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Nonproliferative Diabetic Retinopathy

  • Chapter
Diabetic Retinopathy

Part of the book series: Contemporary Diabetes ((CDI))

Abstract

Nonproliferative diabetic retinopathy (NPDR) is a microvascular complication of diabetes mellitus that can lead to irreversible visual loss. Intraretinal microvascular changes, such as altered retinal vascular permeability and eventual retinal vessel and capillary closure, characterize NPDR. Macular edema, the most frequent cause of visual loss in NPDR, may result from increased vascular leakage. Retinal hypoxia, secondary to chronic hyperglycemia, triggers the pathologic processes of NPDR. Additionally, there is increasing evidence that inflammatory mechanisms may play a role in the pathogenesis. Systemic factors such as glycemic control, hypertension, and serum lipid level also contribute to the development and progression of NPDR. Prompt and appropriate initiation of laser photocoagulation for macular edema or severe retinal nonperfusion, along with optimal control of systemic factors, can prevent visual loss.

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References

  1. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047–1053.

    Article  PubMed  Google Scholar 

  2. D'Amico D. Diseases of the retina. N Engl J Med 1994;331(2):95–106.

    Article  PubMed  Google Scholar 

  3. National Society to Prevent Blindness. Vision problems in the US: data analysis, definitions, data sources, detailed data table, analyses, interpretation. New York, USA, 1980.

    Google Scholar 

  4. Ciulla T, Harris A, Latknay P, Piper HC, Arend O, Garzozi H, Martin B. Ocular perfusion abnormalities in diabetes. Acta Ophthalmol Scand 2002;80(5):468–477.

    Article  PubMed  Google Scholar 

  5. Comer GM, Ciulla TA. Current and future pharmacological intervention for diabetic retinopathy. Expert Opin Emerg Drugs 2005;10(2):441–455.

    Article  PubMed  CAS  Google Scholar 

  6. Esser P, Bresgen M, Fischbach R, Heimann K, Wiedemann P. Intercellular adhesion molecule-1 levels in plasma and vitreous from patients with vitreoretinal disorders. Ger J Ophthalmol 1995;4(5):269–274.

    PubMed  CAS  Google Scholar 

  7. Joussen AM, Poulaki V, Qin W, Kirchhof B, Mitsiades N, Wiegand SJ, Rudge J, Yancopoulos GD, Adamis AP. Retinal vascular endothelial growth factor induces intercellular adhesion molecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo. Am J Pathol 2002;160(2):501–509.

    Article  PubMed  CAS  Google Scholar 

  8. Joussen AM, Poulaki V, Le ML, Koizumi K, Esser C, Janicki H, Schraermeyer U, Kociok N, Fauser S, Kirchhof B, Kern TS, Adamis AP. A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J 2004;18(12):1450–1452.

    PubMed  CAS  Google Scholar 

  9. Miyamoto K, Khosrof S, Bursell SE, Rohan R, Murata T, Clermont AC, Aiello LP, Ogura Y, Adamis AP. Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition. Proc Natl Acad Sci USA 1999;96:10836–10841.

    Article  PubMed  CAS  Google Scholar 

  10. Joussen AM, Murata T, Tsujikawa A, Kirchhof B, Bursell SE, Adamis AP. Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am J Pathol 2001;158:147–152.

    Article  PubMed  CAS  Google Scholar 

  11. Meleth AD, Agron E, Chan CC, Reed GF, Arora K, Byrnes G, Csaky KG, Ferris FL III, Chew EY.Serum inflammatory markers in diabetic retinopathy. Invest Ophthalmol Vis Sci 2005;46(11):4295–4301.

    Article  PubMed  Google Scholar 

  12. Kuwabara T, Cogan DG. Retinal vascular patterns. I. Normal architecture. Arch Ophthalmol 1960;64:904–911.

    PubMed  CAS  Google Scholar 

  13. Bloodworth JMB. Fine structure of retina in human and canine diabetes mellitus. In Kimuara, SJ, Caygill, WM, eds, Vascular complications of diabetes mellitus. St Louis: Mosby, 1967.

    Google Scholar 

  14. Engerman RL. Pathogenesis of diabetic retinopathy. Diabetes 1989;38:1203–1206.

    Article  PubMed  CAS  Google Scholar 

  15. Frank RN. On the pathogenesis of diabetic retinopathy — a 1990 update. Ophthalmology 1991;98:586–593.

    PubMed  CAS  Google Scholar 

  16. Cogan DG, Toussaint D, Kuwabara T. Retinal vascular patterns. I V. Diabetic retinopathy. Arch Ophthalmol 1961;66:366–378.

    PubMed  CAS  Google Scholar 

  17. Frank RN. Etiologic mechanisms in diabetic retinopathy. In Ryan SJ, Schachat AP, Murphy RP, Patz A, eds, Retina, vol 2, Medical retina, 1st ed., St Louis: Mosby, 1989.

    Google Scholar 

  18. Wise GN. Retinal neovascularization. Trans Am Ophthalmol Soc 1956;54:729–826.

    PubMed  CAS  Google Scholar 

  19. De Venecia G, Davis M, Engerman R. Clinicopathologic correlations in diabetic retinopathy. I. Histology and fluorescein angiography of microaneurysms. Arch Ophthalmol 1976;94:1766–1773.

    PubMed  Google Scholar 

  20. Klein R, Meuer SM, Moss SE, Klein BEK. The relationship of retinal microaneurysm counts to the 4-year progression of diabetic retinopathy. Arch Ophthalmol 1989;107:1780–1785.

    PubMed  CAS  Google Scholar 

  21. Klein R, Meuer SM, Moss SE, Klein BEK. Retinal micro-aneurysm counts and 10-year progression of diabetic retinopathy. Arch Ophthalmol 1995;113:1386–1391.

    PubMed  CAS  Google Scholar 

  22. Kohner EM, Sleightholm M, and The Kroc Collaborative Study Group. Does microaneurysm count reflect severity of early diabetic retinopathy? Ophthalmology 1986;93:586–589.

    PubMed  CAS  Google Scholar 

  23. Funatsu H, Yamashita H, Ikeda T, Mimura T, Eguchi S, Hori S. Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology 2003; 110(9):1690–1696.

    Article  PubMed  Google Scholar 

  24. Funatsu H, Yamashita H, Nakamura S, Mimura T, Eguchi S, Noma H, Hori S. Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology 2006;113(2):294–301.

    Article  PubMed  Google Scholar 

  25. Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331(22):1480–1487.

    Article  PubMed  CAS  Google Scholar 

  26. Gardner TW, Antonetti DA, Barber AJ, LaNoue KF, Levision SW. Diabetic retinopathy: more than meets the eye. Surv Ophthalmol 2002;47 (Suppl 2):S253–S262.

    Article  PubMed  Google Scholar 

  27. Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes 1998;47(6):859–866.

    Article  PubMed  CAS  Google Scholar 

  28. Ishii H, Koya D, King GL. Protein kinase C activation and its role in the development of vascular complications in diabetes mellitus. J Mol Med 1998;76(1):21–31.

    Article  PubMed  CAS  Google Scholar 

  29. Aiello LP, Clermont A, Arora V, Davis MD, Sheetz MJ, Bursell SE. Inhibition of PKC beta by oral administration of ruboxistaurin is well tolerated and ameliorates diabetes-induced retinal hemodynamic abnormalities in patients. Invest Ophthalmol Vis Sci 2006;47(1):86–92.

    Article  PubMed  Google Scholar 

  30. Shiba T, Inoguchi T, Sportsman JR, Heath WF, Bursell S, King GL. Correlation of diacylglycerol level and protein kinase C activity in rat retina to retinal circulation. Am J Physiol 1993;265(5 Pt 1):E783–E793.

    PubMed  CAS  Google Scholar 

  31. Yan SF, Lu J, Zou YS, Kisiel W, Mackman N, Leitges M, Steinberg S, Pinsky D, Stern D. Protein kinase C-beta and oxygen deprivation. A novel Egr-1-dependent pathway for fibrin deposition in hypoxemic vasculature. J Biol Chem 2000;275(16):11921–11928.

    Article  PubMed  CAS  Google Scholar 

  32. Wolf BA, Williamson JR, Easom RA, Chang K, Sherman WR, Turk J. Diacylglycerol accumulation and microvascular abnormalities induced by elevated glucose levels. J Clin Invest 1991;87(1):31–38.

    Article  PubMed  CAS  Google Scholar 

  33. Ferris FL III, Patz A. Macular edema: a complication of diabetic retinopathy. Surv Ophthalmol 1984;28 (suppl):452–461.

    Article  PubMed  Google Scholar 

  34. Patz A, Schatz H, Berkow JW, Gittelsohn AM, Ticho U. Macular edema — an overlooked complication of diabetic retinopathy. Trans Am Acad Ophthalmol Otolaryngol 1973;77:34–42.

    Google Scholar 

  35. King RC. Exudative diabetic retinopathy. Br J Ophthalmol 1963;47:666–672.

    Article  PubMed  CAS  Google Scholar 

  36. Sigurdsson R, Begg I. Organized macular plaques in exudative diabetic maculopathy. Br J Ophthalmol 1980;64:392–397.

    Article  PubMed  CAS  Google Scholar 

  37. Chew EY, Klein ML, Ferris FL III, Remaley NA, Murphy RP, Chantry K, Hoogwerf BJ, Miller D, for the Early Treatment Diabetic Retinopathy Study Research Group. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Arch Ophthalmol 1996;114:1079–1084.

    PubMed  CAS  Google Scholar 

  38. Klein BEK, Moss SE, Klein R, Surawicz TS. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XIII. Relationship of serum cholesterol to retinopathy and hard exudates. Ophthalmology 1991;98:1261–1265.

    PubMed  CAS  Google Scholar 

  39. Wilkinson CP. Achieving consensus on an international clinical classification for diabetic retinopathy. Program and abstracts of the American Academy of Ophthalmology 2002 Annual Meeting, Orlando, FL, October 20–23, 2002.

    Google Scholar 

  40. Klein R, Klein B, Moss S, Davis M, DeMets D. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. I V. Diabetic macular edema. Ophthalmology 1984;91:1464–1474.

    PubMed  CAS  Google Scholar 

  41. Brown JC, Soloman S, Bressler SB, Schachat AP, DiBernardo C, Bressler NM. Detection of diabetic foveal edema. Contact lens biomicroscopy compared with optical coherence tomography. Arch Ophthalmol 2004;122:330–335.

    Article  PubMed  Google Scholar 

  42. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema, ETDRS report no 1. Arch Ophthalmol 1985;103:1796–1806.

    Google Scholar 

  43. Davis MD, Fisher MR, Gangnon RE, Barton F, Aiello LM, Chew EY, Ferris FL III, Knatterud GL. Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss, ETDRS report no 18. Invest Ophthalmol Vis Sci 1998;39:233–252.

    PubMed  CAS  Google Scholar 

  44. Klein R, Klein BEK, Moss SE, Davis MD, DeMets DL. Is blood pressure a predictor of the incidence or progression of diabetic retinopathy? Arch Intern Med 1989;149:2427–2432.

    Article  PubMed  CAS  Google Scholar 

  45. 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.

    Article  Google Scholar 

  46. 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 

  47. Diabetes Control and Complications Trial Research Group. The relationship of glycemic exposures (HbA1C) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 1995;44:968–983.

    Article  Google Scholar 

  48. Diabetes Control and Complications Trial Research Group. Perspectives in diabetes: the absence of a glycemic threshold for the development of long-term complications. The perspective of the Diabetes Control and Complications Trial. Diabetes 1996;45:1289–1298.

    Article  Google Scholar 

  49. Reichard P, Nilsson B Y, and Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus, N Engl J Med 1993;329:304–309.

    Article  PubMed  CAS  Google Scholar 

  50. American Diabetes Association. Standards of medical care in diabetes — 2007. Diabetes Care 2007;30:S4–S41.

    Article  CAS  Google Scholar 

  51. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med 2000;342:381–389.

    Article  Google Scholar 

  52. UK Prospective Diabetes Study 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 1988;352:837–853.

    Google Scholar 

  53. Suzuma I, Hata Y, Clermont A, Pokras F, Rook SL, Suzuma K, Feener EP, Aiello LP. Cyclic stretch and hypertension induce retinal expression of vascular endothelial growth factor and vascular endothe-lial growth factor receptor-2: potential mechanisms for exacerbation of diabetic retinopathy by hypertension. Diabetes 2001;50(2):444–454.

    Article  PubMed  CAS  Google Scholar 

  54. Yam JC, Kwok AK. Update on the treatment of diabetic retinopathy. Hong Kong Med J 2007;13(1): 46–60.

    PubMed  Google Scholar 

  55. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes (UKPDS 38). Br Med J 1998;317:703–713.

    Google Scholar 

  56. Chaturvedi N, Sjolie AK, Stephen JM, Heidemarie A, Deipes M, Castellarin A, Rogulja-Pepeonik X, Fuller JH. and the EUCLID Study Group. Effect of lisinopril on progression of retinopathy in normo-tensive people with type 1 diabetes. Lancet 1998;351:28–31.

    Article  PubMed  CAS  Google Scholar 

  57. Schrier RW, Estacio RP, Esler A, Mehler P. Appropriate blood pressure control in hypertensive and normo tensive type 2 diabetes mellitus: a summary of the ABCD trial. Nat Clin Pract Nephrol. 2007 Aug;3(8):428–438.

    Article  PubMed  Google Scholar 

  58. Fong DS, Segal PP, Myers F, Ferris FL, Hubbard LD, Davis MD. Subretinal fibrosis in diabetic macular edema, ETDRS report no 23. Arch Ophthalmol 1997;115:873–877.

    PubMed  CAS  Google Scholar 

  59. Lyons TJ, Jenkins AJ, Zhen D, Lackland DT, McGee D, Garvey WT, Klein RL, the DCCT/EDIC Research Group. Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort. Invest Ophthalmol Vis Sci 2004;45:910–918.

    Article  PubMed  Google Scholar 

  60. Gupta A, Gupta V, Thapar S, Bhansali A. Lipid-lowering drug atorvastatin as an adjunct in the management of diabetic macular edema. Am J Ophthalmol 2004;137(4):675–682.

    PubMed  CAS  Google Scholar 

  61. Sen K, Misra A, Kumar A, Pandey RM.Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia. Diabetes Res Clin Pract 2002;56(1):1–11.

    Article  PubMed  CAS  Google Scholar 

  62. Chew EY, Mills JL, Metzger BE, Remaley NA, Jovanovic-Peterson L, Knopp RH, Conley M, Rand L, Simpson JL, Holmes JB, Aarons J. Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study. Diabetes Care 1995;18:631–637.

    Article  PubMed  CAS  Google Scholar 

  63. Klein BEK, Moss SE, Klein R. Effect of pregnancy on progression of diabetic retinopathy. Diabetes Care 1990;13:34–40.

    Article  PubMed  CAS  Google Scholar 

  64. Phelps RL, Sakol P, Metzger BE, Jampol LM, Freinkel N. Changes in diabetic retinopathy during pregnancy: correlations with regulation of hyperglycemia. Arch Ophthalmol 1986;104: 1806–1810.

    PubMed  CAS  Google Scholar 

  65. The Diabetes Control and Complications Trial Research Group. Effect of pregnancy on the microvas-cular complications. Diabetes Care 2000;23:1084–1091.

    Article  Google Scholar 

  66. Schultz KL, Birnbaum AD, Goldstein DA. Ocular disease in pregnancy. Curr Opin Ophthalmol 2005;16(5):308–314.

    Article  PubMed  Google Scholar 

  67. Janka HU, Warram JH, Rand LI, Krolewski AS. Risk factors for progression of background retinopa-thy in long-standing IDDM. Diabetes 1989;38:460–464.

    Article  PubMed  CAS  Google Scholar 

  68. Rand LI, Prud'homme GJ, Ederer F, Canner PL, and the Diabetic Retinopathy Study Research Group. Factors influencing the development of visual loss in advanced diabetic retinopathy, DRS report no 10. Invest Ophthalmol Vis Sci 1985;26:983–991.

    PubMed  CAS  Google Scholar 

  69. Berman DH, Friedman EA. Partial absorption of hard exudates in patients with diabetic end-stage renal disease and severe anemia after treatment with erythropoietin. Retina 1994;14:1–5.

    PubMed  CAS  Google Scholar 

  70. Qiao Q, Keinanen-Kiukaanniemi S, Laara E. The relationship between hemoglobin levels and diabetic retinopathy. J Clin Epidemiol 1997;50:153–158.

    Article  PubMed  CAS  Google Scholar 

  71. Shorb SR. Anemia and diabetic retinopathy. Am J Ophthalmol 1985;100:434–436.

    PubMed  CAS  Google Scholar 

  72. Krolewski AS, Barzilay J, Warram JH, Martin BC, Pfeifer M, Rand LI. Risk of early-onset proliferative diabetic retinopathy in IDDM is closely related to cardiovascular autonomic neuropathy. Diabetes 1992;41:430–437.

    Article  PubMed  CAS  Google Scholar 

  73. Tesfaye S, Stevens LK, Stephenson JM, et al. Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: The EURODIAB IDDM Complications Study. Diabetologia 1996;39:1377–1384.

    Article  PubMed  CAS  Google Scholar 

  74. Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy, DRS report no 2. Ophthalmology 1978;85:82–105.

    Google Scholar 

  75. Diabetic Retinopathy Study Research Group. Four risk factors for severe visual loss in diabetic retin-opathy, DRS report no 3. Arch Ophthalmol 1979;97:654–655.

    Google Scholar 

  76. Diabetic Retinopathy Study Research Group. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS report no 8. Ophthalmology 1981;88:583–600.

    Google Scholar 

  77. Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopa-thy: relationship of adverse treatment effects to retinopathy severity. Dev Ophthalmol 1981;2:248–261.

    Google Scholar 

  78. Early Treatment Diabetic Retinopathy Study Research Group. Early Treatment Diabetic Retinopathy Study design and baseline patient characteristics, ETDRS report no 7. Ophthalmology 1991; 98:741–756.

    Google Scholar 

  79. Early Treatment Diabetic Retinopathy Study Research Group. Techniques for scatter and local photoco-agulation treatment of diabetic retinopathy, ETDRS report no 3. Int Ophthalmol Clin 1987;27:254–264.

    Article  Google Scholar 

  80. Early Treatment Diabetic Retinopathy Study Research Group. Early photocoagulation for diabetic retinopathy, ETDRS report no 9. Ophthalmology 1991;98 (suppl):767–785.

    Google Scholar 

  81. Ferris F. Early photocoagulation in patients with either type I or type II diabetes. Trans Am Ophthalmol Soc 1996;94:505–537.

    PubMed  CAS  Google Scholar 

  82. Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen HV, Aiello LM, Ferrara N, King GL. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331(22):1480–1487.

    Article  PubMed  CAS  Google Scholar 

  83. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema, ETDRS report no 4. Int Ophthalmol Clin 1987;27:265–272.

    Article  Google Scholar 

  84. Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema, ETDRS report no 2. Ophthalmology 1987;94:761–774.

    Google Scholar 

  85. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema: relationship of treatment effect to fluorescein angiographic and other retinal characteristics at baseline, ETDRS report no 19. Arch Ophthalmol 1995;113:1144–1155.

    Google Scholar 

  86. Han DP, Miller WF, Burton TC. Submacular fibrosis after photocoagulation for diabetic macular edema. Am J Ophthalmol 1992;113:513–521.

    PubMed  CAS  Google Scholar 

  87. Lewis H, Schachat A P, Haimann MH, et al. Choroidal neovascularization after laser photocoagulation for diabetic macular edema. Ophthalmology 1990;97:503–511.

    PubMed  CAS  Google Scholar 

  88. Yamamoto T, Akabane N, Takeuchi S. Vitrectomy for diabetic macular edema: the role of posterior vitreous detachment and epimacular membrane. Am J Ophthalmol 2001;132:369–377.

    Article  PubMed  CAS  Google Scholar 

  89. Lewis H, Abrams G, Blumenkranz M, Campo R. Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology 1992;99:753–759.

    PubMed  CAS  Google Scholar 

  90. Martidis A, Duker JS, Greenberg PB, Rogers AH, Puliafito CA, Reichel E, Baumal C. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology 2002;109:920–927.

    Article  PubMed  Google Scholar 

  91. Jonas JB, Kreissing I, Sofker A, Degenring RF. Intravitreal injection of triamcinolone for diffuse macular edema. Arch Ophthalmol 2003;121:57–61.

    Article  PubMed  CAS  Google Scholar 

  92. Massin P, Audren F, Haouchine B, Erginay A, Bergmann JF, Benosman R, Caulin C, Gaudric A. Intravitreal triamcinolone acetonide for diabetic diffuse macular edema. Ophthalmology 2004; 111:218–225.

    Article  PubMed  Google Scholar 

  93. Gillies MC, Sutter FK, Simpson JM, Larsson J, Ali H, Zhu M. Intravitreal triamcinolone for refractory diabetic macular edema: two-year results of a double-masked, placebo-controlled, randomized clinical trial. Ophthalmology 2006;113(9):1533–1538.

    Article  PubMed  Google Scholar 

  94. Jonas JB, Kamppeter BA, Harder B, Vossmerbaeumer U, Sauder G, Spandau UH. Intravitreal triam-cinolone acetonide for diabetic macular edema: a prospective, randomized study. J Ocul Pharmacol Ther 2006;22(3):200–207.

    Article  PubMed  CAS  Google Scholar 

  95. Yu SY, Damico FM, Viola F, D'Amico DJ, Young LH. Retinal toxicity of intravitreal triamcinolone acetonide: a morphological study. Retina 2006;26(5):531–536.

    Article  PubMed  Google Scholar 

  96. Massin P, Audren F, Haouchine B, Erginay A, Bergmann JF, Benosman R, Caulin C, Gaudric A. Intravitreal triamcinolone acetonide for diabetic diffuse macular edema: preliminary results of a prospective controlled trial. Ophthalmology 2004;111(2):218–225.

    Article  PubMed  Google Scholar 

  97. Dipyridamole Aspirin Microangiopathy of Diabetes Study Group. Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy: a multicenter, randomized, controlled clinical trial. Diabetes 1989;38:491–498.

    Article  Google Scholar 

  98. Ticlopidine Microangiography of Diabetes Study Group. Ticlopidine treatment reduces the progression of nonproliferative diabetic retinopathy. Arch Ophthalmol 1990;108:1577–1583.

    Google Scholar 

  99. Carroll WW, Geeraets WJ. Diabetic retinopathy and salicylates. Ann Ophthalmol 1972;4:1019–1046.

    PubMed  CAS  Google Scholar 

  100. Dobbie JG, Kwaan HC, Colwell JA, et al. The role of platelets in pathogenesis of diabetic retinopathy. Trans Am Acad Ophthalmol Otolaryngol 1973;77:43–46.

    Google Scholar 

  101. Powell EDU, Field RA. Diabetic retinopathy and rheumatoid arthritis. Lancet 1964;2:17–18.

    Article  PubMed  CAS  Google Scholar 

  102. Regnault F. Role des plaguettes dans la pathogenie de la retinopathie diabetique. Sem Hop Paris 1972;48:893–902.

    PubMed  CAS  Google Scholar 

  103. Sagel J, Colwell JA, Crook L, et al. Increased platelet aggregation in early diabetes mellitus. Ann Intern Med 1975;82:733–738.

    PubMed  CAS  Google Scholar 

  104. Chew E Y, Klein ML, Murphy RP, Remalely NA, Ferris FL. Effects of aspirin on vitreous/preretinal hemorrhage in patients with diabetes mellitus, ETDRS report no 20. Arch Ophthalmol 1995; 113:52–55.

    PubMed  CAS  Google Scholar 

  105. 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 

  106. 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.

    Article  Google Scholar 

  107. Zheng L, Howell SJ, Hatala DA, Huang K, Kern TS. Salicylate-based anti-inflammatory drugs inhibit the early lesion of diabetic retinopathy. Diabetes 2007;56(2):337–345.

    Article  PubMed  CAS  Google Scholar 

  108. Frank RN. Perspectives in diabetes: the aldose reductase controversy. Diabetes 1994;43:169–172.

    PubMed  CAS  Google Scholar 

  109. Asnaghi V, Gerhardinger C, Hoehn T, Adeboje A, Lorenzi M. A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes 2003; 52(2):506–511.

    Article  PubMed  CAS  Google Scholar 

  110. Engerman RL, Kern TS. Experimental galactosemia produces diabetic-like retinopathy. Diabetes 1984;33:97–100.

    Article  PubMed  CAS  Google Scholar 

  111. Kador PF, Akagi Y, Takahashi Y, Ikebe H, Wyman M, Kinoshita JH. Prevention of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by aldose reductase inhibitors. Arch Ophthalmol 1990;108:1301–1309.

    PubMed  CAS  Google Scholar 

  112. Kador PF, Akagi Y, Takahashi Y, Wyman M, Kinoshita JH. Prevention of pericyte ghost formation in retinal capillaries of galactose-fed dogs by aldose reductase inhibitors. Arch Ophthalmol 1988;106:1099–1102.

    PubMed  CAS  Google Scholar 

  113. Robison WG Jr, Laver NM, Jacot JL, et al. Diabetic-like retinopathy ameliorated with the aldose reductase inhibitor WAY-121,509. Invest Ophthalmol Vis Sci 1996;37:1149–1156.

    Google Scholar 

  114. Robison WG Jr, Nagata M, Laver N, Hohman TC, Kinoshita JH. Diabetic-like retinopathy in rats prevented with an aldose reductase inhibitor. Invest Ophthalmol Vis Sci 1989;30:2285–2292.

    PubMed  Google Scholar 

  115. 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 

  116. Van Gerven Boot JP, Lemkes HH, van Best JA. Effects of aldose reductase inhibition with tolrestat on diabetic retinopathy in a six months double blind trial. Doc Ophthalmol 1994;87(4):355–365.

    Article  Google Scholar 

  117. Stevens MJ, Henry DN, Thomas TP, Killen PD, Greene DA. Aldose reductase gene expression and osmotic dysregulation in cultured human retinal pigment epithelial cells. Am J Physiol 1993;265(3 Pt 1): E428–E438.

    PubMed  CAS  Google Scholar 

  118. Obrosova IG, Minchenko AG, Vasupuram R, White L, Abatan OI, Kumagai AK, Frank RN, Stevens MJ. Aldose reductase inhibitor fidarestat prevents retinal oxidative stress and vascular endothelial growth factor overexpression in streptozotocin-diabetic rats. Diabetes 2003;52(3):864–871.

    Article  PubMed  CAS  Google Scholar 

  119. Cusick M, Chew E, Ferris F, Cox TA, Chan CC, Kador PF. Effects of aldose reductase inhibitors and galactose withdrawal on fluorescein angiographic lesions in galactose-fed dogs. Arch Ophthalmol 2003;121(12):1745–1751.

    Article  PubMed  CAS  Google Scholar 

  120. Sorbinil Retinopathy Trial Research Group. The sorbinil retinopathy trial: neuropathy results. Neurology 1993;43:1141–1149.

    Google Scholar 

  121. PKC-DRS2 Group, Aiello LP, Davis MD, Girach A, Kles KA, Milton RC, Sheetz MJ, Vignati L, Zhi XE. Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy. Ophthalmology 2006;113(12):2221–2230.

    Article  PubMed  Google Scholar 

  122. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403.

    Article  Google Scholar 

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Acknowledgments

This chapter was based on, and reprinted from, Retina, 4th Edition, Vol. 2 (eds Ryan SJ, Schachat AP), Drs. E.Y. Chew and F.L. Ferris III, “Nonproliferative Diabetic Retinopathy”, pp. 1271–1284, 2006, with permission from Elsevier.

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© 2008 Humana Press, a part of Springer Science + Business Media, LLC

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Meyerle, C.B., Chew, E.Y., Ferris, F.L. (2008). Nonproliferative Diabetic Retinopathy. In: Duh, E.J. (eds) Diabetic Retinopathy. Contemporary Diabetes. Humana Press. https://doi.org/10.1007/978-1-59745-563-3_1

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  • DOI: https://doi.org/10.1007/978-1-59745-563-3_1

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