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Pharmacologic Treatment of Noninfectious Uveitis

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Pharmacologic Therapy of Ocular Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 242))

Abstract

Uveitis encompasses a spectrum of diseases whose common feature is intraocular inflammation, which may be infectious or noninfectious in etiology (Nussenblatt and Whitcup 2010). Infectious causes of uveitis are typically treated with appropriate antimicrobial therapy and will not be discussed in this chapter. Noninfectious uveitides are thought have an autoimmune component to their etiology and are thus treated with anti-inflammatory agents.

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References

  • The Loteprednol Etabonate US Uveitis Study Group (1999) Controlled evaluation of loteprednol etabonate and prednisolone acetate in the treatment of acute anterior uveitis. Loteprednol Etabonate US Uveitis Study Group. Am J Ophthalmol 127:537–544

    Article  Google Scholar 

  • Abu-Shakra M, Shoenfeld Y (2001) Azathioprine therapy for patients with systemic lupus erythematosus. Lupus 10:152–153

    Article  CAS  PubMed  Google Scholar 

  • Akbari M, Shah S, Velayos FS, Mahadevan U, Cheifetz AS (2013) Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease. Inflamm Bowel Dis 19:15–22

    Article  PubMed  Google Scholar 

  • Allison AC, Eugui EM (1993) The design and development of an immunosuppressive drug, mycophenolate mofetil. Springer Semin Immunopathol 14:353–380

    Article  CAS  PubMed  Google Scholar 

  • Allison AC, Eugui EM (2000) Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 47:85–118

    Article  CAS  PubMed  Google Scholar 

  • Amadi-Obi A, Yu C-R, Liu X et al (2007) TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 13:711–718

    Article  CAS  PubMed  Google Scholar 

  • Andrasch RH, Pirofsky B, Burns RP (1978) Immunosuppressive therapy for severe chronic uveitis. Arch Ophthalmol 96:247–251

    Article  CAS  PubMed  Google Scholar 

  • Arida A, Fragiadaki K, Giavri E, Sfikakis PP (2011) Anti-TNF agents for Behcet’s disease: analysis of published data on 369 patients. Semin Arthritis Rheum 41:61–70

    Article  CAS  PubMed  Google Scholar 

  • Avramut M, Zeevi A, Achim CL (2001) The immunosuppressant drug FK506 is a potent trophic agent for human fetal neurons. Brain Res Dev Brain Res 132:151–157

    Article  CAS  PubMed  Google Scholar 

  • Baltatzis S, Tufail F, Yu EN, Vredeveld CM, Foster CS (2003) Mycophenolate mofetil as an immunomodulatory agent in the treatment of chronic ocular inflammatory disorders. Ophthalmologe 110:1061–1065

    Article  Google Scholar 

  • Bar Oz B, Hackman R, Einarson T, Koren G (2001) Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis. Transplantation 71:1051–1055

    Article  CAS  PubMed  Google Scholar 

  • Barbarino JM, Staatz CE, Venkataramanan R, Klein TE, Altman RB (2013) PharmGKB summary: cyclosporine and tacrolimus pathways. Pharmacogenet Genomics 23:563–585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barnes PJ (2011) Glucocorticosteroids: current and future directions. Br J Pharmacol 163:29–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Becker B, Mills DW (1963) Elevated intraocular pressure following corticosteroid eye drops. JAMA 185:884–886

    Article  CAS  PubMed  Google Scholar 

  • Berk PD, Goldberg JD, Silverstein MN et al (1981) Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. N Engl J Med 304:441–447

    Article  CAS  PubMed  Google Scholar 

  • Birnbaum AD, Jiang Y, Tessler HH, Goldstein DA (2011) Elevation of intraocular pressure in patients with uveitis treated with topical difluprednate. Arch Ophthalmol 129:667–668

    PubMed  Google Scholar 

  • Blumenfeld Z, Haim N (1997) Prevention of gonadal damage during cytotoxic therapy. Ann Med 29:199–206

    Article  CAS  PubMed  Google Scholar 

  • Blumenfeld Z, Shapiro D, Shteinberg M, Avivi I, Nahir M (2000) Preservation of fertility and ovarian function and minimizing gonadotoxicity in young women with systemic lupus erythematosus treated by chemotherapy. Lupus 9:401–405

    Article  CAS  PubMed  Google Scholar 

  • Bouma MG, Stad RK, van den Wildenberg FA, Buurman WA (1994) Differential regulatory effects of adenosine on cytokine release by activated human monocytes. J Immunol 153:4159–4168

    CAS  PubMed  Google Scholar 

  • Broekman MTJ, Roelofs HMJ et al (2015) Allopurinol and 5-aminosalicylic acid influence thiopurine-induced hepatotoxicity in vitro. Cell Biol Toxicol 31:161–171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bung P, Molitor D (1991) Pregnancy and postpartum after kidney transplantation and cyclosporine therapy -- review of the literature adding a new case. J Perinat Med 19:397–401

    Article  CAS  PubMed  Google Scholar 

  • Cagini C, Cometa F, Torroni G, Pellegrino A, Pellegrino R, Cavallini GM (2016) Dexamethasone disodium phosphate penetration into the human aqueous humor after topical application. Curr Eye Res 41(7):897–899

    Article  CAS  PubMed  Google Scholar 

  • Callanan DG, Jaffe GJ, Martin DF, Pearson PA, Comstock TL (2008) Treatment of posterior uveitis with a fluocinolone acetonide implant: three-year clinical trial results. Arch Ophthalmol 126:1191–1201

    Article  PubMed  Google Scholar 

  • Calvo-Rio V, Blanco R, Beltran E et al (2014a) Anti-TNF-alpha therapy in patients with refractory uveitis due to Behcet’s disease: a 1-year follow-up study of 124 patients. Rheumatology 53:2223–2231

    Article  PubMed  Google Scholar 

  • Calvo-Rio V, de la Hera D, Blanco R et al (2014b) Golimumab in uveitis previously treated with other anti-TNF-alpha drugs: a retrospective study of three cases from a single centre and literature review. Clin Exp Rheumatol 32:864–868

    PubMed  Google Scholar 

  • Cantarini L, Lopalco G, Caso F et al (2015) Effectiveness and tuberculosis-related safety profile of interleukin-1 blocking agents in the management of Behcet’s disease. Autoimmun Rev 14:1–9

    Article  CAS  PubMed  Google Scholar 

  • Cao JH, Oray M, Cocho L, Stephen Foster C (2016) Rituximab in the treatment of refractory non-infectious scleritis. Am J Ophthalmol 164:22–28

    Article  CAS  PubMed  Google Scholar 

  • Caprilli R, Gassull MA, Escher JC, European Crohn’s and Colitis Organisation et al (2006) European evidence based consensus on the diagnosis and management of Crohn’s disease: special situations. Gut 55:i36–i58

    Article  PubMed  PubMed Central  Google Scholar 

  • Caso F, Rigante D, Vitale A et al (2015) Long-lasting uveitis remission and hearing loss recovery after rituximab in Vogt-Koyanagi-Harada disease. Clin Rheumatol 34:1817–1820

    Article  PubMed  Google Scholar 

  • Chan ES, Cronstein BN (2002) Molecular action of methotrexate in inflammatory diseases. Arthritis Res 4:266–273

    Article  PubMed  PubMed Central  Google Scholar 

  • Chan ES, Cronstein BN (2013) Mechanisms of action of methotrexate. Bull Hosp Joint Dis 71(Suppl 1):S5–S8

    Google Scholar 

  • Chanaud NP 3rd, Vistica BP, Eugui E, Nussenblatt RB, Allison AC, Gery I (1995) Inhibition of experimental autoimmune uveoretinitis by mycophenolate mofetil, an inhibitor of purine metabolism. Exp Eye Res 61:429–434

    Article  CAS  PubMed  Google Scholar 

  • Chang-Lin JE, Attar M, Acheampong AA et al (2011a) Pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone intravitreal implant. Invest Ophthalmol Vis Sci 52:80–86

    Article  CAS  PubMed  Google Scholar 

  • Chang-Lin JE, Burke JA, Peng Q et al (2011b) Pharmacokinetics of a sustained-release dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes. Invest Ophthalmol Vis Sci 52:4605–4609

    Article  CAS  PubMed  Google Scholar 

  • Clifford DB, Ances B, Costello C et al (2011) Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis. Arch Neurol 68:1156–1164

    Article  PubMed  PubMed Central  Google Scholar 

  • Clunie GPR, Lennard L (2004) Relevance of thiopurine methyltransferase status in rheumatology patients receiving azathioprine. Rheumatology 43:13–18

    Article  CAS  PubMed  Google Scholar 

  • Constantin A, Loubet-Lescoulie P, Lambert N et al (1998) Antiinflammatory and immunoregulatory action of methotrexate in the treatment of rheumatoid arthritis: evidence of increased interleukin-4 and interleukin-10 gene expression demonstrated in vitro by competitive reverse transcriptase-polymerase chain reaction. Arthritis Rheum 41:48–57

    Article  CAS  PubMed  Google Scholar 

  • Cordero-Coma M, Salom D, Diaz-Llopis M, Lopez-Prats MJ, Calleja S (2011) Golimumab for uveitis. Ophthalmology 118:1892.e3-4

    Google Scholar 

  • Cordero-Coma M, Calvo-Rio V, Adan A et al (2014) Golimumab as rescue therapy for refractory immune-mediated uveitis: a three-center experience. Mediators Inflamm 2014:717598

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cornish KS, Kuffova L, Forrester JV (2015) Treatment of diffuse subretinal fibrosis uveitis with rituximab. Br J Ophthalmol 99:153–154

    Article  PubMed  Google Scholar 

  • Cox PJ (1979) Cyclophosphamide cystitis--identification of acrolein as the causative agent. Biochem Pharmacol 28:2045–2049

    Article  CAS  PubMed  Google Scholar 

  • Cronstein BN, Naime D, Ostad E (1993) The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 92:2675–2682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cunningham MA, Edelman JL, Kaushal S (2008) Intravitreal steroids for macular edema: the past, the present, and the future. Surv Ophthalmol 53:139–149

    Article  PubMed  Google Scholar 

  • Dal Canto AJ, Downs-Kelly E, Perry JD (2005) Ptosis and orbital fat prolapse after posterior sub-Tenon’s capsule triamcinolone injection. Ophthalmology 112:1092–1097

    Article  PubMed  Google Scholar 

  • Daniel E, Thorne JE, Newcomb CW et al (2010) Mycophenolate mofetil for ocular inflammation. Am J Ophthalmol 149:423–32.e1-2

    Google Scholar 

  • Danovitch GM (1999) Choice of immunosuppressive drugs and individualization of immunosuppressive therapy for kidney transplant patients. Transplant Proc 31:2S–6S

    Article  CAS  PubMed  Google Scholar 

  • Davatchi F, Shams H, Rezaipoor M et al (2010) Rituximab in intractable ocular lesions of Behcet’s disease; randomized single-blind control study (pilot study). Int J Rheum Dis 13:246–252

    Article  PubMed  Google Scholar 

  • de Jonge ME, Huitema AD, Rodenhuis S, Beijnen JH (2005) Clinical pharmacokinetics of cyclophosphamide. Clin Pharmacokinet 44:1135–1164

    Article  PubMed  Google Scholar 

  • De Smet MD, Nussenblatt RB (1993) Clinical use of cyclosporine in ocular disease. Int Ophthalmol Clin 33:31–45

    Article  PubMed  Google Scholar 

  • Deroux A, Chiquet C, Bouillet L (2015) Tocilizumab in severe and refractory Behcet’s disease: four cases and literature review. Semin Arthritis Rheum. doi:10.1016/j.semarthrit.2015.11.012

    PubMed  Google Scholar 

  • Deuter CM, Zierhut M, Igney-Oertel A et al (2016) Tocilizumab in uveitic macular edema refractory to previous immunomodulatory treatment. Ocul Immunol Inflamm 5:1–6 (Epub ahead of print)

    Google Scholar 

  • Diav-Citrin O, Otcheretianski-Volodarsky A, Shechtman S, Ornoy A (2014) Pregnancy outcome following gestational exposure to TNF-alpha-inhibitors: a prospective, comparative, observational study. Reprod Toxicol 43:78–84

    Article  CAS  PubMed  Google Scholar 

  • Díaz-Llopis M, Salom D, Garcia-de-Vicuña C et al (2012) Treatment of refractory uveitis with adalimumab: a prospective multicenter study of 131 patients. Ophthalmology 119:1575–1581

    Article  PubMed  Google Scholar 

  • Djokanovic N, Klieger-Grossmann C, Pupco A, Koren G (2011) Safety of infliximab use during pregnancy. Reprod Toxicol 32:93–97

    Article  CAS  PubMed  Google Scholar 

  • Doycheva D, Zierhut M, Blumenstock G, Stuebiger N, Deuter C (2011) Long-term results of therapy with mycophenolate mofetil in chronic non-infectious uveitis. Graefes Arch Clin Exp Ophthalmol 249:1235–1243

    Article  CAS  PubMed  Google Scholar 

  • Doycheva D, Zierhut M, Blumenstock G et al (2014) Immunomodulatory therapy with tumour necrosis factor alpha inhibitors in children with antinuclear antibody-associated chronic anterior uveitis: long-term results. Br J Ophthalmol 98:523–528

    Article  PubMed  Google Scholar 

  • Durrani K, Papaliodis GN, Foster CS (2004) Pulse IV cyclophosphamide in ocular inflammatory disease: efficacy and short-term safety. Ophthalmology 111:960–965

    Article  PubMed  Google Scholar 

  • Durrani K, Zakka FR, Ahmed M, Memon M, Siddique SS, Foster CS (2011) Systemic therapy with conventional and novel immunomodulatory agents for ocular inflammatory disease. Surv Ophthalmol 56:474–510

    Article  PubMed  Google Scholar 

  • Ekstrom K, Hjalgrim H, Brandt L et al (2003) Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first-degree relatives. Arthritis Rheum 48:963–970

    Article  PubMed  Google Scholar 

  • Elion GB (1989) The purine path to chemotherapy. Science 244:41–47

    Article  CAS  PubMed  Google Scholar 

  • Elion GB (1993) The George Hitchings and Gertrude Elion lecture. The pharmacology of azathioprine. Ann N Y Acad Sci 685:400–407

    Article  CAS  PubMed  Google Scholar 

  • Faez S, Lobo AM, Sobrin L, Papaliodis GN (2014) Treatment of seronegative spondyloarthropathy-associated uveitis with golimumab: retrospective case series. Clin Experiment Ophthalmol 42:392–395

    Article  PubMed  Google Scholar 

  • Farber S, Diamond LK, Mercer RD et al (1948) Temporary remissions in acute leukemia in children produced by folic antagonist 4-aminopteroylglutamic acid (aminopterin). N Engl J Med 238:787–793

    Article  CAS  PubMed  Google Scholar 

  • FDA (2008) Communication about an ongoing safety review of CellCept (mycophenolate mofetil) and Myfortic (mycophenolate acid). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm072438.htm

  • Felinski EA, Cox AE, Phillips BE, Antonetti DA (2008) Glucocorticoids induce transactivation of tight junction genes occludin and claudin-5 in retinal endothelial cells via a novel cis-element. Exp Eye Res 86:867–878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferrante P, Ramsey A, Bunce C, Lightman S (2004) Clinical trial to compare efficacy and side-effects of injection of posterior sub-Tenon triamcinolone versus orbital floor methylprednisolone in the management of posterior uveitis. Clin Experiment Ophthalmol 32:563–568

    Article  PubMed  Google Scholar 

  • Florey HW, Jennings MA et al (1946) Mycophenolic acid; an antibiotic from Penicillium brevicompactum Dlerckx. Lancet 1:46–49

    Article  CAS  PubMed  Google Scholar 

  • Polack FM (1967) Effect of azathioprine (Imuran) on corneal graft reaction. Am J Ophthalmol 64:233–244

    Article  CAS  PubMed  Google Scholar 

  • Foster CS, Davanzo R, Flynn TE, McLeod K, Vogel R, Crockett RS (2010) Durezol (Difluprednate Ophthalmic Emulsion 0.05%) compared with Pred Forte 1% ophthalmic suspension in the treatment of endogenous anterior uveitis. J Ocul Pharmacol Ther 26:475–483

    Article  CAS  PubMed  Google Scholar 

  • Foster CS, Kothari S, Anesi SD et al (2016) The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol 61:1–17

    Article  PubMed  Google Scholar 

  • Frunzi J (2007) From weapon to wonder drug. Hospitalist

    Google Scholar 

  • Gallego-Pinazo R, Dolz-Marco R, Martinez-Castillo S, Arevalo JF, Diaz-Llopis M (2013) Update on the principles and novel local and systemic therapies for the treatment of non-infectious uveitis. Inflamm Allergy Drug Targets 12:38–45

    Article  CAS  PubMed  Google Scholar 

  • Galor A, Perez VL, Hammel JP, Lowder CY (2006) Differential effectiveness of etanercept and infliximab in the treatment of ocular inflammation. Ophthalmology 113:2317–2323

    Article  PubMed  Google Scholar 

  • Galor A, Jabs DA, Leder HA et al (2008) Comparison of antimetabolite drugs as corticosteroid-sparing therapy for noninfectious ocular inflammation. Ophthalmology 115:1826–1832

    Article  PubMed  Google Scholar 

  • Gangaputra S, Newcomb CW, Liesegang TL et al (2009) Methotrexate for ocular inflammatory diseases. Ophthalmology 116:2188–2198.e1

    Article  PubMed  PubMed Central  Google Scholar 

  • Gaujoux-Viala C, Giampietro C, Gaujoux T et al (2012) Scleritis: a paradoxical effect of etanercept? Etanercept-associated inflammatory eye disease. J Rheumatol 39:233–239

    Article  CAS  PubMed  Google Scholar 

  • Geborek P, Bladstrom A, Turesson C et al (2005) Tumour necrosis factor blockers do not increase overall tumour risk in patients with rheumatoid arthritis, but may be associated with an increased risk of lymphomas. Ann Rheum Dis 64:699–703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Genovese MC, Rubbert-Roth A, Smolen JS et al (2013) Longterm safety and efficacy of tocilizumab in patients with rheumatoid arthritis: a cumulative analysis of up to 4.6 years of exposure. J Rheumatol 40:768–780

    Article  CAS  PubMed  Google Scholar 

  • Gerosa M, Meroni PL, Cimaz R (2014) Safety considerations when prescribing immunosuppression medication to pregnant women. Expert Opin Drug Saf 13:1591–1599

    Article  CAS  PubMed  Google Scholar 

  • Ghisdal L, Bouchta NB, Broeders N et al (2008) Conversion from tacrolimus to cyclosporine A for new-onset diabetes after transplantation: a single-centre experience in renal transplanted patients and review of the literature. Transpl Int 21:146–151

    CAS  PubMed  Google Scholar 

  • Giles CL (1974) Bulbar perforation during periocular injection of corticosteroids. Am J Ophthalmol 77:438–441

    Article  CAS  PubMed  Google Scholar 

  • Godfrey WA, Epstein WV, O’Connor GR et al (1974) The use of chlorambucil in intractable idiopathic uveitis. Am J Ophthalmol 78:415–428

    Article  CAS  PubMed  Google Scholar 

  • Goldstein DA, Fontanilla FA, Kaul S, Sahin O, Tessler HH (2002) Long-term follow-up of patients treated with short-term high-dose chlorambucil for sight-threatening ocular inflammation. Ophthalmology 109:370–377

    Article  PubMed  Google Scholar 

  • Goodman LS, Wintrobe MM et al (1946) Nitrogen mustard therapy; use of methyl-bis (beta-chloroethyl) amine hydrochloride and tris (beta-chloroethyl) amine hydrochloride for Hodgkin’s disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. JAMA 132:126–132

    Article  CAS  Google Scholar 

  • Gordon DM, Mc LJ, Koteen H et al (1951) The use of ACTH and cortisone in ophthalmology. Am J Ophthalmol 34:1675–1686

    Article  CAS  PubMed  Google Scholar 

  • Gout T, Ostor AJ, Nisar MK (2011) Lower gastrointestinal perforation in rheumatoid arthritis patients treated with conventional DMARDs or tocilizumab: a systematic literature review. Clin Rheumatol 30:1471–1474

    Article  PubMed  Google Scholar 

  • Greenwood AJ, Stanford MR, Graham EM (1998) The role of azathioprine in the management of retinal vasculitis. Eye 12:783–788

    Article  PubMed  Google Scholar 

  • Greiner K, Varikkara M, Santiago C, Forrester JV (2002) Efficiency of mycophenolate mofetil in the treatment of intermediate and posterior uveitis. Ophthalmologe 99:691–694

    Article  CAS  PubMed  Google Scholar 

  • Group TLMSSGaTUoBCMMA (1999) TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. Neurology 53:457–465

    Article  Google Scholar 

  • Gul FC, Turgut B, Dagli F, Ilhan N, Ozgen M (2013) The comparison of the impact of ghrelin and tacrolimus on vitreous cytokine levels in an experimental uveitis model. Graefes Arch Clin Exp Ophthalmol 251:1235–1241

    Article  CAS  PubMed  Google Scholar 

  • Habot-Wilner Z, Sallam A, Pacheco PA, Do HH, McCluskey P, Lightman S (2011) Intravitreal triamcinolone acetonide as adjunctive treatment with systemic therapy for uveitic macular edema. Eur J Ophthalmol 21(Suppl 6):S56–S61

    Article  PubMed  Google Scholar 

  • Hamuryudan V, Ozyazgan Y, Hizli N et al (1997) Azathioprine in Behçet’s syndrome: effects on long-term prognosis. Arthritis Rheum 40:769–774

    Article  CAS  PubMed  Google Scholar 

  • Hardwig PW, Pulido JS, Erie JC, Baratz KH, Buettner H (2006) Intraocular methotrexate in ocular diseases other than primary central nervous system lymphoma. Am J Ophthalmol 142:883–885

    Article  CAS  PubMed  Google Scholar 

  • Isnard Bagnis C, Tezenas du Montcel S, Beaufils H et al (2002) Long-term renal effects of low-dose cyclosporine in uveitis-treated patients: follow-up study. J Am Soc Nephrol 13:2962–2968

    Article  CAS  PubMed  Google Scholar 

  • Jabs DA, Rosenbaum JT, Foster CS et al (2000) Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol 130:492–513

    Article  CAS  PubMed  Google Scholar 

  • Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature Working Group (2005) Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol 140:509–516

    Article  PubMed  Google Scholar 

  • Kacmaz RO, Kempen JH, Newcomb C et al (2010) Cyclosporine for ocular inflammatory diseases. Ophthalmology 117:576–584

    Article  PubMed  PubMed Central  Google Scholar 

  • Kashani S, Mearza AA (2008) Uses and safety profile of ciclosporin in ophthalmology. Expert Opin Drug Saf 7:79–89

    Article  CAS  PubMed  Google Scholar 

  • Kawashima H, Fujino Y, Mochizuki M (1988) Effects of a new immunosuppressive agent, FK506, on experimental autoimmune uveoretinitis in rats. Invest Ophthalmol Vis Sci 29:1265–1271

    CAS  PubMed  Google Scholar 

  • Kay J, Fleischmann R, Keystone E et al (2015) Golimumab 3-year safety update: an analysis of pooled data from the long-term extensions of randomised, double-blind, placebo-controlled trials conducted in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. Ann Rheum Dis 74:538–546

    Article  CAS  PubMed  Google Scholar 

  • Kearsley-Fleet L, Davies R, Baildam E et al (2016) Factors associated with choice of biologic among children with Juvenile Idiopathic Arthritis: results from two UK paediatric biologic registers. Rheumatology (Oxford) 55(9):1556–1565

    Article  Google Scholar 

  • Keil JM, Liu X, Antonetti DA (2013) Glucocorticoid induction of occludin expression and endothelial barrier requires transcription factor p54 NONO. Invest Ophthalmol Vis Sci 54:4007–4015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kempen JH, Gangaputra S, Daniel E, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Suhler EB, Thorne JE, Foster CS, Jabs DA, Helzlsouer KJ (2008) Long-term risk of malignancy among patients treated with immunosuppresive agents for ocular inflammation: a critical assessment of the evidence. Am J Ophthalmol 146:802–812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan MF, Arlet J, Bloch-Michel H et al (1979) Acute leukemias after treatment using cytotoxic agents for rheumatologic purpose. Nouv Presse Med 8:1393–1397

    Google Scholar 

  • Khan IJ, Barry RJ, Amissah-Arthur KN et al (2013) Ten-year experience of pulsed intravenous cyclophosphamide and methylprednisolone protocol (PICM protocol) in severe ocular inflammatory disease. Br J Ophthalmol 97:1118–1122

    Article  PubMed  Google Scholar 

  • Kilmartin DJ, Forrester JV, Dick AD (1998a) Tacrolimus (FK506) in failed cyclosporine A therapy in endogenous posterior uveitis. Ocul Immunol Inflamm 6:101–109

    Article  CAS  PubMed  Google Scholar 

  • Kilmartin DJ, Forrester JV, Dick AD (1998b) Rescue therapy with mycophenolate mofetil in refractory uveitis. Lancet 352:35–36

    Article  CAS  PubMed  Google Scholar 

  • Kim EC, Foster CS (2006) Immunomodulatory therapy for the treatment of ocular inflammatory disease: evidence-based medicine recommendations for use. Int Ophthalmol Clin 46:141–164

    Article  PubMed  Google Scholar 

  • Knickelbein J, Jaworski L, Hasan J, Kaushal P, Sen HN, Nussenblatt RB (2015) Therapeutic options for the treatment of non-infectious uveitis. Expert Rev Ophthalmol 10:359–373

    Article  CAS  Google Scholar 

  • Koike T, Harigai M, Inokuma S et al (2014) Effectiveness and safety of tocilizumab: postmarketing surveillance of 7901 patients with rheumatoid arthritis in Japan. J Rheumatol 41:15–23

    Article  CAS  PubMed  Google Scholar 

  • Kramer M, Monselise Y, Bahar I, Cohen Y, Weinberger D, Goldenberg-Cohen N (2007) Serum cytokine levels in active uveitis and remission. Curr Eye Res 32:669–675

    Article  CAS  PubMed  Google Scholar 

  • Kruh J, Foster CS (2012) Corticosteroid-sparing agents: conventional systemic immunosuppressants. Dev Ophthalmol 51:29–46

    Article  CAS  PubMed  Google Scholar 

  • Kruh JN, Yang P, Suelves AM, Foster CS (2014) Infliximab for the treatment of refractory noninfectious uveitis: a study of 88 patients with long-term follow-up. Ophthalmology 121:358–364

    Article  PubMed  Google Scholar 

  • Lafranco Dafflon M, Tran VT, Guex-Crosier Y, Herbort CP (1999) Posterior sub-Tenon’s steroid injections for the treatment of posterior ocular inflammation: indications, efficacy and side effects. Graefes Arch Clin Exp Ophthalmol 237:289–295

    Article  CAS  PubMed  Google Scholar 

  • Lally L, Spiera R (2015) Current therapies for ANCA-associated vasculitis. Annu Rev Med 66:227–240

    Article  CAS  PubMed  Google Scholar 

  • Larkin G, Lightman S (1999) Mycophenolate mofetil. A useful immunosuppressive in inflammatory eye disease. Ophthalmology 106:370–374

    Article  CAS  PubMed  Google Scholar 

  • Larson T, Nussenblatt RB, Sen HN (2011) Emerging drugs for uveitis. Expert Opin Emerg Drugs 16:309–322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lau CH, Comer M, Lightman S (2003) Long-term efficacy of mycophenolate mofetil in the control of severe intraocular inflammation. Clin Experiment Ophthalmol 31:487–491

    Article  PubMed  Google Scholar 

  • Lee JC, Gladman DD, Schentag CT, Cook RJ (2001) The longterm use of azathioprine in patients with psoriatic arthritis. J Clin Rheumatol 7:160–165

    Article  CAS  PubMed  Google Scholar 

  • Letko E, Yeh S, Foster CS, Pleyer U, Brigell M, Grosskreutz CL (2015) Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy. Ophthalmology 122:939–948

    Article  PubMed  Google Scholar 

  • Levy-Clarke G, Jabs DA, Read RW, Rosenbaum JT, Vitale A, Van Gelder RN (2014) Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology 121:785–796.e3

    Article  PubMed  Google Scholar 

  • Lim LL, Fraunfelder FW, Rosenbaum JT (2007) Do tumor necrosis factor inhibitors cause uveitis? A registry-based study. Arthritis Rheum 56:3248–3252

    Article  CAS  PubMed  Google Scholar 

  • Lin P (2015) Targeting interleukin-6 for noninfectious uveitis. Clin Ophthalmol 9:1697–1702

    Article  PubMed  PubMed Central  Google Scholar 

  • Llorenc V, Mesquida M, Sainz de la Maza M et al (2015) Certolizumab Pegol, a new anti-TNF-alpha in the armamentarium against ocular inflammation. Ocul Immunol Inflamm 24:167–172

    Google Scholar 

  • Lowder C, Belfort R Jr, Lightman S et al (2011) Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol 129:545–553

    Article  PubMed  Google Scholar 

  • Maiz Alonso O, Blanco Esteban AC, Egues Dubuc CA, Martinez Zabalegui D (2015) Effectiveness of certolizumab pegol in chronic anterior uveitis associated to Crohn’s disease and ankylosing spondylitis. Reumatol Clin 11:189–190

    Article  PubMed  Google Scholar 

  • Maltzman JS, Koretzky GA (2003) Azathioprine: old drug, new actions. J Clin Invest 111:1122–1124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mamo JG (1976) Treatment of Behcet disease with chlorambucil. A follow-up report. Arch Ophthalmol 94:580–583

    Article  CAS  PubMed  Google Scholar 

  • Manz I, Dietrich I, Przybylski M et al (1985) Identification and quantification of metabolite conjugates of activated cyclophosphamide and ifosfamide with mesna in urine by ion-pair extraction and fast atom bombardment mass spectrometry. Biomed Mass Spectrom 12:545–553

    Article  CAS  PubMed  Google Scholar 

  • Marticorena J, Romano V, Gomez-Ulla F (2012) Sterile endophthalmitis after intravitreal injections. Mediators Inflamm 2012:928123

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Martin F, Lauwerys B, Lefebvre C, Devogelaer JP, Houssiau FA (1997) Side-effects of intravenous cyclophosphamide pulse therapy. Lupus 6:254–257

    Article  CAS  PubMed  Google Scholar 

  • Mason JO 3rd, Somaiya MD, Singh RJ (2004) Intravitreal concentration and clearance of triamcinolone acetonide in nonvitrectomized human eyes. Retina 24:900–904

    Article  PubMed  Google Scholar 

  • Masuda K, Nakajima A, Urayama A et al (1989) Double masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behcet’s disease. Lancet 1:1093–1096

    Article  CAS  PubMed  Google Scholar 

  • Mathews JD, Crawford BA, Bignell JL, Mackay IR (1969) Azathioprine in active chronic iridocyclitis. A double-blind controlled trial. Br J Ophthalmol 53:327–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McKay DB, Josephson MA (2008) Pregnancy after kidney transplantation. Clin J Am Soc Nephrol 3(Suppl 2):S117–S125

    Article  PubMed  PubMed Central  Google Scholar 

  • Mesquida M, Molins B, Llorenc V, de la Maza MS, Adan A (2014) Long-term effects of tocilizumab therapy for refractory uveitis-related macular edema. Ophthalmology 121:2380–2386

    Article  PubMed  Google Scholar 

  • Miserocchi E, Baltatzis S, Ekong A, Roque M, Foster CS (2002) Efficacy and safety of chlorambucil in intractable noninfectious uveitis: the Massachusetts Eye and Ear Infirmary experience. Ophthalmology 109:137–142

    Article  PubMed  Google Scholar 

  • Miserocchi E, Modorati G, Pontikaki I, Meroni PL, Gerloni V (2014) Long-term treatment with golimumab for severe uveitis. Ocul Immunol Inflamm 22:90–95

    Article  CAS  PubMed  Google Scholar 

  • Miserocchi E, Modorati G, Berchicci L, Pontikaki I, Meroni P, Gerloni V (2015) Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis. Br J Ophthalmol. doi:10.1136/bjophthalmol-2015-306790

    PubMed  Google Scholar 

  • Moisseiev E, Shulman S (2014) Certolizumab-induced uveitis: a case report and review of the literature. Case Rep Ophthalmol 5:54–59

    Article  PubMed  PubMed Central  Google Scholar 

  • Moller A, Iwasaki K, Kawamura A et al (1999) The disposition of 14C-labeled tacrolimus after intravenous and oral administration in healthy human subjects. Drug Metab Dispos 27:633–636

    CAS  PubMed  Google Scholar 

  • Monach PA, Arnold LM, Merkel PA (2010) Incidence and prevention of bladder toxicity from cyclophosphamide in the treatment of rheumatic diseases: a data-driven review. Arthritis Rheum 62:9–21

    Article  CAS  PubMed  Google Scholar 

  • Mora PF (2010) New-onset diabetes after renal transplantation. J Invest Med 58:755–763

    Article  CAS  Google Scholar 

  • Multicenter Uveitis Steroid Treatment Trial Follow-up Study Research Group (2015) Quality of life and risks associated with systemic anti-inflammatory therapy versus fluocinolone acetonide intraocular implant for intermediate uveitis, posterior uveitis, or panuveitis: fifty-four-month results of the Multicenter Uveitis Steroid Treatment Trial and Follow-up Study. Ophthalmology 122:1976–1986

    Article  Google Scholar 

  • Multicenter Uveitis Steroid Treatment Trial Research Group, Kempen JH, Altaweel MM, Holbrook JT, Jabs DA, Sugar EA (2010) The multicenter uveitis steroid treatment trial: rationale, design, and baseline characteristics. Am J Ophthalmol 149:550–561.e10

    Article  CAS  Google Scholar 

  • Multicenter Uveitis Steroid Treatment Trial Research Group, Kempen JH, Altaweel MM et al (2015) Benefits of systemic anti-inflammatory therapy versus fluocinolone acetonide intraocular implant for intermediate uveitis, posterior uveitis, and panuveitis: fifty-four-month results of the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. Ophthalmology 122:1967–1975

    Article  Google Scholar 

  • Murphy CC, Ayliffe WH, Booth A, Makanjuola D, Andrews PA, Jayne D (2004) Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis. Ophthalmology 111:352–356

    Article  PubMed  Google Scholar 

  • Murphy CC, Greiner K, Plskova J et al (2005) Cyclosporine vs tacrolimus therapy for posterior and intermediate uveitis. Arch Ophthalmol 123:634–641

    Article  CAS  PubMed  Google Scholar 

  • Murray JE, Merrill JP, Harrison JH, Wilson RE, Dammin GJ (1963) Prolonged survival of human-kidney homografts by immunosuppressive drug therapy. N Engl J Med 268:1315–1323

    Article  CAS  PubMed  Google Scholar 

  • Murray PI, Hoekzema R, van Haren MA, de Hon FD, Kijlstra A (1990) Aqueous humor interleukin-6 levels in uveitis. Invest Ophthalmol Vis Sci 31:917–920

    CAS  PubMed  Google Scholar 

  • Muselier A, Bielefeld P, Bidot S, Vinit J, Besancenot J-F, Bron A (2011) Efficacy of tocilizumab in two patients with anti-TNF-alpha refractory uveitis. Ocul Immunol Inflamm 19:382–383

    Article  CAS  PubMed  Google Scholar 

  • Nakamura S, Yamakawa T, Sugita M et al (1994) The role of tumor necrosis factor-alpha in the induction of experimental autoimmune uveoretinitis in mice. Invest Ophthalmol Vis Sci 35:3884–3889

    CAS  PubMed  Google Scholar 

  • Neff RT, Hurst FP, Falta EM et al (2008) Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation. Transplantation 86:1474–1478

    Article  PubMed  Google Scholar 

  • Nevers W, Pupco A, Koren G, Bozzo P (2014) Safety of tacrolimus in pregnancy. Can Fam Physician 60:905–906

    PubMed  PubMed Central  Google Scholar 

  • Nguyen K, Vleugels RA, Velez NF, Merola JF, Qureshi AA (2013) Psoriasiform reactions to anti-tumor necrosis factor alpha therapy. J Clin Rheumatol 19:377–381

    Article  PubMed  Google Scholar 

  • Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J (2009) Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis 68:1580–1584

    Article  CAS  PubMed  Google Scholar 

  • Nussenblatt RB, Whitcup SM (2010) Uveitis: fundamentals and clinical practice, 4th edn. Mosby/Elsevier, Amsterdam/Edinburgh

    Google Scholar 

  • Nussenblatt RB, Palestine AG, Rook AH, Scher I, Wacker W, Gery I (1983a) Treatment of intraocular inflammatory disease with Cyclosporine A. Lancet 2:235–238

    Article  CAS  PubMed  Google Scholar 

  • Nussenblatt RB, Palestine AG, Chan CC (1983b) Cyclosporine A therapy in the treatment of intraocular inflammatory disease resistant to systemic corticosteroids and cytotoxic agents. Am J Ophthalmol 96:275–282

    Article  CAS  PubMed  Google Scholar 

  • Nussenblatt RB, Palestine AG, Chan CC, Stevens G Jr, Mellow SD, Green SB (1991) Randomized, double-masked study of cyclosporine compared to prednisolone in the treatment of endogenous uveitis. Am J Ophthalmol 112:138–146

    Article  CAS  PubMed  Google Scholar 

  • Onishi SM, Asahi MG, Chou C, Gallemore RP (2015) Topical difluprednate for the treatment of Harada’s disease. Clin Ophthalmol 9:157–167

    CAS  PubMed  PubMed Central  Google Scholar 

  • Oshitari T, Kajita F, Tobe A et al (2012) Refractory uveitis in patient with castleman disease successfully treated with tocilizumab. Case Rep Ophthalmol Med 2012:968180

    PubMed  PubMed Central  Google Scholar 

  • Ostensen M, Förger F (2013) How safe are anti-rheumatic drugs during pregnancy? Curr Opin Pharmacol 13:470–475

    Article  PubMed  CAS  Google Scholar 

  • Ozyazgan Y, Yurdakul S, Yazici H et al (1992) Low dose cyclosporin A versus pulsed cyclophosphamide in Behcet’s syndrome: a single masked trial. Br J Ophthalmol 76:241–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palmer R, Doré CJ, Denman AM (1984) Chlorambucil-induced chromosome damage to human lymphocytes is dose-dependent and cumulative. Lancet 1:246–249

    Article  CAS  PubMed  Google Scholar 

  • Papo M, Bielefeld P, Vallet H et al (2014) Tocilizumab in severe and refractory non-infectious uveitis. Clin Exp Rheumatol 32:S75–S79

    PubMed  Google Scholar 

  • Pasadhika S, Kempen JH, Newcomb CW et al (2009) Azathioprine for ocular inflammatory diseases. Am J Ophthalmol 148:500–509.e2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel SS, Dodds EM, Echandi LV et al (2014) Long-term, drug-free remission of sympathetic ophthalmia with high-dose, short-term chlorambucil therapy. Ophthalmology 121:596–602

    Article  PubMed  Google Scholar 

  • Perez R (1951) Case of uveitis of unknown etiology treated with nitrogen mustards. Rev Clin Esp 41:265–267

    Google Scholar 

  • Perez V, Papaliodis G, Chu D, Anzaar F, Christen W, Foster C (2004) Elevated levels of interleukin 6 in the vitreous fluid of patients with pars planitis and posterior uveitis: the Massachusetts eye & ear experience and review of previous studies. Ocul Immunol Inflamm 12:205–214

    Article  CAS  Google Scholar 

  • Pujari SS, Kempen H, Newcomb CW, Gangaputra S, Daniel E, Suhler EB, Thorne JE, Jabs DA, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Foster CS (2010) Cyclophosphamide for ocular inflammatory diseases. Ophthalmology 117:356–365

    Article  PubMed  Google Scholar 

  • Querques L, Querques G, Lattanzio R et al (2013) Repeated intravitreal dexamethasone implant (Ozurdex(R)) for retinal vein occlusion. Ophthalmologica 229:21–25

    Article  CAS  PubMed  Google Scholar 

  • Ragam A, Kolomeyer AM, Fang C, Xu Y, Chu DS (2014) Treatment of chronic, noninfectious, nonnecrotizing scleritis with tumor necrosis factor alpha inhibitors. Ocul Immunol Inflamm 22:469–477

    Article  CAS  PubMed  Google Scholar 

  • Ramos-Cebrian M, Torregrosa JV, Gutierrez-Dalmau A, Oppenheimer F, Campistol JM (2007) Conversion from tacrolimus to cyclosporine could improve control of posttransplant diabetes mellitus after renal transplantation. Transplant Proc 39:2251–2253

    Article  CAS  PubMed  Google Scholar 

  • Rathi M, Rajkumar V, Rao N et al (2015) Conversion from tacrolimus to cyclosporine in patients with new-onset diabetes after renal transplant: an open-label randomized prospective pilot study. Transplant Proc 47:1158–1161

    Article  CAS  PubMed  Google Scholar 

  • Rathinam SR, Babu M, Thundikandy R et al (2014) A randomized clinical trial comparing methotrexate and mycophenolate mofetil for noninfectious uveitis. Ophthalmology 121:1863–1870

    Article  PubMed  PubMed Central  Google Scholar 

  • Reddy AR, Backhouse OC (2003) Does etanercept induce uveitis? Br J Ophthalmol 87:925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reed JB, Morse LS, Schwab IR (1998) High-dose intravenous pulse methylprednisolone hemisuccinate in acute Behcet retinitis. Am J Ophthalmol 125:409–411

    Article  CAS  PubMed  Google Scholar 

  • Restrepo JP, Molina MP (2010) Successful treatment of severe nodular scleritis with adalimumab. Clin Rheumatol 29:559–561

    Article  PubMed  Google Scholar 

  • Rosenbaum JT (1994) Treatment of severe refractory uveitis with intravenous cyclophosphamide. J Rheumatol 21:123–125

    CAS  PubMed  Google Scholar 

  • Rosenbaum JT, Howes EL Jr, Rubin RM, Samples JR (1988) Ocular inflammatory effects of intravitreally-injected tumor necrosis factor. Am J Pathol 133:47–53

    CAS  PubMed  PubMed Central  Google Scholar 

  • Santos Lacomba M, Marcos Martín C, Gallardo Galera JM et al (2001) Aqueous humor and serum tumor necrosis factor-α in clinical uveitis. Ophthalmic Res 33:251–255

    Article  CAS  PubMed  Google Scholar 

  • Sartani G, Silver PB, Rizzo LV et al (1996) Anti-tumor necrosis factor alpha therapy suppresses the induction of experimental autoimmune uveoretinitis in mice by inhibiting antigen priming. Invest Ophthalmol Vis Sci 37:2211–2218

    CAS  PubMed  Google Scholar 

  • Schabert VF, Watson C, Joseph GJ, Iversen P, Burudpakdee C, Harrison DJ (2013) Costs of tumor necrosis factor blockers per treated patient using real-world drug data in a managed care population. J Manag Care Pharm 19:621–630

    PubMed  Google Scholar 

  • Selmi C, Ceribelli A, Naguwa SM, Cantarini L, Shoenfeld Y (2015) Safety issues and concerns of new immunomodulators in rheumatology. Expert Opin Drug Saf 14:389–399

    Article  CAS  PubMed  Google Scholar 

  • Sen HN, Suhler EB, Al-Khatib SQ, Djalilian AR, Nussenblatt RB, Buggage RR (2003) Mycophenolate mofetil for the treatment of scleritis. Ophthalmology 110:1750–1755

    Article  PubMed  Google Scholar 

  • Sen HN, Sangave A, Hammel K, Levy-Clarke G, Nussenblatt RB (2009) Infliximab for the treatment of active scleritis. Can J Ophthalmol 44:e9–e12

    Article  PubMed  PubMed Central  Google Scholar 

  • Sen HN, Vitale S, Gangaputra SS et al (2014) Periocular corticosteroid injections in uveitis: effects and complications. Ophthalmology 121:2275–2286

    Article  PubMed  PubMed Central  Google Scholar 

  • Sendrowski DP, Jaanus SD, Semes LP, Stern ME (2008) Anti-inflammatory drugs. In: Bartlett JD, Jaanus SD (eds) Clinical ocular pharmacology, 5th edn. Butterworh-Heinemann, St. Louis, pp 222–224

    Google Scholar 

  • Shen L, You Y, Sun S, Chen Y, Qu J, Cheng L (2010) Intraocular and systemic pharmacokinetics of triamcinolone acetonide after a single 40-mg posterior subtenon application. Ophthalmology 117:2365–2371

    Article  PubMed  Google Scholar 

  • Sheppard JD, Toyos MM, Kempen JH, Kaur P, Foster CS (2014) Difluprednate 0.05% versus prednisolone acetate 1% for endogenous anterior uveitis: a phase III, multicenter, randomized study. Invest Ophthalmol Vis Sci 55:2993–3002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shibuya M, Fujio K, Morita K, Harada H, Kanda H, Yamamoto K (2013) Successful treatment with tocilizumab in a case of Cogan’s syndrome complicated with aortitis. Mod Rheumatol 23:577–581

    Article  PubMed  Google Scholar 

  • Siepman K, Huber M, Stubiger N, Deuter C, Zierhut M (2006) Mycophenolate mofetil is a highly effective and safe immunosuppressive agent for the treatment of uveitis. Graefes Arch Clin Exp Ophthalmol 244:788–794

    Article  CAS  Google Scholar 

  • Sifontis NM, Coscia LA, Constantinescu S, Lavelanet AF, Moritz MJ, Armenti VT (2006) Pregnancy outcomes in solid organ transplant recipients with exposure to mycophenolate mofetil or sirolimus. Transplantation 82:1698–1702

    Article  CAS  PubMed  Google Scholar 

  • Simonini G, Paudyal P, Jones GT, Cimaz R, Macfarlane GJ (2013) Current evidence of methotrexate efficacy in childhood chronic uveitis: a systematic review and meta-analysis approach. Rheumatology 52:825–831

    Article  CAS  PubMed  Google Scholar 

  • Simonini G, Katie D, Cimaz R, Macfarlane GJ, Jones GT (2014) Does switching anti-TNFalpha biologic agents represent an effective option in childhood chronic uveitis: the evidence from a systematic review and meta-analysis approach. Semin Arthritis Rheum 44:39–46

    Article  CAS  PubMed  Google Scholar 

  • Slabaugh MA, Herlihy E, Ongchin S, van Gelder RN (2012) Efficacy and potential complications of difluprednate use for pediatric uveitis. Am J Ophthalmol 153:932–938

    Article  CAS  PubMed  Google Scholar 

  • Slater CA, Liang MH, McCune JW, Christman GM, Laufer MR (1999) Preserving ovarian function in patients receiving cyclophosphamide. Lupus 8:3–10

    Article  CAS  PubMed  Google Scholar 

  • Smith JR, Levinson RD, Holland GN et al (2001) Differential efficacy of tumor necrosis factor inhibition in the management of inflammatory eye disease and associated rheumatic disease. Arthritis Rheum 45:252–257

    Article  CAS  PubMed  Google Scholar 

  • Smith JR, Rosenbaum JT, Wilson DJ et al (2002) Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement. Ophthalmology 109:1709–1716

    Article  PubMed  Google Scholar 

  • Smith JA, Thompson DJS, Whitcup SM et al (2005) A randomized, placebo-controlled, double-masked clinical trial of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis. Arthritis Care Res 53:18–23

    Article  CAS  Google Scholar 

  • Sourlingas TG, Sekeri-Pataryas KE (1997) S and G2 phase histone biosynthesis of HEp-2 cells after the influence of the bisalkylating agent, chlorambucil. Biochem Mol Biol Int 42:1103–1114

    CAS  PubMed  Google Scholar 

  • Spatz S, Rudnicka A, McDonald CJ (1978) Mycophenolic acid in psoriasis. Br J Dermatol 98:429–435

    Article  CAS  PubMed  Google Scholar 

  • Sturm I, Bosanquet AG, Hermann S, Guner D, Dorken B, Daniel PT (2003) Mutation of p53 and consecutive selective drug resistance in B-CLL occurs as a consequence of prior DNA-damaging chemotherapy. Cell Death Differ 10:477–484

    Article  CAS  PubMed  Google Scholar 

  • Suelves AM, Arcinue CA, Gonzalez-Martin JM, Kruh JN, Foster CS (2013) Analysis of a novel protocol of pulsed intravenous cyclophosphamide for recalcitrant or severe ocular inflammatory disease. Ophthalmology 120:1201–1209

    Article  PubMed  Google Scholar 

  • Suhler EB, Smith JR, Giles TR et al (2009) Infliximab therapy for refractory uveitis: 2-year results of a prospective trial. Arch Ophthalmol 127:819–822

    CAS  PubMed  Google Scholar 

  • Suhler EB, Lowder CY, Goldstein DA et al (2013) Adalimumab therapy for refractory uveitis: results of a multicentre, open-label, prospective trial. Br J Ophthalmol 97:481–486

    Article  PubMed  Google Scholar 

  • Suhler EB, Lim LL, Beardsley RM et al (2014) Rituximab therapy for refractory scleritis: results of a phase I/II dose-ranging, randomized, clinical trial. Ophthalmology 121:1885–1891

    Article  PubMed  Google Scholar 

  • Takeuchi M, Kezuka T, Sugita S et al (2014) Evaluation of the long-term efficacy and safety of infliximab treatment for uveitis in Behcet’s disease: a multicenter study. Ophthalmology 121:1877–1884

    Article  PubMed  Google Scholar 

  • Tappeiner C, Heinz C, Ganser G, Heiligenhaus A (2012) Is tocilizumab an effective option for treatment of refractory uveitis associated with juvenile idiopathic arthritis? J Rheumatol 39:1294–1295

    Article  PubMed  Google Scholar 

  • Tauber M, Buche S, Reygagne P et al (2014) Alopecia areata occurring during anti-TNF therapy: a national multicenter prospective study. J Am Acad Dermatol 70:1146–1149

    Article  PubMed  Google Scholar 

  • Taylor RP, Lindorfer MA (2007) Drug insight: the mechanism of action of rituximab in autoimmune disease--the immune complex decoy hypothesis. Nat Clin Pract Rheumatol 3:86–95

    Article  CAS  PubMed  Google Scholar 

  • Taylor SR, Habot-Wilner Z, Pacheco P, Lightman SL (2009) Intraocular methotrexate in the treatment of uveitis and uveitic cystoid macular edema. Ophthalmology 116:797–801

    Article  PubMed  Google Scholar 

  • Taylor SR, Banker A, Schlaen A et al (2013) Intraocular methotrexate can induce extended remission in some patients in noninfectious uveitis. Retina 33:2149–2154

    Article  CAS  PubMed  Google Scholar 

  • Teoh SC, Hogan AC, Dick AD, Lee RW (2008) Mycophenolate mofetil for the treatment of uveitis. Am J Ophthalmol 146:752–760, 760.e1–3

    Google Scholar 

  • Teruel C, Lopez-San Roman A, Bermejo F et al (2010) Outcomes of pregnancies fathered by inflammatory bowel disease patients exposed to thiopurines. Am J Gastroenterol 105:2003–2008

    Article  CAS  PubMed  Google Scholar 

  • Tessler HH, Jennings T (1990) High-dose short-term chlorambucil for intractable sympathetic ophthalmia and Behcet’s disease. Br J Ophthalmol 74:353–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thorne JE, Jabs DA, Qazi FA, Nguyen QD, Kempen JH, Dunn JP (2005) Mycophenolate mofetil therapy for inflammatory eye disease. Ophthalmology 112:1472–1477

    Article  PubMed  Google Scholar 

  • Tiede I, Fritz G, Strand S et al (2003) CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest 111:1133–1145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tomkins-Netzer O, Taylor SR, Bar A et al (2014) Treatment with repeat dexamethasone implants results in long-term disease control in eyes with noninfectious uveitis. Ophthalmology 121:1649–1654

    Article  PubMed  Google Scholar 

  • Tomkins-Netzer O, Talat L, Seguin-Greenstein S, Bar A, Lightman S (2016) Outcome of treating pediatric uveitis with dexamethasone implants. Am J Ophthalmol 161:110–115.e2

    Article  PubMed  Google Scholar 

  • Tong D, Manolios N, Howe G, Spencer D (2012) New onset sarcoid-like granulomatosis developing during anti-TNF therapy: an under-recognised complication. Intern Med J 42:89–94

    Article  CAS  PubMed  Google Scholar 

  • Urban RC Jr, Cotlier E (1986) Corticosteroid-induced cataracts. Surv Ophthalmol 31:102–110

    Article  CAS  PubMed  Google Scholar 

  • Vallet H, Riviere S, Sanna A et al (2015) Efficacy of anti-TNF alpha in severe and/or refractory Behcet’s disease: multicenter study of 124 patients. J Autoimmun 62:67–74

    Article  CAS  PubMed  Google Scholar 

  • van Oosten BW, Barkhof F, Truyen L et al (1996) Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 47:1531–1534

    Article  PubMed  Google Scholar 

  • Victor RG, Thomas GD, Marban E, O’Rourke B (1995) Presynaptic modulation of cortical synaptic activity by calcineurin. Proc Natl Acad Sci U S A 92:6269–6273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Visser K, Katchamart W, Loza E et al (2009) Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis 68:1086–1093

    Article  CAS  PubMed  Google Scholar 

  • Wakefield D (2014) Does cyclophosphamide still have a role in the treatment of severe inflammatory disease. Ocul Immunol Inflamm 22:306–310

    Article  PubMed  Google Scholar 

  • Wan C-K, He C, Sun L, Egwuagu CE, Leonard WJ (2016) Cutting edge: IL-1 receptor signaling is critical for the development of autoimmune uveitis. J Immunol 196:543–546

    Article  CAS  PubMed  Google Scholar 

  • Weijtens O, Schoemaker RC, Romijn FP, Cohen AF, Lentjes EG, van Meurs JC (2002) Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate. Ophthalmology 109:1887–1891

    Article  PubMed  Google Scholar 

  • Weinshilboum RM, Sladek SL (1980) Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 32:651–652

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wessels JA, Huizinga TW, Guchelaar HJ (2008) Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis. Rheumatology 47:249–255

    Article  CAS  PubMed  Google Scholar 

  • Wolfe F, Michaud K (2007) The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation. Arthritis Rheum 56:1433–1439

    Article  CAS  PubMed  Google Scholar 

  • Wong VG, Hersh EM (1965) Methotrexate in the therapy of cyclitis. Trans Am Acad Ophthalmol Otolaryngol 69:279–293

    Google Scholar 

  • Wong AK, Kerkoutian S, Said J, Rashidi H, Pullarkat ST (2012) Risk of lymphoma in patients receiving antitumor necrosis factor therapy: a meta-analysis of published randomized controlled studies. Clin Rheumatol 31:631–636

    Article  PubMed  Google Scholar 

  • Woodrick RS, Ruderman EM (2011) Safety of biologic therapy in rheumatoid arthritis. Nat Rev Rheumatol 7:639–652

    Article  CAS  PubMed  Google Scholar 

  • Woods AC (1950) Clinical and experimental observation on the use of ACTH and cortisone in ocular inflammatory disease. Am J Ophthalmol 33:1325–1349

    Article  CAS  PubMed  Google Scholar 

  • Wyzgal J, Oldakowska-Jedynak U, Paczek L et al (2003) Posttransplantation diabetus mellitus under calcineurin inhibitor. Transplant Proc 35:2216–2218

    Article  CAS  PubMed  Google Scholar 

  • Yazici H, Pazarli H, Barnes CG et al (1990) A controlled trial of azathioprine in Behçet’s syndrome. N Engl J Med 322:281–285

    Article  CAS  PubMed  Google Scholar 

  • Yokota S, Itoh Y, Morio T et al (2015) Tocilizumab in systemic juvenile idiopathic arthritis in a real-world clinical setting: results from 1 year of postmarketing surveillance follow-up of 417 patients in Japan. Ann Rheum Dis. doi:10.1136/annrheumdis-2015-207818

    PubMed  PubMed Central  Google Scholar 

  • Yoshimura T, Sonoda KH, Ohguro N et al (2009) Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis. Rheumatology 48:347–354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zarranz-Ventura J, Carreno E, Johnston RL et al (2014) Multicenter study of intravitreal dexamethasone implant in noninfectious uveitis: indications, outcomes, and reinjection frequency. Am J Ophthalmol 158:1136–1145.e5

    Article  CAS  PubMed  Google Scholar 

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This research was supported by the Intramural Research Program of the NIH, NEI.

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Correspondence to Robert B. Nussenblatt .

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Knickelbein, J.E., Armbrust, K.R., Kim, M., Sen, H.N., Nussenblatt, R.B. (2016). Pharmacologic Treatment of Noninfectious Uveitis. In: Whitcup, S., Azar, D. (eds) Pharmacologic Therapy of Ocular Disease. Handbook of Experimental Pharmacology, vol 242. Springer, Cham. https://doi.org/10.1007/164_2016_21

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