Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation

Eye

Volumn 26, Issue 1, 2012, Pages 17-28

  Lee, R W J ^a   Dick, A D ^a,b  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b MOORFIELDS EYE HOSPITAL   (United Kingdom)

Author keywords

biomarkers; immunosuppression; inflammation; personalised medicine; uveitis

Indexed keywords

ABATACEPT; ALKYLATING AGENT; ANTIMETABOLITE; AZATHIOPRINE; BIOLOGICAL MARKER; CHLORAMBUCIL; CORTICOSTEROID; CYCLOPHOSPHAMIDE; CYCLOSPORIN A; DACLIZUMAB; DEXAMETHASONE; ESBA 105; FINGOLIMOD; FLUOCINOLONE ACETONIDE; IMMUNOSUPPRESSIVE AGENT; INFLIXIMAB; INTERLEUKIN 10; INTERLEUKIN 6; METHOTREXATE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; NATALIZUMAB; PREDNISOLONE; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; RITUXIMAB; TACROLIMUS; TOCILIZUMAB; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; TUMOR NECROSIS FACTOR INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VOCLOSPORIN;

AUTOIMMUNE DISEASE; BLAU SYNDROME; BLOOD PRESSURE; CHOLESTEROL BLOOD LEVEL; CLINICAL PROTOCOL; DISEASE CLASSIFICATION; DRUG EFFICACY; DRUG SAFETY; EARLY DIAGNOSIS; EXPERIMENTAL MODEL; EYE INFLAMMATION; GENOMICS; HUMAN; IMMUNE RESPONSE; IMMUNOHISTOCHEMISTRY; IMMUNOPATHOLOGY; IMMUNOPHENOTYPING; IMMUNOREGULATION; IMMUNOSTIMULATION; MOLECULAR BIOLOGY; NONHUMAN; PATHOGENESIS; PROGNOSIS; PROTEOMICS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REMISSION; REVIEW; SIDE EFFECT; TRANSCRIPTOMICS; TREATMENT OUTCOME; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; UVEITIS;

EID: 84855861164     PISSN: 0950222X     EISSN: 14765454     Source Type: Journal    
DOI: 10.1038/eye.2011.255     Document Type: Review

References (121)

1. Nguyen QD, Hatef E, Kayen B, Macahilig CP, Ibrahim M, Wang J et al. A cross-sectional study of the current treatment patterns in noninfectious uveitis among specialists in the United States. Ophthalmology 2011; 118(1): 184-190.
2. Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology 2004; 111(3): 491-500; discussion. (Pubitemid 38293104)
3. Suttorp-Schulten MS, Rothova A. The possible impact of uveitis in blindness: a literature survey. Br J Ophthalmol 1996; 80(9): 844-848. (Pubitemid 26345317)
4. Daniel E, Thorne JE, Newcomb CW, Pujari SS, Kacmaz RO, Levy-Clarke GA et al. Mycophenolate mofetil for ocular inflammation. Am J Ophthalmol 2010; 149(3): 423-432, e1-e2.
5. Imrie FR, Dick AD. Nonsteroidal drugs for the treatment of noninfectious posterior and intermediate uveitis. Curr Opin Ophthalmol 2007; 18(3): 212-219. (Pubitemid 46624919)
6. Imrie FR, Dick AD. Biologics in the treatment of uveitis. Curr Opin Ophthalmol 2007; 18(6): 481-486. (Pubitemid 351339402)
7. Thorne JE, Jabs DA, Qazi FA, Nguyen QD, Kempen JH, Dunn JP. Mycophenolate mofetil therapy for inflammatory eye disease. Ophthalmology 2005; 112(8): 1472-1477. (Pubitemid 41074642)
8. Durrani OM, Meads CA, Murray PI. Uveitis: a potentially blinding disease. Ophthalmologica 2004; 218(4): 223-236. (Pubitemid 38969828)
9. Gardiner AM, Armstrong RA, Dunne MC, Murray PI. Correlation between visual function and visual ability in patients with uveitis. Br J Ophthalmol 2002; 86(9): 993-996. (Pubitemid 34953612)
10. Murphy CC, Greiner K, Plskova J, Frost NA, Forrester JV, Dick AD. Validity of using vision-related quality of life as a treatment end point in intermediate and posterior uveitis. Br J Ophthalmol 2007; 91(2): 154-156. (Pubitemid 46202861)
11. Murphy CC, Hughes EH, Frost NA, Dick AD. Quality of life and visual function in patients with intermediate uveitis. Br J Ophthalmol 2005; 89(9): 1161-1165. (Pubitemid 41224468)
12. Caspi RR. Understanding autoimmune uveitis through animal models. The Friedenwald lecture. Invest Ophthalmol Vis Sci 2011; 52(3): 1872-1879.
13. Nanke Y, Kotake S, Goto M, Ujihara H, Matsubara M, Kamatani N. Decreased percentages of regulatory T cells in peripheral blood of patients with Behcet's disease before ocular attack: a possible predictive marker of ocular attack. Mod Rheumatol 2008; 18(4): 354-358.
14. Yeh S, Li Z, Forooghian F, Hwang FS, Cunningham MA, Pantanelli S et al. CD4 + Foxp3 + T-regulatory cells in noninfectious uveitis. Arch Ophthalmol 2009; 127(4): 407-413.
15. Chen L, Yang P, Zhou H, He H, Ren X, Chi W et al. Diminished frequency and function of CD4 + CD25high regulatory T cells associated with active uveitis in Vogt-Koyanagi-Harada syndrome. Invest Ophthalmol Vis Sci 2008; 49(8): 3475-3482.
16. Gallucci S, Matzinger P. Danger signals: SOS to the immune system. Curr Opin Immunol 2001; 13(1): 114-119. (Pubitemid 32096970)
17. Nathan C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 2006; 6(3): 173-182. (Pubitemid 43290987)
18. Nathan C, Ding A. Nonresolving inflammation. Cell 2010; 140(6): 871-882.
19. Carneiro LA, Travassos LH, Girardin SE. Nod-like receptors in innate immunity and inflammatory diseases. Ann Med 2007; 39(8): 581-593. (Pubitemid 350175311)
20. McDermott MF. Genetic clues to understanding periodic fevers, and possible therapies. Trends Mol Med 2002; 8(12): 550-554. (Pubitemid 35408212)
21. McDermott MF, Aksentijevich I. The autoinflammatory syndromes. Curr Opin Allergy Clin Immunol 2002; 2(6): 511-516. (Pubitemid 36105814)
22. Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol 1994; 12: 991-1045. (Pubitemid 24140436)
23. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med 2009; 360(23): 2416-2425.
24. Lachmann HJ, Lowe P, Felix SD, Rordorf C, Leslie K, Madhoo S et al. In vivo regulation of interleukin 1beta in patients with cryopyrin-associated periodic syndromes. J Exp Med 2009; 206(5): 1029-1036.
25. Martin TM, Zhang Z, Kurz P, Rose CD, Chen H, Lu H et al. The NOD2 defect in Blau syndrome does not result in excess interleukin-1 activity Arthritis Rheum 2009; 60(2): 611-618.
26. Dick AD. Immune regulation of uveoretinal inflammation. Dev Ophthalmol 1999; 30: 187-202.
27. Dick AD, Forrester JV, Liversidge J, Cope AP. The role of tumour necrosis factor (TNF-alpha) in experimental autoimmune uveoretinitis (EAU). Prog Retin Eye Res 2004; 23(6): 617-637. (Pubitemid 39243969)
28. Dick AD, Carter D, Robertson M, Broderick C, Hughes E, Forrester JV et al. Control of myeloid activity during retinal inflammation. J Leukoc Biol 2003; 74(2): 161-166. (Pubitemid 38040411)
29. Forrester JV, Xu H, Kuffova L, Dick AD, McMenamin PG. Dendritic cell physiology and function in the eye. Immunol Rev 2010; 234(1): 282-304.
30. Forrester JV. Macrophages eyed in macular degeneration. Nat Med 2003; 9(11): 1350-1351. (Pubitemid 37466177)
31. Xu H, Chen M, Forrester JV. Para-inflammation in the aging retina. Prog Retin Eye Res 2009; 28(5): 348-368.
32. Kerr EC, Copland DA, Dick AD, Nicholson LB. The dynamics of leukocyte infiltration in experimental autoimmune uveoretinitis. Prog Retin Eye Res 2008; 27(5): 527-535.
33. Kerr EC, Raveney BJ, Copland DA, Dick AD, Nicholson LB. Analysis of retinal cellular infiltrate in experimental autoimmune uveoretinitis reveals multiple regulatory cell populations. J Autoimmun 2008; 31(4): 354-361.
34. Gordon S. Alternative activation of macrophages. Nat Rev Immunol 2003; 3(1): 23-35. (Pubitemid 37328697)
35. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005; 5(12): 953-964. (Pubitemid 41746764)
36. Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N et al. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol 2011; 12(3): 231-238.
37. Munder M, Eichmann K, Modolell M. Alternative metabolic states in murine macrophages reflected by the nitric oxide synthase/arginase balance: competitive regulation by CD4+ Tcells correlates with Th1/Th2 phenotype. J Immunol 1998; 160(11): 5347-5354. (Pubitemid 28267823)
38. Robertson M, Liversidge J, Forrester JV, Dick AD. Neutralizing tumor necrosis factor-alpha activity suppresses activation of infiltrating macrophages in experimental autoimmune uveoretinitis. Invest Ophthalmol Vis Sci 2003; 44(7): 3034-3041. (Pubitemid 36759770)
39. Robertson MJ, Erwig LP, Liversidge J, Forrester JV, Rees AJ, Dick AD. Retinal microenvironment controls resident and infiltrating macrophage function during uveoretinitis. Invest Ophthalmol Vis Sci 2002; 43(7): 2250-2257. (Pubitemid 34700655)
40. Taylor PR, Martinez-Pomares L, Stacey M, Lin HH, Brown GD, Gordon S. Macrophage receptors and immune recognition. Annu Rev Immunol 2005; 23: 901-944. (Pubitemid 40563189)
41. Dick AD, Broderick C, Forrester JV, Wright GJ. Distribution of OX2 antigen and OX2 receptor within retina. Invest Ophthalmol Vis Sci 2001; 42: 170-176. (Pubitemid 32059425)
42. Wright GJ, Puklavec MJ, Willis AC, Hoek RM, Sedgwick JD, Brown MH et al. Lymphoid/neuronal cell surface OX2 glycoprotein recognises a novel receptor on macrophages implicated in their control of function. Immunity 2000; 13: 233-238.
43. Broderick C, Hoek RM, Forrester JV, Liversidge J, Sedgwick JD, Dick AD. Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis. Am J Pathol 2002; 161(5): 1669-1677. (Pubitemid 35265526)
44. Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R, Zurawski SM et al. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 2000; 290(5497): 1768-1771. (Pubitemid 32004808)
45. Copland DA, Calder CJ, Raveney BJ, Nicholson LB, Phillips J, Cherwinski H et al. Monoclonal antibody-mediated CD200 receptor signaling suppresses macrophage activation and tissue damage in experimental autoimmune uveoretinitis. Am J Pathol 2007; 171(2): 580-588. (Pubitemid 47344690)
46. Copland DA, Hussain K, Baalasubramanian S, Hughes TR, Morgan BP, Xu H et al. Systemic and local anti-C5 therapy reduces the disease severity in experimental autoimmune uveoretinitis. Clin Exp Immunol 2010; 159(3): 303-314.
47. Rothova A. Corticosteroids in uveitis. Ophthalmol Clin North Am 2002; 15(3): 389-394. (Pubitemid 35244816)
48. Lee RW, Dick AD. Treat early and embrace the evidence in favour of anti-TNF-alpha therapy for Behcet's uveitis. Br J Ophthalmol 2010; 94(3): 269-270.
49. Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol 2000; 130(4): 492-513.
50. Galor A, Jabs DA, Leder HA, Kedhar SR, Dunn JP, Peters III GB et al. Comparison of antimetabolite drugs as corticosteroid-sparing therapy for noninfectious ocular inflammation. Ophthalmology 2008; 115(10): 1826-1832.
51. Hogan AC, McAvoy CE, Dick AD, Lee RW. Long-term efficacy and tolerance of tacrolimus for the treatment of uveitis. Ophthalmology 2007; 114(5): 1000-1006.
52. Kilmartin DJ, Forrester JV, Dick AD. Cyclosporin A therapy in refractory non-infectious childhood uveitis. Br J Ophthalmol 1998; 82(7): 737-742. (Pubitemid 28376899)
53. Kilmartin DJ, Forrester JV, Dick AD. Rescue therapy with mycophenolate mofetil in refractory uveitis. Lancet 1998; 352(9121): 35-36. (Pubitemid 28306570)
54. Kilmartin DJ, Forrester JV, Dick AD. Tacrolimus (FK506) in failed cyclosporin A therapy in endogenous posterior uveitis. Ocul Immunol Inflamm 1998; 6(2): 101-109. (Pubitemid 28380074)
55. Murphy CC, Greiner K, Plskova J, Duncan L, Frost NA, Forrester JV et al. Cyclosporine vs tacrolimus therapy for posterior and intermediate uveitis. Arch Ophthalmol 2005; 123(5): 634-641. (Pubitemid 40695511)
56. Pasadhika S, Kempen JH, Newcomb CW, Liesegang TL, Pujari SS, Rosenbaum JT et al. Azathioprine for ocular inflammatory diseases. Am J Ophthalmol 2009; 148(4): 500-509 e2.
57. Sharma SM, Nestel AR, Lee RW, Dick AD. Clinical review: anti-TNFalpha therapies in uveitis: perspective on 5 years of clinical experience. Ocul Immunol Inflamm 2009; 17(6): 403-414.
58. Teoh SC, Hogan AC, Dick AD, Lee RW. Mycophenolate mofetil for the treatment of uveitis. Am J Ophthalmol 2008; 146(5): 752-760, 60 e1-3.
59. Teoh SC, Sharma S, Hogan A, Lee R, Ramanan AV, Dick AD. Tailoring biological treatment: anakinra treatment of posterior uveitis associated with the CINCA syndrome. Br J Ophthalmol 2007; 91(2): 263-264. (Pubitemid 46202883)
60. Kacmaz RO, Kempen JH, Newcomb C, Daniel E, Gangaputra S, Nussenblatt RB et al. Cyclosporine for ocular inflammatory diseases. Ophthalmology 2010; 117(3): 576-584.
61. Anglade E, Aspeslet LJ, Weiss SL. A new agent for the treatment of noninfectious uveitis: rationale and design of three LUMINATE (Lux Uveitis Multicenter Investigation of a New Approach to Treatment) trials of steroid-sparing voclosporin. Clin Ophthalmol 2008; 2(4): 693-702.
62. Deuter CM. [Systemic voclosporin for uveitis treatment]. Ophthalmologe 2010; 107(7): 672-675.
63. Kempen JH, Daniel E, Dunn JP, Foster CS, Gangaputra S, Hanish A et al. Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study. BMJ 2009; 339: b2480.
64. Kempen JH, Gangaputra S, Daniel E, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT et al. Long-term risk of malignancy among patients treated with immunosuppressive agents for ocular inflammation: a critical assessment of the evidence. Am J Ophthalmol 2008; 146(6): 802-812 e1.
65. Dick AD, Meyer P, James T, Forrester JV, Hale G, Waldmann H et al. Campath-1H therapy in refractory ocular inflammatory disease. Br J Ophthalmol 2000; 84(1): 107-109. (Pubitemid 30251643)
66. Isaacs JD, Hale G, Waldmann H, Dick AD, Haynes R, Forrester JV et al. Monoclonal antibody therapy of chronic intraocular inflammation using Campath-1H. Br J Ophthalmol 1995; 79(11): 1054-1055.
67. Dick AD, Isaacs JD. Immunomodulation of autoimmune responses with monoclonal antibodies and immunoadhesins: treatment of ocular inflammatory disease in the next millennium. Br J Ophthalmol 1999; 83(11): 1230-1234. (Pubitemid 29511802)
68. Dick AD, Duncan L, Hale G, Waldmann H, Isaacs J. Neutralizing TNF-alpha activity modulates T-cell phenotype and function in experimental autoimmune uveoretinitis. J Autoimmun 1998; 11(3): 255-264. (Pubitemid 28319791)
69. Dick AD, McMenamin PG, Korner H, Scallon BJ, Ghrayeb J, Forrester JV et al. Inhibition of tumor necrosis factor activity minimizes target organ damage in experimental autoimmune uveoretinitis despite quantitatively normal activated T cell traffic to the retina. Eur J Immunol 1996; 26(5): 1018-1025.
70. Murphy CC, Duncan L, Forrester JV, Dick AD. Systemic CD4( +) T cell phenotype and activation status in intermediate uveitis. Br J Ophthalmol 2004; 88(3): 412-416. (Pubitemid 38333724)
71. Murphy CC, Greiner K, Plskova J, Duncan L, Frost A, Isaacs JD et al. Neutralizing tumor necrosis factor activity leads to remission in patients with refractory noninfectious posterior uveitis. Arch Ophthalmol 2004; 122(6): 845-851. (Pubitemid 38736243)
72. Rodrigues EB, Farah ME, Maia M, Penha FM, Regatieri C, Melo GB et al. Therapeutic monoclonal antibodies in ophthalmology Prog Retin Eye Res 2009; 28(2): 117-144.
73. Theodossiadis PG, Markomichelakis NN, Sfikakis PP. Tumor necrosis factor antagonists: preliminary evidence for an emerging approach in the treatment of ocular inflammation. Retina 2007; 27(4): 399-413. (Pubitemid 46624278)
74. Yamada Y, Sugita S, Tanaka H, Kamoi K, Kawaguchi T, Mochizuki M. Comparison of infliximab versus ciclosporin during the initial 6-month treatment period in Behcet disease. Br J Ophthalmol 2010; 94(3): 284-288.
75. Yeh S, Wroblewski K, Buggage R, Li Z, Kurup SK, Sen HN et al. High-dose humanized anti-IL-2 receptor alpha antibody (daclizumab) for the treatment of active, non-infectious uveitis. J Autoimmun 2008; 31(2): 91-97.
76. Kenawy N, Cleary G, Mewar D, Beare N, Chandna A, Pearce I. Abatacept: a potential therapy in refractory cases of juvenile idiopathic arthritis-associated uveitis. Graefes Arch Clin Exp Ophthalmol 2011; 249(2): 297-300.
77. Zulian F, Balzarin M, Falcini F, Martini G, Alessio M, Cimaz R et al. Abatacept for severe anti-tumor necrosis factor alpha refractory juvenile idiopathic arthritis-related uveitis. Arthritis Care Res (Hoboken) 2010; 62(6): 821-825.
78. Angeles-Han S, Flynn T, Lehman T. Abatacept for refractory juvenile idiopathic arthritis-associated uveitis- a case report. J Rheumatol 2008; 35(9): 1897-1898.
79. Heiligenhaus A, Miserocchi E, Heinz C, Gerloni V, Kotaniemi K. Treatment of severe uveitis associated with juvenile idiopathic arthritis with anti-CD20 monoclonal antibody (rituximab). Rheumatology (Oxford) 2011; 50(8): 1390-1394.
80. Iaccheri B, Androudi S, Bocci EB, Gerli R, Cagini C, Fiore T. Rituximab treatment for persistent scleritis associated with rheumatoid arthritis. Ocul Immunol Inflamm 2010; 18(3): 223-225.
81. Miserocchi E, Pontikaki I, Modorati G, Bandello F, Meroni PL, Gerloni V. Rituximab for uveitis. Ophthalmology 2011; 118(1): 223-224.
82. Tappeiner C, Heinz C, Specker C, Heiligenhaus A. Rituximab as a treatment option for refractory endogenous anterior uveitis. Ophthalmic Res 2007; 39(3): 184-186. (Pubitemid 46975985)
83. Taylor SR, Salama AD, Joshi L, Pusey CD, Lightman SL. Rituximab is effective in the treatment of refractory ophthalmic Wegener's granulomatosis. Arthritis Rheum 2009; 60(5): 1540-1547.
84. Goodin DS, Cohen BA, O'Connor P, Kappos L, Stevens JC. Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology 2008; 71(10): 766-773.
85. Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G et al. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov 2010; 9(11): 883-897.
86. Raveney BJ, Copland DA, Nicholson LB, Dick AD. Fingolimod (FTY720) as an acute rescue therapy for intraocular inflammatory disease. Arch Ophthalmol 2008; 126(10): 1390-1395.
87. Deuter CM, Zierhut M, Mohle A, Vonthein R, Stobiger N, Kotter I. Long-term remission after cessation of interferon-alpha treatment in patients with severe uveitis due to Behcet's disease. Arthritis Rheum 2010; 62(9): 2796-2805.
88. Plskova J, Greiner K, Forrester JV. Interferon-alpha as an effective treatment for noninfectious posterior uveitis and panuveitis. Am J Ophthalmol 2007; 144(1): 55-61.
89. Bodaghi B, Gendron G, Wechsler B, Terrada C, Cassoux N, Huong du LT 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(3): 335-339. (Pubitemid 46586530)
90. Kotter I, Gunaydin I, Zierhut M, Stubiger N. The use of interferon alpha in Behcet disease: review of the literature. Semin Arthritis Rheum 2004; 33(5): 320-335. (Pubitemid 38496041)
91. Kotter I, Eckstein AK, Stubiger N Zierhut M. Treatment of ocular symptoms of Behcet's disease with interferon alpha 2a: a pilot study. Br J Ophthalmol 1998; 82(5): 488-494.
92. Pivetti-Pezzi P, Accorinti M, Pirraglia MP, Priori R, Valesini G Interferon alpha for ocular Behcet's disease. Acta Ophthalmol Scand 1997; 75(6): 720-722. (Pubitemid 28102747)
93. Kempen JH, Altaweel MM, Holbrook JT, Jabs DA, Sugar EA. The multicenter uveitis steroid treatment trial: rationale, design, and baseline characteristics. Am J Ophthalmol 2010; 149(4): 550-561 e10.
94. Lim LL, Smith JR, Rosenbaum JT. Retisert (Bausch & Lomb/control delivery systems). Curr Opin Investig Drugs 2005; 6(11): 1159-1167. (Pubitemid 41701187)
95. Lowder C, Belfort Jr R, Lightman S, Foster CS, Robinson MR, Schiffman RM et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol 2011; 129(5): 545-553.
96. Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T et al. Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behcet's disease susceptibility loci. Nat Genet 2010; 42(8): 703-706.
97. Remmers EF, Cosan F, Kirino Y, Ombrello MJ, Abaci N Satorius C et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease. Nat Genet 2010; 42(8): 698-702.
98. Atan D, Fraser-Bell S, Plskova J, Kuffova L, Hogan A, Tufail A et al. Cytokine polymorphism in noninfectious uveitis. Invest Ophthalmol Vis Sci 2010; 51(8): 4133-4142.
99. Atan D, Turner SJ, Kilmartin DJ, Forrester JV, Bidwell J, Dick AD et al. Cytokine gene polymorphism in sympathetic ophthalmia. Invest Ophthalmol Vis Sci 2005; 46(11): 4245-4250. (Pubitemid 44264628)
100. Atan D, Fraser-Bell S, Plskova J, Kuffova L, Hogan A, Tufail A et al. Punctate inner choroidopathy and multifocal choroiditis with panuveitis share haplotypic associations with IL10 and TNF loci. Invest Ophthalmol Vis Sci 2011; 52(6): 3573-3581.
101. McKinney EF, Lyons PA, Carr EJ, Hollis JL, Jayne DR, Willcocks LC et al. A CD8 + T cell transcription signature predicts prognosis in autoimmune disease. Nat Med 2010; 16(5): 586-591, 1p following 91.
102. Lyons PA, McKinney EF, Rayner TF, Hatton A, Woffendin HB, Koukoulaki M et al. Novel expression signatures identified by transcriptional analysis of separated leucocyte subsets in systemic lupus erythematosus and vasculitis. Ann Rheum Dis 2010; 69(6): 1208-1213.
103. Intzedy L, Teoh SC, Hogan A, Mangwana S, Mayer EJ, Dick AD et al. Cytopathological analysis of vitreous in intraocular lymphoma. Eye (Lond) 2008; 22(2): 289-293. (Pubitemid 351266473)
104. Sugita S, Shimizu N, Watanabe K, Mizukami M, Morio T, Sugamoto Y et al. Use of multiplex PCR and real-time PCR to detect human herpes virus genome in ocular fluids of patients with uveitis. Br J Ophthalmol 2008; 92(7): 928-932. (Pubitemid 351969672)
105. Ooi KG, Galatowicz G, Towler HM, Lightman SL, Calder VL. Multiplex cytokine detection versus ELISA for aqueous humor: IL-5, IL-10, and IFNgamma profiles in uveitis. Invest Ophthalmol Vis Sci 2006; 47(1): 272-277. (Pubitemid 46780824)
106. Curnow SJ, Falciani F, Durrani OM, Cheung CM, Ross EJ, Wloka K et al. Multiplex bead immunoassay analysis of aqueous humor reveals distinct cytokine profiles in uveitis. Invest Ophthalmol Vis Sci 2005; 46(11): 4251-4259. (Pubitemid 44264629)
107. Martin TM, Rosenbaum JT. Genetics in uveitis. Int Ophthalmol Clin 2005; 45(2): 15-30. (Pubitemid 40570750)
108. Martin TM, Kurz DE, Rosenbaum JT. Genetics of uveitis. Ophthalmol Clin North Am 2003; 16(4): 555-565. (Pubitemid 38044990)
109. Mackensen F, David F, Schwenger V, Smith LK, Rajalingam R, Levinson RD et al. HLA-DRB1*0102 is associated with TINU syndrome and bilateral, sudden-onset anterior uveitis but not with interstitial nephritis alone. Br J Ophthalmol 2010; 95(7): 971-975.
110. Zamecki KJ, Jabs DA. HLA typing in uveitis: use and misuse. Am J Ophthalmol 2010; 149(2): 189-193 e2.
111. Tiercy JM, Rathinam SR, Gex-Fabry M, Baglivo E. A shared HLA-DRB1 epitope in the DR beta first domain is associated with Vogt-Koyanagi-Harada syndrome in Indian patients. Mol Vis 2010; 16: 353-358.
112. Gulati N, Forooghian F, Lieberman R, Jabs DA. Vascular endothelial growth factor inhibition in uveitis: a systematic review. Br J Ophthalmol 2011; 95(2): 162-165.
113. Martin CM, Lacomba MS, Molina CI, Chamond RR, Galera JM, Estevez EC Levels of soluble ICAM-1 and soluble IL-2R in the serum and aqueous humor of uveitis patients. Curr Eye Res 2000; 20(4): 287-292. (Pubitemid 30428159)
114. Arocker-Mettinger E, Asenbauer T, Ulbrich S, Grabner G Serum interleukin 2-receptor levels in uveitis. Curr Eye Res 1990; 9(Suppl): 25-29. (Pubitemid 20295596)
115. Plskova J, Greiner K, Muckersie E, Duncan L, Forrester JV. Interferon-alpha: a key factor in autoimmune disease? Invest Ophthalmol Vis Sci 2006; 47(9): 3946-3950. (Pubitemid 46044311)
116. Kilmartin DJ, Fletcher ZJ, Almeida JA, Liversidge J, Forrester JV, Dick AD. CD69 expression on peripheral CD4 + T cells parallels disease activity and is reduced by mycophenolate mofetil therapy in uveitis. Invest Ophthalmol Vis Sci 2001; 42(6): 1285-1292. (Pubitemid 32381971)
117. Dick AD. Serological tests for monitoring and predicting disease severity, course, and outcome of autoimmune intraocular inflammation. Br J Ophthalmol 1998; 82(8): 856-857. (Pubitemid 28408139)
118. Dick AD, Cheng YF, Purdie AT, Liversidge J, Forrester JV. Immunocytochemical analysis of blood lymphocytes in uveitis. Eye (Lond) 1992; 6(Pt 6): 643-647. (Pubitemid 23056672)
119. Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med 2005; 201(9): 1479-1486. (Pubitemid 40664091)
120. Lee RW, Schewitz LP, Nicholson LB, Dayan CM, Dick AD. Steroid refractory CD4 + T cells in patients with sight-threatening uveitis. Invest Ophthalmol Vis Sci 2009; 50(9): 4273-4278.
121. Xu H, Manivannan A, Goatman KA, Liversidge J, Sharp PF, Forrester JV et al. Improved leukocyte tracking in mouse retinal and choroidal circulation. Exp Eye Res 2002; 74(3): 403-410. (Pubitemid 34948386)