Current Treatment of Retinal Vein Occlusion

European Ophthalmic Review, 2011,5(1):62-8

Abstract:

Retinal vein occlusion (RVO) was first described more than 150 years ago. Even though much has been written about this frequent condition, the aetiopathology appears to be multifactorial with many unclear aspects and varied expression, making it difficult to define treatment guidelines. The management of the patient with RVO is complex and a multidisciplinary approach is required in order to identify and correct the associated risk factors. In the past, laser therapy was the gold standard in RVO, but only modest functional improvement has been shown in branch retinal occlusion forms. Current multicentre studies of intravitreal drugs present them as an option to combine with laser. Anti-vascular endothelial growth factor, corticosteroids and sustained-release implants are attractive options to halt disease progression and achieve a better visual outcome. Consequently, it is useful to clarify some aspects of the pathology that allow better patient management.
Keywords: Central retinal vein occlusion, branch retinal vein occlusion
Disclosure: Shani Golan and Naomi Fisher have no conflicts of interest to declare. Anat Lowenstein is a consultant to Alcon Inc., Allergan Inc., Forsightlabs, Lumenis Ltd, Notal Vision Ltd and Orabio Ltd.
Received: January 10, 2011 Accepted April 22, 2011 Citation European Ophthalmic Review, 2011,5(1):62-8
Correspondence: Shani Golan, Department of Ophthalmology, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel. E: shanigol2@walla.com

Retinal vein occlusion (RVO) is a common vascular disorder with a prevalence of 0.7–1.56%.1,2 It occurs due to thrombosis of a retinal vein and is defined by the location of the obstruction (central, hemi or branch vein occlusion).3–5 Branch RVO (BRVO) occurs at arteriovenous crossing sites that share a common adventitia.5 Central retinal vein occlusion (CRVO) is thought to be caused by external compression of the central retinal artery, which shares a common fibrous sleeve with the vein.6
Visual handicap occurs due to macular oedema and neovascularisation, which are secondary to retinal ischaemia.7–11 A number of inflammatory chemokines are thought to be involved in these processes and are found in elevated concentrations in the aqueous humour. Interleukin 6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), IL1-α, vascular endothelial growth factor (VEGF) and platelet-derived growth factor AA (PDGF-AA) are found to be elevated in CRVO. There are mixed results in terms of their concentrations in BRVO.12,13
Pathogenesis and Risk Factors
The pathogenesis of RVO is believed to follow the principles of Virchow's triad for thrombogenesis: vessel damage, stasis and hypercoagulability.14 Contributing factors include: atherosclerosis, inflammatory disease and hypercoagulable/thrombophilia states.15–17 A major risk factor for RVO is hypertension.18–22 Dyslipidaemia is also a prevalent finding.22 Associations have also been reported for diabetes mellitus,18–22 renal disease,23 cigarette smoking18,23 and thrombophilia.16–18,24–26 An additional ocular risk factor is glaucoma or elevated intraocular pressure (IOP), which may compromise retinal venous outflow.18 More than 90% of cases of RVO occur in the >50 age group.14 In patients >50 years of age a cardiovascular risk factor is usually present. In patients <50 years of age there is no obvious risk factor in up to 40% of cases.27,28
References:
  1. Klein R, Klein BE, Moss SE, The epidemiology of retinal vein occlusion: The Beaver Dam Eye Study, Trans Am Ophthalmol Soc, 2000;98:133–41.
  2. Mitchell P, Smith W, Chang A, Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study, Arch Ophthalmol, 1996;114:1243–7.
  3. Green WR, Chan CC, Hutchins GM, et al., Central retinal vein occlusions: A prospective histopathologic study of 29 eyes in 28 cases, Retina, 1981;1:27–55.
  4. Green WR, Retina. In: Spencer WH (ed), Ophthalmic pathology. An Atlas and Textbook, 3rd Ed., Philadephia: WB Saunders, 1985;589.
  5. Frangieh GT, Green WR, Barraquer-Soers E, et al., Histopathologic study of nine branch retinal vein occlusions, Arch Ophthalmol, 1982;100:1132–40.
  6. Haymore JG, Mejico LJ, Retinal vascular occlusion syndromes, Int Opthalmol Clin, 2009;49:63–79
  7. The Branch Vein Occlusion Study Group: Argon laser photocoagulation for macular oedema in branch vein occlusion, Am J Ophthalmol, 1984;98:271–82.
  8. The Branch Vein Occlusion Study Group, Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion. A randomized clinical trial, Arch Ophthalmol, 1986;104:34–41.
  9. The Central Vein Occlusion Study Group, Baseline and early natural history report: the Central Vein Occlusion Study, Arch Ophthalmol, 1993;111:1087–95.
  10. The Central Vein Occlusion Study Group, A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion, Ophthalmology, 1995;102:1434–44.
  11. The Central Vein Occlusion Study Group, Natural history and clinical management of central retinal vein occlusion, Arch Ophthalmol, 1997;115:486–91.
  12. Yoshimura T, Sonoda KH, Sugahara M, et al., Comprehensive analysis of inflammartory immune mediators in vitreoretinal diseases, PLoS One, 2009;4:e8158.
  13. Funk M, Kriechbaum K, Prager F, et al., Intraocular Concentrations of Growth Factors and Cytokines in Retinal Vein Occlusion and the Effect of Therapy with Bevacizumab, Invest Ophthalmol Vis Sci, 2009;50:1025–32.
  14. Yau JW, Lee P, Wong TY, et al., Retinal vein occlusion: an approach to diagnosis, systemic risk factors and management, Intern Med J, 2008;38:904–10.
  15. Greiner K, Hafner G, Dick B, et al., Retinal vascular occlusion and deficiencies in the protein C pathway, Am J Ophthalmol, 1999;128:69–74.
  16. Lahey JM, Tunc M, Kearney J, et al., Laboratory evaluation of hypercoagulable states in patients with central retinal vein occlusion who are less than 56 years of age, Ophthalmology, 2002;109:126–13.
  17. Janssen MC, den Heijer M, Cruysberg JR, et al., Retinal vein occlusion: a form of venous thrombosis or a complication of atherosclerosis? A meta-analysis of thrombophilic factors, Thromb Haemost, 2005;93:1021–6.
  18. Wong TY, Scott IU, Retinal-Vein Occlusion, N Engl J Med, 363;22:2136–44.
  19. Rath EZ, Frank RN, Shin DH, Kim C, Risk factors for retinal vein occlusions: a case-control study, Ophthalmology, 1992;99:509–14.
  20. Hayreh SS, Zimmerman B, McCarthy MJ, Podhajsky P, Systemic diseases associated with various types of retinal vein occlusion, Am J Ophthalmol, 2001;131:61–77.
  21. Elman MJ, Bhatt AK, Quinlan PM, Enger C, The risk for systemic vascular diseases and mortality in patients with central retinal vein occlusion, Ophthalmology, 1990;97:1543–8.
  22. Wong TY, Larsen EK, Klein R, et al., Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities & Cardiovascular Health studies, Ophthalmology, 2005;112:540–7.
  23. Cheung N, Klein R, Wang JJ, et al., Traditional and novel cardiovascular risk factors for retinal vein occlusion: the Multiethnic Study of Atherosclerosis, Invest Ophthalmol Vis Sci, 2008;49:4297–302.
  24. Fegan CD, Central retinal vein occlusion and thrombophilia, Eye, 2002;11:98–106.
  25. Bertram B, Remky A, Arend O, et al., Protein C, protein S, and antithrombin III in acute ocular occlusive diseases, Ger J Ophthalmol, 1995;4:332–5.
  26. Larsson J, Hillarp A, Olafsdottir E, Bauer B, Activated protein C resistance an anticoagulant proteins in young adults with central retinal vein occlusion, Acta Ophthalmol Scand, 1999;77:634–7.
  27. Dodson PM, Kritzinger EE, Medical cardiovascular treatment trials: relevant to medical ophthalmology in 1997?, Eye, 1997;11:3–11.
  28. Dodson PM, Kritzinger EE, Clough CG, Diabetes mellitus and retinal vein occlusion in patients of Asian, West Indian and White European origin, Eye, 1992;6:66–8.
  29. Rogers SL, McIntosh RL, Lim L, et al., Natural history of branch retinal vein occlusion, Ophthalmology, 2010;117(6):1094.
  30. Finkelstein D, Ischemic macular edema: recognition and favorable natural history in branch vein occlusion, Arch Ophthalmol, 1992;110:1427–34.
  31. McIntosh RL, Rogers SL, Lim L, et al., Natural history of central retinal vein occlusion: an evidence-based systematic review, Ophthalmology, 2010;117:1113.
  32. Tsaloumas MD, Kirwan J, Vinall H, et al., Nine year follow-up study of morbidity and mortality in retinal vein occlusion, Eye, 2000;14:821–7.
  33. Christoffersen N, Gade E, Knudsen L, et al., Mortality in patients with branch retinal vein occlusion, Ophthalmology, 2007;114:1186–9.
  34. Cugati S, Wang JJ, Knudtson MD, et al., Retinal vein occlusion and vascular mortality: pooled data analysis of 2 population-based cohorts, Ophthalmology, 2007;114:520-4.
  35. Shahid H, Hossain P, Amoaku WM, The management of retinal vein occlusion: is interventional ophthalmology the way forward?, Br J Ophthalmol, 2006;90:627–39.
  36. Hayreh SS, Venous occlusive disease: management 25 years ago, Retina, 2006;26:51–62.
  37. The Central Vein Occlusion Study Group. Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion: the Central Vein Occlusion Study Group M report, Ophthalmology, 1995;102:1425–33.
  38. Opremcak EM, Bruce RA, Lomeo MD, et al., Radial optic neurotomy for central retinal vein occlusion, A retrospective pilot study of 11 consecutive cases, Retina, 2001;21:408–15.
  39. Williamson TH, Poon W, Whitefield L, et al., A pilot study of pars plana vitrectomy, intraocular gas and radial neurotomy in ischaemic central retinal vein occlusion, Br J Ophthalmol, 2003;87:1126–9.
  40. Nomoto H, Shiraga F, Yamaji H, et al., Evaluation of radial optic neurotomy for central retinal vein occlusion by indocyanine green videoangiography and image analysis, Am J Ophthalmol, 2004;138:612–9.
  41. Spaide RF, Klancnik JM Jr, Gross NE, Retinal choroidal collateral circulation after radial optic neurotomy correlated with the lessening of macular oedema, Retina, 2004;24:356–9.
  42. Hasselbach HC, Ruefer F, Feltgen N, et al., Treatment of central retinal vein occlusion by radial optic neurotomy in 107 cases, Graefes Arch Clin Exp Ophthalmol, 2007;245:1145–56.
  43. Hayreh SS, Management of central retinal vein occlusion, Ophthalmologica, 2003;217:167–88.
  44. Martinez-Jardon CS, Meza-de Regil A, Dalma-Weiszhausz J, et al., Radial optic neurotomy for ischaemic central vein occlusion, Br J Ophthalmol, 2005;89:558–61.
  45. Arevalo JF, Garcia RA, Wu L, et al., Radial optic neurotomy for central retinal vein occlusion: results of the Pan-American Collaborative Retina Study Group (PACORES). Retina, 2008;28:1044–52.
  46. Sharma A, D’Amico D, Medical and surgical management of central retinal vein occlusion, Int Ophthalmol Clin, 2004;44:1–16.
  47. McAllister IL, Douglas JP, Constable IJ, Yu DY, Laser-induced chorioretinal venous anastomosis for non-ischaemic central retinal vein occlusion: evaluation of the complications and their risk factors, Am J Ophthalmol, 1998;126:219–29.
  48. Peyman GA, Kishore K, Conway MD, Surgical chorioretinal venous anastomosis for ischaemic central retinal vein occlusion, Ophthalmic Surg Lasers, 1999;30:605–14.
  49. McAllister IL, Gillies ME, Smithies LA, et al., The Central Retinal Vein Bypass Study: a trial of laser-induced chorioretinal venous anastomosis for central retinal vein occlusion, Ophthalmology, 2010;117:954–65
  50. Quiroz-Mercado H, Sanchez-Buenfil E, Guerrero-Naranjo JL, et al., Successful erbium:YAG laser-induced chorioretinal venous anastomosis for the management of ischaemic central retinal vein occlusion. A report of two cases, Graefes Arch Clin Exp Ophthalmol, 2001;239:872–5.
  51. Mirshahi A, Roohipoor R, Lashay A, et al., Surgical induction of chorioretinal venous anastomosis in ischaemic central retinal vein occlusion: a non-randomized controlled clinical trial, Br J Ophthalmol, 2005;89:64–9.
  52. Koizumi K, Nishiura M, Yamamoto T, et al., Intentional complete interruption of a retinal vein after vitrectomy might improve the rate of successful chorioretinal venous anastomosis formation in central retinal vein occlusion, Graefes Arch Clin Exp Ophthalmol, 2002;240:787–94.
  53. Liang XL, Chen HY, Huang YS, et al., Pars plana vitrectomy and internal limiting membrane peeling for macular oedema secondary to retinal vein occlusion: a pilot study, Ann Acad Med Singapore, 2007;36:293–7.
  54. Mandelcorn MS, Nrusimhadevara RK, Internal limiting membrane peeling for decompression of macular oedema in retinal vein occlusion: a report of 14 cases, Retina, 2004;24:348–55.
  55. Park DH, Kim IT, Long-term effects of vitrectomy and internal limiting membrane peeling for macular edema secondary to central retinal vein occlusion and hemiretinal vein occlusion, Retina, 2010;30:117–24.
  56. Funatsu H, Yamashita H, Ikeda T, et al., Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular oedema, Ophthalmology 2003;110:1690–6.
  57. Funatsu H, Yamashita H, Ikeda T, et al., Relation of diabetic macular oedema to cytokines and posterior vitreous detachment, Am J Ophthalmol, 2003;135:321–7.
  58. Saika S, Tanaka T, Miyamoto T, Ohnishi Y, Surgical posterior vitreous detachment combined with gas/air tamponade for treating macular oedema associated with branch retinal vein occlusion: retinal tomography and visual outcome, Graefes Arch Clin Exp Ophthalmol, 2001;239:729–32.
  59. Noma H, Funatsu H, Sakata K, et al., Macular microcirculation before and after vitrectomy for macular edema with branch retinal vein occlusion, Graefes Arch Clin Exp Ophthalmol, 2010;248:443–5.
  60. Radetzky S, Walter P, Fauser S, et al., Visual outcome of patients with macular oedema after pars plana vitrectomy and indocyanine green-assisted peeling of the internal limiting membrane, Graefes Arch Clin Exp Ophthalmol, 2004;242:273–8.
  61. Weiss JN, Bynoe LA, Injection of tissue plasminogen activator into a branch retinal vein in eyes with central retinal vein occlusion, Ophthalmology, 2001;108:2249–57.
  62. Feltgen N, Junker B, Agostini H, Hansen LL, Retinal endovascular lysis in ischaemic central retinal vein occlusion, One-year results of a pilot study, Ophthalmology, 2007;114:716–23.
  63. Hattenbach L, Friedrich Arndt C, Lerche R, et al., Retinal vein occlusion and low-dose fibrinolytic therapy (ROLF). A prospective, randomized, controlled multicenter study of low-dose recombinant tissue plasminogen activator versus hemodilution in retinal vein occlusion, Retina, 2009;29:932–40.
  64. Osterloh MD, Charles S, Surgical decompression of branch retinal vein occlusion, Arch Ophthalmol, 1988;106:1469–71.
  65. Avci R, Inan UU, Kaderli B, Evaluation of arteriovenous crossing sheathotomy for decompression of branch retinal vein occlusion, Eye, 2008;22:120–7.
  66. Oh IK, Kim S, Oh J, Huh K, Long-term visual outcome of arteriovenous adventitial sheathotomy on branch retinal vein occlusion induced macular edema, Korean J Ophthalmol, 2008;22:1–5.
  67. Chung EJ, Lee H, Koh HJ, Arteriovenous crossing sheathotomy versus intravitreal triamcinolone acetonide injection for treatment of macular edema associated with branch retinal vein occlusion, Graefes Arch Clin Exp Ophthalmol, 2008;246:967–74.
  68. Amsterdam A, Tajima K, Sasson R, et al., Cell-specific regulation of apoptosis by glucocorticoids: implication to their anti-inflammatory action, Biochem Pharmacol, 2002; 64:843–50.
  69. Tamura H, Miyamoto K, Kiryu J, et al., Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina, Invest Ophthalmol Vis Sci, 2005;46:1440–4.
  70. Del Maschio A, Zanetti A, Corada M, et al., Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions, J Cell Biol, 1996;135:497–510.
  71. Itakura H, Akiyama H, Hagimura N, et al., Triamcinolone acetonide suppresses interleukin-1 beta-mediated increase in vascular endothelial growth factor expression in cultured rat Müller cells, Graefes Arch Clin Exp Ophthalmol, 2006;244:226–31.
  72. Nauck M, Roth M, Tamm M, et al., Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is down regulated by corticosteroids, Am J Resp Cell Mol Biol, 1998;16:398–406.
  73. Greenberg PB, Martidis A, Rogers AH, et al., Intravitreal triamcinolone acetonide for macular oedema due to central retinal vein occlusion, Br J Ophthalmol, 2002;86:247–8.
  74. Williamson TH, O’Donnell A, Intravitreal triamcinolone acetonide for cystoid macular edema in nonischemic central retinal vein occlusion, Am J Ophthalmol, 2005;139:860–6.
  75. Ip MS, Scott IU, Van Veldhuisen PC, et al., A randomized trial compaqring the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular edema secondary to central retinal vein occlusion: the Standard Care vrs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 5, Arch Ophthalmol, 2009;127:1101-14.
  76. Scott IU, Vanveldhuisen PC, Oden NL, et al., SCORE Study Investigator Group. SCORE Study Report 1: Baseline Associations between Central Retinal Thickness and Visual Acuity in Patients with Retinal Vein Occlusion, Ophthalmology, 2009;116:504–12.
  77. Scott IU, Ip MS, VanVeldhuisen PC, et al., A randomized trial compaqring the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6, Arch Ophthalmol, 2009;127:1115–28.
  78. Gewaily D, Greenberg PB, Intravitreal steroids versus observation for macular edema secondary to central retinal vein occlusion, Cochrane Database Syst Rev, 2009;21:(1)CD007324.
  79. Cakir M, Dogan M, Bayraktar Z, et al., Efficacy of intravitreal triamcinolone for the treatment of macular edema secondary to branch retinal vein occlusion in eyes with or without grid laser photocoagulation, Retina, 2008;28:465–72.
  80. Bearelly S, Cooney MJ, Stinnett S, Fekrat S, Intravitreal triamcinolone for cystoid macular edema related to branch retinal vein occlusion, Ann Ophthalmol (Skokie), 2006;38:317–20.
  81. Oh JY, Seo JH, Ahn JK, et al., Early versus late intravitreal triamcinolone acetonide for macular edema associated with branch retinal vein occlusion, Korean J Ophthalmol, 2007;21:18–20.
  82. Tano Y, Sugita G, Abrams G, Machemer R, Inhibition of intraocular proliferations with intravitreal corticosteroids, Am J Ophthalmol, 1980;89:131–6.
  83. Cheng CK, Berger AS, Pearson PA, Ashton P, Jaffe GJ, Intravitreal sustained-release dexamethasone device in the treatment of experimental uveitis, Invest Ophthalmol Vis Sci, 1995;36:442–53.
  84. Haller JA, Bandello F, Belfort R Jr, et al., OZURDEX GENEVA Study Group. Randomised, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion, Ophthalmology, 2010;117:1134–46 e3.
  85. Lanzetta P, Oral presentation, Benefits of Early treatment with Dexamethasone Intravitreal Implant for Macular Oedema due to BRVO or CRVO for 12 months, EuRETINA, Paris, September 2010.
  86. Electronic Medicines Compendium, OZURDEX Summary of Product Characteristics. Available at: www.medicines.org.uk/EMC/medicine/23422/SPC/Ozurdex/ (accessed 22 June 2011).
  87. Fung AE, A novel sustained-release intravitreal drug delivery system for retinal vascular disease, Retina Today, 2010;5:51–3.
  88. Mohammad DA, Sweet BV, Elner SG, Retisert: is the new advance in treatment of uveitis a good one?, Ann Pharmacother, 2007;41:449–54.
  89. Mahajan VB, Gehrs KM, Goldstein DA, et al., Management of sympathetic ophthalmia with the fluocinolone acetonide implant, Ophthalmology, 2009;116:552–7.
  90. Callanan DG, Jaffe GJ, Martin DF, et al., Treatment of posterior uveitis with a fluocinolone acetonide implant: three-year clinical trial results, Arch Ophthalol, 2008;126:1181–201.
  91. Ramchandran RS, Fekrat S, Stinnett SS, Jaffe GJ, Fluocinolone acetonide sustained drug delivery device for chronic central retinal vein occlusion: 12-month results, Am J Ophthalmol, 2008;146:285–91.
  92. Campochiaro PA, Hafiz G, Shah SM, et al., Famous Study Group Sustained ocular delivery of fluocinolone acetonide by an intravitreal insert, Ophthalmology, 2010;117:1393–9.e3.
  93. Lattanzio R, Gimeno AT, Parodi MB, Bandello F, Retinal Vein Occlusion: Current Treatment, Ophthalmologica, 2011;225:135–43.
  94. Noma H, Funutsu H, Mimura T, et al., Increase of vascular endothelial growth factor and interleukin-6 in the aqueous humour of patients with macular edema and central retinal vein occlusion, Acta OphthalmoI, 2010;88:646–51.
  95. Noma H, Minamoto A, Funatsu H, et al., Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion, Graefes Arch Clin Exp Ophthalmol, 2006;244:309–15.
  96. Pieramici DJ, Rabena MD, Anti-VEGF therapy: comparison of current and future agents, Eye, 2008;22;1330–6.
  97. Campochiaro PA, Hafiz G, Shah SM, et al., Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator, Mol Ther, 2008;16:791–9.
  98. Badalà F, The treatment of branch retinal vein occlusion with bevacizumab, Curr Opin Ophthalmol, 2008;19:234–8.
  99. Rosenfeld PJ, Fung AE, Puliafito CA, Optical coherence tomography findingsafter an intravitreal injection of bevacizumab (avastin) for macular edema from central retinal vein occlusion, Ophthalmic Surg Lasers Imaging, 2005;36:336–9
  100. Iturralde D, Spaide RF, Meyerle CB, et al., Intravitreal bevacizumab (Avastin) treatment of macular edema in central retinal vein occlusion: a short-term study, Retina, 2006;26:279–84.
  101. Rabena MD, Pieramici DJ, Castellarin AA, et al., Intravitreal bevacizumab (Avastin) in the treatment of macular edema secondary to branch retinal vein occlusion, Retina, 2007;27:419–25.
  102. Stahl A, Agostini H, Hansen LL, Feltgen N, Bevacizumab in retinal vein occlusion-results of a prospective case series, Graefes Arch Clin Exp Ophthalmol, 2007;245:1429–36.
  103. Pai SA, Shetty R, Vijayan PB, et al., Clinical, anatomic, and electrophysiologic evaluation following intravitreal bevacizumab for macular edema in retinal vein occlusion, Am J Ophthalmol, 2007;143:601–6.
  104. Schaal KB, Höh AE, Scheuerle A, Schütt F, Dithmar S, Bevacizumab for the treatment of macular edema secondary to retinal vein occlusion, Ophthalmologe, 2007;104:285–9.
  105. Cinal A, Ziemssen F, Bartz-Schmidt KU, Gelisken F, Intravitreal bevacizumab for treatment of serous macular detachment in central retinal vein occlusion, Graefes Arch Clin Exp Ophthalmol, 2010; (Epub ahead of print).
  106. Hsu J, Kaiser RS, Sivalingam A, et al., Intravitreal bevacizumab (Avastin) in central retinal vein occlusion, Retina, 2007;27:1013–9.
  107. Costa RA, Jorge R, Calucci D, et al., Intravitreal bevacizumab (Avastin) for central and retinal vein occlusions. IBeVo study, Retina, 2007;27:141–9.
  108. Fish GE, Intravitreous bevacizumab in the treatment of macular edema from branch retinal vein occlusion and hemisphere retinal vein occlusion (an AOS thesis), Trans Am Ophthalmol Soc, 2008;106:276–300.
  109. Wu L, Arevalo JF, Roca JA, et al., Comparison of two doses of intravitreal bevacizumab (Avastin) for treatment of macular edema secondary to branch retinal vein occlusion: results from the Pan-American Collaborative Retina Study (PACORES) Group at 6 months of follow-up, Retina, 2008;28:212–9.
  110. Chung EJ, Hong YT, Lee SC, et al., Prognostic factors for visual outcome after intravitreal bevacizumab for macular edema due to branch retinal vein occlusion, Graefes Arch Clin Exp Ophthalmol, 2008;246:1241–7.
  111. Ahmadi AA, Chou JY, Banashkevich A, et al., The effects of intravitreals bevacizumab on patients with macular edema secondary to branch retinal vein occlusion, Can J Ophthalmol, 2009;44:154–9.
  112. Prager F, Michels S, Kriechbaum K, et al., Intravitreal bevacizumab (Avastin) for macular oedema secondary to retinal vein occlusion: 12-month results of a prospective clinical trial, Br J Ophthalmol, 2009;93:452–6.
  113. Kondo M, Kondo N, Ito Y, et al., Intravitreal injection of bevacizumab for macular edema secondary to branch retinal vein occlusion. Results after 12 months and multiple regression analysis, Retina, 2000;29:1242–8.
  114. Ach T, Hoeh AE, Schaal KB, et al., Predictive factors for changes in macular edema in intravitreal bevacizumab therapy of retinal vein occlusion, Graefes Arch Clin Exp Ophthalmol, 2010;248:155–9.
  115. Douat J, Auriol S, Mahieu-Durringer L, et al., Intravitreal bevacizumab for treatment of neovascular glaucoma. Report of 20 cases, J Fr Ophtalmol, 2009;32:652–63.
  116. Ciulla TA, Rosenfeld PJ, Anti-vascular endothelial growth factor therapy for neovascular ocular diseases other than agerelated macular degeneration, Curr Opin Ophthalmol, 2009;20:166–74.
  117. Pieramici DJ, Rabena M, Castellarin AA, et al., Ranibizumab for the treatment of macular edema associated with perfused central retinal vein occlusions, Ophthalmology, 2008;115:e47–e54.
  118. Spaide RF, Chang LK, Klancnik JM, et al., Prospective study of ranibizumab as a treatment of decreased visual acuity secondary to central retinal vein occlusion, Am J Ophthalmol, 2009;147:298–306.
  119. Rouvas A, Petrou P, Vergados I, et al., Intravitreal ranibizumab (Lucentis) for treatment of central retinal vein occlusion: a prospective study, Graefes Arch Clin Exp Ophthalmol, 2009;247:1609–16.
  120. Campochiaro PA, Heier JS, Feiner L, et al., BRAVO Investigators: Ranibizumab for macular edema following branch retinal vein occlusion six-month primary end point results of a phase III study, Ophthalmology, 2010;117:1102–12.
  121. Brown DM, Campochiaro PA, Singh RP, et al., CRUISE Investigators: Ranibizumab for macular edema following central retinal vein occlusion six-month primary end point results of a phase III study, Ophthalmology, 2010;117:1124–33.
  122. Brown DM, Clinical implications of the BRAVO and CRUISE trials, Retina Today, 2010;5:38–40.
  123. Bennet MD, Pegaptanib for the treatment of ischemic retinopathy in patients with diabetes and retinal vascular occlusive disorders, Retina Today, 2009;4:63–6.
  124. Wroblewski JJ, Wells JA 3rd, Gonzales CR, Pegaptanib sodium for macular edema secondary to branch retinal vein occlusion, Am J Ophthalmol, 2010;149:147–154.
  125. Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Central Retinal Vein Occlusion (CRVO) (GALILEO). Available at: http://clinicaltrials. gov/ct2/show/NCT01012973 (accessed 22 July 2011).
  126. Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Central Retinal Vein Occlusion (CRVO). Available at: http://clinicaltrials.gov /ct2/show/NCT00943072?term=Copernicus&rank=3 (accessed 22 June 2011).
  127. Hoeh AE, Ach T, Schaal KB, Scheuerle AF, Dithmar S, Long-term follow-up of OCT-guided bevacizumab treatment of macular edema due to retinal vein occlusion, Graefes Arch Clin Exp Ophthalmol, 2009;247:1635–41.
  128. Park SP, Ahn JK, Changes of aqueous vascular endothelial growth factor and pigment epithelium-derived factor following intravitreal bevacizumab for macular oedema secondary to branch retinal vein occlusion, Clin Experiment Ophthalmol, 2009;37:490–5.
  129. Parodi MB, Bandello F, Branch retinal vein occlusion: classification and treatment. Ophthalmologica, 2009;223:298–301.
  130. Byrnes MJ, Sena D, Tzekov R, Combination Therapies for the Treatment of Retinal Vein Occlusion, Retina Today, 2009:3;53–5.
  131. Riese J, Loukopoulos V, Meier C, et al., Combined intravitreal triamcinlone injection and laser photocoagulation in eyes with persistent macular edema after branch retinal vein Occlusion, Graefes Arch Clin Exp Ophthalmol, 2008;246:1671–6.
  132. Polito A, Pognuz DR, Lanzetta P, et al., Intravitreal triamcinolone as adjunctive treatment to laser photocoagulation for cystoid macular edema due to branch retinal vein occulusion, Invest Ophthalmol Vis Sci, 2006;47:E–abstract 4291.
  133. Sakamoto T, Shimura M, Yasuda K, et al., Combination therapy for retinal vein occlusion, Ophthalmology, 2010;117:1858.e1–3.
  134. Parodi MB, Iacono P, Ravalico G, Intravitreal triamcinolone acetonide combined with subthreshold grid laser treatment for macular oedema in branch retinal vein occlusion: a pilot study, Br J Ophthalmol, 2008;92:1046–50.
  135. Ai E, Yang SS, Venous occlusive disease: the latest in current management, Retina, 2006;26(Suppl. 6):S63–S4.
  136. Ekdawi NS, Bakri SJ, Intravitreal triamcinolone and bevacizumab combination therapy formacular edema due to central retinal vein occlusion refractory to either treatment alone, Eye, 2007;21:1128–30.
  137. Ehrlich R, Ciulla TA, Moss AM, Harris A, Combined treatment of intravitreal bevacizumab and intravitreal triamcinolone in patients with retinal vein occlusion: 6 months of follow-up, Graefes Arch Clin Exp Ophthalmol, 2010;248:375–80.
  138. MECROV (Treatment of Bevacizumab and Triamcinolone in Treatment or Macular Edema Secondary to CRVO). Available at: http://clinicaltrials.gov/ct2/show/NCT00566761 (accessed 22 July 2011).
  139. Intravitreal Avastin Versus Intravitreal Avastin and Triamcinolone in Central Retinal Vein Occlusion (CRVO). Available at: http://clinicaltrials.gov/ct2/show /NCT00370630?term=The+intravitreal+avastin+versus+intravi treal+avastin+and+triamcinolone+in+central+retinal+vein+oc clusion%28CRVO%29&rank=1 (accessed 22 July 2011).
  140. Jin M, Ke Y, Zheng Z, Xiajing T, Twenty-five-gauge vitrectomy and triamcinolone acetonide-assisted internal limiting membrane peeling for chronic macular edema associated with branch retinal vein occlusion, Retina, 2008;28:947–56.
  141. Uemura A, Yamamoto S, Sato E, et al., Vitrectomy alone versus vitrectomy with simultaneous injection of triamcinolone for macular edema associated with branch retinal vein occlusion, Ophthalmic Surg Lasers Imaging, 2009;40:6–12.
  142. Ma J, Yao K, Zhang Z, Tang X, 25-gauge vitrectomy and triamcinolone acetonide-assisted internal limiting membrane peeling for chronic cystoid macular edema associated with branch retinal vein occlusion, Retina, 2008;28:947–56.
  143. Opremcak EM, Rehmar AJ, Ridenour CD, et al., Radial optic neurotomy with adjunctive intraocular triamcinolone for central retinal vein occlusion: 63 consecutive cases, Retina, 2006;26:306–31
  144. Garcia-Arumi J, Boixedera A, Martinez-Castillo V, et al., Chorioretinal anastomosis alter radial optic neurotomy for central retinal vein occlusion, Arch Ophthalmol, 2003;121:1385–91.
  145. Oono Y, Tsuru H, Teruya K, et al., Long-term outcomes of radial optic neurotomy with or without adjunctive intraocular triamcinolone acetonide in central retinal vein occlusion, Invest Ophthalmol Vis Sci, 2008;49:E-abstract 4692.
  146. Hwang JC, Gelman SK, Fine HF, et al., Combined arteriovenous sheathotomy and intraoperative intravitreal triamcinolone acetonide for branch retinal vein occlusion, Br J Ophthalmol, 2010;94:1483–9.
  147. Kim E, Koreen S, Fine HF, et al., Combined arteriovenous sheathotomy and intraoperative intravitreal triamcinolone acetonide for branch retinal vein occlusion, Invest Ophthalmol Vis Sci, 2008;49:5982.
  148. Garcia-Arumi J, Martinez-Castillo V, Boixadera A, et al., Management of macular edema in branch retinal vein occlusion with sheathotomy and recombinant tissue plasminogen activator, Retina, 2004;24:530–40.
  149. Ferrari TM, Sborgia L, Furino C, et al., Radial optic neurotomy, internal limiting membrane peeling and intravitreal triamcinolone in the occlusion of the central retinal vein occlusion, Invest Ophthalmol Vis Sci, 2004;45: E-abstract 5219.
  150. Fortunato P, Pollazzi L, Baroni M, et al., Venous retinal flow reperfusion mechanisms following radial optic neurotomy with adjunctive intraocular triamcinolonein central retinal vein occlusion, Graefes Arch Clin Exp Ophthalmol, 2010;248:167–73.
  151. Serny C, Mura F, Rebollo B, et al., Hemodilution with and without triamcinolone at the initial phase of vein occlusion: A retrospective comparative study, Invest Ophthalmol Vis Sci, 2007;48:E-abstract 298.
  152. Lewis GM, Morris R, Treatment of cystoid macular edema in branch retinal vein occlusion with grid photocoagulation, intravitreal triamcinolone, and pneumatic maculopexy, Invest Ophthalmol Vis Sci, 2006;47:E-abstract 5207.
  153. Koss MJ, Naser H, Sener A, et al., Combination therapy in diabetic macular oedema and retinal vein occlusion – past and present, Acta Ophthalmol, 2010; (Epub ahead of print).
Keywords: Central retinal vein occlusion, branch retinal vein occlusion