Endocrine

, Volume 46, Issue 2, pp 199–208 | Cite as

The changing role of the endocrinologist in the care of patients with diabetic retinopathy

Review

Abstract

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and still represents a leading cause of visual impairment in working age in industrialized countries. It develops following non proliferative (mild, moderate, or severe) and proliferative stages, the earliest being often asymptomatic and with diabetic macular edema potentially developing at any of these. The prevalence and incidence of DR increase with diabetes duration and worsening of metabolic and blood pressure control. Current approaches to prevent and/or treat DR include optimized control of blood glucose and blood pressure and screening for early identification of high risk, though still asymptomatic retinal lesions. Results from the recent clinical trials suggest a role for blockers of the renin–angiotensin system (angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers) and for fenofibrate in reducing progression and/or inducing regression of mild to moderate non proliferative DR. Intra-vitreal administration of anti-vascular endothelial growth factor agents was shown to reduce visual loss in more advanced stages of DR, especially in macular edema.

Keywords

Diabetes mellitus Diabetic retinopathy Renin–angiotensin system Serum lipids Vascular endothelial growth factor 

References

  1. 1.
    World Health Organization. The World Health Report (2010), http://www.who.int/mediacentre/factsheets/fs312/en/. Accessed 22 Sep 2013
  2. 2.
    World Health Organization. The World Health Report (2010), http://www.who.int/diabetes/facts/world_figures/en/. Accessed 22 Sep 2013
  3. 3.
    R. Chibber, S. Chibber, E. Kohner, 21st Century treatment of diabetic retinopathy. Expert Rev. Endocrinol. Metab. 2, 623–631 (2007)CrossRefGoogle Scholar
  4. 4.
    D.S. Fong, L.P. Aiello, F.L. Ferris, R. Klein, Diabetic retinopathy. Diabetes Care 27, 2540–2553 (2004)PubMedCrossRefGoogle Scholar
  5. 5.
    R. Klein, B.E. Klein, S.E. Moss, D.L. DeMets, I. Kaufman, P.S. Voss, Prevalence of diabetes mellitus in southern Wisconsin. Am. J. Epidemiol. 119, 54–61 (1984)PubMedGoogle Scholar
  6. 6.
    R. Klein, B.E.K. Klein, Are individuals with diabetes seeing better?: a long-term epidemiological perspective. Diabetes 59, 1853–1860 (2010)PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    M. Porta, F. Bandello, Diabetic retinopathy. A clinical update. Diabetologia 45, 1617–1634 (2002)PubMedCrossRefGoogle Scholar
  8. 8.
    D.A. Antonetti, A.J. Barber, S.K. Bronson, W.M. Freeman, T.W. Gardner, L.S. Jefferson, M. Kester, S.R. Kimball, J.K. Krady, K.F. LaNoue, C.C. Norbury, P.G. Quinn, L. Sandirasegarane, I. Simpson, Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes 55, 2401–2411 (2006)PubMedCrossRefGoogle Scholar
  9. 9.
    E. Lieth, T.W. Gardner, A.J. Barber, D.A. Antonetti, Retinal neurodegeneration: early pathology in diabetes. Clin. Experiment. Ophthalmol. 28, 3–8 (2000)PubMedCrossRefGoogle Scholar
  10. 10.
    E. Rungger-Brändle, A.A. Dosso, P.M. Leuenberger, Glial reactivity, an early feature of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 41, 1971–1980 (2000)PubMedGoogle Scholar
  11. 11.
    M. Lorenzi, C. Gerhardinger, Early cellular and molecular changes induced by diabetes in the retina. Diabetologia 44, 791–804 (2001)PubMedCrossRefGoogle Scholar
  12. 12.
    M. Garcia-Ramírez, C. Hernández, M. Villarroel, F. Canals, M.A. Alonso, R. Fortuny, L. Masmiquel, A. Navarro, J. García-Arumí, R. Simó, Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy. Diabetologia 52, 2633–2641 (2009)PubMedCrossRefGoogle Scholar
  13. 13.
    M.S. Roy, R.D. Gunkel, M.J. Podgor, Color vision defects in early diabetic retinopathy. Arch. Ophthalmol. 104, 225–228 (1986)PubMedCrossRefGoogle Scholar
  14. 14.
    Y. Shirao, K. Kawasaki, Electrical responses from diabetic retina. Prog. Retin. Eye Res. 17, 59–76 (1998)PubMedCrossRefGoogle Scholar
  15. 15.
    A.J. Barber, A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Prog. Neuropsychopharmacol. Biol. Psychiatry 27, 283–290 (2003)PubMedCrossRefGoogle Scholar
  16. 16.
    M.A. Bearse, A.J. Adams, Y. Han, M.E. Schneck, J. Ng, K. Bronson-Castain, S. Barez, A multifocal electroretinogram model predicting the development of diabetic retinopathy. Prog. Retin. Eye Res. 25, 425–448 (2006)PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    K. Bronson-Castain, M.A. Bearse, J. Neuville, S. Jonasdottir, B. King-Hooper, S. Barez, M.E. Schneck, Adolescents with type 2 diabetes: early indications of focal retinal neuropathy, retinal thinning, and venular dilation. Retina 29, 618–626 (2009)PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    E.L. Fletcher, J.A. Phipps, M.M. Ward, T. Puthussery, J.L. Wilkinson-Berka, Neuronal and glial cell abnormality as predictors of progression of diabetic retinopathy. Curr. Pharm. Des. 13, 2699–2712 (2007)PubMedCrossRefGoogle Scholar
  19. 19.
    V. Asnaghi, C. Gerhardinger, T. Hoehn, A. Adeboje, M. Lorenzi, A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes 52, 506–511 (2003)PubMedCrossRefGoogle Scholar
  20. 20.
    J.R. Williamson, K. Chang, M. Frangos, K.S. Hasan, Y. Ido, T. Kawamura, J.R. Nyengaard, M. van den Enden, C. Kilo, R.G. Tilton, Hyperglycemic pseudohypoxia and diabetic complications. Diabetes 42, 801–813 (1993)PubMedCrossRefGoogle Scholar
  21. 21.
    M. Brownlee, Biochemistry and molecular cell biology of diabetic complications. Nature 414, 813–820 (2001)PubMedCrossRefGoogle Scholar
  22. 22.
    Sorbinil Retinopathy Trial Research Group, A randomized trial of sorbinil, an aldose reductase inhibitor, in diabetic retinopathy. Arch. Ophthalmol. 108, 1234–1244 (1990)CrossRefGoogle Scholar
  23. 23.
    I. Giardino, D. Edelstein, M. Brownlee, Nonenzymatic glycosylation in vitro and in bovine endothelial cells alters basic fibroblast growth factor activity. A model for intracellular glycosylation in diabetes. J. Clin. Investig. 94, 110–117 (1994)PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    A.S. Charonis, L.A. Reger, J.E. Dege, K. Kouzi-Koliakos, L.T. Furcht, R.M. Wohlhueter, E.C. Tsilibary, Laminin alterations after in vitro nonenzymatic glycosylation. Diabetes 39, 807–814 (1990)PubMedCrossRefGoogle Scholar
  25. 25.
    H.P. Hammes, S. Martin, K. Federlin, K. Geisen, M. Brownlee, Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. Proc. Natl. Acad. Sci. USA 88, 11555–11558 (1991)PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    D. Koya, G.L. King, Protein kinase C activation and the development of diabetic complications. Diabetes 47, 859–866 (1998)PubMedCrossRefGoogle Scholar
  27. 27.
    D. Koya, M.R. Jirousek, Y.W. Lin, H. Ishii, K. Kuboki, G.L. King, Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats. J. Clin. Investig. 100, 115–126 (1997)PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    T. Nishikawa, D. Edelstein, X.L. Du, S. Yamagishi, T. Matsumura, Y. Kaneda, M.A. Yorek, D. Beebe, P.J. Oates, H.P. Hammes, I. Giardino, M. Brownlee, Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404, 787–790 (2000)PubMedCrossRefGoogle Scholar
  29. 29.
    M.J. Sheetz, L.P. Aiello, N. Shahri, M.D. Davis, K.A. Kles, R.P. Danis, Effect of ruboxistaurin (RBX) On visual acuity decline over a 6-year period with cessation and reinstitution of therapy: results of an open-label extension of the Protein Kinase C Diabetic Retinopathy Study 2 (PKC-DRS2). Retina 31, 1053–1059 (2011)PubMedCrossRefGoogle Scholar
  30. 30.
    X.L. Du, D. Edelstein, L. Rossetti, I.G. Fantus, H. Goldberg, F. Ziyadeh, J. Wu, M. Brownlee, Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc. Natl. Acad. Sci. USA 97, 12222–12226 (2000)PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    X.L. Du, T. Matsumura, D. Edelstein, L. Rossetti, Z. Zsengellér, C. Szabó, M. Brownlee, Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J. Clin. Investig. 112, 1049–1057 (2003)PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    E. Beltramo, E. Berrone, S. Tarallo, M. Porta, Effects of thiamine and benfotiamine on intracellular glucose metabolism and relevance in the prevention of diabetic complications. Acta Diabetol. 45, 131–141 (2008)PubMedCrossRefGoogle Scholar
  33. 33.
    A.F. Omar, P.S. Silva, J.K. Sun, Genetics of diabetic retinopathy. Semin. Ophthalmol. 28, 337–346 (2013)PubMedCrossRefGoogle Scholar
  34. 34.
    T.A. Ciulla, A.G. Amador, B. Zinman, Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care 26, 2653–2664 (2003)PubMedCrossRefGoogle Scholar
  35. 35.
    C.A. Kiire, M. Porta, V. Chong, Medical management for the prevention and treatment of diabetic macular edema. Surv. Ophthalmol. 58, 459–465 (2013)PubMedCrossRefGoogle Scholar
  36. 36.
    The Diabetes Control and Complications Trial, (DCCT) 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. 329, 977–986 (1993)CrossRefGoogle Scholar
  37. 37.
    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 352, 837–853 (1998)CrossRefGoogle Scholar
  38. 38.
    The Diabetes Control and Complications Trial/Epidemiology of Diabetes, Interventions and Complications (DCCT/EDIC) Research Group. 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 (1983-2. Arch. Intern. Med. 169, 1307–1316 (2009)CrossRefGoogle Scholar
  39. 39.
    R. Boussageon, T. Bejan-Angoulvant, M. Saadatian-Elahi, S. Lafont, C. Bergeonneau, B. Kassaï, S. Erpeldinger, J.M. Wright, F. Gueyffier, C. Cornu, Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ 343, d4169 (2011)PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    The Action to Control Cardiovascular Risk in Diabetes Group., Effects of intensive glucose lowering in type 2 diabetes. N. Engl. J. Med. 358, 2545–2559 (2008)CrossRefGoogle Scholar
  41. 41.
    P. Home, Safety of very tight blood glucose control in type 2 diabetes. BMJ 336, 458–459 (2008)PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    R. Klein, B.E. Klein, S.E. Moss, K.J. Cruickshanks, The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology 105, 1801–1815 (1998)PubMedCrossRefGoogle Scholar
  43. 43.
    UK Prospective Diabetes Study Group, Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 317, 703–713 (1998)PubMedCentralCrossRefGoogle Scholar
  44. 44.
    ADVANCE Collaborative Group, Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 370, 829–840 (2007)CrossRefGoogle Scholar
  45. 45.
    The ACCORD Study Group and ACCORD Eye Study Group, Effects of medical therapies on retinopathy progression in type 2 diabetes. N. Engl. J. Med. 363, 233–244 (2010)CrossRefGoogle Scholar
  46. 46.
    R.O. Estacio, B.W. Jeffers, N. Gifford, R.W. Schrier, Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes. Diabetes Care 23(Suppl 2), B54–B64 (2000)PubMedGoogle Scholar
  47. 47.
    R.W. Grant, J.B. Buse, J.B. Meigs, Quality of diabetes care in U.S. academic medical centers: low rates of medical regimen change. Diabetes Care 28, 337–442 (2005)PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    G. Prévost, T.M. Phan, C. Mounier-Vehier, P. Fontaine, Control of cardiovascular risk factors in patients with type 2 diabetes and hypertension in a French national study (Phenomen). Diabetes Metab. 31, 479–485 (2005)PubMedCrossRefGoogle Scholar
  49. 49.
    G.V. Gill, A. Woodward, S. Pradhan, M. Wallymahmed, T. Groves, P. English, J.P. Wilding, Intensified treatment of type 2 diabetes—positive effects on blood pressure, but not glycaemic control. QJM 96, 833–836 (2003)PubMedCrossRefGoogle Scholar
  50. 50.
    G. De Berardis, F. Pellegrini, M. Franciosi, M. Belfiglio, B. Di Nardo, S. Greenfield, S.H. Kaplan, M.C.E. Rossi, M. Sacco, G. Tognoni, M. Valentini, A. Nicolucci, Quality of care and outcomes in type 2 diabetic patients: a comparison between general practice and diabetes clinics. Diabetes Care 27, 398–406 (2004)PubMedCrossRefGoogle Scholar
  51. 51.
    M. Trento, S. Gamba, L. Gentile, G. Grassi, V. Miselli, G. Morone, P. Passera, L. Tonutti, M. Tomalino, P. Bondonio, F. Cavallo, M. Porta, Rethink Organization to iMprove Education and Outcomes (ROMEO): a multicenter randomized trial of lifestyle intervention by group care to manage type 2 diabetes. Diabetes Care 33, 745–747 (2010)PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    S.A. Saunders, M. Wallymahmed, I.A. MacFarlane, Glycaemic control in a type 1 diabetes clinic for younger adults. QJM 97, 575–580 (2004)PubMedCrossRefGoogle Scholar
  53. 53.
    E.R. Mathiesen, B. Kinsley, S.A. Amiel, S. Heller, D. McCance, S. Duran, S. Bellaire, A. Raben, Maternal glycemic control and hypoglycemia in type 1 diabetic pregnancy: a randomized trial of insulin aspart versus human insulin in 322 pregnant women. Diabetes Care 30, 771–776 (2007)PubMedCrossRefGoogle Scholar
  54. 54.
    E.S. Ford, C. Li, R.R. Little, A.H. Mokdad, Trends in A1C concentrations among U.S. adults with diagnosed diabetes from 1999 to 2004. Diabetes Care 31, 102–104 (2008)PubMedCrossRefGoogle Scholar
  55. 55.
    P. Hovind, L. Tarnow, K. Rossing, P. Rossing, S. Eising, N. Larsen, C. Binder, H. Parving, Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes. Diabetes Care 26, 1258–1264 (2003)PubMedCrossRefGoogle Scholar
  56. 56.
    R. Klein, M.D. Knudtson, K.E. Lee, R. Gangnon, B.E.K. Klein, The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XXII the twenty-five-year progression of retinopathy in persons with type 1 diabetes. Ophthalmology 115, 1859–1868 (2008)PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    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 276, 1409–1415 (1996)CrossRefGoogle Scholar
  58. 58.
    L. Zhang, G. Krzentowski, A. Albert, P.J. Lefebvre, Risk of developing retinopathy in Diabetes Control and Complications Trial type 1 diabetic patients with good or poor metabolic control. Diabetes Care 24, 1275–1279 (2001)PubMedCrossRefGoogle Scholar
  59. 59.
    Early Treatment Diabetic Retinopathy Study Research Group, Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Ophthalmology 98, 766–785 (1991)CrossRefGoogle Scholar
  60. 60.
    The Diabetic Retinopathy Vitrectomy Study Research Group, Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Two-year results of a randomized trial. Diabetic Retinopathy Vitrectomy Study report 2. Arch. Ophthalmol. 103, 1644–1652 (1985)CrossRefGoogle Scholar
  61. 61.
    E. Stefánsson, T. Bek, M. Porta, N. Larsen, J.K. Kristinsson, E. Agardh, Screening and prevention of diabetic blindness. Acta Ophthalmol. Scand. 78, 374–385 (2000)PubMedCrossRefGoogle Scholar
  62. 62.
    P.H. Scanlon, The English national screening programme for sight-threatening diabetic retinopathy. J. Med. Screen. 15, 1–4 (2008)PubMedCrossRefGoogle Scholar
  63. 63.
    N. Chaturvedi, A.K. Sjolie, J.M. Stephenson, H. Abrahamian, M. Keipes, A. Castellarin, Z. Rogulja-Pepeonik, J. Fuller, Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus. Lancet 351, 28–31 (1998)PubMedCrossRefGoogle Scholar
  64. 64.
    J.W.J. Beulens, A. Patel, J.R. Vingerling, J.K. Cruickshank, A.D. Hughes, A. Stanton, J. Lu, S.A. McG Thom, D.E. Grobbee, R.P. Stolk, Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial. Diabetologia 52, 2027–2036 (2009)PubMedCrossRefGoogle Scholar
  65. 65.
    N. Chaturvedi, M. Porta, R. Klein, T. Orchard, J. Fuller, H. Parving, R. Bilous, A.K. Sjølie, Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials. Lancet 372, 1394–1402 (2008)PubMedCrossRefGoogle Scholar
  66. 66.
    A.K. Sjølie, R. Klein, M. Porta, T. Orchard, J. Fuller, H. Parving, R. Bilous, N. Chaturvedi, Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial. Lancet 372, 1385–1393 (2008)PubMedCrossRefGoogle Scholar
  67. 67.
    M. Mauer, B. Zinman, R. Gardiner, S. Suissa, A. Sinaiko, T. Strand, K. Drummond, S. Donnelly, P. Goodyer, M.C. Gubler, R. Klein, Renal and retinal effects of enalapril and losartan in type 1 diabetes. N. Engl. J. Med. 361, 40–51 (2009)PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    B. Gordon, S. Chang, M. Kavanagh, M. Berrocal, L. Yannuzzi, C. Robertson, A. Drexler, The effects of lipid lowering on diabetic retinopathy. Am. J. Ophthalmol. 112, 385–391 (1991)PubMedGoogle Scholar
  69. 69.
    A.C. Keech, P. Mitchell, P.A. Summanen, J. O’Day, T.M.E. Davis, M.S. Moffitt, M.R. Taskinen, R.J. Simes, D. Tse, E. Williamson, A. Merrifield, L.T. Laatikainen, M.C. D’Emden, D.C. Crimet, R.L. O’Connell, P.G. Colman, Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 370, 1687–1697 (2007)PubMedCrossRefGoogle Scholar
  70. 70.
    L.S. Lim, G. Liew, N.Cheung, P. Mitchell, T.Y. Wong, Mixed messages on systemic therapies for diabetic retinopathy. Lancet 376, 1461; author reply 1462 (2010)Google Scholar
  71. 71.
    A.J. Scheen, L.F. Van Gaal, Clinical study of the month. Accord-lipid and accord-eye: towards a new positioning of fenofibrate in the management of type 2 diabetes. Rev. Med. Liege 65, 533–539 (2010)PubMedGoogle Scholar
  72. 72.
    The DAMAD Study Group, Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy. A multicenter randomized controlled clinical trial. Diabetes 38, 491–498 (1989)CrossRefGoogle Scholar
  73. 73.
    The TIMAD Study Group, Ticlopidine treatment reduces the progression of nonproliferative diabetic retinopathy. Arch. Ophthalmol. 108, 1577–1583 (1990)CrossRefGoogle Scholar
  74. 74.
    Early Treatment Diabetic Retinopathy Study Research Group, Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Ophthalmology 98, 757–765 (1991)CrossRefGoogle Scholar
  75. 75.
    H. Funatsu, H. Yamashita, T. Ikeda, T. Mimura, S. Eguchi, S. Hori, Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology 110, 1690–1696 (2003)PubMedCrossRefGoogle Scholar
  76. 76.
    N. Bhagat, R.A. Grigorian, A. Tutela, M.A. Zarbin, Diabetic macular edema: pathogenesis and treatment. Surv. Ophthalmol. 54, 1–32 (2008)CrossRefGoogle Scholar
  77. 77.
    M. Michaelides, A. Kaines, R.D. Hamilton, S. Fraser-Bell, R. Rajendram, F. Quhill, C.J. Boos, W. Xing, C. Egan, T. Peto, C. Bunce, R. Leslie, P.G. Hykin, 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 117, 1078–1086.e2 (2010)PubMedCrossRefGoogle Scholar
  78. 78.
    P. Massin, F. Bandello, J.G. Garweg, L.L. Hansen, S.P. Harding, M. Larsen, P. Mitchell, D. Sharp, U.E.K. Wolf-Schnurrbusch, M. Gekkieva, A. Weichselberger, S. Wolf, Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care 33, 2399–2405 (2010)PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    E.T. Cunningham, A.P. Adamis, M. Altaweel, L.P. Aiello, N.M. Bressler, D.J. D’Amico, M. Goldbaum, D.R. Guyer, B. Katz, M. Patel, S.D. Schwartz, A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology 112, 1747–1757 (2005)PubMedCrossRefGoogle Scholar
  80. 80.
    D.V. Do, Q.D. Nguyen, D. Boyer, U. Schmidt-Erfurth, D.M. Brown, R. Vitti, A.J. Berliner, B. Gao, O. Zeitz, R. Ruckert, T. Schmelter, R. Sandbrink, J.S. Heier, One-year outcomes of the DA VINCI Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology 119, 1658–1665 (2012)PubMedCrossRefGoogle Scholar
  81. 81.
    H. Ahmadieh, A. Ramezani, N. Shoeibi, B. Bijanzadeh, A. Tabatabaei, M. Azarmina, M. Soheilian, G. Keshavarzi, M.R. Mohebbi, Intravitreal bevacizumab with or without triamcinolone for refractory diabetic macular edema; a placebo-controlled, randomized clinical trial. Graefes Arch. Clin. Exp. Ophthalmol. 246, 483–489 (2008)PubMedCrossRefGoogle Scholar
  82. 82.
    Diabetic Retinopathy Clinical Research Network (DRCR.net), Three-year follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch. Ophthalmol. 127, 245–251 (2009)CrossRefGoogle Scholar
  83. 83.
    Diabetic Retinopathy Clinical Research Network (DRCR.net), Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 118, 609–614 (2011)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Diabetic Retinopathy Centre, Department of Medical SciencesUniversity of TurinTurinItaly
  2. 2.Department of Medical SciencesUniversity of TurinTurinItaly

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