Eye Disease in Behçet’s Syndrome



Ocular involvement is the main cause of morbidity in Behçet’s syndrome (BS). While the overall frequency is ∼50%, the young males have ∼70% while the older females have ∼20% chance of acquiring eye disease. It starts within the first few years of the disease, involves both eyes in the majority of the patients and runs a more severe course in males. It is a nongranulomatous panuveitis and retinal vasculitis that has a periodic course characterized by activations and remissions. Impairment or blurring of vision and ocular discomfort are the main symptoms during an attack which usually subsides within a few weeks. Cellular infiltration within the anterior chamber is a common presenting sign. It can be accompanied by exudation of protein from the inflamed iris vessels. When the cellular infiltrate and fibrinous deposits are extensive a hypopyon is formed due to gravity. Recurrent inflammatory activity in the anterior chamber may lead to anterior and posterior synechia, secondary glaucoma and cataract. Vitreal inflammatory signs in the form of haze or cells are the main inflammatory findings of posterior segment involvement. Occlusive retinal vasculitis, which is the hallmark of ocular disease of BS, almost always accompanies posterior segment involvement. In severe disease, fundoscopic examination may show vitreal deposits, choroidal or retinal exudates, sheathing of blood vessels, retinal edema, hemorrhages, and macular degeneration. In advanced stages, the visual loss becomes permanent and each acute flare adds more to the degree of visual loss. Visual prognosis of BS has dramatically improved in the last two to three decades by better use of conventional immunosuppressors such as cyclosporine and azathioprine, and more recently biologics like anti-TNF alpha agents and interferon alpha. Ophtalmic surgery has also become much more successful.


Uveitis Retinal vasculitis Iridocyclitis Optic disk edema Hypopyon Slit lamp Vitreous haze Synechia Cystoid macular edema Cataracts Secondary glaucoma Visual loss Blindness Corticosteroids Azathioprine Cyclosporine Anti-TNF alpha agents Interferon alpha 


  1. 1.
    Sakane T, Takeno M, Suzuki N, Inaba G (1999) Behçet’s disease. N Engl J Med 341: 1284–1291PubMedCrossRefGoogle Scholar
  2. 2.
    Yazici H, Tüzün Y, Pazarli H et al (1984) Influence of age of onset and patient’s sex on the prevalence and severity of manifestations of Behçet’s syndrome. Ann Rheum Dis 43:783–789PubMedCrossRefGoogle Scholar
  3. 3.
    Kazokoglu H, Onal S, Tugal-Tutkun I et al (2008) Demographic and clinical features of uveitis in tertiary centers in Turkey. Ophthalmic Epidemiol 15:285–293PubMedCrossRefGoogle Scholar
  4. 4.
    Mishima S, Masuda K, Izawa Y et al (1979) Behçet’s diesae in Japan: ophthalmologic aspects. Tr Am Ophthalmol Soc 76:225–279Google Scholar
  5. 5.
    Goto H, Mochizuki M, Yamaki K et al (2007) Epidemiological survey of intraocular inflammation in Japan. Jpn J Ophthalmol 51:41–44PubMedCrossRefGoogle Scholar
  6. 6.
    Rodriguez A, Calonge M, Pedroza-Serez M et al (1996) Referral patterns of uveitis in a tertiary eye care center. Arch Ophthalmol 114:593–599PubMedCrossRefGoogle Scholar
  7. 7.
    Kural-Seyahi E, Fresko I, Seyahi N et al (2003) The long-term mortality and morbidity of Behçet’s syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine 82:60–76PubMedCrossRefGoogle Scholar
  8. 8.
    Tugal-Tutkun I, Onal S, Altan Yaycıoglu R et al (2004) Uveitis in Behçet’s disease: an analysis of 880 patients. Am J Ophthalmol 138:373–380PubMedCrossRefGoogle Scholar
  9. 9.
    Tunc R, Keyman E, Melikoglu M, Fresko I, Yazici H (2002) Target organ associations in Turkish patients with Behçet’s disease: a cross sectional study with exploratory factor analysis. J Rheumatol 29:2393–2396PubMedGoogle Scholar
  10. 10.
    Nussenblatt RB, Whitcup SM, Paletsine AG (2004) Behçet’s disease. In: Nussenblatt RB, Whitcup SM, Paletsine AG (eds) Uveitis: fundamentals and clinical practice. Mosby, Philadelphia, pp 350–371Google Scholar
  11. 11.
    Jabs DA, Nussenblatt RB, Rosenbaum JT (2005) Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 140:509–516PubMedCrossRefGoogle Scholar
  12. 12.
    George RK, Chan CC, Whitcup SM et al (1997) Ocular immunopathology of Behçet’s disease. Surv Ophthalmol 42:157–162PubMedCrossRefGoogle Scholar
  13. 13.
    Ramsay A, Lightman S (2001) Hypopyon uveitis. Surv Ophthalmol 46:1–18PubMedCrossRefGoogle Scholar
  14. 14.
    Pazarlı H, Ozyazgan Y, Aktunc T (1989) Clinical observations on hypopyon attacks of Behçet’s disease in Turkey. In: Seventh international conference on Behçet’s disease (abstracts), Rochester, MN, 14–15 SeptGoogle Scholar
  15. 15.
    Tugal-Tutkun I, Urgancioglu M, Foster CS (1995) Immunopathologic study of the conjunctiva in patients with Behçet’s disease. Ophthalmology 102:1660–1668PubMedGoogle Scholar
  16. 16.
    Zamir E, Bodaghi B, Tugal-Tutkun I et al (2003) Conjunctival ulcers in Behçet’s disease. Ophthalmology 110:1137–1141PubMedCrossRefGoogle Scholar
  17. 17.
    Elgin U, Berker N, Batman A (2004) Incidence of secondary glaucoma in Behçet’s disease. J Glaucoma 13:441–444PubMedCrossRefGoogle Scholar
  18. 18.
    Yalvaç IS, Sungur G, Turhan E et al (2004) Trabeculectomy with mitomycin-C in uveitic glaucoma associated with Behçet’s disease. J Glaucoma 13:450–453PubMedCrossRefGoogle Scholar
  19. 19.
    Baer JC, Raizman MB, Foster CS (1990) Ocular Behçet’s disease in the United States: clinical presentation and visual outcome in 29 patients. In: Masahiko U, Shigeaki O, Koki A (eds) Proceedings of the 5th international symposium on the immunology and immunopathology of the eye, Tokyo. Elsevier Science, New York, p 383Google Scholar
  20. 20.
    Ehrlich GE (1997) Vasculitis in Behçet’s disease. Int Rev Immunol 14:81–88PubMedCrossRefGoogle Scholar
  21. 21.
    Akman-Demir G, Serdaroglu P, Tasci B (1999) Clinical patterns of neurological involvement in Behçet’s disease: evaluation of 200 patients. The Neuro-Behçet’s Study Group. Brain 122:2171–2182PubMedCrossRefGoogle Scholar
  22. 22.
    Foster CS, Vitale AT (2002) Adamantiades-Behçet’s disease. In: Foster CS, Vitale AT (eds) Diagnosis and treatment of uveitis. W.B. Saunders Company, Philadelphia, pp 632–652Google Scholar
  23. 23.
    Kacmaz RO, Kempen JH, Newcomb C et al, Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study Group (2008) Ocular inflammation in Behçet’s disease: incidence of ocular complications and of loss of visual acuity. Am J Ophthalmol 146:828–836PubMedCrossRefGoogle Scholar
  24. 24.
    Atmaca LS (1989) Fundus changes associated with Behçet’s disease. Graefes Arch Clin Exp Ophthalmol 227:340–344PubMedCrossRefGoogle Scholar
  25. 25.
    Bozzoni-Pantaleoni F, Gharbiya M, Pirraglia MP et al (2001) Indocyanine gren angiographic findings in Behçet’s disease. Retina 21:230–236PubMedCrossRefGoogle Scholar
  26. 26.
    Atmaca LS, Sönmez PA (2003) Fluorescein and indocyanine green angiography findings in Behçet’s disease. Br J Ophthalmol 87:1466–1468PubMedCrossRefGoogle Scholar
  27. 27.
    Gedik S, Akova YA, Yılmaz G et al (2005) Indocyanine green and fundus fluorescein angiographic findings in patients with active ocular Behçet’s disease. Ocul Immunol Inflamm 13:51–58PubMedCrossRefGoogle Scholar
  28. 28.
    Winter FC, Yukins RE (1966) The ocular pathology of Behçet’s disease. Am J Ophthmol 62:257–262Google Scholar
  29. 29.
    Mullaney J, Collum LM (1985) Ocular vasculitis in Behçet’s disease: a pathological and immunohistochemical study. Int Ophthalmol 7:183–191PubMedCrossRefGoogle Scholar
  30. 30.
    Hegab S, Al-Mutawa S (2000) Immunopathogenesis of Behçet’s diseae. Clin Immunol 96:174–186PubMedCrossRefGoogle Scholar
  31. 31.
    Atmaca LS, Batioglu F, Idil A (1996) Retinal and disc neovascularization in Behçet’s disease and efficacy of laser photocoagulation. Graefes Arch Clin Exp Ophthalmol 234:94–99PubMedCrossRefGoogle Scholar
  32. 32.
    El Belhadji M, Hamdani M, Laouissi N et al (1997) L’attente ophthalmologique dans la maladie d Behçet: a propos de 520 cas. J Fr Ophthalmol 20:592–598Google Scholar
  33. 33.
    Ando K, Fujino Y, Hijikata K et al (1999) Epidemiological features and viusal prognosis of visual prognosis of Behçet’s disease. Jpn J Ophthalmol 43:312–317PubMedCrossRefGoogle Scholar
  34. 34.
    Sakamoto M, Akazawa K, Nishioka Y et al (1995) Prognostic factors of vision in patients with Behçet’s disease. Ophthalmology 102:317–321PubMedGoogle Scholar
  35. 35.
    Nussenblatt RB, Pelestine AG, Chan CC et al (1985) Standardization of vitreal inflammatory activity in intermediate and posteror uveitis. Ophthalmology 92:467–471PubMedGoogle Scholar
  36. 36.
    Tugal-Tutkun I, Cingu K, Kir N, Yeniad B, Urgancioglu M, Gul A (2008) Use of laser flare-cell photometry to quantify intraocular inflammation in patients with Behçet’s uveitis. Graefes Arch Clin Exp Ophthalmol 246:1169–1177PubMedCrossRefGoogle Scholar
  37. 37.
    Mamo JG (1970) The rate of visual loss in Behçet’s disease. Arch Ophthalmol 84:451–452PubMedCrossRefGoogle Scholar
  38. 38.
    Yazici H, Pazarli H, Barnes CG et al (1990) A controlled trial of azathioprine in Behçet’s syndrome. N Engl J Med 322:281–285PubMedCrossRefGoogle Scholar
  39. 39.
    Hamuryudan V, Ozyazgan Y, Hizli N et al (1997) Azathioprine in Behçet’s syndrome: effects on long-term prognosis. Arthritis Rheum 40:769–774PubMedCrossRefGoogle Scholar
  40. 40.
    BenEzra D, Cohen E, Chajek T et al (1988) Evaluation of conventional therapy versus cyclosporine A in Behçet’s syndrome. Transplant Proc 20(3 Suppl 4):136–143PubMedGoogle Scholar
  41. 41.
    Masuda K, Nakajima A, Urayama A, Nakae K, Kogure M, Inaba G (1989) Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behçet’s disease. Lancet 1:1093–1096PubMedCrossRefGoogle Scholar
  42. 42.
    Ozyazgan Y, Yurdakul S, Yazici H et al (1992) Low dose cyclosporin A versus pulsed cyclophosphamide in Behçet’s syndrome: a single masked trial. Br J Ophthalmol 76:241–243PubMedCrossRefGoogle Scholar
  43. 43.
    Hatemi G, Silman A, Bang D et al (2008) Management of Behçet’s disease: a systematic literature review for the EULAR evidence based recommendations for the management of Behçet’s disease. Ann Rheum Dis 68:1528–1534PubMedCrossRefGoogle Scholar
  44. 44.
    Sfikakis PP, Markomichelakis N, Alpsoy E et al (2007) Anti-TNF therapy in the management of Behçet’s disease – review and basis for recommendations. Rheumatology (Oxford) 46:736–741CrossRefGoogle Scholar
  45. 45.
    Sfikakis PP, Theodossiadis PG, Katsiari CG, Kaklamanis P, Markomichelakis NN (2001) Effect of infliximab on sight-threatening panuveitis in Behçet’s disease. Lancet 358:295–296PubMedCrossRefGoogle Scholar
  46. 46.
    Tugal-Tutkun I, Mudun A, Urgancioglu M et al (2005) Efficacy of infliximab in the treatment of uveitis that is resistant to treatment with the combination of azathioprine, cyclosporine, and corticosteroids in Behçet’s disease: an open-label trial. Arthritis Rheum 52:2478–2484PubMedCrossRefGoogle Scholar
  47. 47.
    Sfikakis PP, Kaklamanis PH, Elezoglou A et al (2004) Infliximab for recurrent, sight-threatening ocular inflammation in Adamantiades-Behçet’s disease. Ann Intern Med 140:404–406PubMedGoogle Scholar
  48. 48.
    Ohno S, Nakamura S, Hori S et al (2004) Efficacy, safety, and pharmacokinetics of multiple administration of infliximab in Behçet’s disease with refractory uveoretinitis. J Rheumatol 31:1362–1368PubMedGoogle Scholar
  49. 49.
    Tabbara KF, Al-Hemidan AI (2008) Infliximab effects compared to conventional therapy in the management of retinal vasculitis in Behçet’s disease. Am J Ophthalmol 146:845.e1–850.e1Google Scholar
  50. 50.
    Bodaghi B, Bui Quoc E, Wechsler B et al (2005) Therapeutic use of infliximab in sight threatening uveitis: retrospective analysis of efficacy, safety, and limiting factors. Ann Rheum Dis 64:962–964PubMedCrossRefGoogle Scholar
  51. 51.
    Niccoli L, Nannini C, Benucci M et al (2007) Long-term efficacy of infliximab in refractory posterior uveitis of Behçet’s disease: a 24-month follow-up study. Rheumatology (Oxford) 46:1161–1164CrossRefGoogle Scholar
  52. 52.
    Mushtaq B, Saeed T, Situnayake RD, Murray PI (2007) Adalimumab for sight-threatening uveitis in Behçet’s disease. Eye 21:824–825PubMedCrossRefGoogle Scholar
  53. 53.
    van Laar JA, Missotten T, van Daele PL, Jamnitski A, Baarsma GS, van Hagen PM (2007) Adalimumab: a new modality for Behçet’s disease? Ann Rheum Dis 66:565–566PubMedCrossRefGoogle Scholar
  54. 54.
    Melikoglu M, Fresko I, Mat C et al (2005) Short-term trial of etanercept in Behçet’s disease: a double blind, placebo controlled study. J Rheumatol 32:98–105PubMedGoogle Scholar
  55. 55.
    Durand JM, Soubeyrand J (1994) Interferon-alpha 2b for refractory ocular Behçet’s disease. Lancet 344:333PubMedCrossRefGoogle Scholar
  56. 56.
    Feron EJ, Rothova A, van Hagen PM, Baarsma GS, Suttorp-Schulten MS (1994) Interferon-alpha 2b for refractory ocular Behçet’s disease. Lancet 343:1428PubMedCrossRefGoogle Scholar
  57. 57.
    Pivetti-Pezzi P, Accorinti M, Pirraglia MP, Priori R, Valesini G (1997) Interferon alpha for ocular Behçet’s disease. Acta Ophthalmol Scand 75:720–722PubMedCrossRefGoogle Scholar
  58. 58.
    Sánchez Román J, Pulido Aguilera MC, Castillo Palma MJ et al (1996) [The use of interferon alfa-2r in the treatment of autoimmune uveitis (primary or associated with Behçet’s disease)]. Rev Clin Esp 196:293–298PubMedGoogle Scholar
  59. 59.
    Kötter I, Eckstein AK, Stübiger N, Zierhut M (1998) Treatment of ocular symptoms of Behçet’s disease with interferon alpha 2a: a pilot study. Br J Ophthalmol 82:488–494PubMedCrossRefGoogle Scholar
  60. 60.
    Kotter I, Deuter C, Stubiger N, Zierhut M (2005) Interferon-a (IFN-a) application versus tumor necrosis factor-a antagonism for ocular Behçet’s disease: focusing more on IFN. J Rheumatol 32:1633PubMedGoogle Scholar
  61. 61.
    Kötter I, Vonthein R, Zierhut M et al (2004) Differential efficacy of human recombinant interferon-alpha2a on ocular and extraocular manifestations of Behçet’s disease: results of an open 4-center trial. Semin Arthritis Rheum 33:311–319PubMedCrossRefGoogle Scholar
  62. 62.
    Kötter I, Zierhut M, Eckstein A et al (2003) Human recombinant interferon-alpha2a (rhIFN alpha2a) for the treatment of Behçet’s disease with sight-threatening retinal vasculitis. Adv Exp Med Biol 528:521–523PubMedCrossRefGoogle Scholar
  63. 63.
    Kötter I, Zierhut M, Eckstein AK et al (2003) Human recombinant interferon alfa-2a for the treatment of Behçet’s disease with sight threatening posterior or panuveitis. Br J Ophthalmol 87:423–431PubMedCrossRefGoogle Scholar
  64. 64.
    Bodaghi B, Gendron G, Wechsler B et al (2007) Efficacy of interferon alpha in the treatment of refractory and sight threatening uveitis: a retrospective monocentric study of 45 patients. Br J Ophthalmol 91:335–339PubMedCrossRefGoogle Scholar
  65. 65.
    Krause L, Turnbull JR, Torun N, Pleyer U, Zouboulis CC, Foerster MH (2003) Interferon alfa-2a in the treatment of ocular Adamantiades-Behçet’s disease. Adv Exp Med Biol 528:511–519PubMedCrossRefGoogle Scholar
  66. 66.
    Tugal-Tutkun I, Güney-Tefekli E, Urgancioglu M (2006) Results of interferon-alfa therapy in patients with Behçet’s uveitis. Graefes Arch Clin Exp Ophthalmol 244:1692–1695PubMedCrossRefGoogle Scholar
  67. 67.
    Gueudry J, Wechsler B, Terrada C et al (2008) Long-term efficacy and safety of low-dose interferon alpha2a therapy in severe uveitis associated with Behçet’s disease. Am J Ophthalmol 146:837.e1–844.e1CrossRefGoogle Scholar
  68. 68.
    Buggage RR, Levy-Clarke G, Sen HN et al (2007) A double-masked, randomized study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behçet’s disease. Ocul Immunol Inflamm 15:63–70PubMedCrossRefGoogle Scholar
  69. 69.
    Atmaca LS, Yalcindag FN, Ozdemir O (2007) Intravitreal triamcinolone acetonide in the management of cystoid macular edema in Behçet’s disease. Graefes Arch Clin Exp Ophthalmol 245:451–456PubMedCrossRefGoogle Scholar
  70. 70.
    Karacorlu M, Mudun B, Ozdemir H, Karacorlu SA, Burumcek E (2004) Intravitreal triamcinolone acetonide for the treatment of cystoid macular edema secondary to Behçet’s disease. Am J Ophthalmol 138:289–291PubMedCrossRefGoogle Scholar
  71. 71.
    Ohguro N, Yamanaka E, Otori Y, Saishin Y, Tano Y (2006) Repeated intravitreal triamcinolone injections in Behçet’s disease that is resistant to conventional therapy: one-year results. Am J Ophthalmol 141:218–220PubMedCrossRefGoogle Scholar
  72. 72.
    Oueghlani E, Pavesio CE (2008) Intravitreal triamcinolone injection for unresponsive cystoid macular oedema in probable Behçet’s disease as an additional therapy. Klin Monatsbl Augenheilkd 225:497–499PubMedCrossRefGoogle Scholar
  73. 73.
    Tuncer S, Yilmaz S, Urgancioglu M, Tugal-Tutkun I (2007) Results of intravitreal triamcinolone acetonide (IVTA) injection for the treatment of panuveitis attacks in patients with Behçet’s disease. J Ocul Pharmacol Ther 23:395–401PubMedCrossRefGoogle Scholar
  74. 74.
    Saidel MA, Berreen J, Margolis TP (2005) Cytomegalovirus retinitis after intravitreous triamcinolone in an immunocompetent patient. Am J Ophthalmol 140:1141–1143PubMedCrossRefGoogle Scholar
  75. 75.
    Mirshahi A, Namavari A, Djalilian A, Moharamzad Y, Chams H (2009) Intravitreal bevacizumab (Avastin) for the treatment of cystoid macular edema in Behçet’s disease. Ocul Immunol Inflamm 17:59–64PubMedCrossRefGoogle Scholar
  76. 76.
    Erdurman FC, Durukan AH, Mumcuoglu T, Hürmeric V (2009) Intravitreal bevacizumab treatment of macular edema due to optic disc vasculitis. Ocul Immunol Inflamm 17:56–58PubMedCrossRefGoogle Scholar
  77. 77.
    Elgin U, Berker N, Batman A, Soykan E (2007) Nd:YAG laser iridotomy in the management of secondary glaucoma associated with Behçet’s disease. Eur J Ophthalmol 17:191–195PubMedGoogle Scholar
  78. 78.
    Elgin U, Berker N, Batman A, Soykan E (2007) Trabeculectomy with mitomycin C in econdary glaucoma associated with Behçet’s disease. J Glaucoma 16:68–72PubMedCrossRefGoogle Scholar
  79. 79.
    Berker N, Soykan E, Elgin U, Ozkan SS (2004) Phacoemulsification cataract extraction and intraocular lens implantation in patients with Behçet’s disease. Ophthalmic Surg Lasers Imaging 35:215–218PubMedGoogle Scholar
  80. 80.
    Kadayifcilar S, Gedik S, Eldem B, Irkec M (2002) Cataract surgery in patients with Behçet’s disease. J Cataract Refract Surg 28:316–320PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Ophthalmology, Cerrahpasa Medical FacultyUniversity of IstanbulIstanbulTurkey

Personalised recommendations