Advertisement

Diabetic Retinopathy

  • Lloyd Paul Aiello
  • Jerry Cavallerano
Part of the Contemporary Cardiology book series (CONCARD)

Abstract

Diabetic retinopathy (DR) is a microvascular complication that eventually afflicts virtually all patients with diabetes mellitus (DM) (1). Despite decades of research, there is presently no known cure or means of preventing DR, and DR remains the leading cause of new-onset blindness in working-aged Americans (1). Several nationwide clinical trials have demonstrated that scatter (panretinal) laser photocoagulation reduces the 5-year risk of severe vision loss (i.e., best corrected visual acuity of 5/200 or worse) from proliferative DR from as high as 60% to less than 4%. Additionally, timely and appropriate focal laser photocoagulation for clinically significant diabetic macular edema (DME) reduces the risk of moderate vision loss (i.e., a doubling of the visual angle) from DME from nearly 30% to approx 12%. Vitrectomy surgery, with endolaser photocoagulation as indicated, can frequently prevent further vision loss or restore useful vision in eyes that have nonresolving vitreous hemorrhage or traction retinal detachment threatening central vision. Although numerous new therapies are under investigation with some already in phase 2 or 3 clinical trials, until a prevention or cure for diabetes is discovered, the keys to preventing vision loss from DR are regular eye examinations to determine the need for timely laser photocoagulation and rigorous control of blood glucose and any accompanying systemic medical conditions, such as hypertension, renal disease, and dyslipidemias.

Keywords

Diabetic Retinopathy Macular Edema Diabetic Macular Edema Proliferative Diabetic Retinopathy Laser Photocoagulation 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Klein R, Klein BEK. Vision disorders in diabetes. National Institutes of Health: National Institute of Diabetes and Digestive and Kidney Diseases. NIH Publication No. 95-1468, 1995, p. 293.Google Scholar
  2. 2.
    Cogan DG, Toussaint D, Kuwabara T. Retinal vascular patterns: IV. Diabetic Retinopathy. Arch Ophthalmol 1961;66:366.PubMedGoogle Scholar
  3. 3.
    Cogan DG, Kuwabara T. Capillary shunts in the pathogenesis of diabetic retinopathy. Diabetes 1963;12:293.PubMedGoogle Scholar
  4. 4.
    Cogan DG, Kuwabara T. The mural cells in perspective. Arch Ophthalmol 1967;78:137.Google Scholar
  5. 5.
    Michaelson IC. The mode of development of the vascular system of the retina, with some observations on its significance for certain retinal diseases. Trans Ophthalmol Soc UK 1948;68:137–180.Google Scholar
  6. 6.
    Ashton N, Ward B, Supell G. Effect of oxygen on developing retinal vessels with particular reference to the problem of retrolental fibroplasia. Br J Ophthalmol 1954;38:397–432.PubMedCrossRefGoogle Scholar
  7. 7.
    Engerman RI, Kern TS. Experimental galactosemia produces diabetic-like retinopathy. Diabetes 1984;33:97.PubMedCrossRefGoogle Scholar
  8. 8.
    Engerman RI. Pathogenesis of diabetic retinopathy. Diabetes 1989;38:1203.PubMedCrossRefGoogle Scholar
  9. 9.
    Engerman RI, Kern TS. Progression of incipient diabetic retinopathy during good glycemic control. Diabetes 1987;36:808.PubMedCrossRefGoogle Scholar
  10. 10.
    Engerman RL, Kern TS. Is diabetic retinopathy preventable? International Ophthalmology Clinics 1987;27:225–229.PubMedCrossRefGoogle Scholar
  11. 11.
    Engerman RI, Kern TS. Aldose reductase inhibition fails to prevent retinopathy in diabetic and galactosemic dogs. Diabetes 1993;42:820.PubMedCrossRefGoogle Scholar
  12. 12.
    Kikkawa U, Nishizuka Y. The role of protein kinase C in transmembrane signaling. Ann Rev Cell Biol 1986;2:149.PubMedCrossRefGoogle Scholar
  13. 13.
    Pu X, Aiello LP, Ishii H, et al. Characterization of vascular endothelial growth factor’s effect on the activation of protein kinase C, its isoforms and endothelial growth. J Clin Invest 1996;98:2018–2026.Google Scholar
  14. 14.
    The Sorbinil Retinopathy Trial Research Group. A Randomized trial of sorbinil, an aldose reductase inhibitor in diabetic retinopathy. Arch Ophthalmol 1990;108:1234–1244.Google Scholar
  15. 15.
    The Sorbinil Retinopathy Trial Research Group. The sorbinil retinopathy trial: Neurology results. Neurology 1993;43:1141–1149.Google Scholar
  16. 16.
    Ishii H, Jirousek MR, Koya D, et al. Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor. Science 1996;272:728–731.PubMedCrossRefGoogle Scholar
  17. 17.
    Aiello LP, Bursell SE, Clermont A, et al. Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor. Diabetes 1997;46:1473–1480.PubMedCrossRefGoogle Scholar
  18. 18.
    Danis Rp, Bingaman DP, Jirousek M, Yang Y. Inhibition of intraocular neovascularization caused by retinal ischemia in pigs by PKC beta inhibition with LY333531. Invest Ophthalmol Vis Sci 1998;39:171–179.PubMedGoogle Scholar
  19. 19.
    Xia P, Aiello LP, Ishii H, et al. Characterization of vascular endothelial growth factor’s effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. J Clin Invest 1996;98:2018–2026.PubMedCrossRefGoogle Scholar
  20. 20.
    Klein R, Klein BEK, Moss SE, et al. The Wisconsin Epidemilogic 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
  21. 21.
    Klein R, Klein BEK, Moss SE, et al. The Wisconsin Epidemilogic 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
  22. 22.
    Diabetes Control and Complications Trial Research Group. Are continuing studies of metabolic control and microvascular complications in insulin-dependent diabetes mellitus justified? N Engl J Med 1988;318:246–250.CrossRefGoogle Scholar
  23. 23.
    The Diabetes Control and Complications Trial Research Group. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 1995;44:968–983.CrossRefGoogle Scholar
  24. 24.
    The Diabetes Control and Complications Trial Research Group. Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and Complications Trial. Ophthalmology 1995;102:647–661.Google Scholar
  25. 25.
    The Diabetes Control and Complications Trial Research Group. Hypoglycemia in the Diabetes Control and Complications Trial. Diabetes 1997;46:271–286.CrossRefGoogle Scholar
  26. 26.
    The Diabetes Control and Complications Trial Research Group. Lifetime benefits and costs of intensive therapy as practiced in the Diabetes Control and Complications Trial. JAMA 1996;276:1409–1415.CrossRefGoogle Scholar
  27. 27.
    The 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;329:977–986.CrossRefGoogle Scholar
  28. 28.
    Chase HP, Jackson WE, Hoops SL et al. Glucose control in the renal and retinal complications of insulin-dependent diabetes. JAMA 1989;261:1155–1160.PubMedCrossRefGoogle Scholar
  29. 29.
    The Kroc Collaborative Study Group. Blood glucose control and the evolution of diabetic retinopathy and albuminuria. N Engl J Med 1984;311:365–372.CrossRefGoogle Scholar
  30. 30.
    Krowlewski AS, Canessa M, Warram JH et al. Predisposition to hypertension and susceptibility to renal disease in insulin-dependent diabetes mellitus: N Engl J Med 1988;318:140–145.CrossRefGoogle Scholar
  31. 31.
    Stern MP, Patterson JK, Haffner SM et al. Lack of awareness and treatment of hyperlipidemia in Type II diabetes in a community survey. JAMA 1989;262:360–364.PubMedCrossRefGoogle Scholar
  32. 32.
    Moloney JEM, Drury MI. The effect of pregnancy on the natural course of diabetic retinopathy. Am J Ophthalmol 1982;93:745–756.PubMedGoogle Scholar
  33. 33.
    Serup L. Influence of pregnancy on diabetic retinopathy. Acta Endocrinol 1986;277:122–124.Google Scholar
  34. 34.
    Phelps RL, Sakol P, Metzger BE et al. Changes in diabetic retinopathy during pregnancy: Correlations with regulation of hyperglycemia. Arch Ophthalmol 1986;104:1806–1810.PubMedGoogle Scholar
  35. 35.
    Diabetic Retinopathy Study Research Group. Preliminary report on effects of photocoagulation therapy. DRS Report No. 1. Am J Ophthalmol 1976;81:1–14.Google Scholar
  36. 36.
    Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy. DRS Report No. 2. Ophthalmology 1978;85:82–106.Google Scholar
  37. 37.
    Diabetic Retinopathy Study Research Group. Four risk factors for severe visual loss in diabetic retinopathy. DRS Report No. 3. Arch Ophthalmol 1979;97:654–655.Google Scholar
  38. 38.
    Diabetic Retinopathy Study Research Group. A short report of long-term results. DRS Report No. 4. Proc 10th Congr Int Diabetes Fed. Vienna, September 9–14, 1979. North Holland: Excerpta Medica, 1980, pp. 789–794.Google Scholar
  39. 39.
    Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy: relationship of adverse treatment effects to retinopathy severity. DRS Report No. 5. Dev Ophthalmol 1981;2:248–261.Google Scholar
  40. 40.
    Diabetic Retinopathy Study Research Group. Design methods and baseline results. DRS Report No. 6. Invest Ophthalmol 1981;21(1, Pt 2):149–209.Google Scholar
  41. 41.
    Diabetic Retinopathy Study Research Group. A modification of the Airlie House classification of diabetic retinopathy. DRS Report No. 7. Invest Ophthalmol 1981;21(1, Pt 2):210–226.Google Scholar
  42. 42.
    Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy. Clinical applications of Diabetic Retinopathy Study (DRS) findings. DRS Report No. 8. Ophthalmology 1981;88:583–600.Google Scholar
  43. 43.
    Ederer F, Podgor MJ, DRS Research Group. Assessing possible late treatment effects in stopping a clinical trial early: a case study. DRS Report No. 9. Cont Clin Trials 1984;5:373–381.CrossRefGoogle Scholar
  44. 44.
    Rand LI, Prud’homme GJ, Ederer F, Canner PL, DRS Research Group. Factors influencing the development of visual loss in advanced diabetic retinopathy. DRS Report No. 10. Invest Ophthalmol 1985;26:983–991.Google Scholar
  45. 45.
    Kaufman SC, Ferris F, Swartz M, DRS Research Group. Intraocular pressure following panretinal photocoagulation for diabetic retinopathy. DRS Report No. 11. Arch Ophthalmol 1987;102:807–809.Google Scholar
  46. 46.
    Diabetic Retinopathy Study Research Group. Macular edema in diabetic retinopathy study patients. DRS Report No. 12. Ophthalmology 1987;94:754–760.Google Scholar
  47. 47.
    Diabetic Retinopathy Study Report Number 13: Factors associated with visual outcome after photocoagulation for diabetic retinopathy. Invest Ophthalmol 1989;30:23–28.Google Scholar
  48. 48.
    Diabetic Retinopathy Study Research Group. Indications for photocoagulation treatment of diabetic retinopathy. DRS Report No. 14. Int Ophthalmol Clin 1987;27:239–253.CrossRefGoogle Scholar
  49. 49.
    Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. ETDRS Report No. 1. Arch Ophthalmol 1985;103:1796–1806.Google Scholar
  50. 50.
    Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. ETDRS Report No. 2. Ophthalmology 1987;96:761–774.Google Scholar
  51. 51.
    Early Treatment Diabetic Retinopathy Study Research Group. Techniques for scatter and local photocoagulation treatment of diabetic retinopathy. ETDRS Report No. 3. Int Ophthalmol Clin 1987;27:254–264.CrossRefGoogle Scholar
  52. 52.
    Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. ETDRS Report No. 4. Int Ophthalmol Clin 1987;27:265–272.CrossRefGoogle Scholar
  53. 53.
    Early Treatment Diabetic Retinopathy Study Research Group. Case reports to accompany early treatment diabetic retinopathy study reports Nos. 3 and 4. Int Ophthalmol Clin 1987;27:273–333.CrossRefGoogle Scholar
  54. 54.
    Early Treatment Diabetic Retinopathy Study Research Group. Detection of diabetic macular edema: Ophthalmoscopy versus photography. ETDRS Report No. 5. Ophthalmology 1989;96:746–751.Google Scholar
  55. 55.
    Early Treatment Diabetic Retinopathy Study Research Group. C-peptide and the classification of diabetes patients in the Early Treatment Diabetic Retinopathy Study. ETDRS Report No. 6. Ann Epidemiol 1993;3:9–17.CrossRefGoogle Scholar
  56. 56.
    Early Treatment Diabetic Retinopathy Study Research Group. Design and baseline patient characteristics. ETDRS Report No. 7. Ophthalmology 1991;98:741–756.Google Scholar
  57. 57.
    Early Treatment Diabetic Retinopathy Study Research Group. Effects of aspirin treatment on diabetic retinopathy. ETDRS Report No. 8. Ophthalmology 1991;98:757–765.Google Scholar
  58. 58.
    Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for diabetic retinopathy. ETDRS Report No. 9. Ophthalmology 1991;98:766–785.Google Scholar
  59. 59.
    Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs: an extension of the modified Airlie House classification. ETDRS Report No. 10. Ophthalmology 1991;98:786–806.Google Scholar
  60. 60.
    Early Treatment Diabetic Retinopathy Study Research Group. Classification of diabetic retinopathy from fluorescein angiograms. ETDRS Report No. 11. Ophthalmology 1991;98:807–822.Google Scholar
  61. 61.
    Early Treatment Diabetic Retinopathy Study Research Group. Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS Report No. 12. Ophthalmology 1991;98:823–833.Google Scholar
  62. 62.
    Early Treatment Diabetic Retinopathy Study Research Group. Fluorescein angiographic risk factors for progression of diabetic retinopathy. ETDRS Report No. 13. Ophthalmology 1991;98:834–840.Google Scholar
  63. 63.
    Early Treatment Diabetic Retinopathy Study Research Group. Aspirin effects on mortality and morbidity in patients with diabetes mellitus. ETDRS Report No. 14. JAMA 1992;268:1292–1300.CrossRefGoogle Scholar
  64. 64.
    Early Treatment Diabetic Retinopathy Study Research Group. Aspirin effects on the development of cataracts in patients with diabetes mellitus. ETDRS Report No. 16. Arch Ophthalmol 1992;110:339–342.Google Scholar
  65. 65.
    Early Treatment Diabetic Retinopathy Study Research Group. Pars plana vitrectomy in the early treatment diabetic retinopathy study. ETDRS Report No. 17. Ophthalmology 1992;99:1351–1357.Google Scholar
  66. 66.
    Early Treatment Diabetic Retinopathy Study Report Number 19. Focal photocoagulation treatment of diabetic macular edema: Relationship of treatment effect to fluorescein angiographic and other retinal characteristics at baseline. Arch Ophthalmol 1995;113:1144–1155.Google Scholar
  67. 67.
    Chew EY, Klein ML, Murphy RP, Remaley NA, Ferris FL III, ETDRS Research Group. Early Treatment Diabetic Retinopathy Study Report Number 20. Effects of aspirin on vitreous/preretinal hemorrhage in patients with diabetes mellitus. Arch Ophthalmol 1995;13:52–55.Google Scholar
  68. 68.
    Chew EY, Klein ML, Ferris FL III, Remaley NA, Murphy RP, Chantry K, Hoogwerf BJ, Miller D, ETDRS Research Group. Early Treatment Diabetic Retinopathy Study Report Number 22. Association of elevated serum lipid levels with retinal hard exudates in diabetic retinopathy. Arch Ophthalmol 1996;114:1079–1084.PubMedGoogle Scholar
  69. 69.
    Diabetic Retinopathy Vitrectomy Study Research Group. Two-year course of visual acuity in severe proliferative diabetic retinopathy with conventional management. DRVS Report No. 1. Ophthalmology 1985;92:492–502.Google Scholar
  70. 70.
    Diabetic Retinopathy Vitrectomy Study Research Group. Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Two year results of a randomized trial. DRVS Report No. 2. Arch Ophthalmol 1985;103:1644–1652.Google Scholar
  71. 71.
    Diabetic Retinopathy Vitrectomy Study Research Group. Early vitrectomy for severe proliferative diabetic retinopathy in eyes with useful vision. Results of a randomized trial. DRVS Report No. 3. Ophthalmology 1988;95:1307–1320.Google Scholar
  72. 72.
    Diabetic Retinopathy Vitrectomy Study Research Group. Early vitrectomy for severe proliferative diabetic retinopathy in eyes with useful vision. DRVS Report No. 4. Ophthalmology 1988;95:1321–1334.Google Scholar
  73. 73.
    Diabetic Retinopathy Vitrectomy Study Report Number 5: Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Four-year results of a randomized trial. Arch Ophthalmol 1990;108:958–964.Google Scholar
  74. 74.
    Ferris FL III. Early photocoagulation in patients with either Type I or Type II diabetes. Tr AM Ophth Soc 1996;94:505–537.PubMedGoogle Scholar
  75. 75.
    Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications. A new perspective on an old paradigm. Diabetes 1999;48:1–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Kunisaki M, Bursell SE, Clermont AC, Ishii H, Ballas LM, Jirousek MR et al. Vitamin E prevents diabetes-induced abnormal retinal blood flow via the diacylglycerol-protein kinase C pathway. Am J Physiol 1995;269:E239–E246.PubMedGoogle Scholar
  77. 77.
    Aiello LP, Pierce EA, Foley ED, Takagi H, Chen H, Riddle L et al. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-recptor chimeric proteins. Proc Natl Acad Sci U S A 1995;92:10,457–10,461.PubMedCrossRefGoogle Scholar
  78. 78.
    Robinson GS, Pierce EA, Rook SL, Foley E, Webb R, Smith LE. Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy. Proc Natl Acad Sci USA 1996;93:4851–4856.PubMedCrossRefGoogle Scholar
  79. 79.
    Adamis AP, Shima DT, Tolentino MJ, Gragoudas ES, Ferrara N, Folkman J et al. Inhibition of vascular endothelial growth factor prevents retinal ischemia-assoociated iris neovasculrization in a nonhuman primate. Arch Ophthalmol 1996;114:66–71.PubMedGoogle Scholar
  80. 80.
    Position Statement: American Diabetes Association. Diabetic Retinopathy. Diabetes Care 2004;27:584–587.CrossRefGoogle Scholar
  81. 81.
    Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352(9131):837–853 (Erratum in: Lancet 1999;354(9178):602).Google Scholar
  82. 82.
    Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ 1998;317(7160):713–720.Google Scholar
  83. 83.
    Chew EY, Klein ML, Ferris FL 3rd, et al. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol 1996;114(9):1079–1084.PubMedGoogle Scholar
  84. 84.
    Davis MD, Fisher MR, Gangnon RE, et al. Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18. Invest Ophthalmol Vis Sci 1998;39(2):233–252.PubMedGoogle Scholar
  85. 85.
    Aiello LP, Cahill MT, Wong JS. Systemic considerations in the management of diabetic retinopathy. Am J Ophthalmol 2001;132(5):760–776.PubMedCrossRefGoogle Scholar
  86. 86.
    Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 2003;110:1677–1682.Google Scholar
  87. 87.
    Kern TS, Engerman RL. Pharmacological inhibition of diabetic retinopathy: aminoguanidine and aspirin. Diabetes 2001;50:1636–1642.PubMedCrossRefGoogle Scholar
  88. 88.
    Joussen AM, Poulaki V, Mitsiades N, Kirchhof B, Koizumi K, Dohmen S, Adamis AP. Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. FASEB J 2002;16(3):438–440.PubMedGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • Lloyd Paul Aiello
    • 1
  • Jerry Cavallerano
    • 2
  1. 1.Beetham Eye Institute, Joslin Diabetes CenterHarvard Medical SchoolBoston
  2. 2.Joslin Diabetes CenterHarvard Medical SchoolBoston

Personalised recommendations