  215. 215.
    Fryczkowski AW, Hodes BL, Walker J. Diabetic choroidal and iris vasculature scanning electron microscopy findings. Int Ophthalmol. 1989;13:269–279.PubMedGoogle Scholar
  216. 216.
    Takahashi A, Nagaoka T, Sato E, Yoshida A. Effect of panretinal photocoagulation on choroidal circulation in the foveal region in patients with severe diabetic retinopathy. Br J Ophthalmol. 2008;92:1369–1373.PubMedGoogle Scholar
  217. 217.
    Augsten R, Konigsdorffer E, Schweitzer D, Strobel J. Nonproliferative diabetic retinopathy-reflection spectra of the macula before and after laser photocoagulation. Ophthalmologica. 1998;212:105–111.PubMedGoogle Scholar
  218. 218.
    Sebag J, Tang M, Brown S, et al. Effects of pentoxifylline on choroidal blood flow in nonproliferative diabetic retinopathy. Angiology. 1994;45:429–433.PubMedGoogle Scholar
  219. 219.
    Li L, Yi Z, Tisch R, Wang B. Immunotherapy of type 1 diabetes. Arch Immunol Ther Exp (Warsz). 2008;56:227–236.Google Scholar
  220. 220.
    Eldor R, Kassem S, Raz I. Immune modulation in type 1 diabetes mellitus using DiaPep277: a short review and update of recent clinical trial results. Diabetes Metab Res Rev. 2009;25:316–20.Google Scholar
  221. 221.
    Ogden CL, Carroll MD, Curtin LR, et al. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA. 2006;295:1549–1555.PubMedGoogle Scholar
  222. 222.
    Henricsson M, Nystrom L, Blohme G, et al. The incidence of retinopathy 10 years after diagnosis in young adult people with diabetes: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS). Diabetes Care. 2003;26:349–354.PubMedGoogle Scholar
  223. 223.
    Klein R, Knudtson MD, Lee KE, et al. The Wisconsin epidemiologic study of diabetic retinopathy: XXII the twenty-five-year progression of retinopathy in persons with type 1 diabetes. Ophthalmology. 2008;115:1859–1868.PubMedGoogle Scholar
  224. 224.
    Figueroa MS, Contreras I, Noval S. Surgical and anatomical outcomes of pars plana vitrectomy for diffuse nontractional diabetic macular edema. Retina. 2008;28:420–426.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of OphthalmologyUniversity Community Hospital, University of South FloridaTampaUSA

Personalised recommendations