ABSTRACT
Behçet’s disease is a chronic, multisystem inflammatory disorder characterized by relapsing inflammation. Although its etiopathogenesis has not yet been clarified, both the adaptive and innate immune systems, genetic predisposition, and environmental factors have all been implicated. It is more frequent and more severe in males in the third and fourth decades of life. The eye is the most frequently involved organ in the course of the disease. Ocular involvement (Behçet’s uveitis) is characterized by bilateral recurrent non-granulomatous panuveitis and occlusive retinal vasculitis. Recurrent inflammatory episodes in the posterior segment may lead to permanent vision loss due to irreversible retinal damage and complications such as macular scarring, macular atrophy, and optic atrophy. Early and aggressive immunomodulatory treatment and the use of biologic agents when needed are crucial for preventing recurrences and improving visual prognosis.
Keywords:
Behçet’s uveitis, imaging, treatment, biologics, prognosis
Introduction
First identified by Turkish Dermatology Professor Hulusi Behçet in 1937, Behçet’s disease (BD) is a chronic, multisystemic vasculitis of unknown etiology that involves various organs and tissues and is characterized by inflammatory episodes.1,2 The skin, eyes, gastrointestinal tract, and central nervous system are among the affected organs, tissues, and systems. Ocular involvement is the most common vital organ involvement and has poor prognosis, potentially culminating in blindness despite many advances in diagnosis and treatment.
Conclusion
BU is the leading cause of non-infectious uveitis in Turkey. It is characterized by recurrent episodes of non-granulomatous panuveitis and occlusive retinal vasculitis. As it is more common among young adults and is potentially blinding, early diagnosis and potent treatment are crucial.
References
1
Tugal-Tutkun I. Behçet’s Uveitis. Middle East Afr J Ophthalmol. 2009;16:219-224.
2
Behçet H. Über rezidivierende aphthöse durch ein Virus verursachte Geschwüre am Mund, am Auge und an den Genitalien. Dermatol Wochenschr. 1937;105:1152-1157.
3
Keino H, Okada AA. Behçet’s disease: global epidemiology of an Old Silk Road disease. Br J Ophthalmol. 2007;91:1573-1574.
4
Khairallah M, Accorinti M, Muccioli C, Kahloun R, Kempen JH. Epidemiology of Behçet disease. Ocul Immunol Inflamm. 2012;20:324-335.
5
Azizlerli G, Köse AA, Sarica R, Gül A, Tutkun IT, Kulaç M, Tunç R, Urgancioğlu M, Dişçi R. Prevalence of Behçet’s disease in Istanbul, Turkey. Int J Dermatol. 2003;42:803-806.
6
Calamia KT, Wilson FC, Icen M, Crowson CS, Gabriel SE, Kremers HM. Epidemiology and clinical characteristics of Behçet’s disease in the US: a population-based study. Arthritis Rheum. 2009;61:600-604.
7
Tugal-Tutkun I, Urgancıoglu M. Childhood-onset uveitis in Behçet disease: a descriptive study of 36 cases. Am J Ophthalmol. 2003;136:1114-1119.
8
Yıldız M, Köker O, Adrovic A, Şahin S, Barut K, Kasapçopur Ö. Pediatric Behçet’s disease - clinical aspects and current concepts. Eur J Rheumatol. 2019;7(Suppl 1):1-10.
9
Kural-Seyahi E, Fresko I, Seyahi N, Ozyazgan Y, Mat C, Hamuryudan V, Yurdakul S, Yazici H. The long-term mortality and morbidity of Behçet syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine (Baltimore). 2003;82:60-76.
10
Yalçındağ FN, Özdal PC, Özyazgan Y, Batıoğlu F, Tugal-Tutkun I, BUST Study Group. Demographic and clinical characteristics of uveitis in Turkey: The First National Registry Report. Ocul Immunol Inflamm. 2018;26:17-26.
11
Ozdal PC, Sen E, Yazici A, Ozturk F. Patterns of childhood-onset uveitis in a referral center in Turkey. J Ophthalmic Inflamm Infect. 2012;2:13-9.
12
Nalcacioglu-Yuksekkaya P, Ozdal PC, Yazici A, Tirhis H. Clinical and demographic characteristics of patients with uveitis starting later in life. Ocul Immunol Inflamm. 2015;23:304-310.
13
Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, Huseyin Altunbas H, Urgancioglu M. Uveitis in Behçet disease: an analysis of 880 patients. Am J Ophthalmol. 2004;138:373-80.
14
Özdal PÇ, Ortaç S, Taskintuna I, Firat E. Posterior segment involvement in ocular Behçet’s disease. Eur J Ophthalmol. 2002;12:424-431.
15
Gül A. Behçet’s disease as an autoinflammatory disorder. Curr Drug Targets Inflamm Allergy. 2005;4:81-83.
16
Direskeneli H. Autoimmunity vs autoinflammation in Behçet’s disease: Do we oversimplify a complex disorder? Rheumatology. 2006;45:1461-1465.
17
Gül A, Ohno S. Genetics of Behçet’s disease. In: Yazici Y, Yazici H, eds. Behçet’s syndrome. New York: Springer;2010:265-76.
18
Horie Y, Meguro A, Ohta T, Lee EB, Namba K, Mizuuchi K, Iwata D, Mizuki N, Ota M, Inoko H, Ishida S, Ohno S, Kitaichi N. HLA-B51 Carriers are Susceptible to Ocular Symptoms of Behçet Disease and the Association between the Two Becomes Stronger towards the East along the Silk Road: A Literature Survey. Ocul Immunol Inflamm. 2017;25:37-40.
19
Gül A, Uyar FA, Inanc M, Ocal L, Tugal-Tutkun I, Aral O, Koniçe M, Saruhan-Direskeneli G. Lack of association of HLA-B*51 with a severe disease course in Behçet’s disease. Rheumatology (Oxford). 2001;40:668-672.
20
Kaburaki T, Takamoto M, Numaga J, Kawashima H, Araie M, Ohnogi Y, Harihara S, Kuwata S, Takeuchi F. Genetic association of HLA-A*2601 with ocular Behçet’s disease in Japanese patients. Clin Exp Rheumatol. 2010;28(4 suppl 60):39-44.
21
Onal S, Tugal-Tutkun I. Behçet Disease. In : Biswas J, Majumder PD (eds). Uveitis: An Update. India: Springer 2016. p.17-31.
22
Papoutsis NG, Abdel-Naser MB, Altenburg A, Orawa H, Kötter I, Krause L, Pleyer U, Djawari D, Stadler R, Wollina U, Kohl PK, Gollnick HP, Kirch W, Ochsendorf FR, Keitel W, Martus P, Zouboulis CC. Prevalence of Adamantiades-Behçet’s disease in Germany and the municipality of Berlin: results of a nationwide survey. Clin Exp Rheumatol. 2006;24(Suppl 42):125.
23
Direskeneli H, Mumcu G. Possible decline in the incidence and severity of Behçet’s disease: implications for an infectious etiology and oral health. Clin Exp Rheumatol. 2010;28(4 Suppl 60):86-90.
24
Seyahi E, Ugurlu S, Seyahi N, Celik AF, Melikoglu M, Fresko I, Hamuryudan V, Yurdakul S, Yazici H. A survey of socioeconomic status Behçet’s Syndrome. XI International Conference on Behçet’s disease. Clin Exp Rheumatol 2004;22 (Suppl. 34): 4: A27.
25
Mochizuki M, Akduman L, Nussenblatt RB. Behcet’s disease. In: Pepose JS, Holland GN, Wilhelmus KR, eds. Ocular infection and immunity. St Louis; Mosby;1996:663-675.
26
Criteria for diagnosis of Behçet’s disease. International Study Group for Behçet’s Disease. Lancet. 1990;335:1078-1080.
27
Evereklioglu C. Ocular Behçet disease: current therapeutic approaches. Curr Opin Ophthalmol. 2011;22:508-516.
28
Atmaca LS. Fundus changes associated with Behçet’s disease.Graefes Arch Clin Exp Ophthalmol. 1989;227:340-324.
29
Khairallah M, Attia S, Yahia SB, Jenzeri S, Ghrissi R, Jelliti B, Zaouali S, Messaoud R. Pattern of uveitis in Behçet’s disease in a referral center in Tunisia, North Africa. Int Ophthalmol. 2009;29:135-141.
30
Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, Kir N, Urgancioglu M. Neovascularization of the optic disc in Behçet’s disease. Jpn J Ophthalmol. 2006;50:256-265.
31
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.
32
Onal S, Tugal-Tutkun I, Neri P, P Herbort C. Optical coherence tomography imaging in uveitis. Int Ophthalmol. 2014;34:401-435.
33
Tugal-Tutkun I. Imaging in the diagnosis and management of Behçet disease.Int Ophthalmol Clin. 2012;52:183-190.
34
Yu HG, Kim MJ, Oh FS. Fluorescein angiography and visual acuity in active uveitis with Behçet disease. Ocul Immunol Inflamm. 2009;17:41-46.
35
Kim M, Kwon HJ, Choi EY, Kim SS, Koh HJ, Lee SC. Correlation between fluorescein angiographic findings and visual acuity in Behçet retinal vasculitis. Yonsei Med J. 2015;56:1087-1096.
36
Takeuchi M, Hokama H, Tsukahara R, Kezuka T, Goto H, Sakai JI, Usui M. Risk and prognostic factors of poor visual outcome in Behcet’s disease with ocular involvement. Graefes Arch Clin Exp Ophthalmol. 2005;243:1147-1152.
37
Bazvand F, Zarei M, Ebrahimiadib N, Karkhaneh R, Davoudi S, Soleimanzadeh M, Sharifian E, Roohipoor R, Modjtahedi BS. Ocular manifestations, conventional fundus fluorescein angiographic findings, and relationship between angiographic findings and visual acuity in Behçet’s disease. Semin Ophthalmol. 2017;32:764-771.
38
Tugal-Tutkun I, Herbort CP, Khairallah M; Angiography Scoring for Uveitis Working Group (ASUWOG). Scoring of dual fluorescein and ICG inflammatory angiographic signs for the grading of posterior segment inflammation (dual fluorescein and ICG angiographic scoring system for uveitis). Int Ophthalmol. 2010;30:539-553.
39
Kang HM, Lee SC. Long-term progression of retinal vasculitis in Behçet patients using a fluorescein angiography scoring system. Graefes Arch Clin Exp Ophthalmol. 2014;252:1001-1008.
40
Keino H, Okada AA, Watanabe T, Taki W. Decreased ocular inflammatory attacks and background retinal and disc vascular leakage in patients with Behcet’s disease on infliximab therapy. Br J Ophthalmol. 2011;95:1245-1250.
41
Keino H, Okada AA, Watanabe T, Taki W. Long-term efficacy of infliximab on background vascular leakage in patients with Behçet’s disease.Eye (Lond). 2014;28:1100-1106.
42
Leder HA, Campbell JP, Sepah YJ, Gan T, Dunn JP, Hatef E, Cho B, Ibrahim M, Bittencourt M, Channa R, Do DV, Nguyen QD. Ultra-wide-field retinal imaging in the management of non-infectious retinal vasculitis. J Ophthalmic Inflamm Infect. 2013;3:30.
43
Jones NP, Sala-Puigdollers A, Stanga PE. Ultra-wide field fundus fluorescein angiography in the diagnosis and management of retinal vasculitis. Eye (Lond). 2017;31:1546-1549.
44
Mesquida M, Llorenç V, Fontenla JR, Navarro MJ, Adán A. Use of ultrawide-field retinal imaging in the management of active Behçet retinal vasculitis. Retina. 2014;34:2121-2127.
45
Gedik S, Akova Y, Yilmaz G, Bozbeyoğlu S. Indocyanine green and fundus fluorescein angiographic findings in patients with active ocular Behcet’s disease. Ocul Immunol Inflamm. 2005;13:51-58.
46
Klaeger A, Tran VT, Hiroz CA, Morisod L, Herbort CP. Indocyanine green angiography in Behçet’s uveitis. Retina. 2000;20:309-314.
47
Atmaca LS, Sonmez PA. Fluorescein and indocyanine green angiography findings in Behçet’s disease. Br J Ophthalmol. 2003;87:1466-1468.
48
Ossewaarde-van Norel A, Rothova A. Imaging methods for inflammatory macular edema. Int Ophthalmol Clin. 2012;52:55-66.
49
Ozdemir H, Mudun B, Karacorlu M, Karacorlu S. Serous detachment of macula in Behçet disease. Retina. 2005;25:361-362.
50
Eser Öztürk H, Eşki Yücel Ö, Süllü Y. Vitreomacular interface disorders in Behçet’s uveitis. Turk J Ophthalmol. 2017;47:261-266.
51
Kang HM, Koh HJ, Lee SC. Spectral domain optical coherence tomography as an adjunctive tool for screening Behcet uveitis. PLoS One. 2018;13:0208254.
52
Oray M, Onal S, Bayraktar S, Izgi B, Tugal-Tutkun I. Nonglaucomatous localized retinal nerve fiber layer defects in Behçet uveitis. Am J Ophthalmol. 2015;159:475-481.
53
Onal S, Uludag G, Oray M, Mengi E, Herbort CP, Akman M, Metin MM, Koc Akbay A, Tugal-Tutkun I. Quantitative analysis of structural alterations in the choroid of patients with active Behçet uveitis. Retina. 2018;38:828-840.
54
Khairallah M, Abroug N, Khochtali S, Mahmoud A, Jelliti B, Coscas G, Lupidi M, Kahloun R, Ben Yahia S. Optical coherence tomography angiography in patients with Behçet uveitis. Retina. 2017;37:1678-1691.
55
Somkijrungroj T, Vongkulsiri S, Kongwattananon W, Chotcomwongse P, Luangpitakchumpol S, Jaisuekul K. 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;2180723.
56
Emre S, Güven-Yılmaz S, Ulusoy MO, Ateş H. Optical coherence tomography angiography findings in Behcet patients. Int Ophthalmol. 2019;2391-2399.
57
Zierhut M, Abu El-Asrar AM, Bodaghi B, Tugal-Tutkun I. Therapy of ocular Behçet disease. Ocul Immunol Inflamm. 2014;22:64-76.
58
Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, Nussenblatt RB, Stiehm ER, Tessler H, Van Gelder RN, Whitcup SM, Yocum D. Guidelines for the use of immunosuppressive drugs in patients with ocular infl ammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000;130:492-513.
59
Yalçindag FN, Can E, Ozdemir O. Intravenous methylprednisolone pulse therapy for acute posterior segment uveitis attacks in Behçet’s disease. Ann Ophthalmol (Skokie). 2007;39:194-197.
60
Karacorlu M, Mudun B, Ozdemir H, Arf Karacorlu S, Burumcek E. Intravitreal triamcinolone acetonide for the treatment of cystoid macular edema secondary to Behçet disease. Am J Ophthalmol. 2004;138:289-291.
61
Yalcinbayir O, Caliskan E, Ucan Gunduz G, Gelisken O, Kaderli B, Yucel AA. Efficacy of Dexamethasone Implants in Uveitic Macular Edema in Cases with Behçet Disease. Ophthalmologica. 2019;241:190-194.
62
Markomichelakis N, Delicha E, Masselos S, Fragiadaki K, Kaklamanis P, Sfikakis PP. A single infl iximab infusion vs corticosteroids for acute panuveitis attacks in Behçet’s disease: a comparative 4-week study. Rheumatology (Oxford). 2011;50:593-597.
63
Yazici H, Pazarli H, Barnes CG, Tüzün Y, Ozyazgan Y, Silman A, Serdaroğlu S, Oğuz V, Yurdakul S, Yurdakul S, Lovatt GE, Yazici B, Somani S, Müftüoğlu A. A controlled trial of azathioprine in Behcet’s syndrome. N Engl J Med. 1990;322:281-285.
64
Hamuryudan V, Ozyazgan Y, Hizli N, Mat C, Yurdakul S, Tüzün Y, Senocak M, Yazici H. Azathioprine in Behçet’s syndrome: effects on long-term prognosis. Arthritis Rheum. 1997;40:769-774.
65
Masuda K, Urayama A, Kogure M, Nakae K, Kogure M, Inaba G. Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behçet’sdisease. Lancet. 1989;1:1093-1096.
66
Ozyazgan Y, Yurdakul S, Yazici H, Tüzün B, Işçimen A, Tüzün Y, Aktunç T, Pazarli H, Hamuryudan V, Müftüoğlu A. Low dose cyclosporin A versus pulsed cyclophosphamide in Behçet’s syndrome: a single masked trial. Br J Ophthalmol. 1992;76:241-243.
67
Saadoun D, Wechsler B, Terrada C, Hajage D, Le Thi Huong D, Resche-Rigon M, Cassoux N, Le Hoang P, Amoura Z, Bodaghi B, Cacoub P. Azathioprine in severe uveitis of Behçet’s disease. Arthritis Care Res (Hoboken). 2010;62:1733-1738.
68
Díaz-Llopis M, Cervera M, Menezo JL. Cyclosporin A treatment of Behçet’s disease: a long-term study. Curr Eye Res. 1990;9 Suppl:17-23.
69
Whitcup SM, Salvo EC Jr, Nussenblatt RB. Combined cyclosporine and corticosteroid therapy for sight-threatening uveitis in Behçet’s disease.Am J Ophthalmol. 1994;118:39-45.
70
Özdal PÇ, Ortaç S, Taskıntuna I, Fırat E. Long-term therapy with low dose cyclosporin-A in ocular Behçet’s disease. Doc Ophthalmol. 2002;105:301-312.
71
Kötter I, Dürk H, Saal J, Fierlbeck G, Pleyer U, Ziehut M. Therapy of Behçet’s disease. Ger J Ophthalmol. 1996;5:92-97.
72
Akman-Demir G, Ayranci O, Kurtuncu M, Vanli EN, Mutlu M, Tugal-Tutkun I. Cyclosporine for Behçet’s uveitis: is it associated with an increased risk of neurological involvement? Clin Exp Rheumatol. 2008;26 Suppl 50:84-90.
73
Teoh SC, Hogan AC, Dick AD, Lee RW. Mycophenolate mofetil for the treatment of uveitis. Am J Ophthalmol. 2008;146:752-760.
74
Hatemi G, Silman A, Bang D, Bodaghi B, Chamberlain AM, Gul A, Houman MH, Kötter I, Olivieri I, Salvarani C, Sfikakis PP, Siva A, Stanford MR, Stübiger N, Yurdakul S, Yazici H; EULAR Expert Committee. EULAR recommendations for the management of Behcet disease. Ann Rheum Dis. 2008;67:1656-1662.
75
Hatemi G, Christensen R, Bang D, Bodaghi B, Celik AF, Fortune F, Gaudric J, Gul A, Kötter I, Leccese P, Mahr A, Moots R, Ozguler Y, Richter J, Saadoun D, Salvarani C, Scuderi F, Sfikakis PP, Siva A, Stanford M, Tugal-Tutkun I, West R, Yurdakul S, Olivieri I, Yazici H. 2018 update of the EULAR recommendations for the management of Behçet’s syndrome. Ann Rheum Dis. 2018;77:808-818.
76
Levy-Clarke G, Jabs DA, Read RW, Rosenbaum JT, Vitale A, Van Gelder RN. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology. 2014;121:785-96.e3.
77
Tugal-Tutkun I, Mudun A, Urgancioglu M, Kamali S, Kasapoglu E, Inanc M, Gül A. 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;52:2478-2484.
78
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 disease. Arch Ophthalmol.2012;130:592-598.
79
Takeuchi M, Kezuka T, Sugita S, Keino H, Namba K, Kaburaki T, Maruyama K, Nakai K, Hijioka K, Shibuya E, Komae K, Hori J, Ohguro N, Sonoda KH, Mizuki N, Okada AA, Ishibashi T, Goto H, Mochizuki M. Evaluation of the long-term efficacy and safety of infliximab treatment for uveitis in Behçet’s disease: a multicenter study. Ophthalmology. 2014;121:1877-1884.
80
Keino H, Okada AA, Watanabe T, Nakayama M, Nakamura T. Efficacy of Infliximab for Early Remission Induction in Refractory Uveoretinitis Associated with Behçet Disease: A 2-year Follow-up Study. Ocul Immunol Inflamm. 2017;25:46-51.
81
Mushtaq B, Saeed T, Situnayake RD, Murray PI. Adalimumab for sight-threatening uveitis in Behçet’s disease. Eye (Lond). 2007;21:824-825.
82
Bawazeer A, Raffa LH, Nizamuddin SH. Clinical experience with adalimumab in the treatment of ocular Behçet disease. Ocul Immunol Inflamm. 2010;18:226-232.
83
Leccese P, Latanza L, D’Angelo S, Padula A, Olivieri I. Efficacy of switching to adalimumab in a patient with refractory uveitis of Behçet’s disease to infliximab. Clin Exp Rheumatol. 2011;29(4 Suppl 67):S93.
84
Tabbara KF, Al-Hemidan AI. Infliximab effects compared to conventional therapy in the management of retinal vasculitis in Behçet disease. Am J Ophthalmol. 2008;146:845-850.
85
Cordero-Coma M, Sobrin L. Anti-tumor necrosis factor-a therapy in uveitis. Surv Ophthalmol. 2015;60:575-589.
86
Vallet H, Seve P, Biard L, Baptiste Fraison J, Bielefeld P, Perard L, Bienvenu B, Abad S, Rigolet A, Deroux A, Sene D, Perlat A, Marie I, Feurer E, Hachulla E, Fain O, Clavel G, Riviere S, Bouche PA, Gueudry J, Pugnet G, Le Hoang P, Resche Rigon M, Cacoub P, Bodaghi B, Saadoun D; French Uveitis Network. Infliximab Versus Adalimumab in the Treatment of Refractory Inflammatory Uveitis: A Multicenter Study From the French Uveitis Network. Arthritis Rheumatol. 2016;68:1522-1530.
87
Atienza-Mateo B, Martín-Varillas JL, Calvo-Río V, Demetrio-Pablo R, Beltrán E, Sánchez-Bursón J, Mesquida M, Adan A, Hernández MV, Hernández-Garfella M Valls-Pascual E, Martínez-Costa L, Sellas-Fernández A, Cordero-Coma M, Díaz-Llopis M, Gallego R, García-Serrano JL, Ortego-Centeno N, Herreras JM, Fonollosa A, Garcia-Aparicio AM, Maíz-Alonso O, Blanco A, Torre-Salaberri I, Fernandez-Espartero C, Jovaní V, Peiteado D, Pato E, Cruz J, FérnandeV C, z-Cid, Aurrecoechea E, García-Arias Miriam, Castañeda S, Caracuel-Ruiz MA, Montilla-Morales CA, Antonio Atanes-Sandoval, Francisco F, Insua S, González-Suárez S, Sanchez-Andrade A, Gamero F, Ferrando LFL, Romero-Bueno F, García-González A, González RA, Muro EM, Carrasco-Cubero C, Olive A, Prior A, Vázquez J, Ruiz-Moreno O, Jiménez-Zorzo F, Manero J, Fernandez SM, Fernández-Carballido C, Rubio-Romero E, Pages FA, de Miera FJTS, Martinez MG, Díaz-Valle D, Longo FJL, Nolla JM, Álvarez ER, Martínez MR, González-López JL, Rodríguez-Cundin P, Hernández JL, González-Gay MA, Blanco R. Comparative study of infliximab versus adalimumab in refractory uveitis due to Behçet’s disease, National multicenter study of 177 cases. Arthritis Rheumatol. 2019 Jun 25. doi: 10.1002/art.41026.
88
Jaffe GJ, Dick AD, Brézin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, Chu DS, Camez A, Kwatra NV, Song AP, Kron M, Tari S, Suhler EB. Adalimumab in Patients with Active Non-infectious Uveitis. N Engl J Med. 2016;375:932-943.
89
Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, Schlaen A, Pavesio C, Cimino L, Van Calster J, Camez AA, Kwatra NV, Song AP, Kron M, Tari S, Brézin AP. Adalimumab for prevention of uveitis 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;388:1183-1192.
90
Kötter I, Zierhut M, Eckstein AK, Vonthein R, Ness T, Günaydin I, Grimbacher B, Blaschke S, Meyer-Riemann W, Peter HH, Stübiger N. Human recombinant interferon alfa-2a for the treatment of Behçet’s disease with sight threatening posterior or panuveitis. Br J Ophthalmol. 2003;87:423-431.
91
Tugal-Tutkun I, Güney-Tefekli E, Urgancioglu M. Results of interferon-alfa therapy in patients with Behçet uveitis. Graefes Arch Clin Exp Ophthalmol. 2006;244:1692-1695.
92
Gueudry J, Wechsler B, Terrada C. Long-term effi cacy and safety of low-dose interferon alpha2a therapy in severe uveitis associated with Behçet disease. Am J Ophthalmol. 2008;146:837-844.
93
Onal S, Kazokoglu H, Koc A, Akman M, Bavbek T, Direskeneli H, Yavuz S. Long-term efficacy and safety of low-dose and dose-escalating interferon alfa-2a therapy in refractory Behçet uveitis. Arch Ophthalmol. 2011;129:288-294.
94
Yalçindağ FN, Uzun A. Results of interferon alpha-2a therapy in patients with Behcet’s disease. J Ocul Pharmacol Ther. 2012;28:439-443.
95
Deuter CM, Zierhut M, Möhle A, Möhle A, Vonthein R, Stöbiger N, Kötter I. Long-term remission after cessation of interferon-a treatment in patients with severe uveitis due to Behçet’s disease. Arthritis Rheum. 2010;62:2796-2805.
96
Diwo E, Gueudry J, Saadoun D, Weschler B, LeHoang P, Bodaghi B. Long-term efficacy of interferon in severe uveitis associated with Behçet disease. Ocul Immunol Inflamm. 2017;25:76-84.
97
Ozguler Y, Leccese P, Christensen R, Esatoglu SN, Bang D, Bodaghi B, Çelik AF, Fortune F, Gaudric J, Gul A, Kötter I, Mahr A, Moots RJ, Richter J, Saadoun D, Salvarani C, Scuderi F, Sfikakis PP, Siva A, Stanford M, Tugal-Tutkun I, West R, Yurdakul S, Olivieri I, Yazici H, Hatemi G. Management of major organ involvement of Behçet’s syndrome: a systematic review for update of the EULAR recommendations. Rheumatology (Oxford). 2018;57:2200-2212.
98
Yalçindag N, Köse HC. Comparison of the treatment results for Behçet uveitis in patients treated with infliximab and interferon. Ocul Immunol Inflamm. 2019;3:1-10.
99
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;26:1005-1014.
100
Fabiani C, Sota J, Rigante D, Vitale A, Emmi G, Vannozzi L, Franceschini R, Bacherini D, Frediani B, Galeazzi M, Tosi GM, Cantarini L.Rapid and Sustained Efficacy of Golimumab in the Treatment of Multirefractory Uveitis Associated with Behçet’s Disease. Ocul Immunol Inflamm. 2019;27:58-63.
101
Fabiani C, Vitale A, Rigante D, Emmi G, Lopalco G, Di Scala G, Sota J, Orlando I, Franceschini R, Frediani B, Galeazzi M, Iannone F, Tosi GM, Cantarini L.The Presence of Uveitis Is Associated with a Sustained Response to the Interleukin (IL)-1 Inhibitors Anakinra and Canakinumab in Behçet’s Disease. Ocul Immunol Inflamm. 2018 Aug 27:1-7.
102
Wakefield D, McCluskey P, Wildner G, Thurau S, Carr G, Chee SP, Forrester J, Dick A, Hudson B, Lightman S, Smith J, Tugal-Tutkun I; pre-treatment assessment review panel. Inflammatory eye disease: Pre-treatment assessment of patients prior to commencing immunosuppressive and biologic therapy: Recommendations from an expert committee. Autoimmun Rev. 2017;16:213-222.
103
Kisacik B, Pamuk ON, Onat AM, Erer SB, Hatemi G, Ozguler Y, Pehlivan Y, Kilic L, Ertenli I, Can M, Direskeneli H, Keser G, Oksel F, Dalkilic E, Yilmaz S, Pay S, Balkarli A, Cobankara V, Cetin GY, Sayarlioglu M, Cefle A, Yazici A, Avci AB, Terzioglu E, Ozbek S, Akar S, Gul A. Characteristics Predicting Tuberculosis Risk under Tumor Necrosis Factor-a Inhibitors: Report from a Large Multicenter Cohort with High Background Prevalence. J Rheumatol. 2016;43:524-529.
104
Anti-TNF kullanan hastalarda tüberküloz rehberi, Sağlık Bakanlığı, Türkiye Halk Sağlığı Kurumu, Ankara 2016.
105
Tugal-Tutkun I, Cingü K, Kir N, Yeniad B, Urgancıoglu M, Gül A. Use of laser flare-cell photometry to quantify intraocular inflammation in patients with Behçet uveitis. Graefes Arch Clin Exp Ophthalmol. 2008;246:1169-1177.
106
Kaçmaz RO, Kempen JH, Newcomb C, Gangaputra S, Daniel E, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Suhler EB, Thorne JE, Jabs DA, Foster CS; Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study Group. Ocular inflammation in Behçet disease: incidence of ocular complications and of loss of visual acuity. Am J Ophthalmol. 2008;146:828-836.
107
Kump LI, Moeller KL, Reed GF, Kurup SK, Nussenblatt RB, Levy-Clarke GA. Behçet’s disease: comparing 3 decades of treatment response at the National Eye Institute. Can J Ophthalmol. 2008;43:468-472.
108
Cingu AK, Onal S, Urgancioglu M, Tugal-Tutkun I. Comparison of presenting features and three-year disease course in Turkish patients with Behçet uveitis who presented in the early 1990s and the early 2000s. Ocul Immunol Inflamm. 2012;20:423-428.
109
Taylor SR, Singh J, Menezo V, Wakefield D, McCluskey P, Lightman S. Behcet disease: visual prognosis and factors influencing the development of visual loss. Am J Ophthalmol. 2011;152:1059-1066.
