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Diabetic Retinopathy

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Diabetes and Cardiovascular Disease

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

Diabetic retinopathy (DR) is a microvascular complication that afflicts virtually all patients who have had diabetes mellitus for more than a decade (Klein R, Klein BE, Diabetes in America 1:293-<last-page>, 1995). Despite many years of research, DR remains the leading cause of new-onset blindness in working-aged Americans (<Spi_Author>, Atlanta, GA: Centers for Disease Control and Prevention. U.S, Dept of Health and Human Services, 2020). However, older and newer therapies exist which can be remarkably effective if DR is identified in a timely manner, graded appropriately, and correct intervention is initiated when indicated. This chapter reviews the pathophysiology of DR, the clinical manifestations of the disease, and current guidelines for appropriate disease management.

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Abbreviations

CSME:

Clinically significant diabetic macular edema

DCCT:

Diabetes Control and Complications Trial

DME:

Diabetic macular edema

DR:

Diabetic retinopathy

EDIC:

Epidemiology of Diabetes Interventions and Complications study

H/Ma:

Hemorrhages and microaneurysms

IRMA:

Intraretinal microvascular abnormalities

NPDR:

Nonproliferative diabetic retinopathy

NVD:

New vessels on the disc

NVE:

New vessels elsewhere

PDR:

Proliferative diabetic retinopathy

PKC:

Protein kinase C

PPV:

Pars plana vitrectomy

PRP:

Panretinal photocoagulation (scatter laser treatment)

UKPDS:

United Kingdom Prospective Diabetes Study

VCAB:

Venous caliber abnormalities

VEGF:

Vascular endothelial growth factor

WESDR:

Wisconsin Epidemiologic Study of Diabetic Retinopathy

References

  1. Klein R, Klein BE. Vision disorders in diabetes. Diabetes in America. 1995;1:293.

    Google Scholar 

  2. National Diabetes Statistics Report, 2020. Atlanta, GA: centers for disease control and prevention, U.S. Dept of Health and Human Services, 2020.

    Google Scholar 

  3. Cogan DG, Toussaint D, Kuwabara T. Retinal vascular patterns. IV. Diabetic retinopathy. Arch Ophthalmol. 1961;66:366–78.

    Article  CAS  PubMed  Google Scholar 

  4. Cogan DG, Kuwabara T. Capillary shunts in the pathogenesis of diabetic retinopathy. Diabetes. 1963;12:293–300.

    Article  CAS  PubMed  Google Scholar 

  5. Cogan DG, Kuwabara T. The mural cell in perspective. Arch Ophthalmol. 1967;78:133–9.

    Article  CAS  PubMed  Google Scholar 

  6. Michaelson IC. The mode of development of the vascular system in the retina: with some observations on its significance for certain retinal diseases. Trans Ophthalmol Soc. 1948;68:137–80.

    Google Scholar 

  7. Ashton N, Ward B, Serpell G. Effect of oxygen on develo** retinal vessels with particular reference to the problem of retrolental fibroplasia. Br J Ophthalmol. 1954;38:397–432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Engerman RL, Kern TS. Progression of incipient diabetic retinopathy during good glycemic control. Diabetes. 1987;36:808–12.

    Article  CAS  PubMed  Google Scholar 

  10. Engerman RL, Kern TS. Is diabetic retinopathy preventable? Int Ophthalmol Clin. 1987;27:225–9.

    Article  CAS  PubMed  Google Scholar 

  11. Engerman RL. Pathogenesis of diabetic retinopathy. Diabetes. 1989;38:1203–6.

    Article  CAS  PubMed  Google Scholar 

  12. Engerman RL, Kern TS. Aldose reductase inhibition fails to prevent retinopathy in diabetic and galactosemic dogs. Diabetes. 1993;42:820–5.

    Article  CAS  PubMed  Google Scholar 

  13. Kikkawa U, Nishizuka Y. The role of protein kinase C in transmembrane signalling. Annu Rev Cell Biol. 1986;2:149–78.

    Article  CAS  PubMed  Google Scholar 

  14. **a 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;98:2018–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Monnier VM, Kohn RR, Cerami A. Accelerated age-related browning of human collagen in diabetes mellitus. Proc Natl Acad Sci U S A. 1984;81:583–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. A randomized trial of sorbinil, an aldose reductase inhibitor, in diabetic retinopathy. Sorbinil retinopathy trial research group. Arch Ophthalmol. 1990;108:1234–44.

    Google Scholar 

  17. The sorbinil retinopathy trial: Neuropathy results. Sorbinil Retinopathy Trial Research Group. Neurology. 1993;43:1141–9.

    Google Scholar 

  18. 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.

    Article  CAS  PubMed  Google Scholar 

  19. 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;46:1473–80.

    Article  CAS  PubMed  Google Scholar 

  20. Danis RP, Bingaman DP, Jirousek M, Yang Y. Inhibition of intraocular neovascularization caused by retinal ischemia in pigs by PKCbeta inhibition with LY333531. Invest Ophthalmol Vis Sci. 1998;39:171–9.

    CAS  PubMed  Google Scholar 

  21. Aiello LP, Davis MD, Girach A, et al. Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy. Ophthalmology. 2006;113:2221–30.

    Article  PubMed  Google Scholar 

  22. Davis MD, Sheetz MJ, Aiello LP, et al. Effect of ruboxistaurin on the visual acuity decline associated with long-standing diabetic macular edema. Invest Ophthalmol Vis Sci. 2009;50:1–4.

    Article  PubMed  Google Scholar 

  23. Grunwald JE, Brucker AJ, Schwartz SS, et al. Diabetic glycemic control and retinal blood flow. Diabetes. 1990;39:602–7.

    Article  CAS  PubMed  Google Scholar 

  24. Bain SC, Gill GV, Dyer PH, et al. Characteristics of type 1 diabetes of over 50 years duration (the Golden years cohort). Diabet Med. 2003;20:808–11.

    Article  CAS  PubMed  Google Scholar 

  25. Yokomizo H, Maeda Y, et al. Retinol binding protein 3 is increased in the retina of patients with diabetes resistant to diabetic retinopathy. Sci Transl Med. 2019;11:eaau6627.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Leslie RD, Pyke DA. Diabetic retinopathy in identical twins. Diabetes. 1982;31:19–21.

    Article  CAS  PubMed  Google Scholar 

  27. Keenan HA, Costacou T, Sun JK, et al. Clinical factors associated with resistance to microvascular complications in diabetic patients of extreme disease duration: the 50-year medalist study. Diabetes Care. 2007;30:1995–7.

    Article  CAS  PubMed  Google Scholar 

  28. Clustering of long-term complications in families with diabetes in the diabetes control and complications trial. The diabetes control and complications trial research group. Diabetes. 1997;46:1829–39.

    Google Scholar 

  29. 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.

    Article  CAS  PubMed  Google Scholar 

  30. Aiello LP. Angiogenic pathways in diabetic retinopathy. N Engl J Med. 2005;353:839–41.

    Article  CAS  PubMed  Google Scholar 

  31. Miller JW, Adamis AP, Aiello LP. Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy. Diabetes Metab Rev. 1997;13:37–50.

    Article  CAS  PubMed  Google Scholar 

  32. Han L, Zhang L, **ng W, et al. The associations between VEGF gene polymorphisms and diabetic retinopathy susceptibility: a meta-analysis of 11 case-control studies. J Diabetes Res. 2014;2014:805801.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Qiu M, **ong W, Liao H, Li F. VEGF -634G>C polymorphism and diabetic retinopathy risk: a meta-analysis. Gene. 2013;518:310–5.

    Article  CAS  Google Scholar 

  34. Lu Y, Ge Y, Shi Y, Yin J, Huang Z. Two polymorphisms (rs699947, rs2010963) in the VEGFA gene and diabetic retinopathy: an updated meta-analysis. BMC Ophthalmol. 2013;13:56.

    Article  PubMed Central  Google Scholar 

  35. **e XJ, Yang YM, Jiang JK, Lu YQ. Association between the vascular endothelial growth factor single nucleotide polymorphisms and diabetic retinopathy risk: a meta-analysis. J Diabetes. 2017;9:738–53.

    Article  CAS  Google Scholar 

  36. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Watanabe D, Suzuma K, Matsui S, et al. Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. N Engl J Med. 2005;353:782–92.

    Article  CAS  PubMed  Google Scholar 

  38. Sobrin L, Green T, Sim X, et al. Candidate gene association study for diabetic retinopathy in persons with type 2 diabetes: the candidate gene association resource (CARe). Invest Ophthalmol Vis Sci. 2011;52:7593–602.

    Article  CAS  PubMed Central  Google Scholar 

  39. Chang M, He L, Cai L. An overview of Genome-Wide association Studies. Methods Mol Biol. 2018;1754:97–108.

    Article  CAS  Google Scholar 

  40. Dehghan A. Genome-Wide Association Studies. Methods Mol Biol. 2018;1793:37–49.

    Article  CAS  PubMed  Google Scholar 

  41. Fu YP, Hallman DM, Gonzalez VH, et al. Identification of diabetic retinopathy genes through a Genome-Wide association study among Mexican-Americans from Starr County, Texas. J Ophthalmol. 2010;2010:861291.

    PubMed  PubMed Central  Google Scholar 

  42. Grassi MA, Tikhomirov A, Ramalingam S, Below JE, Cox NJ, Nicolae DL. Genome-wide meta-analysis for severe diabetic retinopathy. Hum Mol Genet. 2011;20:2472–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Meng W, Shah KP, Pollack S, et al. A genome-wide association study suggests new evidence for an association of the NADPH oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes. Acta Ophthalmol. 2018;96:e811–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Awata T, Yamashita H, Kurihara S, et al. A genome-wide association study for diabetic retinopathy in a Japanese population: potential association with a long intergenic non-coding RNA. PLoS One. 2014;9:e111715.

    Article  PubMed Central  Google Scholar 

  45. Cho H, Sobrin L. Genetics of diabetic retinopathy. Curr Diab Rep. 2014;14:515.

    Article  PubMed Central  Google Scholar 

  46. Lalonde E, Albrecht S, Ha KC, et al. Unexpected allelic heterogeneity and spectrum of mutations in fowler syndrome revealed by next-generation exome sequencing. Hum Mutat. 2010;31:918–23.

    Article  CAS  Google Scholar 

  47. Shtir C, Aldahmesh MA, Al-Dahmash S, et al. Exome-based case-control association study using extreme phenotype design reveals novel candidates with protective effect in diabetic retinopathy. Hum Genet. 2016;135:193–200.

    Article  CAS  PubMed  Google Scholar 

  48. Ung C, Sanchez AV, Shen L, et al. Whole exome sequencing identification of novel candidate genes in patients with proliferative diabetic retinopathy. Vis Res. 2017;139:168–76.

    Article  PubMed  Google Scholar 

  49. https://idf.org/aboutdiabetes/what-is-diabetes/facts-figures.html.

  50. Cho NH, Shaw JE, Karuranga S, et al. IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271–81.

    Article  CAS  PubMed  Google Scholar 

  51. Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35:556–64.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IX. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol. 1989;107:237–43.

    Article  CAS  PubMed  Google Scholar 

  53. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. X. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is 30 years or more. Arch Ophthalmol. 1989;107:244–9.

    Article  CAS  Google Scholar 

  54. Liew G, Michaelides M, Bunce C. A comparison of the causes of blindness certifications in England and Wales in working age adults (16–64 years), 1999–2000 with 2009–2010. BMJ Open. 2014;4:e004015.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. 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;102:520–6.

    Article  CAS  PubMed  Google Scholar 

  56. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. 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;102:527–32.

    Article  CAS  Google Scholar 

  57. Diabetic Retinopathy. https://www.cdc.gov/visionhealth/pdf/factsheet.pdf.

  58. DCCT Research Group. Are continuing studies of metabolic control and microvascular complications in insulin-dependent diabetes mellitus justified? The diabetes control and complications trial. N Engl J Med. 1988;318:246–50.

    Article  Google Scholar 

  59. Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the epidemiology of diabetes interventions and complications (EDIC) study. JAMA. 2003;290:2159–67.

    Article  Google Scholar 

  60. Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA. 2002;287:2563–9.

    Article  Google Scholar 

  61. Hypoglycemia in the Diabetes Control and Complications Trial. The diabetes control and complications trial research group. Diabetes. 1997;46:271–86.

    Article  Google Scholar 

  62. Lifetime benefits and costs of intensive therapy as practiced in the diabetes control and complications trial. The Diabetes Control and Complications Trial Research Group. JAMA. 1996;276:1409–15.

    Google Scholar 

  63. Nathan DM, Genuth S, Lachin J, et al. 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.

    Article  CAS  Google Scholar 

  64. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial. Diabetes. 1995;44:968–83.

    Google Scholar 

  65. Progression of retinopathy with intensive versus conventional treatment in the diabetes control and complications trial. Diabetes control and complications trial research group. Ophthalmology. 1995;102:647–61.

    Google Scholar 

  66. Moriarty AP, Spalton DJ, Shilling JS, Ffytche TJ, Bulsara M. Breakdown of the blood-aqueous barrier after argon laser panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology. 1996;103:833–8.

    Article  CAS  PubMed  Google Scholar 

  67. Aiello LP, Sun W, Das A, et al. Intensive diabetes therapy and ocular surgery in type 1 diabetes. N Engl J Med. 2015;372:1722–33.

    Article  Google Scholar 

  68. 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;352:837–53.

    Google Scholar 

  69. Holman RR, Paul SK, Bethel MA, Neil HA, Matthews DR. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med. 2008;359:1565–76.

    Article  CAS  Google Scholar 

  70. Chase HP, Jackson WE, Hoops SL, Cockerham RS, Archer PG, O'Brien D. Glucose control and the renal and retinal complications of insulin-dependent diabetes. JAMA. 1989;261:1155–60.

    Article  CAS  PubMed  Google Scholar 

  71. Blood glucose control and the evolution of diabetic retinopathy and albuminuria. A preliminary multicenter trial. N Engl J Med. 1984;311:365–72.

    Google Scholar 

  72. Krolewski 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;318:140–5.

    Article  CAS  PubMed  Google Scholar 

  73. 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;114:1079–84.

    Article  CAS  PubMed  Google Scholar 

  74. Chew EY, Klein ML, Murphy RP, Remaley NA, Ferris FL 3rd. Effects of aspirin on vitreous/preretinal hemorrhage in patients with diabetes mellitus. Early treatment diabetic retinopathy study report no. 20. Arch Ophthalmol. 1995;113:52–5.

    Article  CAS  PubMed  Google Scholar 

  75. Chew EY, Williams GA, Burton TC, Barton FB, Remaley NA, Ferris FL 3rd. Aspirin effects on the development of cataracts in patients with diabetes mellitus. Early treatment diabetic retinopathy study report 16. Arch Ophthalmol. 1992;110:339–42.

    Article  CAS  PubMed  Google Scholar 

  76. Aiello LP, Cahill MT, Wong JS. Systemic considerations in the management of diabetic retinopathy. Am J Ophthalmol. 2001;132:760–76.

    Article  CAS  PubMed  Google Scholar 

  77. Moloney JB, Drury MI. The effect of pregnancy on the natural course of diabetic retinopathy. Am J Ophthalmol. 1982;93:745–56.

    Article  CAS  Google Scholar 

  78. Serup L. Influence of pregnancy on diabetic retinopathy. Acta Endocrinol Suppl (Copenh). 1986;277:122–4.

    CAS  PubMed  Google Scholar 

  79. Phelps RL, Sakol P, Metzger BE, Jampol LM, Freinkel N. Changes in diabetic retinopathy during pregnancy. Correlations with regulation of hyperglycemia. Arch Ophthalmol. 1986;104:1806–10.

    Article  CAS  Google Scholar 

  80. Wilkinson CP, Ferris FL 3rd, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110:1677–82.

    Article  CAS  PubMed  Google Scholar 

  81. Browning DJ, Glassman AR, Aiello LP, et al. Optical coherence tomography measurements and analysis methods in optical coherence tomography studies of diabetic macular edema. Ophthalmology. 2008;115(1366–71):1371.e1.

    PubMed  Google Scholar 

  82. Chalam KV, Bressler SB, Edwards AR, et al. Retinal thickness in people with diabetes and minimal or no diabetic retinopathy: Heidelberg Spectralis optical coherence tomography. Invest Ophthalmol Vis Sci. 2012;53:8154–61.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Bressler SB, Edwards AR, Andreoli CM, et al. Reproducibility of Optovue RTVue optical coherence tomography retinal thickness measurements and conversion to equivalent Zeiss stratus metrics in diabetic macular edema. Transl Vis Sci Technol. 2015;4:5.

    Article  PubMed  PubMed Central  Google Scholar 

  84. 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;114:525–36.

    Article  PubMed  Google Scholar 

  85. Diabetic Retinopathy Study Research Group. Preliminary report on effects of photocoagulation therapy. Am J Ophthalmol. 1976;81:383–96.

    Article  Google Scholar 

  86. Photocoagulation treatment of proliferative diabetic retinopathy: The second report of diabetic retinopathy study findings. Ophthalmology. 1978;85:82–106.

    Google Scholar 

  87. Four risk factors for severe visual loss in diabetic retinopathy. The third report from the diabetic retinopathy study. The diabetic retinopathy study research group. Arch Ophthalmol. 1979;97:654–5.

    Google Scholar 

  88. Photocoagulation treatment of proliferative diabetic retinopathy: relationship of adverse treatment effects to retinopathy severity. Diabetic retinopathy study report no. 5. Dev Ophthalmol 1981;2:248–261.

    Google Scholar 

  89. Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of diabetic retinopathy study (DRS) findings, DRS report number 8. The diabetic retinopathy study research group. Ophthalmology. 1981;88:583–600.

    Google Scholar 

  90. Diabetic retinopathy study. Report Number 6. Design, methods, and baseline results. Report Number 7. A modification of the Airlie House classification of diabetic retinopathy. Prepared by the Diabetic Retinopathy. Invest Ophthalmol Vis Sci 1981;21:1–226.

    Google Scholar 

  91. Ederer F, Podgor MJ. Assessing possible late treatment effects in stop** a clinical trial early: a case study. Diabetic Retinopathy Study report No. 9. Control Clin Trials. 1984;5:373–81.

    Article  CAS  PubMed  Google Scholar 

  92. Rand LI, Prud'homme GJ, Ederer F, Canner PL. Factors influencing the development of visual loss in advanced diabetic retinopathy. Diabetic Retinopathy Study (DRS) Report No. 10. Invest Ophthalmol Vis Sci. 1985;26:983–91.

    CAS  PubMed  Google Scholar 

  93. Ferris FL 3rd, Podgor MJ, Davis MD. Macular edema in diabetic retinopathy study patients. Diabetic retinopathy study report number 12. Ophthalmology. 1987;94:754–60.

    Article  PubMed  Google Scholar 

  94. Kaufman SC, Ferris FL 3rd, Swartz M. Intraocular pressure following panretinal photocoagulation for diabetic retinopathy. Diabetic retinopathy report no. 11. Arch Ophthalmol. 1987;105:807–9.

    Article  CAS  PubMed  Google Scholar 

  95. Kaufman SC, Ferris FL 3rd, Seigel DG, Davis MD, DeMets DL. Factors associated with visual outcome after photocoagulation for diabetic retinopathy. Diabetic retinopathy study report #13. Invest Ophthalmol Vis Sci. 1989;30:23–8.

    CAS  PubMed  Google Scholar 

  96. Photocoagulation for diabetic macular edema. Early treatment diabetic retinopathy study report number 1. Early treatment diabetic retinopathy study research group. Arch Ophthalmol. 1985;103:1796–806.

    Google Scholar 

  97. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early treatment diabetic retinopathy study report number 2. Early treatment diabetic retinopathy study research group. Ophthalmology. 1987;94:761–74.

    Google Scholar 

  98. Kinyoun J, Barton F, Fisher M, Hubbard L, Aiello L, Ferris F 3rd. Detection of diabetic macular edema. Ophthalmoscopy versus photography--Early Treatment Diabetic Retinopathy Study Report Number 5. The ETDRS Research Group. Ophthalmology. 1989;96:746–50; discussion 750-1

    Article  CAS  PubMed  Google Scholar 

  99. Prior MJ, Prout T, Miller D, Ewart R, Kumar D. C-peptide and the classification of diabetes mellitus patients in the early treatment diabetic retinopathy study. Report number 6. The ETDRS research group. Ann Epidemiol. 1993;3:9–17.

    Article  CAS  PubMed  Google Scholar 

  100. Techniques for scatter and local photocoagulation treatment of diabetic retinopathy: Early Treatment Diabetic Retinopathy Study Report no. 3. The Early Treatment Diabetic Retinopathy Study Research Group. Int Ophthalmol Clin. 1987;27:254–64.

    Google Scholar 

  101. Case reports to accompany early treatment diabetic retinopathy study reports 3 and 4. The early treatment diabetic retinopathy study research group. Int Ophthalmol Clin. 1987;27:273–333.

    Google Scholar 

  102. Flynn HW Jr, Chew EY, Simons BD, Barton FB, Remaley NA, Ferris FL 3rd. Pars plana vitrectomy in the early treatment diabetic retinopathy study. ETDRS report number 17. The early treatment diabetic retinopathy study research group. Ophthalmology. 1992;99:1351–7.

    Article  PubMed  Google Scholar 

  103. 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;113:1144–55.

    Google Scholar 

  104. Two-year course of visual acuity in severe proliferative diabetic retinopathy with conventional management. Diabetic retinopathy vitrectomy study (DRVS) report #1. Ophthalmology. 1985;92:492–502.

    Google Scholar 

  105. Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Two-year results of a randomized trial. Diabetic retinopathy vitrectomy study report 2. The diabetic retinopathy vitrectomy study research group. Arch Ophthalmol. 1985;103:1644–52.

    Google Scholar 

  106. Early vitrectomy for severe proliferative diabetic retinopathy in eyes with useful vision. Results of a randomized trial--Diabetic Retinopathy Vitrectomy Study Report 3. The Diabetic Retinopathy Vitrectomy Study Research Group. Ophthalmology. 1988;95:1307–20.

    Google Scholar 

  107. Early vitrectomy for severe proliferative diabetic retinopathy in eyes with useful vision. Clinical application of results of a randomized trial--Diabetic Retinopathy Vitrectomy Study Report 4. The Diabetic Retinopathy Vitrectomy Study Research Group. Ophthalmology. 1988;95:1321–34.

    Google Scholar 

  108. Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Four-year results of a randomized trial: diabetic retinopathy vitrectomy study report 5. Arch Ophthalmol. 1990;108:958–64.

    Google Scholar 

  109. UK Prospective Diabetes Study Group. 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;317:713–20.

    Article  PubMed Central  Google Scholar 

  110. 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 

  111. Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Early treatment diabetic retinopathy study research group. Ophthalmology. 1991;98:823–33.

    Google Scholar 

  112. Classification of diabetic retinopathy from fluorescein angiograms. ETDRS report number 11. Early treatment diabetic retinopathy study research group. Ophthalmology. 1991;98:807–22.

    Google Scholar 

  113. Fluorescein angiographic risk factors for progression of diabetic retinopathy: ETDRS report number 13. Ophthalmology. 1991;98:834–40.

    Google Scholar 

  114. Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early treatment diabetic retinopathy study research group. Ophthalmology. 1991;98:766–85.

    Google Scholar 

  115. Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Early treatment diabetic retinopathy study research group. Ophthalmology. 1991;98:757–65.

    Google Scholar 

  116. Ferris F. Early photocoagulation in patients with either type I or type II diabetes. Trans Am Ophthalmol Soc. 1996;94:505–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Aiello LP, Wong JS. Role of vascular endothelial growth factor in diabetic vascular complications. Kidney Int Suppl. 2000;77:S113–9.

    Article  CAS  PubMed  Google Scholar 

  118. Avery RL. Regression of retinal and iris neovascularization after intravitreal bevacizumab (Avastin) treatment. Retina. 2006;26:352–4.

    Article  PubMed  Google Scholar 

  119. Adamis AP, Shima DT, Tolentino MJ, et al. Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. Arch Ophthalmol. 1996;114:66–71.

    Article  CAS  PubMed  Google Scholar 

  120. Brucker AJ, Qin H, Antoszyk AN, et al. Observational study of the development of diabetic macular edema following panretinal (scatter) photocoagulation given in 1 or 4 sittings. Arch Ophthalmol. 2009;127:132–40.

    Article  PubMed  Google Scholar 

  121. Gross JG, Glassman AR, Jampol LM, et al. Panretinal photocoagulation vs Intravitreous Ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA. 2015;314:2137–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Sivaprasad S, Prevost AT, Vasconcelos JC, et al. Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial. Lancet. 2017;389:2193–203.

    Article  CAS  PubMed  Google Scholar 

  123. Gross JG, Glassman AR, Liu D, et al. Five-year outcomes of Panretinal photocoagulation vs Intravitreous Ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA Ophthalmol. 2018;136:1138–48.

    Article  PubMed  PubMed Central  Google Scholar 

  124. Obeid A, Su D, Patel SN, et al. Outcomes of eyes lost to follow-up with proliferative diabetic retinopathy that received Panretinal photocoagulation versus intravitreal anti-vascular endothelial growth factor. Ophthalmology. 2019;126:407–13.

    Article  PubMed  Google Scholar 

  125. Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008;115:1447–9, 1449.e1–10.

    Google Scholar 

  126. Chew E, Strauber S, Beck R, et al. Randomized trial of peribulbar triamcinolone acetonide with and without focal photocoagulation for mild diabetic macular edema: a pilot study. Ophthalmology. 2007;114:1190–6.

    Article  CAS  PubMed  Google Scholar 

  127. Elman MJ, Aiello LP, Beck RW, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117:1064–1077.e35.

    Article  PubMed  Google Scholar 

  128. Elman MJ, Bressler NM, Qin H, et al. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011;118:609–14.

    Article  PubMed  Google Scholar 

  129. Elman MJ, Ayala A, Bressler NM, et al. Intravitreal Ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results. Ophthalmology. 2015;122:375–81.

    Article  PubMed  Google Scholar 

  130. Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372:1193–203.

    Article  CAS  PubMed  Google Scholar 

  131. Jampol LM, Glassman AR, Bressler NM, Wells JA, Ayala AR. Anti-vascular endothelial growth factor comparative effectiveness trial for diabetic macular edema: additional efficacy post hoc analyses of a randomized clinical trial. JAMA Ophthalmol. 2016;134

    Google Scholar 

  132. Baker CW, Glassman AR, Beaulieu WT, et al. Effect of initial management with Aflibercept vs laser photocoagulation vs. observation on vision loss among patients with diabetic macular edema involving the Center of the Macula and Good Visual Acuity: a randomized clinical trial. JAMA. 2019;321:1880–94.

    Article  CAS  PubMed Central  Google Scholar 

  133. Antoszyk AN, Glassman AR, Beaulieu WT, et al. Effect of Intravitreous Aflibercept vs vitrectomy with Panretinal photocoagulation on visual acuity in patients with vitreous hemorrhage from proliferative diabetic retinopathy: a randomized clinical trial. JAMA. 2020;324:2383–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849–61.

    Article  CAS  PubMed  Google Scholar 

  135. 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.

    Article  CAS  PubMed  Google Scholar 

  136. Chew EY, Ambrosius WT, Davis MD, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010;363:233–44.

    Article  PubMed  Google Scholar 

  137. 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.

    Article  CAS  PubMed  Google Scholar 

  138. Clermont A, Murugesan N, Zhou Q, et al. Plasma Kallikrein mediates vascular endothelial growth factor-induced retinal dysfunction and thickening. Invest Ophthalmol Vis Sci. 2016;57:2390–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. KalVista pharmaceuticals reports phase 2 clinical trial results in patients with diabetic macular edema. business wire. This is a press release: https://www.businesswire.com/news/home/20191209005372/en/KalVista-Pharmaceuticals-Reports-Phase-2-Clinical-Trial-Results-in-Patients-with-Diabetic-Macular-Edema

  140. Ohashi H, Takagi H, Koyama S, et al. Alterations in expression of angiopoietins and the Tie-2 receptor in the retina of streptozotocin induced diabetic rats. Mol Vis. 2004;10:608–17.

    CAS  PubMed  Google Scholar 

  141. Oh H, Takagi H, Suzuma K, Otani A, Matsumura M, Honda Y. Hypoxia and vascular endothelial growth factor selectively up-regulate angiopoietin-2 in bovine microvascular endothelial cells. J Biol Chem. 1999;274:15732–9.

    Article  CAS  PubMed  Google Scholar 

  142. Peters S, Cree IA, Alexander R, et al. Angiopoietin modulation of vascular endothelial growth factor: effects on retinal endothelial cell permeability. Cytokine. 2007;40:144–50.

    Article  CAS  Google Scholar 

  143. Menden H, Welak S, Cossette S, Ramchandran R, Sampath V. Lipopolysaccharide (LPS)-mediated angiopoietin-2-dependent autocrine angiogenesis is regulated by NADPH oxidase 2 (Nox2) in human pulmonary microvascular endothelial cells. J Biol Chem. 2015;290:5449–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Ziegler T, Horstkotte J, Schwab C, et al. Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis. J Clin Invest. 2013;123:3436–45.

    Article  CAS  PubMed Central  Google Scholar 

  145. Sahni J, Patel SS, Dugel PU, et al. Simultaneous inhibition of Angiopoietin-2 and vascular endothelial growth factor-a with Faricimab in diabetic macular edema: BOULEVARD phase 2 randomized trial. Ophthalmology. 2019;126:1155–70.

    Article  Google Scholar 

  146. https://www.roche.com/media/releases/med-cor-2020-12-21.htm.

  147. Tang J, Du Y, Lee CA, Talahalli R, Eells JT, Kern TS. Low-intensity far-red light inhibits early lesions that contribute to diabetic retinopathy: in vivo and in vitro. Invest Ophthalmol Vis Sci. 2013;54:3681–90.

    Article  PubMed  PubMed Central  Google Scholar 

  148. Saliba A, Du Y, Liu H, et al. Photobiomodulation mitigates diabetes-induced retinopathy by direct and indirect mechanisms: evidence from intervention Studies in pigmented mice. PLoS One. 2015;10:e0139003.

    Article  PubMed  PubMed Central  Google Scholar 

  149. Cheng Y, Du Y, Liu H, Tang J, Veenstra A, Kern TS. Photobiomodulation inhibits long-term structural and functional lesions of diabetic retinopathy. Diabetes. 2018;67:291–8.

    Article  CAS  Google Scholar 

  150. Tang J, Herda AA, Kern TS. Photobiomodulation in the treatment of patients with non-center-involving diabetic macular oedema. Br J Ophthalmol. 2014;98:1013–5.

    Article  Google Scholar 

  151. Eells JT, Gopalakrishnan S, Connor TB, et al. 670 nm Photobiomodulation as a therapy for diabetic macular edema: a pilot study. Invest Ophthalmol Vis Sci. 2017;58:932.

    Google Scholar 

  152. Fong DS, Aiello L, Gardner TW, et al. Retinopathy in diabetes. Diabetes care. 2004;27:s84–7.

    Article  Google Scholar 

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Authors and Affiliations

  1. Beetham Eye Institute, Joslin Diabetes Center, Boston, MA, USA

    Mohamed Ashraf, Jennifer K. Sun, Paolo S. Silva, Jerry Cavallerano & Lloyd Paul Aiello

  2. Department of Ophthalmology, Harvard Medical School, Boston, MA, USA

    Mohamed Ashraf, Jennifer K. Sun, Paolo S. Silva, Jerry Cavallerano & Lloyd Paul Aiello

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  1. Mohamed Ashraf
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  2. Jennifer K. Sun
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  3. Paolo S. Silva
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  4. Jerry Cavallerano
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  5. Lloyd Paul Aiello
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Correspondence to Lloyd Paul Aiello .

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  1. Steward St. Elizabeth’s Medical Center, Tufts University Medical School, Brighton, MA, USA

    Michael Johnstone

  2. Beth Israel Deaconess Medical Center / Harvard Medical School, Boston, MA, USA

    Aristidis Veves

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Ashraf, M., Sun, J.K., Silva, P.S., Cavallerano, J., Aiello, L.P. (2023). Diabetic Retinopathy. In: Johnstone, M., Veves, A. (eds) Diabetes and Cardiovascular Disease. Contemporary Cardiology. Humana, Cham. https://doi.org/10.1007/978-3-031-13177-6_15

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