Acta Diabetologica

, Volume 50, Issue 1, pp 1–20

Pathophysiology and treatment of diabetic retinopathy

  • Francesco Bandello
  • Rosangela Lattanzio
  • Ilaria Zucchiatti
  • Claudia Del Turco
Review Article


In the past years, the management of diabetic retinopathy (DR) relied primarily on a good systemic control of diabetes mellitus, and as soon as the severity of the vascular lesions required further treatment, laser photocoagulation or vitreoretinal surgery was done to the patient. Currently, even if the intensive metabolic control is still mandatory, a variety of different clinical strategies could be offered to the patient. The recent advances in understanding the complex pathophysiology of DR allowed the physician to identify many cell types involved in the pathogenesis of DR and thus to develop new treatment approaches. Vasoactive and proinflammatory molecules, such as vascular endothelial growth factor (VEGF), play a key role in this multifactorial disease. Current properly designed trials, evaluating agents targeting VEGF or other mediators, showed benefits in the management of DR, especially when metabolic control is lacking. Other agents, directing to the processes of vasopermeability and angiogenesis, are under investigations, giving more hope in the future management of this still sight-threatening disease.


Diabetic macular edema Proliferative diabetic retinopathy Laser Intravitreal anti-VEGF Dexamethasone implant Vitrectomy 


  1. 1.
    Saddine JB, Honeycutt AA, Narayan KM et al (2008) Projection of diabetic retinopathy and other major eye diseases among people with diabetes mellitus: United States, 2005–2050. Arch Ophtahlmol 126:1740–1747CrossRefGoogle Scholar
  2. 2.
    Diabetes Control and Complications Trial Research Group (1993) 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 329:977–986CrossRefGoogle Scholar
  3. 3.
    UK Prospective Diabetes Study Group (1998) 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 352:837–853CrossRefGoogle Scholar
  4. 4.
    Fong DS, Aiello LP, Ferris FL, Klein R (2004) Diabetic retinopathy. Diabetes Care 10:2540–2553CrossRefGoogle Scholar
  5. 5.
    Bhagat N, Grigorian RA, Tutela A, Zarbin MA (2009) Diabetic macular edema: pathogenesis and treatment. Surv Ophthalmol 54:1–32PubMedCrossRefGoogle Scholar
  6. 6.
    Goh SY, Cooper ME (2008) Clinical review: the role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 93:1143–1152PubMedCrossRefGoogle Scholar
  7. 7.
    Pinach S, Burt D, Berrone E et al (2011) Retinal heat shock protein 25 in early experimental diabetes. Acta Diabetol (epub ahead of print)Google Scholar
  8. 8.
    Ghanem AA, Elewa A, Arafa LF (2011) Pentosidine and N-carboxymethyl-lysine: biomarkers for type 2 diabetic retinopathy. Eur J Ophtahlmol 21:48–54CrossRefGoogle Scholar
  9. 9.
    Zong H, Ward M, Stitt AW (2011) AGEs, RAGE, and diabetic retinopathy. Curr DiabRep 11:244–252CrossRefGoogle Scholar
  10. 10.
    Chung SS, Chung SK (2005) Aldose reductase in diabetic microvascular complications. Curr Drug Targets 6:475–486PubMedCrossRefGoogle Scholar
  11. 11.
    Lorenzi M (2007) The polyol pathway as a mechanism for diabetic retinopathy: attractive, elusive, and resilient. Exp Diabetes Res 2007:61038PubMedCrossRefGoogle Scholar
  12. 12.
    Geraldes P, King GL (2010) Activation of protein kinase C isoforms and its impact on diabetic complications. Circ Res 106:1319–1331PubMedCrossRefGoogle Scholar
  13. 13.
    Coral K, Angayarkanni N, Gomathy N et al (2009) Homocysteine levels in the vitreous of proliferative diabetic retinopathy and rhegmatogenous retinal detachment: its modulating role on lysyl oxidase. Invest Ophthalmol Vis Sci 50:3607–3612PubMedCrossRefGoogle Scholar
  14. 14.
    Madsen-Bouterse SA, Kowluru RA (2008) Oxidative stress and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Rev Endocr Metab Disord 9:315–327PubMedCrossRefGoogle Scholar
  15. 15.
    Adamis AP, Berman AJ (2008) Immunological mechanisms in the pathogenesis of diabetic retinopathy. Semin Immunopathol 30:65–84PubMedCrossRefGoogle Scholar
  16. 16.
    Abu El-Asrar AM, Mohammad G, Nawaz MI et al (2012) Expression of lysophosphatidic acid, autotaxin and acylglycerol kinase as biomarkers in diabetic retinopathy. Acta Diabetol (epub ahead of print)Google Scholar
  17. 17.
    Zhang X, Bao S, Hambly BD, Gillies MC (2009) Vascular endothelial growth factor-A: a multifunctional molecular player in diabetic retinopathy. Int J Biochem Cell Biol 41:2368–2371PubMedCrossRefGoogle Scholar
  18. 18.
    Aiello LP, Bursell S-E, Clermont A et al (1997) 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 46:1473–1480PubMedCrossRefGoogle Scholar
  19. 19.
    Antonetti DA, Barber AJ, Hollinger LA et al (1999) Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occludin and zonula occluden 1. J Biol Chem 274:23463–23467PubMedCrossRefGoogle Scholar
  20. 20.
    Aiello LP, Avery RL, Arrigg PG et al (1994) Vascular endothelial growth factor in ocular fluids of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487PubMedCrossRefGoogle Scholar
  21. 21.
    Aiello LP, Northrup JM, Keyt BA et al (1995) Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol 1131:1538–1544CrossRefGoogle Scholar
  22. 22.
    Funatsu H, Yamashita H, Ikeda T et al (2002) Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders. Am J Ophthalmol 133:537–543PubMedCrossRefGoogle Scholar
  23. 23.
    Liu C, Lv XH, Li HX et al (2012) Angiotensin-(1–7) suppresses oxidative stress and improves glucose uptake via Mas receptor in adipocytes. Acta Diabetol 49:291–299PubMedCrossRefGoogle Scholar
  24. 24.
    Yousefzade G, Nakhaee A (2011) Insulin-induced hypoglycemia and stress oxidative state in healthy people. Acta Diabetol (epub ahead of print)Google Scholar
  25. 25.
    Gilbert RE, Kelly DJ, Cox AJ et al (2000) Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hypermeability in experimental diabetes. Diabetologia 43:1360–1367PubMedCrossRefGoogle Scholar
  26. 26.
    Antonetti D, Klein R, Gardner T (2012) Diabetic retinopathy. Mechanisms of disease. N Engl J Med 366:1227–1239PubMedCrossRefGoogle Scholar
  27. 27.
    Bearse M, Han Y, Schneck M et al (2004) Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy. Invest Ophthalmol Vis Sci 45:3259–3265PubMedCrossRefGoogle Scholar
  28. 28.
    Han Y, Adams A, Bearse M et al (2004) Multifocal electroretinogram and short-wavelenght automated perimetry measures in diabetic eyes with little or no retinopathy. Arch Ophthalmol 122:1809–1815PubMedCrossRefGoogle Scholar
  29. 29.
    Zhang Y, Bhavnani BR (2006) Glutamate-induced apoptosis in neuronal cells is mediated via caspase-dependent and independent mechanisms involving calpain and caspase-3 proteases as well as apoptosis inducing factor (AIF) and this process is inhibited by equine estrogens. BMC Neurosci 7:49PubMedCrossRefGoogle Scholar
  30. 30.
    Davalli AM, Perego C, Folli FB (2012) The potential role of glutamate in the current diabetes epidemic. Acta Diabetol 49:167–183PubMedCrossRefGoogle Scholar
  31. 31.
    The PKC-DRS2 Group (2006) Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy. Ophthalmology 113:2221–2230CrossRefGoogle Scholar
  32. 32.
    VanGuilder HD, Brucklacher AR, Patel K et al (2008) Diabetes downregulates presynaptic proteins and reduced basal synapsin 1 phosphorylation in rat retina. Eur J Neurosci 28:1–11PubMedCrossRefGoogle Scholar
  33. 33.
    Seki M, Tanaka T, Nawa H et al (2004) 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 53:2412–2419PubMedCrossRefGoogle Scholar
  34. 34.
    Wong HC, Boulton M, McLeod D et al (1988) Retinal pigment epithelial cells in culture produce retinal vascular mitogens. Arch Ophthalmol 106:1439–1443PubMedCrossRefGoogle Scholar
  35. 35.
    Wang J, Xu X, Elliott MH et al (2010) Müller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage. Diabetes 59:2297–2305PubMedCrossRefGoogle Scholar
  36. 36.
    Murakami T, Felinski EA, Antonetti DA (2009) Occludin phosphorylation and ubiquitination regulate tight junction trafficking and vascular endothelial growth factor-induced permeability. J Biol Chem 284:21036–21046PubMedCrossRefGoogle Scholar
  37. 37.
    Enge M, Bjarnegård M, Gerhardt H et al (2002) Endothelium-specific platelet-derived growth factor-β ablation mimics diabetic retinopathy. EMBO J 21:4307–4316PubMedCrossRefGoogle Scholar
  38. 38.
    Tarallo S, Beltramo E, Berrone E, Porta M (2012) Human pericyte–endothelial cell interactions in co-culture models mimicking the diabetic retinal microvascular environment. Acta Diabetol (epub ahead of print)Google Scholar
  39. 39.
    Gao BB, Clermont A, Rook S et al (2007) Extracellular carbonic anhydrase mediates haemorrhagic retinal and cerebral vascular permeability through prekallikrein activation. Nat Med 13:181–188PubMedCrossRefGoogle Scholar
  40. 40.
    El-Mesallamy HO, Hamdy NM, Sallam AA (2012) Effect of obesity and glycemic control on serum lipocalins and insulin-like growth factor axis in type 2 diabetic patients. Acta Diabetol (epub ahead of print)Google Scholar
  41. 41.
    Suraci C, Mulas F, Rossi MC et al (2012) Management of newly diagnosed patients with type 2 diabetes: what are the attitudes of physicians? A SUBITO!AMD survey on the early diabetes treatment in Italy. Acta Diabetol (epub ahead of print)Google Scholar
  42. 42.
    Sartore G, Chilelli NC, Burlina S et al (2012) The importance of HbA1c and glucose variability in patients with type 1 and type 2 diabetes: outcome of continuous glucose monitoring (CGM). Acta Diabetol (epub ahead of print)Google Scholar
  43. 43.
    Mannucci E, Monami M, Lamanna C, Adalsteinsson JE (2012) Post-prandial glucose and diabetic complications: systematic review of observational studies. Acta Diabetol 49:307–314PubMedCrossRefGoogle Scholar
  44. 44.
    Miller ME, Bonds DE, Gerstein HC, for the ACCORD Investigators et al (2010) The effects of baseline characteristics, glycaemia treatment approach, and glycated hemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study. BMJ 340:b5444. doi:10.1136/bmj.b5444 PubMedCrossRefGoogle Scholar
  45. 45.
    Klein R, Klein BE, Moss SE et al (1989) Is blood pressure a predictor of the incidence or progression of diabetic retinopathy? Arch Intern Med 149:2427–2432PubMedCrossRefGoogle Scholar
  46. 46.
    UK Prospective Diabetes Study Group (1998) Tight blood pressure control and risk of microvascular complications in type 2 diabetes. UKPDS 38. BMJ 317:703–713CrossRefGoogle Scholar
  47. 47.
    Ruggenenti P, Iliev I, Filipponi M et al (2010) Effect on trandolapril on regression of retinopathy in hypertensive patients with type 2 diabetes: a prespecified analysis of the BENEDICT trial. J Ophthalmol 2010:106384PubMedGoogle Scholar
  48. 48.
    Chaturvedi N, Sjolie AK, Stephenson JM et al (1998) Effects 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 351:28–31Google Scholar
  49. 49.
    Chatuvedi N, Porta M, Klein R et al (2008) Effects of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials. Lancet 372:1394–1402CrossRefGoogle Scholar
  50. 50.
    Gattu AK, Birkenfeld AL, Jornayvaz F et al (2012) Insulin resistance is associated with elevated serum pigment epithelium-derived factor (PEDF) levels in morbidly obese patients. Acta Diabetol (epub ahead of print)Google Scholar
  51. 51.
    Sambataro M, Perseghin G, Lattuada G et al (2012) Lipid accumulation in overweight type 2 diabetic subjects: relationships with insulin sensitivity and adipokines. Acta Diabetol (epub ahead of print)Google Scholar
  52. 52.
    Keech AC, Mitchell P, Summanen PA et al (2007) Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 370:1687–1697PubMedCrossRefGoogle Scholar
  53. 53.
    Biscetti F, Gaetani E, Flex A et al (2008) Selective activation of peroxisome proliferator-activated receptor (PPAR) alpha and PPAR gamma induces neoangiogenesis through a vascular endothelial frowth factor-dependant mechanism. Diabetes 57:1394–1404PubMedCrossRefGoogle Scholar
  54. 54.
    da Vico L, Monami M, Biffi B et al (2012) Targeting educational therapy for type 2 diabetes: identification of predictors of therapeutic success. Acta Diabetol (epub ahead of print)Google Scholar
  55. 55.
    Bresnik GH (1986) Diabetic macular edema: a review. Ophthalmology 93:989–997Google Scholar
  56. 56.
    Diabetes Control and Complications Trial/Epidemiology of Diabetes Inteventions and Complications (DCCT/EDIC) Research Group (2009) Modern-day clinical course of type 1 diabetes mellitus after 30 years’ duration. Arch Int Med 169:1307–1316CrossRefGoogle Scholar
  57. 57.
    Zhang X, Saaddine JB, Chou CF et al (2010) Prevalence of diabetic retinopathy in the United States, 2005–2008. JAMA 304:649–656PubMedCrossRefGoogle Scholar
  58. 58.
    Klein R, Lee KE, Gangnon RE et al (2010) The 25-year incidence of visual impairment in type 1 diabets mellitus. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Ophthalmology 117:63–70PubMedCrossRefGoogle Scholar
  59. 59.
    Grauslund J, Green A, Sjolie AK et al (2009) Blindness in a 25-year follow-up of a population-based cohort of Danish type 1 diabetic patients. Ophthalmology 116:2170–2174PubMedCrossRefGoogle Scholar
  60. 60.
    Chen E, Looman M, Laouri M et al (2010) Burden of ilness of diabetic macular edema: literature review. Curr Med Res Opin 26:1587–1597PubMedCrossRefGoogle Scholar
  61. 61.
    Javitt JC, Aiello LP (1996) Cost-effectiveness of detecting and treating diabetic retinopathy. Ann Intern Med 124:164–169PubMedGoogle Scholar
  62. 62.
    Aiello LP, Gardner TW, King GL et al (1998) Diabetic retinopathy. Diabetes Care 21:78–94Google Scholar
  63. 63.
    Bandello F, Battaglia Parodi M, Tremolada G et al (2010) Steroids as part of combination treatment: the future for the management of macular edema? Ophthalmologica 224(Suppl 1):41–45PubMedCrossRefGoogle Scholar
  64. 64.
    Early Treatment Diabetic Retinopathy Study Research Group (1987) Photocoagulation for diabetic macular edema: ETDRS report number 4. Int Ophthalmol Clin 27:265–272CrossRefGoogle Scholar
  65. 65.
    Early Treatment Diabetic Retinopathy Study Research Group (1985) Photocoagulation for diabetic macular edema: Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol 103:1796–1806CrossRefGoogle Scholar
  66. 66.
    Schatz H, Madeira D, McDonald HR, Johnson RN (1991) Progressive enlargement of laser scars following grid laser photocoagulation for diffuse diabetic macular edema. Arch Ophthalmol 109:1549–5151PubMedCrossRefGoogle Scholar
  67. 67.
    Jain A, Collen J, Kaines A et al (2010) Short-duration focal pattern grid macular photocoagulation for diabetic macular edema: four-month outcomes. Retina 30:1622–1626PubMedCrossRefGoogle Scholar
  68. 68.
    Early Treatment Diabetic Retinopathy Study Research Group (1987) Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 2. Ophthalmology 94:761–774Google Scholar
  69. 69.
    Brancato R, Menchini U, Scialdone A, Bandello F (1988) Focal versus scattered argon-green in diffuse macular edema: a prospective randomized trial. In: Gitter KA, Schatz H, Yannuzzi LA, Mc Donald HR (eds) Laser photocoagulation of retinal disease. San Francisco Pacific Medical Press, pp 69–73Google Scholar
  70. 70.
    Writing Committee for the Diabetic Retinopathy Clinical Research Network (2007) Comparison of the modified early treatment diabetic retinopathy study and mild macular grid laser photocoagulation strategies for diabetic macular edema. Arch Ophthalmol 125:469–480CrossRefGoogle Scholar
  71. 71.
    Bandello F, Polito A, Borrello MD et al (2005) ‘Light’ versus ‘classic’ laser treatment for clinically significant diabetic macular oedema. Br J Ophthalmol 89:864–870PubMedCrossRefGoogle Scholar
  72. 72.
    Desmettre TJ, Mordon SR, Buzawa DM et al (2006) Micropulse and continuous wave diode retinal photocoagulation: visible and subvisible lesion parameters. Br J Ophthalmol 90:709–712PubMedCrossRefGoogle Scholar
  73. 73.
    Vujosevic S, Bottega E, Casciano M et al (2010) Microperimetry and fundus autofluorescence in diabetic macular edema: subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation. Retina 30:908–916PubMedCrossRefGoogle Scholar
  74. 74.
    Kumar V, Ghosh B, Mehta DK, Goel N (2010) Functional outcome of subthreshold versus threshold diode laser photocoagulation in diabetic macular oedema. Eye 24:1459–1465PubMedCrossRefGoogle Scholar
  75. 75.
    Figueira J, Khan J, Nunes S et al (2008) Prospective randomized controlled trial comparing subthreshold micropulse diode laser photocoagulation and conventional green laser for clinically significant diabetic macular oedema. Br J Ophthalmol 93:1341–1344PubMedCrossRefGoogle Scholar
  76. 76.
    Lavinsky D, Cardillo JA, Melo LAS et al (2011) Randomized clinical trial evaluating mETDRS versus normal or high-density micropulse photocoagulation for diabetic macular edema. Invest Ophthalmol Vis Sci 52:4314–4323PubMedCrossRefGoogle Scholar
  77. 77.
    Cardillo JA (2012) 577 nm MicroPulse laser therapy: addressing the immediate need of our patients with DME. In: Retina Today, vol 7, pp 11–14Google Scholar
  78. 78.
    Paulus YM, Jain A, Nomoto H et al (2011) Selective retinal therapy with microsecond exposures using a continuous line scanning laser. Retina 31:380–388PubMedCrossRefGoogle Scholar
  79. 79.
    Blumenkranz MS, Yellachich D, Andersen DE et al (2006) Semiautomated patterned scanning laser for retinal photocoagulation. Retina 26:370–376PubMedCrossRefGoogle Scholar
  80. 80.
    Paulus YM, Jain A, Gariano RF et al (2008) Healing of retinal photocoagulation lesions. Invest Ophthalmol Vis Sci 49:5540–5545PubMedCrossRefGoogle Scholar
  81. 81.
    Muqit MM, Marcellino GR, Gray JC et al (2010) Pain responses of Pascal 20 ms multi-spot and 100 ms single-spot panretinal photocoagulation: Manchester Pascal Study, MAPASS report 2. Br J Ophthalmol 94:1493–1498PubMedCrossRefGoogle Scholar
  82. 82.
    Nagpal M, Marlecha S, Nagpal K (2010) Comparison of laser photocoagulation for diabetic retinopathy using 532-nm standard laser versus multispot pattern scan laser. Retina 30:452–458PubMedCrossRefGoogle Scholar
  83. 83.
    Sheth S, Lanzetta P, Veritti D et al (2011) Experience with the Pascal® photocoagulator: an analysis of over 1,200 laser procedures with regard to parameter refinement. Indian J Ophthalmol 59:87–91PubMedCrossRefGoogle Scholar
  84. 84.
    Inagaki K, Ohkoshi K, Ohde S (2012) Spectral-domain optical coherence tomography imaging of retinal changes after conventional multicolor laser, subthreshold micropulse diode laser, or pattern scanning laser therapy in Japanese with macular edema. Retina 32:1592–1600PubMedCrossRefGoogle Scholar
  85. 85.
    Kozak I, Oster SF, Cortes MA et al (2011) Clinical evaluation and treatment accuracy in diabetic macular edema using navigated laser photocoagulator NAVILAS. Ophthalmology 118:1119–1124PubMedCrossRefGoogle Scholar
  86. 86.
    Kernt M, Cheuteu RE, Cserhati S et al (2012) Pain and accuracy of focal laser treatment for diabetic macular edema using a retinal navigated laser (Navilas). Clin Ophthalmol 6:289–296PubMedCrossRefGoogle Scholar
  87. 87.
    Ober MD, Kernt M, Cortes MA, Kozak I (2012) Time required for navigated macular laser photocoagulation treatment with the Navilas®. Graefes Arch Clin Exp Ophthalmol (epub ahead of print)Google Scholar
  88. 88.
    Diabetic Retinopathy Group (1978) Photocoagulation of proliferative diabetic retinopathy study findings. Ophthalmology 85:82–105Google Scholar
  89. 89.
    Diabetic Retinopathy Study Research Group (1976) Preliminary report on effects of photocoagulation therapy. Am J Ophthalmol 1976:383–396Google Scholar
  90. 90.
    Early Treatment Diabetic Retinopathy Study Research Group (1991) Early photocoagulation for diabetic retinopathy: ETDRS report number 9. Ophthalmology 98:S766–S785Google Scholar
  91. 91.
    Jain A, Blumenkranz MS, Paulus Y et al (2008) Effect of pulse duration on size and character of the lesion in retinal photocfoagulation. Arch Ophthalmol 126:78–85PubMedCrossRefGoogle Scholar
  92. 92.
    Sanghvi C, Mc Lauchlan R, Delgado C et al (2008) Initial experience with the Pascal® Photocoagulator: a pilot study of 75 procedures. Br J Ophthalmol 92:1061–1064PubMedCrossRefGoogle Scholar
  93. 93.
    Muqit MM, Gray JC, Marcellino GR et al (2009) Fundus autofluorescence and Fourier-domain optical coherence tomography imaging of 10 and 20 millisecond Pascal® photocoagulation treatment. Br J Ophthalmol 3:518–525CrossRefGoogle Scholar
  94. 94.
    DRCR Network (2009) Observational study of the development of diabetic macula edema following panretinal (scatter) photocoagulation (PRP) given in 1 or 4 sittings. Arch Ophthalmol 127:132–140CrossRefGoogle Scholar
  95. 95.
    Neubauer AS, Kernt M, Haritoglou C et al (2010) Image quality of a novel navigated retina laser (NAVILAS). Fort Lauderdale: ARVO 2010 (Abstract 1639)Google Scholar
  96. 96.
    Kernt M, Cheuteu R, Vounotrypidis E et al (2011) Focal and panretinal photocoagulation with a navigated laser (NAVILAS®). Acta Ophthalmol 89(8):e662–e664. doi:10.1111/j.1755-3768.2010.02017.x PubMedCrossRefGoogle Scholar
  97. 97.
    Lee SS, Hughes PM, Robinson MR (2009) Recent advances in drug delivery systems for treating ocular complications of systemic diseases. Curr Opin Ophthalmol 20:511–519PubMedCrossRefGoogle Scholar
  98. 98.
    Nauck M, Roth M, Tamm M et al (1998) Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is down-regulated by corticosteroids. Am J Respir Cell Mol Biol 16:398–406Google Scholar
  99. 99.
    Tamura H, Miyamoto K, Kiryu J et al (2005) Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina. Invest Ophthalmol Vis Sci 46:1440–1444PubMedCrossRefGoogle Scholar
  100. 100.
    Haller JA, Bandello F, Belfort R Jr, OZURDEX GENEVA Study Group et al (2010) Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 117:1134–1146PubMedCrossRefGoogle Scholar
  101. 101.
    Antonetti DA, Barber AJ, Khin S, Penn State Retina Research Group et al (1998) Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin content in retinal endothelial cells. Diabetes 47:1953–1959PubMedCrossRefGoogle Scholar
  102. 102.
    Antonetti DA, Wolpert EB, DeMaio L et al (2002) Hydrocortisone decrease retinal endothelial cell water and solute flux coincident with increased content and decreased phosphorylation of occludin. J Neurochem 80:667–677PubMedCrossRefGoogle Scholar
  103. 103.
    Nauck M, Karakiulakis G, Perruchoud AP et al (1998) Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur J Pharmacol 341:309–315PubMedCrossRefGoogle Scholar
  104. 104.
    Diabetic Retinopathy Clinical Research Network (2009) Three-year follow-up of a randomized clinical trial comparing focal/grid laser photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol 127:245–251CrossRefGoogle Scholar
  105. 105.
    Diabetic Retinopathy Clinical Research Network (2010) Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 117:1064–1077.e35CrossRefGoogle Scholar
  106. 106.
    Diabetic Retinopathy Clinical Research Network (2011) Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 118:609–614CrossRefGoogle Scholar
  107. 107.
    Campochiaro PA, Brown DM, Pearson A, Ciulla T, FAME Study Group et al (2011) Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmology 118:626–635PubMedCrossRefGoogle Scholar
  108. 108.
    Haller JA, Kuppermann BD, Blumenkranz MS et al (2010) Randomized controlled trial of an intravitreous dexamethasone drug delivery system in patients with diabetic macular edema. Arch Ophthalmol 128:289–296PubMedCrossRefGoogle Scholar
  109. 109.
    Blankenship GW (1991) Evaluation of a single intravitreal injection of dexamethasone phosphate in vitrectomy surgery for diabetic retinopathy complications. Graefes Arch Clin Exp Ophthalmol 229:62–65PubMedCrossRefGoogle Scholar
  110. 110.
    Cunningham MA, Edelman JL, Kaushal S (2008) Intravitreal steroids for macular edema: the past, the present, and the future. Surv Ophthalmol 53:139–149PubMedCrossRefGoogle Scholar
  111. 111.
    Grover D, Li TJ, Chong CC (2008) Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev (1):CD005656Google Scholar
  112. 112.
    Kuo CH, Gillies MC (2009) Role of steroids in the treatment of diabetic macular edema. Int Ophthalmol Clin 49:121–134PubMedCrossRefGoogle Scholar
  113. 113.
    Cheung N, Mitchell P, Wong TY (2010) Diabetic retinopathy. Lancet 376:124–136PubMedCrossRefGoogle Scholar
  114. 114.
    Silva PS, Sun JK, Aiello LP (2009) Role of steroids in the management of diabetic macular edema and proliferative diabetic retinopathy. Semin Ophthalmol 24:93–99PubMedCrossRefGoogle Scholar
  115. 115.
    Yilmaz T, Weaver CD, Gallagher MJ et al (2009) Intravitreal triamcinolone acetonide injection for treatment of refractory diabetic macular edema: a systematic review. Ophthalmology 116:902–911PubMedCrossRefGoogle Scholar
  116. 116.
    Audren F, Erginay A, Haouchine B et al (2006) Intravitreal triamcinolone acetonide for diffuse diabetic macular oedema: 6-month results of a prospective controlled trial. Acta Ophthalmol Scand 84:624–630PubMedCrossRefGoogle Scholar
  117. 117.
    Massin P, Audren F, Haouchine B et al (2004) Intravitreal triamcinolone acetonide for diabetic diffuse macular edema: preliminary results of a prospective controlled trial. Ophthalmology 111:218–224PubMedCrossRefGoogle Scholar
  118. 118.
    Avitabile T, Longo A, Reibaldi A (2005) Intravitreal triamcinolone compared with macular laser grid photocoagulation for the treatment of cystoid macular edema. Am J Ophthalmol 140:695–702PubMedCrossRefGoogle Scholar
  119. 119.
    Jonas JB, Kampperter BA, Harder B et al (2006) Intravitreal triamcinolone acetonide for diabetic macular edema: a prospective, randomized study. J Ocul Pharmacol Ther 22:200–207PubMedCrossRefGoogle Scholar
  120. 120.
    Gillies MC, Sutter FK, Simpson JM et al (2006) Intravitreal triamcinolone for refractory diabetic macular edema two-year results of a double-masked, placebo-controlled, randomized clinical trial. Ophthalmology 113:1533–1538PubMedCrossRefGoogle Scholar
  121. 121.
    Sutter FK, Simpson JM, Gillies MC (2004) Intravitreal triamcinolone for diabetic macular edema that persists after laser treatment: three-month efficacy and safety results of a prospective, randomized, double-masked, placebo controlled clinical trial. Ophthalmology 111:2044–2049PubMedCrossRefGoogle Scholar
  122. 122.
    Bressler NM, Edwards AR, Beck RW et al (2009) Exploratory analysis of diabetic retinopathy progression through 3 years in a randomized clinical trial that compares intravitreal triamcinolone acetonide with focal/grid photocoagulation. Arch Ophthalmol 127:1566–1571PubMedCrossRefGoogle Scholar
  123. 123.
    Gillies MC, Simpson JM, Gaston C et al (2009) Five-year results of a randomized trial with open-label extension of triamcinolone acetonide for refractory diabetic macular edema. Ophthalmology 116:2182–2187PubMedCrossRefGoogle Scholar
  124. 124.
    Diabetic Retinopathy Clinical Research Network (2011) Randomized trial evaluating short-term effects of intravitreal ranibizumab or triamcinolone acetonide on macular edema after focal/grid laser for diabetic macular edema in eyes also receiving panretinal photocoagulation. Retina 31:1009–1027CrossRefGoogle Scholar
  125. 125.
    Gillies MC, McAllister IL, Zhu M, Wong W, Louis D, Arnold JJ, Wong TY (2011) Intravitreal triamcinolone prior to laser treatment of diabetic macular edema: 24-month results of a randomized controlled trial. Ophthalmology 118:866–872PubMedCrossRefGoogle Scholar
  126. 126.
    Mirshahi A, Shenazandi H, Lashay A et al (2010) Intravitreal triamcinolone as an adjunct to standard laser therapy in coexisting high-risk proliferative diabetic retinopathy and clinically significant macular edema. Retina 30:254–259PubMedCrossRefGoogle Scholar
  127. 127.
    Funatsu H, Noma H, Mimura T et al (2009) Association of vitreous inflammatory factors with diabetic macular edema. Ophthalmology 116:73–79PubMedCrossRefGoogle Scholar
  128. 128.
    Haller JA, Dugel P, Weinberg DV et al (2009) Evaluation of safety and performance of an applicator for a novel intravitreal dexamethasone drug delivery system for the treatment of macular edema. Retina 29:46–51PubMedCrossRefGoogle Scholar
  129. 129.
    Kuppermann BD, Blumenkranz MS, Haller JA et al (2007) Dexamethasone DDS Phase II Study Group. Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema. Arch Ophthalmol 125:309–317PubMedCrossRefGoogle Scholar
  130. 130.
    Chin HS, Park TS, Moon YS, Oh JH (2005) Difference in clearance of intravitreal triamcinolone acetonide between vitrectomized and non-vitrectomized eyes. Retina 25:556–560PubMedCrossRefGoogle Scholar
  131. 131.
    Boyer DS, Faber D, Gupta S, for the Ozurdex Champlain Study Group et al (2011) Dexamethasone intravitreal implant for treatment of diabetic macular edema in vitrectomized patients. Retina 31:915–923PubMedCrossRefGoogle Scholar
  132. 132.
    A study of the safety and efficacy of a new treatment for diabetic macular edema ( identifier NCT00168389). US National Institutes of Health, (online). Available from Accessed 24 Sep 2012
  133. 133.
    A study of the safety and efficacy of a new treatment for diabetic macular edema ( identifier NCT00168337). US National Institutes of Health, (online). Available from Accessed 24 Sep 2010
  134. 134.
    Jaffe GJ, Martin D, Callanan D, Fluocinolone Acetonide Uveitis Study Group et al (2006) Fluocinolone acetonide implant (Retisert) for non infectious posterior uveitis: thirty-four-week results of a multicenter randomized clinical study. Ophthalmology 113:1020–1027PubMedCrossRefGoogle Scholar
  135. 135.
    Pearson PA, Comstock TL, Ip M et al (2011) Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial. Ophthalmology 118:1580–1587PubMedCrossRefGoogle Scholar
  136. 136.
    Campochiaro PA, Hafiz G, Shah SM, Famous Study Group et al (2010) Sustained ocular delivery of fluocinolone acetonide by an intravitreal insert. Ophthalmology 117:1393–1399PubMedCrossRefGoogle Scholar
  137. 137.
    Campochiaro PA, Brown DM, Pearson A et al (2012) Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology 119:2125–2132Google Scholar
  138. 138.
    Bandello F, Cunha-Vaz J, Chong NV et al (2012) New approaches for the treatment of diabetic macular oedema: recommendations by an expert panel. Eye 26:485–493PubMedCrossRefGoogle Scholar
  139. 139.
    Massin P, Bandello F, Garweg JG et al (2010) Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care 33:2399–2405PubMedCrossRefGoogle Scholar
  140. 140.
    Nguyen QD, Brown DM, Marcus DM, RISE and RIDE Research Group et al (2012) Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 119:789–801PubMedCrossRefGoogle Scholar
  141. 141.
    Nguyen QD, Shah SM, Heier JS, READ-2 Study Group et al (2009) Primary end point (six months) results of the ranibizumab for edema of the macula in diabetes (READ-2) study. Ophthalmology 116:2175–2181.e1PubMedCrossRefGoogle Scholar
  142. 142.
    Nguyen QD, Shah SM, Khwaja AA, READ-2 Study Group et al (2010) Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study. Ophthalmology 117:2146–2151PubMedCrossRefGoogle Scholar
  143. 143.
    Mitchell P, Bandello F, Schmidt-Erfurth U, RESTORE Study Group et al (2011) The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 118:615–625PubMedCrossRefGoogle Scholar
  144. 144.
    Nguyen QD, Tatlipinar S, Shah SM et al (2006) Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. Am J Ophthalmol 142:961–969PubMedCrossRefGoogle Scholar
  145. 145.
    Dosing study of ranibizumab for diabetic retinal and macular edema. ( identifier NCT01476449). US National Institutes of Health, (online). Available from Accessed 24 Sep 2012
  146. 146.
    Efficacy and safety of ranibizumab in two “treat and extend” treatment algorithms versus ranibizumab as needed in patients with macular edema and visual impairment secondary to diabetes mellitus (RETAIN). ( identifier NCT001171976). US National Institutes of Health, (online). Available from Accessed 24 Sep 2012
  147. 147.
    Ranibizumab for edema of the macula in diabetes: Protocol 3 with high dose—the READ 3 Study ( identifier NCT01077401). US National Institutes of Health, (online). Available from Accessed 24 Sep 2012
  148. 148.
    Filho JA, Messias A, Almeida FP et al (2011) Panretinal photocoagulation (PRP) versus PRP plus intravitreal ranibizumab for high-risk proliferative diabetic retinopathy. Acta Ophthalmol 89:e567–e572. doi:10.1111/j.1755-3768.2011.02184.x PubMedCrossRefGoogle Scholar
  149. 149.
    Multicenter 12 months clinical study to evaluate efficacy and safety of ranibizumab alone or in combination with laser photocoagulation vs. laser photocoagulation alone in proliferative diabetic retinopathy (PRIDE) ( identifier NCT01594281). US National Institutes of Health, (online). Available from Accessed 24 Sep 2012
  150. 150.
    Diabetic Retinopathy Clinical Research Network, Scott IU, Edwards AR, Beck RW, Bressler NM et al (2007) A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 114:1860–1867PubMedCrossRefGoogle Scholar
  151. 151.
    Lam DS, Lai TY, Lee VY et al (2009) Efficacy of 1.25 MG versus 2.5 MG intravitreal bevacizumab for diabetic macular edema: six-month results of a randomized controlled trial. Retina 29:292–299PubMedCrossRefGoogle Scholar
  152. 152.
    Arevalo JF, Sanchez JG, Wu L, Pan-American Collaborative Retina Study Group et al (2009) Primary intravitreal bevacizumab for diffuse diabetic macular edema: the Pan-American Collaborative Retina Study Group at 24 months. Ophthalmology 116:1488–1497PubMedCrossRefGoogle Scholar
  153. 153.
    Kook D, Wolf A, Kreutzer T et al (2008) Long-term effect of intravitreal bevacizumab (avastin) in patients with chronic diffuse diabetic macular edema. Retina 28:1053–1060PubMedCrossRefGoogle Scholar
  154. 154.
    Michaelides M, Kaines A, Hamilton RD et al (2010) 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.e2PubMedCrossRefGoogle Scholar
  155. 155.
    Rajendram R, Fraser-Bell S, Kaines A et al (2012) A 2-year prospective randomized controlled trial of intravitreal bevacizumab or laser therapy (BOLT) in the management of diabetic macular edema: 24-month data: report 3. Arch Ophthalmol 130:972–979Google Scholar
  156. 156.
    Paccola L, Costa RA, Folgosa MS et al (2008) Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study). Br J Ophthalmol 92:76–80PubMedCrossRefGoogle Scholar
  157. 157.
    Shimura M, Nakazawa T, Yasuda K et al (2008) Comparative therapy evaluation of intravitreal bevacizumab and triamcinolone acetonide on persistent diffuse diabetic macular edema. Am J Ophthalmol 145:854–861PubMedCrossRefGoogle Scholar
  158. 158.
    Soheilian M, Ramezani A, Obudi A et al (2009) Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema. Ophthalmology 116:1142–1150PubMedCrossRefGoogle Scholar
  159. 159.
    Avery RL, Pearlman J, Pieramici DJ et al (2006) Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 113:1695.e1-15PubMedGoogle Scholar
  160. 160.
    Jorge R, Costa RA, Calucci D et al (2006) Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study). Retina 26:1006–1013PubMedCrossRefGoogle Scholar
  161. 161.
    Moradian S, Ahmadieh H, Malihi M et al (2008) Intravitreal bevacizumab in active progressive proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 246:1699–1705PubMedCrossRefGoogle Scholar
  162. 162.
    Huang YH, Yeh PT, Chen MS et al (2009) Intravitreal bevacizumab and panretinal photocoagulation for proliferative diabetic retinopathy associated with vitreous hemorrhage. Retina 29:1134–1140PubMedCrossRefGoogle Scholar
  163. 163.
    Mirshahi A, Roohipoor R, Lashay A et al (2008) Bevacizumab-augmented retinal laser photocoagulation in proliferative diabetic retinopathy: a randomized double-masked clinical trial. Eur J Ophthalmol 18:263–269PubMedGoogle Scholar
  164. 164.
    Grover S, Gupta S, Sharma R et al (2009) Intracameral bevacizumab effectively reduces aqueous vascular endothelial growth factor concentrations in neovascular glaucoma. Br J Ophthalmol 93:273–274PubMedCrossRefGoogle Scholar
  165. 165.
    Costagliola C, Cipollone U, Rinaldi M et al (2008) Intravitreal bevacizumab (Avastin) injection for neovascular glaucoma: a survey on 23 cases throughout 12-month follow-up. Br J Clin Pharmacol 66:667–673PubMedGoogle Scholar
  166. 166.
    Lim TH, Bae SH, Cho YJ et al (2009) Concentration of vascular endothelial growth factor after intracameral bevacizumab injection in eyes with neovascular glaucoma. Korean J Ophthalmol 23:188–192PubMedCrossRefGoogle Scholar
  167. 167.
    Eid TM, Radwan A, el-Manawy W, el-Hawary I (2009) Intravitreal bevacizumab and aqueous shunting surgery for neovascular glaucoma: safety and efficacy. Can J Ophthalmol 44:451–456PubMedCrossRefGoogle Scholar
  168. 168.
    Hasanreisoglu M, Weinberger D, Mimouni K et al (2009) Intravitreal bevacizumab as an adjunct treatment for neovascular glaucoma. Eur J Ophthalmol 19:607–612PubMedGoogle Scholar
  169. 169.
    Ciftci S, Sakalar YB, Unlu K et al (2009) Intravitreal bevacizumab combined with panretinal photocoagulation in the treatment of open angle neovascular glaucoma. Eur J Ophthalmol 19:1028–1033PubMedGoogle Scholar
  170. 170.
    Gragoudas ES, Adamis AP, Cunningham ET Jr, VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group et al (2004) Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 351:2805–2816PubMedCrossRefGoogle Scholar
  171. 171.
    Cunningham ET Jr, Adamis AP, Altaweel M, Macugen Diabetic Retinopathy Study Group et al (2005) A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology 112:1747–1757PubMedCrossRefGoogle Scholar
  172. 172.
    Loftus JV, Sultan MB, Pleil AM, Macugen 1013 Study Group (2011) Changes in vision- and health-related quality of life in patients with diabetic macular edema treated with pegaptanib sodium or sham. Invest Ophthalmol Vis Sci 52:7498–7505PubMedCrossRefGoogle Scholar
  173. 173.
    Sultan MB, Zhou D, Loftus J, Macugen 1013 Study Group et al (2011) A phase 2/3, multicenter, randomized, double-masked, 2-year trial of pegaptanib sodium for the treatment of diabetic macular edema. Ophthalmology 118:1107–1118PubMedCrossRefGoogle Scholar
  174. 174.
    Adamis AP, Altaweel M, Bressler NM, Macugen Diabetic Retinopathy Study Group et al (2006) Changes in retinal neovascularization after pegaptanib (Macugen) therapy in diabetic individuals. Ophthalmology 113:23–28PubMedCrossRefGoogle Scholar
  175. 175.
    González VH, Giuliari GP et al (2009) Intravitreal injection of pegaptanib sodium for proliferative diabetic retinopathy. Br J Ophthalmol 93:1474–1478PubMedCrossRefGoogle Scholar
  176. 176.
    Hornan D, Edmeades N, Krishnan R et al (2010) Use of pegaptanib for recurrent and non-clearing vitreous haemorrhage in proliferative diabetic retinopathy. Eye 24:1315–1319PubMedCrossRefGoogle Scholar
  177. 177.
    Do DV, Schmidt-Erfurth U, Gonzalez VH et al (2011) The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema. Ophthalmology 118:1819–1826PubMedCrossRefGoogle Scholar
  178. 178.
    Do DV, Nguyen QD, Boyer D, DA VINCI Study Group et al (2012) One-year outcomes of the DA VINCI Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology 119:1658–1665PubMedCrossRefGoogle Scholar
  179. 179.
    Safety and efficacy study of small interfering RNA molecule (Cand5) to treat diabetic macular edema ( identifier NCT00306904). US National Institutes of Health, (online). Available from Accessed 24 Sep 2012
  180. 180.
    Singerman LJ (2007) Intravitreal bevasiranib in exudative age-related macular degeneration or diabetic macular edema. 25th annual meeting of the American Society of Retina Specialists, Indian WellsGoogle Scholar
  181. 181.
    Krishnadev N, Forooghian F, Cukras C et al (2011) Subconjunctival sirolimus in the treatment of diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 249:1627–1633PubMedCrossRefGoogle Scholar
  182. 182.
    Dugel PU, Blumenkranz MS, Haller JA et al (2012) A randomized, dose-escalation study of subconjunctival and intravitreal injections of sirolimus in patients with diabetic macular edema. Ophthalmology 119:124–131PubMedCrossRefGoogle Scholar
  183. 183.
    Stefansson E (2006) Ocular oxygenation and the treatment of diabetic retinopathy. Surv Ophthalmol 51:364–380PubMedCrossRefGoogle Scholar
  184. 184.
    Stefansson E, Hatchell DL, Fisher BL et al (1986) Panretinal photocoagulation and retinal oxygenation in normal and diabetic cats. Am J Ophthalmol 101:657–664PubMedGoogle Scholar
  185. 185.
    Stefansson E, Landers MBI, Wolbarsht ML (1981) Increased retinal oxygen supply following panretinal photocoagulation and vitrectomy and lensectomy. Trans Am Acad Ophthalmol Soc 79:307–334Google Scholar
  186. 186.
    Wakabayashi Y, Usui Y, Okunuki Y et al (2012) Intraocular VEGF level as a risk factor for postoperative complications after vitrectomy for proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 53:6403–6410Google Scholar
  187. 187.
    Yamamoto T, Akabane N, Takeuchi S (2001) Vitrectomy for diabetic macular edema: the role of posterior vitreous detachment and epimacular membrane. Am J Ophthalmol 132:369–377PubMedCrossRefGoogle Scholar
  188. 188.
    Ikeda T, Sato K, Katano T, Hayashi Y (2000) Improved visual acuity following pars plana vitrectomy for diabetic cystoid macular edema and detached posterior hyaloid. Retina 20:220–222PubMedCrossRefGoogle Scholar
  189. 189.
    Lewis H, Abrams GW, Blumenkranz MS, Campo RV (1992) Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology 99:753–759PubMedGoogle Scholar
  190. 190.
    Watanabe M, Oshima Y, Emi K (2000) Optical cross-sectional observation of resolved diabetic macular edema associated with vitreomacular separation. Am J Ophthalmol 129:264–267PubMedCrossRefGoogle Scholar
  191. 191.
    Helbig H (2007) Surgery for diabetic retinopathy. Ophthalmologica 221:103–111PubMedCrossRefGoogle Scholar
  192. 192.
    Laidlaw DA (2008) Vitrectomy for diabetic macular oedema. Eye 22:1337–1341PubMedCrossRefGoogle Scholar
  193. 193.
    Diabetic Retinopathy Clinical Research Network Writing Committee, on behalf of the (2010) Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology 117:1087–1093.e3Google Scholar
  194. 194.
    Kumagai K, Furukawa M, Ogino N et al (2009) Long-term follow-up of vitrectomy for diffuse non tractional diabetic macular edema. Retina 29:464–472PubMedCrossRefGoogle Scholar
  195. 195.
    Gandorfer A, Messmer EM, Ulbig MW, Kampik A (2000) Resolution of diabetic macular edema after surgical removal of the posterior hyaloid and the inner limiting membrane. Retina 20:126–133PubMedCrossRefGoogle Scholar
  196. 196.
    van Wijngaarden P, Coster DJ, Williams KA (2005) Inhibitors of ocular neovascularization: promises and potential problems. JAMA 293:1509–1513PubMedCrossRefGoogle Scholar
  197. 197.
    Machemer R, Buettner H, Norton EW, Parel JM (1971) Vitrectomy: a pars plana approach. Trans Am Acad Ophthalmol Otolaryngol 75:813–820PubMedGoogle Scholar
  198. 198.
    Diabetic Retinopathy Vitrectomy Study Group (1990) Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Four-year results of a randomized trial: Diabetic Retinopathy Vitrectomy Study Report 5. Arch Ophthalmol 108:958–964CrossRefGoogle Scholar
  199. 199.
    Thompson JT, de Bustros S, Michels RG, Rice TA (1987) Results and prognostic factors in vitrectomy for diabetic traction retinal detachment of the macula. Arch Ophthalmol 105:497–502PubMedCrossRefGoogle Scholar
  200. 200.
    Williams DF, Williams GA, Hartz A et al (1989) Results of vitrectomy for diabetic traction retinal detachments using the en bloc excision technique. Ophthalmology 96:752–758PubMedGoogle Scholar
  201. 201.
    Yang CM, Su PY, Yeh PT, Chen MS (2008) Combined rhegmatogenous and traction retinal detachment in proliferative diabetic retinopathy: clinical manifestations and surgical outcome. Can J Ophthalmol 43:192–198PubMedCrossRefGoogle Scholar
  202. 202.
    Shen YD, Yang CM (2007) Extended silicone oil tamponade in primary vitrectomy for complex retinal detachment in proliferative diabetic retinopathy: a long-term follow-up study. Eur J Ophthalmol 17:954–960PubMedGoogle Scholar
  203. 203.
    Virata SR, Kylstra JA, Singh HT (1999) Corneal epithelial defects following vitrectomy surgery using hand-held, sew-on, and noncontact viewing lenses. Retina 19:287–290PubMedCrossRefGoogle Scholar
  204. 204.
    Yorston D, Wickham L, Benson S et al (2008) Predictive clinical features and outcomes of vitrectomy for proliferative diabetic retinopathy. Br J Ophthalmol 92:365–368PubMedCrossRefGoogle Scholar
  205. 205.
    Newman DK (2010) Surgical management of the late complications of proliferative diabetic retinopathy. Eye 24:441–449PubMedCrossRefGoogle Scholar
  206. 206.
    Gupta B, Wong R, Sivaprasad S, Williamson TH (2012) Surgical and visual outcome following 20-gauge vitrectomy in proliferative diabetic retinopathy over a 10-year period, evidence for change in practice. Eye 26:576–582PubMedCrossRefGoogle Scholar
  207. 207.
    Jonas JB, Söfker A, Degenring R (2003) Intravitreal triamcinolone acetonide as an additional tool in pars plana vitrectomy for proliferative diabetic retinopathy. Eur J Ophthalmol 13:468–473PubMedGoogle Scholar
  208. 208.
    Lee GH, Ahn JK, Park YG (2008) Intravitreal triamcinolone reduces the morphologic changes of ciliary body after pars plana vitrectomy for retinal vascular diseases. Am J Ophthalmol 145:1037–1044PubMedCrossRefGoogle Scholar
  209. 209.
    Kim YT, Kang SW, Kim SJ et al (2012) Combination of vitrectomy, IVTA, and laser photocoagulation for diabetic macular edema unresponsive to prior treatments; 3-year results. Graefes Arch Clin Exp Ophthalmol 250:679–984PubMedCrossRefGoogle Scholar
  210. 210.
    Yamakiri K, Sakamoto T, Noda Y et al (2008) One-year results of a multicenter controlled clinical trial of triamcinolone in pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol 246:959–966PubMedCrossRefGoogle Scholar
  211. 211.
    Rizzo S, Genovesi-Ebert F, Di Bartolo E et al (2008) Injection of intravitreal bevacizumab (Avastin) as a preoperative adjunct before vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy (PDR). Graefes Arch Clin Exp Ophthalmol 246:837–842PubMedCrossRefGoogle Scholar
  212. 212.
    West JF, Gregor ZJ (2000) Fibrovascular ingrowth and recurrent haemorrhage following diabetic vitrectomy. Br J Ophthalmol 84:822–825PubMedCrossRefGoogle Scholar
  213. 213.
    Oshima Y, Shima C, Wakabayashi T et al (2009) Microincision vitrectomy surgery and intravitreal bevacizumab as a surgical adjunct to treat diabetic traction retinal detachment. Ophthalmology 116:927–938PubMedCrossRefGoogle Scholar
  214. 214.
    Arevalo JF, Maia M, Flynn HW Jr et al (2008) Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy. Br J Ophthalmol 92:213–216PubMedCrossRefGoogle Scholar
  215. 215.
    Lopez-Lopez F, Rodriguez-Blanco M, Gomez-Ulla F et al (2009) Enzymatic vitreolysis. Curr Diabetes Rev 5:57–62PubMedCrossRefGoogle Scholar
  216. 216.
    Kuppermann BD, Thomas EL, de Smet MD et al (2005) Pooled efficacy results from two multinational randomized controlled clinical trials of a single intravitreous injection of highly purified ovine hyaluronidase (Vitrase) for the management of vitreous hemorrhage. Am J Ophthalmol 140:573–584PubMedCrossRefGoogle Scholar
  217. 217.
    Benz MS, Packo KH, Gonzalez V et al (2010) A placebo-controlled trial of microplasmin intravitreous injection to facilitate posterior vitreous detachment before vitrectomy. Ophthalmology 117:791–797PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Francesco Bandello
    • 1
  • Rosangela Lattanzio
    • 1
  • Ilaria Zucchiatti
    • 1
  • Claudia Del Turco
    • 1
  1. 1.Department of Ophthalmology, Scientific Institute San RaffaeleUniversity Vita-SaluteMilanItaly

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