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Eye Disease in Behçet Syndrome

  • Yılmaz ÖzyazganEmail author
  • Ilknur Tugal-Tutkun
Chapter

Abstract

Ocular involvement is the main cause of morbidity in Behçet 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, redness, 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 synechiae, secondary glaucoma, and cataract. Vitreal inflammatory signs in the form of haze and 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. During activations, funduscopic examination may show vitreal deposits, retinal infiltrates, retinal edema, hemorrhages, and macular edema. In advanced stages, the visual loss becomes permanent and sheathing of blood vessels, ghost vessels, atrophic and pigmentary macular changes, and optic atrophy are seen. Visual prognosis of BS has dramatically improved in the last two to three decades by better use of conventional immunosuppressives such as cyclosporine and azathioprine and more recently biologics like anti-TNF alpha agents and interferon alpha. Ophthalmic surgery for secondary cataract and glaucoma as well as for vitreoretinal complications has also become much more successful.

Keywords

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

References

  1. 1.
    Sakane T, Takeno M, Suzuki N, Inaba G. Behçet’s disease. N Engl J Med. 1999;341:1284–91.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Yazici H, Tüzün Y, Pazarli H, et al. Influence of age of onset and patient’s sex on the prevalence and severity of manifestations of Behçet’s syndrome. Ann Rheum Dis. 1984;43:783–9.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Yalçındağ FN, Özdal PC, Özyazgan Y, et al. Demographic and clinical characteristics of uveitis in Turkey: The First National Registry Report. Ocul Immunol Inflamm. 2018;26:17–26.PubMedCrossRefGoogle Scholar
  4. 4.
    Mishima S, Masuda K, Izawa Y, et al. Behçet’s disease in Japan: ophthalmologic aspects. Trans Am Ophthalmol Soc. 1979;76:225–79.Google Scholar
  5. 5.
    Goto H, Mochizuki M, Yamaki K, et al. Epidemiological survey of intraocular inflammation in Japan. Jpn J Ophthalmol. 2007;51:41–4.CrossRefGoogle Scholar
  6. 6.
    Rodriguez A, Calonge M, Pedroza-Serez M, et al. Referral patterns of uveitis in a tertiary eye care center. Arch Ophthalmol. 1996;114:593–9.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Kural-Seyahi E, Fresko I, Seyahi N, et al. The long-term mortality and morbidity of Behçet’s syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine. 2003;82:60–76.PubMedCrossRefGoogle Scholar
  8. 8.
    Tugal-Tutkun I, Onal S, Altan Yaycıoglu R, et al. Uveitis in Behçet’s disease: an analysis of 880 patients. Am J Ophthalmol. 2004;138:373–80.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Tunc R, Keyman E, Melikoglu M, Fresko I, Yazici H. Target organ associations in Turkish patients with Behçet’s disease: a cross sectional study with exploratory factor analysis. J Rheumatol. 2002;29:2393–6.Google Scholar
  10. 10.
    Nussenblatt RB, Whitcup SM, Paletsine AG. Behçet’s disease. In: Nussenblatt RB, Whitcup SM, Paletsine AG, editors. Uveitis: fundamentals and clinical practice. Philadelphia: Mosby; 2004. p. 350–71.Google Scholar
  11. 11.
    Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005;140:509–16.PubMedCrossRefGoogle Scholar
  12. 12.
    George RK, Chan CC, Whitcup SM, et al. Ocular immunopathology of Behçet’s disease. Surv Ophthalmol. 1997;42:157–62.PubMedCrossRefGoogle Scholar
  13. 13.
    Ramsay A, Lightman S. Hypopyon uveitis. Surv Ophthalmol. 2001;46:1–18.PubMedCrossRefGoogle Scholar
  14. 14.
    Pazarlı H, Ozyazgan Y, Aktunc T. Clinical observations on hypopyon attacks of Behçet’s disease in Turkey. In: Seventh international conference on Behçet’s disease (abstracts), Rochester, MN, 14–15 Sept 1989.Google Scholar
  15. 15.
    Tugal-Tutkun I, Urgancioglu M, Foster CS. Immunopathologic study of the conjunctiva in patients with Behçet’s disease. Ophthalmology. 1995;102:1660–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Zamir E, Bodaghi B, Tugal-Tutkun I, et al. Conjunctival ulcers in Behçet’s disease. Ophthalmology. 2003;110:1137–41.PubMedCrossRefGoogle Scholar
  17. 17.
    Elgin U, Berker N, Batman A. Incidence of secondary glaucoma in Behçet’s disease. J Glaucoma. 2004;13:441–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Yalvaç IS, Sungur G, Turhan E, et al. Trabeculectomy with mitomycin-C in uveitic glaucoma associated with Behçet’s disease. J Glaucoma. 2004;13:450–3.PubMedCrossRefGoogle Scholar
  19. 19.
    Baer JC, Raizman MB, Foster CS. Ocular Behçet’s disease in the United States: clinical presentation and visual outcome in 29 patients. In: Masahiko U, Shigeaki O, Koki A, editors. Proceedings of the 5th international symposium on the immunology and immunopathology of the eye, Tokyo. New York: Elsevier Science; 1990. p. 383.Google Scholar
  20. 20.
    Ehrlich GE. Vasculitis in Behçet’s disease. Int Rev Immunol. 1997;14:81–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Akman-Demir G, Serdaroglu P, Tasci B. Clinical patterns of neurological involvement in Behçet’s disease: evaluation of 200 patients. The Neuro-Behçet’s Study Group. Brain. 1999;122:2171–82.CrossRefGoogle Scholar
  22. 22.
    Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, et al. Neovascularization of the optic disc in Behçet’s disease. Jpn J Ophthalmol. 2006;50:256–65.PubMedCrossRefGoogle Scholar
  23. 23.
    Foster CS, Vitale AT. Adamantiades-Behçet’s disease. In: Foster CS, Vitale AT, editors. Diagnosis and treatment of uveitis. Philadelphia: W.B. Saunders; 2002. p. 632–52.Google Scholar
  24. 24.
    Kacmaz RO, Kempen JH, Newcomb C, Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study Group, et al. Ocular inflammation in Behçet’s disease: incidence of ocular complications and of loss of visual acuity. Am J Ophthalmol. 2008;146:828–36.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Tugal-Tutkun I, Ozdal PC, Oray M, Onal S. Review for diagnostics of the year: multimodal imaging in Behçet uveitis. Ocul Immunol Inflamm. 2017;25:7–19.PubMedCrossRefGoogle Scholar
  26. 26.
    Atmaca LS. Fundus changes associated with Behçet’s disease. Graefes Arch Clin Exp Ophthalmol. 1989;227:340–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Mesquida M, Llorenç V, Fontenla JR, et al. Use of ultrawide-field retinal imaging in the management of active Behçet retinal vasculitis. Retina. 2014;34:2121–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Bozzoni-Pantaleoni F, Gharbiya M, Pirraglia MP, et al. Indocyanine green angiographic findings in Behçet’s disease. Retina. 2001;21:230–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Atmaca LS, Sönmez PA. Fluorescein and indocyanine green angiography findings in Behçet’s disease. Br J Ophthalmol. 2003;87:1466–8.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Gedik S, Akova YA, Yılmaz G, et al. Indocyanine green and fundus fluorescein angiographic findings in patients with active ocular Behçet’s disease. Ocul Immunol Inflamm. 2005;13:51–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Onal S, Uludag G, Oray M, et al. Quantitative analysis of structural alterations in the choroid of patients with active Behçet uveitis. Retina. 2018;38:828–40.PubMedCrossRefGoogle Scholar
  32. 32.
    Yesilirmak N, Lee WH, Gur Gungor S, et al. Enhanced depth imaging optical coherence tomography in patients with different phases of Behcet’s panuveitis. Can J Ophthalmol. 2017;52:48–53.PubMedCrossRefGoogle Scholar
  33. 33.
    Khairallah M, Abroug N, Khochtali S, et al. Optical coherence tomography angiography in patients with Behçet uveitis. Retina. 2017;37:1678–91.PubMedCrossRefGoogle Scholar
  34. 34.
    Somkijrungroj T, Vongkulsiri S, Kongwattananon W, et al. Assessment of vascular change using swept-source optical coherence tomography angiography: a new theory explains central visual loss in Behcet’s disease. J Ophthalmol. 2017;2017:2180723.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Winter FC, Yukins RE. The ocular pathology of Behçet’s disease. Am J Ophthalmol. 1966;62:257–62.PubMedCrossRefGoogle Scholar
  36. 36.
    Mullaney J, Collum LM. Ocular vasculitis in Behçet’s disease: a pathological and immunohistochemical study. Int Ophthalmol. 1985;7:183–91.PubMedCrossRefGoogle Scholar
  37. 37.
    Hegab S, Al-Mutawa S. Immunopathogenesis of Behçet’s disease. Clin Immunol. 2000;96:174–86.PubMedCrossRefGoogle Scholar
  38. 38.
    Atmaca LS, Batioglu F, Idil A. Retinal and disc neovascularization in Behçet’s disease and efficacy of laser photocoagulation. Graefes Arch Clin Exp Ophthalmol. 1996;234:94–9.PubMedCrossRefGoogle Scholar
  39. 39.
    El Belhadji M, Hamdani M, Laouissi N, et al. L’attente ophthalmologique dans la maladie d Behçet: a propos de 520 cas. J Fr Ophthalmol. 1997;20:592–8.Google Scholar
  40. 40.
    Ando K, Fujino Y, Hijikata K, et al. Epidemiological features and visual prognosis of visual prognosis of Behçet’s disease. Jpn J Ophthalmol. 1999;43:312–7.CrossRefGoogle Scholar
  41. 41.
    Sakamoto M, Akazawa K, Nishioka Y, et al. Prognostic factors of vision in patients with Behçet’s disease. Ophthalmology. 1995;102:317–21.CrossRefGoogle Scholar
  42. 42.
    Nussenblatt RB, Pelestine AG, Chan CC, et al. Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology. 1985;92:467–71.PubMedCrossRefGoogle Scholar
  43. 43.
    Davis JL, Madow B, Cornett J, et al. Scale for photographic grading of vitreous haze in uveitis. Am J Ophthalmol. 2010;150:637–41.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Tugal-Tutkun I, Cingu K, Kir N, et al. Use of laser flare-cell photometry to quantify intraocular inflammation in patients with Behçet’s uveitis. Graefes Arch Clin Exp Ophthalmol. 2008;246:1169–77.PubMedCrossRefGoogle Scholar
  45. 45.
    Kaburaki T, Namba K, Sonoda KH, et al. Behcet’s disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab. Jpn J Ophthalmol. 2014;58:120–30.PubMedCrossRefGoogle Scholar
  46. 46.
    Yalcindag FN, Bingol Kiziltunc P, Savku E. Evaluation of intraocular inflammation with laser flare photometry in Behçet uveitis. Ocul Immunol Inflamm. 2017;25:41–5.PubMedCrossRefGoogle Scholar
  47. 47.
    Hatemi G, Silman A, Bang D, et al. 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. 2008;68:1528–34.PubMedCrossRefGoogle Scholar
  48. 48.
    Levy-Clarke G, Jabs DA, Read RW, et al. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology. 2014;121:785–96.CrossRefGoogle Scholar
  49. 49.
    Onal S, Tugal-Tutkun I. Re: Levy-Clarke et al.: Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders (Ophthalmology 2014;121:785–96). Ophthalmology. 2014;121(10):e57–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Palestine AG, Kolfenbach JR, Ozzello DJ. Rheumatologists and ophthalmologists differ in treatment decisions for ocular Behçet disease. J Clin Rheumatol. 2016;22:316–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Hatemi G, Christensen R, Bang D, et al. 2018 update of the EULAR recommendations for the management of Behçet’s syndrome. Ann Rheum Dis. 2018;77:808.Google Scholar
  52. 52.
    Yazici H, Pazarli H, Barnes CG, et al. A controlled trial of azathioprine in Behçet’s syndrome. N Engl J Med. 1990;322:281–5.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Hamuryudan V, Ozyazgan Y, Hizli N, et al. Azathioprine in Behçet’s syndrome: effects on long-term prognosis. Arthritis Rheum. 1997;40:769–74.CrossRefGoogle Scholar
  54. 54.
    BenEzra D, Cohen E, Chajek T, et al. Evaluation of conventional therapy versus cyclosporine A in Behçet’s syndrome. Transplant Proc. 1988;20(3 Suppl 4):136–43.Google Scholar
  55. 55.
    Masuda K, Nakajima A, Urayama A, et al. Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behçet’s disease. Lancet. 1989;1:1093–6.CrossRefGoogle Scholar
  56. 56.
    Ozyazgan Y, Yurdakul S, Yazici H, et al. Low dose cyclosporin A versus pulsed cyclophosphamide in Behçet’s syndrome: a single masked trial. Br J Ophthalmol. 1992;76:241–3.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Akman-Demir G, Ayranci O, Kurtuncu M, et al. Cyclosporine for Behçet’s uveitis: is it associated with an increased risk of neurological involvement? Clin Exp Rheumatol. 2008;26(Suppl 50):S84–90.PubMedGoogle Scholar
  58. 58.
    Durand JM, Soubeyrand J. Interferon-alpha 2b for refractory ocular Behçet’s disease. Lancet. 1994;344:333.PubMedCrossRefGoogle Scholar
  59. 59.
    Feron EJ, Rothova A, van Hagen PM, Baarsma GS, Suttorp-Schulten MS. Interferon-alpha 2b for refractory ocular Behçet’s disease. Lancet. 1994;343:1428.PubMedCrossRefGoogle Scholar
  60. 60.
    Kötter I, Eckstein AK, Stübiger N, Zierhut M. Treatment of ocular symptoms of Behçet’s disease with interferon alpha 2a: a pilot study. Br J Ophthalmol. 1998;82:488–94.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Kötter I, Zierhut M, Eckstein AK, et al. Human recombinant interferon alfa-2a for the treatment of Behçet’s disease with sight threatening posterior or panuveitis. Br J Ophthalmol. 2003;87:423–31.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Bodaghi B, Gendron G, Wechsler B, et al. Efficacy of interferon alpha in the treatment of refractory and sight threatening uveitis: a retrospective monocentric study of 45 patients. Br J Ophthalmol. 2007;91:335–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Krause L, Turnbull JR, Torun N, et al. Interferon alfa-2a in the treatment of ocular Adamantiades-Behçet’s disease. Adv Exp Med Biol. 2003;528:511–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Tugal-Tutkun I, Güney-Tefekli E, Urgancioglu M. Results of interferon-alfa therapy in patients with Behçet’s uveitis. Graefes Arch Clin Exp Ophthalmol. 2006;244:1692–5.PubMedCrossRefGoogle Scholar
  65. 65.
    Yang P, Huang G, Du L, et al. Long-term efficacy and safety of interferon alpha-2a in the treatment of Chinese patients with Behçet’s uveitis not responding to conventional therapy. Ocul Immunol Inflamm. 2019;27:7–14.PubMedCrossRefGoogle Scholar
  66. 66.
    Shi J, Zhao C, Zhou J, et al. Effectiveness and safety of interferon a2a as an add-on treatment for refractory Behçet’s uveitis. Ther Adv Chronic Dis. 2019;10:1–9.CrossRefGoogle Scholar
  67. 67.
    Gueudry J, Wechsler B, Terrada C, et al. Long-term efficacy and safety of low-dose interferon alpha2a therapy in severe uveitis associated with Behçet’s disease. Am J Ophthalmol. 2008;146:837–44.e1.PubMedCrossRefGoogle Scholar
  68. 68.
    Sobaci G, Erdem U, Durukan AH, et al. Safety and effectiveness of interferon alpha-2a in treatment of patients with Behçet’s uveitis refractory to conventional treatments. Ophthalmology. 2010;117:1430–5.PubMedCrossRefGoogle Scholar
  69. 69.
    Onal S, Kazokoglu H, Koc A, et al. Long-term efficacy and safety of low-dose and dose-escalating interferon alfa-2a therapy in refractory Behçet uveitis. Arch Ophthalmol. 2011;129:288–94.PubMedCrossRefGoogle Scholar
  70. 70.
    Deuter CME, Zierhut M, Mohle A, et al. Long-term remission after cessation of interferon-a treatment in patients with severe uveitis due to Behçet’s disease. Arthritis Rheum. 2010;62:2796–805.PubMedCrossRefGoogle Scholar
  71. 71.
    Diwo E, Gueudry J, Saadoun D, et al. Long-term efficacy of interferon in severe uveitis associated with Behçet disease. Ocul Immunol Inflamm. 2017;25:76–84.CrossRefGoogle Scholar
  72. 72.
    Keskin Y, Seyahi E, Poyraz C, et al. Interferon alfa-associated depression in patients with Behçet’s syndrome: a prospective controlled study. Clin Exp Rheumatol. 2014;32(4 Suppl 84):S175.PubMedGoogle Scholar
  73. 73.
    Sfikakis PP, Theodossiadis PG, Katsiari CG, et al. Effect of infliximab on sight-threatening panuveitis in Behçet’s disease. Lancet. 2001;358:295–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Tugal-Tutkun I, Mudun A, Urgancioglu M, et al. 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. 2005;52:2478–84.CrossRefGoogle Scholar
  75. 75.
    Sfikakis PP, Kaklamanis PH, Elezoglou A, et al. Infliximab for recurrent, sight-threatening ocular inflammation in Adamantiades-Behçet’s disease. Ann Intern Med. 2004;140:404–6.CrossRefGoogle Scholar
  76. 76.
    Ohno S, Nakamura S, Hori S, et al. Efficacy, safety, and pharmacokinetics of multiple administration of infliximab in Behçet’s disease with refractory uveoretinitis. J Rheumatol. 2004;31:1362–8.Google Scholar
  77. 77.
    Okada AA, Goto H, Ohno S, Mochizuki M, Ocular Behçet’s Disease Research Group of Japan. Multicenter study of infliximab for refractory uveoretinitis in Behçet’s disease. Arch Ophthalmol. 2012;130:592–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Abu El-Asrar AM, Abboud EB, Aldibhi H, et al. Long-term safety and efficacy of infliximab therapy in refractory uveitis due to Behçet’s disease. Int Ophthalmol. 2005;26:83–92.PubMedCrossRefGoogle Scholar
  79. 79.
    Niccoli L, Nannini C, Benucci M, et al. Long-term efficacy of infliximab in refractory posterior uveitis of Behçet’s disease: a 24-month follow-up study. Rheumatology (Oxford). 2007;46:1161–4.CrossRefGoogle Scholar
  80. 80.
    Bodaghi B, Bui Quoc E, Wechsler B, et al. Therapeutic use of infliximab in sight threatening uveitis: retrospective analysis of efficacy, safety, and limiting factors. Ann Rheum Dis. 2005;64:962–4.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Tabbara KF, Al-Hemidan AI. Infliximab effects compared to conventional therapy in the management of retinal vasculitis in Behçet’s disease. Am J Ophthalmol. 2008;146:845.e1–50.e1.Google Scholar
  82. 82.
    Capella MJ, Foster CS. Long-term efficacy and safety of infliximab in the treatment of Behçet’s disease. Ocul Immunol Inflamm. 2012;20:198–202.PubMedCrossRefGoogle Scholar
  83. 83.
    Takeuchi M, Asukata Y, Kawagoe T, et al. Infliximab monotherapy versus infliximab and colchicine combination therapy in patients with Behcet’s disease. Ocul Immunol Inflamm. 2012;20:193–7.PubMedCrossRefGoogle Scholar
  84. 84.
    Keino H, Okada AA, Watanabe T, Taki W. Decreased ocular inflammatory attacks and background retinal and disc vascular leakage in patients with Behçet’s disease on infliximab therapy. Br J Ophthalmol. 2011;95:1245–50.PubMedCrossRefGoogle Scholar
  85. 85.
    Guzelant G, Ucar D, Esatoglu SN, et al. Infliximab for uveitis of Behçet’s syndrome: a trend for earlier initiation. Clin Exp Rheumatol. 2017;35 Suppl 108(6):86–9.Google Scholar
  86. 86.
    Fabiani C, Sota J, Vitale A, et al. Ten-year retention rate of infliximab in patients with Behçet’s disease-related uveitis. Ocul Immunol Inflamm. 2019;27:34–9.  https://doi.org/10.1080/09273948.2017.1391297.CrossRefPubMedGoogle Scholar
  87. 87.
    Bawazeer A, Raffa LH, Nizamuddin SH. Clinical experience with adalimumab in the treatment of ocular Behçet disease. Ocul Immunol Inflamm. 2010;18:226–32.PubMedCrossRefGoogle Scholar
  88. 88.
    Fabiani C, Vitale A, Emmi G, et al. Efficacy and safety of adalimumab in Behçet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol. 2017;36:183–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Fabiani C, Sota J, Vitale A, et al. Cumulative retention rate of adalimumab in patients with Behçet’s disease-related uveitis: a four-year follow-up study. Br J Ophthalmol. 2018;102:637–41.PubMedCrossRefGoogle Scholar
  90. 90.
    Jaffe GJ, Dick AD, Brézin AP, et al. Adalimumab in patients with active noninfectious uveitis. N Engl J Med. 2016;375:932–43.CrossRefGoogle Scholar
  91. 91.
    Nguyen QD, Merrill PT, Jaffe GJ, et al. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet. 2016;388:1183–92.CrossRefGoogle Scholar
  92. 92.
    Fabiani C, Sota J, Rigante D, et al. Rapid and sustained efficacy of golimumab in the treatment of multirefractory uveitis associated with Behçet’s disease. Ocul Immunol Inflamm. 2019;27:58–63.  https://doi.org/10.1080/09273948.2017.1351573.CrossRefPubMedGoogle Scholar
  93. 93.
    Llorenç V, Mesquida M, Sainz de la Maza M, et al. Certolizumab Pegol, a new anti-TNF-αin the armamentarium against ocular inflammation. Ocul Immunol Inflamm. 2016;24:167–72.PubMedGoogle Scholar
  94. 94.
    Lopalco G, Emmi G, Gentileschi S, et al. Certolizumab Pegol treatment in Behcet’s disease with different organ involvement: a multicenter retrospective observational study. Mod Rheumatol. 2017;27:1031–5.CrossRefGoogle Scholar
  95. 95.
    Atienza-Mateo B, Calvo-Río V, Beltrán E, et al. Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behçet’s disease: multicentre retrospective study. Rheumatology (Oxford). 2018;57:856–64.CrossRefGoogle Scholar
  96. 96.
    Eser Ozturk H, Oray M, Tugal-Tutkun I. Tocilizumab for the treatment of Behçet uveitis that failed interferon alpha and anti-tumor necrosis factor-alpha therapy. Ocul Immunol Inflamm. 2018;26:1005–14.PubMedCrossRefGoogle Scholar
  97. 97.
    Cantarini L, Vitale A, Scalini P, et al. Anakinra treatment in drug-resistant Behcet’s disease: a case series. Clin Rheumatol. 2015;34:1293–301.CrossRefGoogle Scholar
  98. 98.
    Fabiani C, Vitale A, Emmi G, et al. Interleukin (IL)-1 inhibition with anakinra and canakinumab in Behçet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol. 2017;36:191–7.CrossRefGoogle Scholar
  99. 99.
    Tugal-Tutkun I, Pavesio C, De Cordoue A, et al. Use of gevokizumab in patients with Behçet’s disease uveitis: an international, randomized, double-masked, placebo-controlled study and open-label extension study. Ocul Immunol Inflamm. 2018;26:1023–33.PubMedCrossRefGoogle Scholar
  100. 100.
    Gül A, Tugal-Tutkun I, Dinarello CA, et al. Interleukin-1β-regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behcet’s disease: an open-label pilot study. Ann Rheum Dis. 2012;71:563–6.PubMedCrossRefGoogle Scholar
  101. 101.
    Tugal-Tutkun I, Kadayifcilar S, Khairallah M, et al. Safety and efficacy of gevokizumab in patients with Behçet’s disease uveitis: results of an exploratory phase 2 study. Ocul Immunol Inflamm. 2017;25:62–70.CrossRefGoogle Scholar
  102. 102.
    Buggage RR, Levy-Clarke G, Sen HN, et al. 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. 2007;15:63–70.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Dick AD, Tugal-Tutkun I, Foster S, et al. Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology. 2013;120:777–87.PubMedCrossRefGoogle Scholar
  104. 104.
    Tuncer S, Yilmaz S, Urgancioglu M, Tugal-Tutkun I. Results of intravitreal triamcinolone acetonide (IVTA) injection for the treatment of panuveitis attacks in patients with Behçet’s disease. J Ocul Pharmacol Ther. 2007;23:395–401.PubMedCrossRefGoogle Scholar
  105. 105.
    Park UC, Park JH, Yu HG. Long-term outcome of intravitreal triamcinolone acetonide injection for the treatment of uveitis attacks in Behçet disease. Ocul Immunol Inflamm. 2014;22:27–33.PubMedCrossRefGoogle Scholar
  106. 106.
    Atmaca LS, Yalcindag FN, Ozdemir O. Intravitreal triamcinolone acetonide in the management of cystoid macular edema in Behçet’s disease. Graefes Arch Clin Exp Ophthalmol. 2007;245:451–6.PubMedCrossRefGoogle Scholar
  107. 107.
    Karacorlu M, Mudun B, Ozdemir H, Karacorlu SA, Burumcek E. Intravitreal triamcinolone acetonide for the treatment of cystoid macular edema secondary to Behçet’s disease. Am J Ophthalmol. 2004;138:289–91.PubMedCrossRefGoogle Scholar
  108. 108.
    Ohguro N, Yamanaka E, Otori Y, Saishin Y, Tano Y. Repeated intravitreal triamcinolone injections in Behçet’s disease that is resistant to conventional therapy: one-year results. Am J Ophthalmol. 2006;141:218–20.PubMedCrossRefGoogle Scholar
  109. 109.
    Tugal-Tutkun I, Araz B, Cagatay A. CMV retinitis after intravitreal triamcinolone acetonide injection in a patient with Behçet’s uveitis. Int Ophthalmol. 2010;30:591–3.PubMedCrossRefGoogle Scholar
  110. 110.
    Coşkun E, Celemler P, Kimyon G, et al. Intravitreal dexamethasone implant for treatment of refractory Behçet posterior uveitis: one-year follow-up results. Ocul Immunol Inflamm. 2015;23:437–43.PubMedCrossRefGoogle Scholar
  111. 111.
    Fabiani C, Emmi G, Lopalco G, et al. Intravitreal dexamethasone implant as an adjunct weapon for severe and refractory uveitis in Behçet’s disease. Isr Med Assoc J. 2017;19:415–9.PubMedGoogle Scholar
  112. 112.
    Oh EK, Lee EK, Yu HG. Long-term results of fluocinolone acetonide intravitreal implant in Behçet intractable posterior uveitis. Can J Ophthalmol. 2014;49:273–8.PubMedCrossRefGoogle Scholar
  113. 113.
    Sangwan VS, Pearson PA, Paul H, Comstock TL. Use of the fluocinolone acetonide intravitreal implant for the treatment of noninfectious posterior uveitis: 3-year results of a randomized clinical trial in a predominantly Asian population. Ophthalmol Ther. 2015;4:1–19.PubMedCrossRefGoogle Scholar
  114. 114.
    Mirshahi A, Namavari A, Djalilian A, et al. Intravitreal bevacizumab (Avastin) for the treatment of cystoid macular edema in Behçet’s disease. Ocul Immunol Inflamm. 2009;17:59–64.PubMedCrossRefGoogle Scholar
  115. 115.
    Ghassemi F, Mirak SA, Chams H, et al. Characteristics of macular edema in Behcet disease after intravitreal bevacizumab injection. J Ophthalmic Vis Res. 2017;12:44–52.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Markomichelakis NN, Aissopou EK, Maselos S, et al. Biologic treatment options for retinal neovascularization in Behçet’s disease. Ocul Immunol Inflamm. 2019;27:51–7.  https://doi.org/10.1080/09273948.2017.1332228.CrossRefPubMedGoogle Scholar
  117. 117.
    Hu K, Lei B, Kijlstra A, Li P, et al. Male sex, erythema nodosum, and electroretinography as predictors of visual prognosis after cataract surgery in patients with Behçet disease. J Cataract Refract Surg. 2012;38:1382–8.PubMedCrossRefGoogle Scholar
  118. 118.
    Berker N, Soykan E, Elgin U, Ozkan SS. Phacoemulsification cataract extraction and intraocular lens implantation in patients with Behçet’s disease. Ophthalmic Surg Lasers Imaging. 2004;35:215–8.PubMedCrossRefGoogle Scholar
  119. 119.
    Krause L, Altenburg A, Bechrakis NE, et al. Intraocular surgery under systemic interferon-alpha therapy in ocular Adamantiades-Behçet’s disease. Graefes Arch Clin Exp Ophthalmol. 2007;245:1617–21.PubMedCrossRefGoogle Scholar
  120. 120.
    Alfawaz A, Alrashidi S, Kalantan H, et al. Cataract surgery under systemic infliximab therapy in patients with refractory uveitis associated with Behcet disease. Ann Saudi Med. 2014;34:328–33.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Nishida T, Shibuya E, Asukata Y, et al. Clinical course before and after cataract and glaucoma surgery under systemic infliximab therapy in patients with Behçet’s disease. Case Rep Ophthalmol. 2011;2:189–92.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Fan F, Jia Z, Li K, Zhao X, Ma Q. Cataract surgery combined with micro-incision vitrectomy in patients with Behcet’s disease uveitis. BMC Ophthalmol. 2018;18:158.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Komae K, Takamoto M, Tanaka R, et al. Initial trabeculectomy with mitomycin-c for secondary glaucoma-associated with uveitis in Behçet disease patients. J Glaucoma. 2017;26:603–7.PubMedCrossRefGoogle Scholar
  124. 124.
    Elgin U, Berker N, Batman A, Soykan E. Trabeculectomy with mitomycin C in secondary glaucoma associated with Behçet’s disease. J Glaucoma. 2007;16:68–72.PubMedCrossRefGoogle Scholar
  125. 125.
    Mesquida M, Pelegrín L, Llorenç V, et al. Pars plana vitrectomy for vitreoretinal complications of Behçet uveitis. Eur J Ophthalmol. 2013;23:119–28.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Ophthalmology, Cerrahpasa Medical FacultyIstanbul UniversityIstanbulTurkey
  2. 2.Department of Ophthalmology, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey

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