Diabetic retinopathy

New England Journal of Medicine

Volumn 366, Issue 13, 2012, Pages 1227-1239

  Antonetti, David A ^a   Klein, Ronald ^b   Gardner, Thomas W ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BEVACIZUMAB; CANDESARTAN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALAPRIL; ETANERCEPT; FENOFIBRATE; FENOFIBRATE PLUS SIMVASTATIN; FIBRIC ACID DERIVATIVE; FLUOCINOLONE; GELATINASE A; GELATINASE B; INSULIN; LISINOPRIL; LOSARTAN; PEGAPTANIB; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN KINASE C; PROTEIN KINASE C BETA; RANIBIZUMAB; RUBOXISTAURIN; SULFONYLUREA DERIVATIVE; UNCLASSIFIED DRUG;

AWARENESS; BLOOD PRESSURE REGULATION; CELL INTERACTION; CLINICAL FEATURE; CONTRAST SENSITIVITY; COST EFFECTIVENESS ANALYSIS; DIABETIC MACULAR EDEMA; DIABETIC RETINOPATHY; DRUG EFFICACY; GENE; GENETIC ASSOCIATION; GLIA CELL; GLYCEMIC CONTROL; HUMAN; INCIDENCE; INSULIN DEPENDENT DIABETES MELLITUS; LASER COAGULATION; LEUKOSTASIS; LIPID PEROXIDATION; METABOLIC REGULATION; NERVE CELL; NEUROTRANSMISSION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OPHTHALMOSCOPY; PATHOGENESIS; PREVALENCE; PRIORITY JOURNAL; PROMOTER REGION; REVIEW; SIGNAL TRANSDUCTION; SUBRETINAL FLUID; TREATMENT RESPONSE; VEGF GENE; VISUAL ACUITY; VISUAL FIELD; VITRECTOMY;

EID: 84859012407     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMra1005073     Document Type: Article

References (96)

1. Photocoagulation treatment of proliferative diabetic retinopathy: the second report of Diabetic Retinopathy Study findings. Ophthalmology 1978;85:82-105.
2. Photocoagulation for diabetic macular edema: Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol 1985;103:1796-806.
3. Klein R, Lee KE, Gangnon RE, Klein BE. The 25-year incidence of visual impairment in type 1 diabetes mellitus: the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Ophthalmology 2010;117: 63-70.
4. Hovind P, Tarnow L, Rossing K, et al. Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes. Diabetes Care 2003;26:1258-64. (Pubitemid 36929282)
5. Nordwall M, Bojestig M, Arnqvist HJ, Ludvigsson J. Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of Type 1 diabetes - the Linkoping Diabetes Complications Study. Diabetologia 2004;47:1266-72. (Pubitemid 39093322)
6. Kempen JH, O'Colmain BJ, Leske MC, et al. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol 2004;122:552-63. (Pubitemid 38456292)
7. Sloan FA, Belsky D, Ruiz D Jr, Lee P. Changes inincidence of diabetes mellitusrelated eye disease among US elderly persons, 1994-2005. Arch Ophthalmol 2008; 126:1548-53.
8. Klein R, Klein BE. Are individuals with diabetes seeing better? A long-term epidemiological perspective. Diabetes 2010; 59:1853-60.
9. 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- 86.
10. 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: 837-53. [Erratum, Lancet 1999;354:602.]
11. Idem. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703-13.
12. Mauer M, Zinman B, Gardiner R, et al. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med 2009;361:40-51.
13. Mann DM, Woodward M, Ye F, Krousel- Wood M,Muntner P. Trends in medication use among US adults with diabetes mellitus: glycemic control at the expense of controlling cardiovascular risk factors. Arch Intern Med 2009;169:1718-20.
14. Saydah SH, Fradkin J, Cowie CC. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA 2004;291:335-42. (Pubitemid 38101606)
15. Suh DC, Kim CM, Choi IS, Plauschinat CA, Barone JA. Trends inblood pressure control and treatment among type 2 diabetes with comorbid hypertension in the United States: 1988-2004. J Hypertens 2009;27:1908-16.
16. 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: 1047-53. (Pubitemid 38579764)
17. Al-Rubeaan K. Type 2diabetes mellitus red zone. Int J Diabetes Mellitus 2010; 2(1):1-2.
18. Rema M, Premkumar S, Anitha B, Deepa R, Pradeepa R, Mohan V. Prevalence of diabetic retinopathy in urban India: the Chennai Urban Rural Epidemiology Study (CURES) eye study, I. Invest Ophthalmol Vis Sci 2005;46:2328-33. (Pubitemid 43119476)
19. Hirsch IB, Brownlee M. Beyond hemoglobin A1c -need for additional markers of risk for diabetic microvascular complications. JAMA 2010;303:2291-2.
20. Klein R. The epidemiology of diabetic retinopathy. In: Duh E, ed. Diabetic retinopathy. Totowa, NJ: Humana, 2008:67- 107.
21. West SD, Groves DC, Lipinski HJ, et al. The prevalence of retinopathy in men with Type 2 diabetes and obstructive sleep apnoea. Diabet Med 2010;27:423-30.
22. Targher G, Bertolini L, Chonchol M, et al. Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and retinopathy in type 1 diabetic patients. Diabetologia 2010;53:1341-8.
23. Arnold E, Rivera JC, Thebault S, et al. High levels of serum prolactin protect against diabetic retinopathy by increasing ocular vasoinhibins. Diabetes 2010;59: 3192-7.
24. Zietz B, Buechler C, Kobuch K, Neumeier M, Scholmerich J, Schaffler A. Serum levels of adiponectin are associated with diabetic retinopathy and with adiponectin gene mutations in Caucasian patients with diabetes mellitus type 2. Exp Clin Endocrinol Diabetes 2008;116:532-6.
25. Nguyen TT, Alibrahim E, Islam FM, et al. Inflammatory, hemostatic, and other novel biomarkers for diabetic retinopathy: the multi-ethnic study of atherosclerosis. Diabetes Care 2009;32:1704-9.
26. Tong Z, Yang Z, Patel S, et al. Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications. Proc Natl Acad Sci U S A 2008;105:6998-7003. (Pubitemid 351754519)
27. Nathan DM, Zinman B, Cleary PA, et al. Modern-day clinical course of type 1 diabetes mellitus after 30 years' duration: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications and Pittsburgh Epidemiology of Diabetes Complications experience (1983-2005). Arch Intern Med 2009;169:1307-16.
28. Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and Complications Trial. Ophthalmology 1995;102:647-61.
29. Chaturvedi N, Sjolie AK, Stephenson JM, et al. Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. Lancet 1998; 351:28-31. (Pubitemid 28020163)
30. Stratton IM, Kohner EM, Aldington SJ, et al. UKPDS 50: risk factors for incidence and progression of retinopathy in Type II diabetes over 6 years from diagnosis. Diabetologia 2001;44:156-63. (Pubitemid 32156199)
31. Matthews DR, Stratton IM, Aldington SJ, Holman RR, Kohner EM. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus: UKPDS 69. Arch Ophthalmol 2004;122:1631-40. (Pubitemid 39473407)
32. Chaturvedi N, Porta M, Klein R, et al. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials. Lancet 2008;372:1394-402.
33. Sjølie AK, Klein R, Porta M, et al. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo- controlled trial. Lancet 2008;372:1385- 93.
34. Joussen AM, Poulaki V, Qin W, et al. 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;160:501-9. (Pubitemid 34160327)
35. The Diabetic Retinopathy Clinical Research Network. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 2010;117(6):1064.e35- 1077.e35.
36. The ACCORD Study Group and ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010; 363:233-44. [Erratum, N Engl J Med 2011; 364:190.]
37. Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 2007;370:1687-97. (Pubitemid 350100775)
38. Wright AD, Dodson PM. Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies. Eye (Lond) 2011;25:843-9.
39. Nguyen QD, Shah SM, Khwaja AA, et al. Two-year outcomes of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) study. Ophthalmology 2010;117: 2146-51.
40. Michaelides M, Kaines A, Hamilton RD, et al. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology 2010;117(6): 1078.e2-1086.e2.
41. Sultan MB, Zhou D, Loftus J, Dombi T, Ice KS. A phase 2/3, multicenter, randomized, double-masked, 2-year trial of pegaptanib sodium for the treatment of diabetic macular edema. Ophthalmology 2011;118:1107-18.
42. Pearson PA, Comstock TL, Ip M, et al. Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial. Ophthalmology 2011;118:1580- 7.
43. Campochiaro PA, Brown DM, Pearson A, et al. Long-term benefit of sustaineddelivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmology 2011;118(4):626.e2-635.e2.
44. Antonetti DA, Wolpert EB, Demaio L, Harjaj NS, Scaduto RC Jr. Hydrocortisone decreases retinal endothelial cell water and solute flux coincident with increased content and decreased phosphorylation of occludin. J Neurochem 2002;80:667-77. (Pubitemid 34809975)
45. Felinski EA, Cox AE, Phillips BE, Antonetti DA. Glucocorticoids induce transactivation of tight junction genes occludin and claudin-5 in retinal endothelial cells via a novel cis-element. Exp Eye Res 2008; 86:867-78.
46. Su EJ, Fredriksson L, Schielke GP, Eriksson U, Lawrence DA. Tissue plasminogen activator-mediated PDGF signaling and neurovascular coupling in stroke. J Thromb Haemost 2009;7:Suppl 1:155-8.
47. Hawkins BT, Davis TP. The bloodbrain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005;57:173- 85.
48. Zlokovic BV. The blood-brain barrier inhealth and chronic neurodegenerative disorders. Neuron 2008;57:178-201.
49. Nag S, Kapadia A, Stewart DJ. Review: molecular pathogenesis of blood-brain barrier breakdown in acute brain injury. Neuropathol Appl Neurobiol 2011;37:3-23.
50. del Zoppo GJ. The neurovascular unit in the setting of stroke. J Intern Med 2010;267:156-71.
51. Pournaras CJ, Rungger-Brändle E, Riva CE, Hardarson SH, Stefansson E. Regulation of retinal blood flow in health and disease. Prog Retin Eye Res 2008;27:284- 330.
52. Diabetic Retinopathy Clinical Research Network. Relationship between optical coherence tomography-measured central retinal thickness and visual acuity in diabetic macular edema. Ophthalmology 2007;114:525-36.
53. Gardner TW, Larsen M, Girach A, Zhi X. Diabetic macular oedema and visual loss: relationship to location, severity and duration. Acta Ophthalmol 2009;87:709- 13.
54. Bai Y, Ma JX, Guo J, et al. Müller cellderived VEGF isa significant contributor to retinal neovascularization. J Pathol 2009;219:446-54.
55. Wang J, Xu X, Elliott MH, Zhu M, Le YZ. Müller cell-derived VEGF isessential for diabetes-induced retinal inflammation and vascular leakage. Diabetes 2010; 59:2297-305.
56. Ishii H, Jirousek MR, Koya D, et al. Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor. Science 1996;272:728-31. (Pubitemid 26000279)
57. Harhaj NS, Felinski EA, Wolpert EB, Sundstrom JM, Gardner TW, Antonetti DA. VEGF activation of protein kinase C stimulates occludin phosphorylation and contributes to endothelial permeability. Invest Ophthalmol Vis Sci 2006;47:5106- 15.
58. Murakami T, Felinski EA, Antonetti DA. Occludin phosphorylation and ubiquitination regulate tight junction trafficking and vascular endothelial growth factor- induced permeability. J Biol Chem 2009;284:21036-46.
59. Murakami T, Frey T, Lin C, Antonetti DA. Protein kinase Cβ phosphorylates occludin regulating tight junction trafficking in vascular endothelial growth factorinduced permeability in vivo. Diabetes (in press).
60. The PKC-DRS2 Group. Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy. Ophthalmology 2006;113:2221-30.
61. Effect of ruboxistaurin in patients with diabetic macular edema: thirty-month results of the randomized PKC-DMES clinical trial. Arch Ophthalmol 2007;125:318- 24.
62. Scheppke L, Aguilar E, Gariano RF, et al. Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits. J Clin Invest 2008;118:2337-46. (Pubitemid 351872350)
63. Gao BB, Clermont A, Rook S, et al. Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation. Nat Med 2007;13:181-8.
64. Clermont A, Chilcote TJ, Kita T, et al. Plasma kallikrein mediates retinal vascular dysfunction and induces retinal thickening in diabetic rats. Diabetes 2011;60: 1590-8.
65. Yang J, Duh EJ, Caldwell RB, Behzadian MA. Antipermeability function of PEDF involves blockade of the MAP kinase/ GSK/beta-catenin signaling pathway and uPAR expression. Invest Ophthalmol Vis Sci 2010;51:3273-80.
66. Navaratna D, McGuire PG, Menicucci G, Das A. Proteolytic degradation of VE cadherin alters the blood-retinal barrier in diabetes. Diabetes 2007;56:2380-7. (Pubitemid 47358245)
67. Enge M, Bjarnegård M, Gerhardt H, et al. Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy. EMBO J 2002;21:4307-16.
68. Geraldes P, Hiraoka-Yamamoto J, Matsumoto M, et al. Activation of PKCdelta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy. Nat Med 2009;15:1298-306.
69. Adamis AP, Miller JW, Bernal MT, et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 1994;118:445-50.
70. Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331:1480-7. (Pubitemid 24356306)
71. Watanabe D, Suzuma K, Matsui S, et al. Erythropoietin as aretinal angiogenic factor in proliferative diabetic retinopathy. N Engl J Med 2005;353:782-92. (Pubitemid 41215487)
72. Kuiper EJ, Van Nieuwenhoven FA, de Smet MD, et al. The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy. PLoS One 2008;3(7): e2675.
73. Gowda K, Zinnanti WJ, LaNoue KF. The influence of diabetes on glutamate metabolism in retinas. J Neurochem 2011; 117:309-20.
74. VanGuilder HD, Brucklacher AR, Patel K, et al. Diabetes downregulates presynaptic proteins and reduces basal synapsin 1 phosphorylation in rat retina. Eur J Neurosci 2008;28:1-11.
75. Gastinger MJ, Kunselman AR, Conboy EE, Bronson SK, Barber AJ. Dendrite remodeling and other abnormalities in the retinal ganglion cells of Ins2 Akita diabetic mice. Invest Ophthalmol Vis Sci 2008;49:2635-42.
76. Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW. Neural apoptosis in the retina during experimental and human diabetes: early onset and effect of insulin. J Clin Invest 1998;102: 783-91. (Pubitemid 28399611)
77. Zeng HY, Green WR, Tso MO. Microglial activation inhuman diabetic retinopathy. Arch Ophthalmol 2008;126:227-32. (Pubitemid 351240852)
78. Reiter CEN, Wu X, Sandirasegarane L, et al. Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic and local insulin. Diabetes 2006; 55:1148-56. (Pubitemid 44100194)
79. Kondo T, Kahn CR. Altered insulin signaling inretinal tissue in diabetic states. J Biol Chem 2004;279:37997-8006. (Pubitemid 39195515)
80. Rajala RV, Wiskur B, Tanito M, Callegan M, Rajala A. Diabetes reduces autophosphorylation of retinal insulin receptor and increases protein-tyrosine phosphatase-1B activity. Invest Ophthalmol Vis Sci 2009;50:1033-40.
81. Fort PE, Losiewicz MK, Reiter CEN, et al. Differential roles of hyperglycemia and hypoinsulinemia in diabetes induced retinal cell death: evidence for retinal insulin resistance. PLoS One 2011;6(10): e26498.
82. Seki M, Tanaka T, Nawa H, et al. Involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocin- induced diabetes in rats: therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells. Diabetes 2004;53:2412-9. (Pubitemid 39145597)
83. Bearse MA Jr, Han Y, Schneck ME, Barez S, Jacobsen C, Adams AJ. Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy. Invest Ophthalmol Vis Sci 2004;45: 3259-65. (Pubitemid 39121864)
84. Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444:860- 7.
85. Wilkinson-Berka JL, Tan G, Jaworski K, Miller AG. Identification of aretinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on retinal vascular pathology. Circ Res 2009;104:124-33.
86. Joussen AM, Poulaki V, Mitsiades N, et al. Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. FASEB J 2002; 16:438-40.
87. Aveleira CA, Lin CM, Abcouwer SF, Ambrosio AF, Antonetti DA. TNF-alpha signals through PKCzeta/NF-kappaB to alter the tight junction complex and increase retinal endothelial cell permeability. Diabetes 2010;59:2872-82.
88. Schram MT, Chaturvedi N, Schalkwijk CG, Fuller JH, Stehouwer CD. Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes - the EURODIAB Prospective Complications Study. Diabetologia 2005;48:370-8. (Pubitemid 40543311)
89. Demircan N, Safran BG, Soylu M, Ozcan AA, Sizmaz S. Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy. Eye (Lond) 2006; 20:1366-9. (Pubitemid 44921137)
90. Field MG, Elner VM, Puro DG, et al. Rapid, noninvasive detection of diabetesinduced retinal metabolic stress. Arch Ophthalmol 2008;126:934-8. (Pubitemid 352008373)
91. Harrison WW, Bearse MA Jr, Schneck ME, et al. Prediction, by retinal location, of the onset of diabetic edema in patients with nonproliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 2011;52:6825-31.
92. Holfort SK, Norgaard K, Jackson GR, et al. Retinal function inrelation to improved glycaemic control in type 1 diabetes. Diabetologia 2011;54:1853-61.
93. Parravano M, Oddone F, Mineo D, et al. The role of Humphrey Matrix testing in the early diagnosis of retinopathy in type 1 diabetes. Br J Ophthalmol 2008;92:1656-60.
94. Jackson JR, Scott IU, Quillen DA WL, Hershey ME, Gardner TW. Inner retinal visual dysfunction is a sensitive marker of nonproliferative diabetic retinopathy. Br J Ophthalmol 2011 December 15 (Epub ahead of print).
95. van Dijk HW, Kok PH, Garvin M, et al. Selective loss of inner retinal layer thickness in type 1 diabetic patients with minimal diabetic retinopathy. Invest Ophthalmol Vis Sci 2009;50:3404-9.
96. van Dijk HW, Verbraak FD, Kok PH, et al. Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes. Invest Ophthalmol Vis Sci 2010;51:3660-5.