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Noninfectious Immune-Mediated Uveitis and Ocular Inflammation

Current Allergy and Asthma Reports volume 14, Article number: 409 (2014) Cite this article

Abstract

Noninfectious uveitis encompasses a diverse group of ocular inflammatory disorders that share an underlying immune etiology and may be associated with systemic disease or confined primarily to the eye. Uveitis is commonly classified by anatomical location of inflammation into anterior, intermediate, posterior, and panuveitis. The treatment of noninfectious uveitis consists of corticosteroids, immunosuppressive agents, and surgically placed steroid implants. We review the epidemiology, immunopathology, and clinical features of several noninfectious immune-mediated uveitides, including HLA-B27 acute anterior uveitis, juvenile idiopathic arthritis, intermediate uveitis, sarcoidosis, Behcet’s disease, Vogt-Koyanagi-Harada syndrome, sympathetic ophthalmia, and white dot syndromes. We also discuss the stepwise approach to medical treatment of immune-mediated uveitis as well as the characteristics, safety, and efficacy of immunosuppressive agents used to treat ocular inflammatory disease.

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References

  1. Kempen JH, Altaweel MM, Holbrook JT, et al. Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the Multicenter Uveitis Steroid Treatment (MUST) Trial. Ophthalmology. 2011;118:1916–26.

    PubMed Central  PubMed  Article  Google Scholar 

  2. Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol. 1996;80:332–6.

    CAS  PubMed  Article  Google Scholar 

  3. Chang JH, McCluskey PJ, Fracs F, Wakefield D. Acute anterior uveitis and HLA-B27. Surv Ophthalmol. 2005;50:364–88.

    PubMed  Article  Google Scholar 

  4. Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature (SUN) for reporting clinical data. -Results of the First International Workshop. Am J Ophthalmol. 2005;150:509–16.

    Google Scholar 

  5. D’Alessandro LP, Forster DJ, Rao NA. Anterior uveitis and hypopyon. Am J Ophthalmol. 1991;112(3):317–21.

    PubMed  Google Scholar 

  6. Lyons JL, Rosenbaum JT. Uveitis associated with inflammatory bowel disease compared with uveitis associated with spondyloarthropathy. Arch Ophthalmol. 1997;115:61.

    CAS  PubMed  Article  Google Scholar 

  7. Paiva ES, Macaluso DC, Edwards A, Rosenbaum JT. Characterisation of uveitis in patients with psoriatic arthritis. Ann Rheum Dis. 2000;59:67.

    CAS  PubMed  Article  Google Scholar 

  8. Bayen H, Bayen MC, De Curzon HP, et al. Involvement of the posterior eye segment in HLA B27 (+) iridocyclitis. J Fr Ophthalmol. 1988;11:561–6.

    CAS  Google Scholar 

  9. Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58(1):15–25.

    PubMed  Article  Google Scholar 

  10. Leak AM, Ansell BM, Burman SJ. Antinuclear antibody studies in juvenile chronic arthritis. Arch Dis Child. 1986;61:168–72.

    CAS  PubMed  Article  Google Scholar 

  11. Kotaniemi K, Savolainen A, Karma A, Aho K. Recent advances in uveitis of juvenile idiopathic arthritis. Surv Ophthalmol. 2003;48(5):489–502.

    PubMed  Article  Google Scholar 

  12. Gregory 2nd AC, Kempen JH, Daniel E, Kacmaz RO, Foster CS, et al. Risk factors for loss of visual acuity among patients with uveitis associated with juvenile idiopathic arthritis: the Systemic Immunosuppressive Therapy for Eye Diseases Study. Ophthalmology. 2013;120:186–92.

    PubMed Central  PubMed  Article  Google Scholar 

  13. Ophthalmologic examinations in children with juvenile rheumatoid arthritis. Pediatrics. 2006; 117(5):1843–1845.

  14. Southward TR, Ryder CA. Ophthalmological screening in juvenile arthritis: should the frequency of screening be based on the risk of developing chronic iridocyclitis? Br J Rheumatol. 1992;31:633–4.

    Article  Google Scholar 

  15. Henderly DE, Haymond RS, Rao NA, Smith RE. The significance of the pars plana exudates in pars planitis. Am J Ophthalmol. 1987;103:669–71.

    CAS  PubMed  Google Scholar 

  16. David JI, Mittal KK, Nussenblatt RB. HLA in intermediate uveitis. Dev Ophthalmol. 1992;23:35–7.

    Google Scholar 

  17. Zein G, Berta A, Foster CS. Multiple sclerosis-associated uveitis. Ocul Immunol Inflamm. 2004;12:137.

    PubMed  Article  Google Scholar 

  18. Prieto JF, Dios E, Gutierrez JM, et al. Pars planitis: epidemiology, treatment, and association with multiple sclerosis. Ocul Immunol Inflamm. 2001;9:93.

    CAS  PubMed  Article  Google Scholar 

  19. Obenauf CD, Shaw HE, Sydnor CF, Klintworth GK. Sarcoidosis and its ophthalmic manifestations. Am J Ophthalmol. 1978;86:648.

    CAS  PubMed  Google Scholar 

  20. James DG. Ocular sarcoidosis. Ann N Y Acad Sci. 1986;465:551.

    CAS  PubMed  Article  Google Scholar 

  21. Jabs DA, Johns CJ. Ocular involvement in chronic sarcoidosis. Am J Ophthalmol. 1986;102:297–301.

    CAS  PubMed  Google Scholar 

  22. Hegab S, Al-Mutawa S. Immunopathogenesis of Behcet’s disease. Clin Immunol. 2000;96:174–86.

    CAS  PubMed  Article  Google Scholar 

  23. Criteria for diagnosis of Behçet's disease. International Study Group for Behçet's Disease. Lancet 1990;335:1078.

    Google Scholar 

  24. Mamo JG. The rate of visual loss in Behçet's disease. Arch Ophthalmol. 1970;84:451.

    CAS  PubMed  Article  Google Scholar 

  25. Atmaca LS. Fundus changes associated with Behçet's disease. Graefe's Arch Clin Exp Ophthalmol. 1989;227:340–4.

    CAS  Article  Google Scholar 

  26. Masuda K, Inaba G, Mizushima II. A nationwide survey of Behcet’s disease in Japan. Jpn J Ophthalmol. 1974;19:278–85.

    Google Scholar 

  27. 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(5):592–8.

    CAS  PubMed  Article  Google Scholar 

  28. Rubsamen PE, Gass JD. Vogt-Koyanagi-Harada syndrome. Clinical course, therapy, and long-term visual outcome. Arch Ophthalmol. 1991;109:682.

    CAS  PubMed  Article  Google Scholar 

  29. Zhang XY, Wang XM, Hu TS. Profiling human leukocyte antigens in Vogt-Koyanagi-Harada syndrome. Am J Ophthalmol. 1992;113:567.

    CAS  PubMed  Google Scholar 

  30. Snyder DA, Tessler HH. Vogt-Koyanagi-Harada syndrome. Am J Ophthalmol. 1980;90:69–75.

    CAS  PubMed  Google Scholar 

  31. Moorthy RS, Inomata H, Rao NAL. Vogt-Koyanagi-Harada syndrome. Surv Ophthalmol. 1995;39:265–92.

    CAS  PubMed  Article  Google Scholar 

  32. Duke-Elder S, Perkins ES. Sympathetic ophthalmitis, in Duke-Elder S: Diseases of the uveal tract. Mosby: St Louis; 1966. p. 558–93.

    Google Scholar 

  33. Rao NA, Forster DJ, Spalton DJ. Sympathetic ophthalmia. In: Podos SM, Yanoff M, editors. The uvea uveitis and intraocular neoplasms, vol. 2. USA: Mosby-Wolfe; 1995. p. 8.10–3. Chapter 8.

    Google Scholar 

  34. Kilmartin DJ, Dick AD, Forrester JV. Prospective surveillance of sympathetic ophthalmia in the UK and Republic of Ireland. Br J Ophthalmol. 2000;84:259–63.

    CAS  PubMed  Article  Google Scholar 

  35. Watzke RC, Packer AJ, Folk JC, et al. Punctate inner choroidopathy. Am J Ophthalmol. 1984;98:572–84.

    CAS  PubMed  Google Scholar 

  36. Schlaegel Jr TF. Eye histoplasmosis. Ann Ophthalmol. 1979;11:1645–54.

    PubMed  Google Scholar 

  37. Gass JD. Acute posterior multifocal placoid pigment epitheliopathy. Arch Ophthalmol. 1968;80:177–85.

    CAS  PubMed  Article  Google Scholar 

  38. Sinan C, Thierry V, Jeffrey SR, Neil AB. Neurological manifestations of acute posterior multifocal placoid pigment epitheliopathy. Stroke. 1996;27:996–1001.

    Article  Google Scholar 

  39. O’Halloran HS, Berger JR, Lee WB, et al. Acute multifocal placoid pigment epitheliopathy and central nervous system involvement. Nine new cases and a review of the literature. Ophthalmology. 2001;108:861–8.

    PubMed  Article  Google Scholar 

  40. Palestine AG, Nussenblatt RB, Chan CC, et al. Histopathology of the subretinal fibrosis and uveitis syndrome. Ophthalmology. 1985;92:838–44.

    CAS  PubMed  Article  Google Scholar 

  41. LeHoang P, Ozdemir N, Benhamou A, et al. HLA-A29.2 subtype associated with birdshot retinochoroidopathy. Am J Ophthalmol. 1992;113:33.

    CAS  PubMed  Google Scholar 

  42. Durrani K, Zakka FR, Ahmed M, Memon M, Siddique SS, Foster CS. Systemic therapy with conventional and novel immunomodulatory agents for ocular inflammatory disease. Surv Ophthalmol. 2011;56(6):474–510.

    PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  44. Miserocchi E, Modorati G, Foster CS. New treatments in noninfectious uveitis. Dev Ophthalmol Basel, Karger. 2012;51:1–6.

    Article  Google Scholar 

  45. 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. 2011;50:1390–4.

    CAS  PubMed  Article  Google Scholar 

  46. Foster CS, Vitale AT. Immunosuppressive chemotherapy. In: Foster CS, Vitale AT, editors. Diagnosis and treatment of uveitis. 1st ed. Philadelphia, PA: WB Saunders; 2002. p. 177–214.

    Google Scholar 

  47. Pasadhika S, Kempen JH, Newcomb CW, et al. Azathioprine for ocular inflammatory diseases. Am J Ophthalmol. 2009;148:500–9.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  48. Sobrin L, Christen W, Foster CS. Mycophenolate mofetil after methotrexate failure or intolerance in the treatment of scleritis and uveitis. Ophthalmology. 2008;115:1416–21.

    PubMed  Article  Google Scholar 

  49. Fauc AS, Doppman JL, Wolff SM. Cyclophosphamide-induced remissions in advanced polyarteritis nodosa. Am J Med. 1978;64:890–4.

    Article  Google Scholar 

  50. Fosdick WM, Parsons JL, Hill DF. Long-term cyclophosphamide therapy in rheumatoid arthritis. Arthritis Rheum. 1968;11:151–61.

    CAS  PubMed  Article  Google Scholar 

  51. Martin-Suarez I, D’Cruz D, Mansoor M, et al. Immunosuppressive treatment in severe connective tissue diseases: effects of low dose intravenous cyclophosphamide. Ann Rhem Dis. 1997;56:481–7.

    CAS  Article  Google Scholar 

  52. Kacmaz RO, Kempen JH, Newcomb C, et al. Cyclosporine for ocular inflammatory diseases. Ophthalmology. 2010;117:576–84.

    PubMed Central  PubMed  Article  Google Scholar 

  53. Murphy CC, Greiner K, Plskova J, et al. Cyclosporine vs tacrolimus therapy for posterior and intermediate uveitis. Arch Ophthalmol. 2005;123:634–41.

    CAS  PubMed  Article  Google Scholar 

  54. Braun J, Baraliakos X, Listing J, Sieper J. Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum. 2005;52:2447.

    CAS  PubMed  Article  Google Scholar 

  55. Suhler EB, Smith JR, Wertheim MS, et al. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes. Arch Ophthalmol. 2005;123:903.

    CAS  PubMed  Article  Google Scholar 

  56. Kempen JH, Daniel E, Dunn JP, et al. Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: retrospective cohort study. BMJ. 2009;339:2480.

    Article  Google Scholar 

  57. Okada AA, Goto H, Ohno S, Mochizuki M. Multicenter study of infliximab for refractory uveoretinitis in Behcet disease. Arch Ophthalmol. 2012;13:592–8.

    Google Scholar 

  58. Miserocchi E, Pontikaki I, Modorati G, Gattinara M, Meroni PL, Gerloni V. Anti-CD 20 monoclonal antibody (rituximab) treatment for inflammatory ocular diseases. Autoimmun Rev. 2011;11(1):35–9.

    CAS  PubMed  Article  Google Scholar 

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Conflict of Interest

Rex McCallum has received royalties from UpToDate.

Jennifer Pan and Manuj Kapur declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Affiliations

  1. Texas Tech University Health Sciences Center – Paul L. Foster School of Medicine, El Paso, TX, 79905, USA

    Jennifer Pan

  2. University of Texas Medical Branch at Galveston, 301 University Blvd., Galveston, TX, 77555-1106, USA

    Manuj Kapur

  3. University of Texas Medical Branch at Galveston, 301 University Blvd., Galveston, TX, 77555-0133, USA

    Rex McCallum

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  1. Jennifer Pan
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  2. Manuj Kapur
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  3. Rex McCallum
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Correspondence to Rex McCallum.

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This article is part of the Topical Collection on Autoimmunity

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Pan, J., Kapur, M. & McCallum, R. Noninfectious Immune-Mediated Uveitis and Ocular Inflammation. Curr Allergy Asthma Rep 14, 409 (2014). https://doi.org/10.1007/s11882-013-0409-1

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  • DOI: https://doi.org/10.1007/s11882-013-0409-1

Keywords

  • Uveitis
  • Ocular inflammation
  • Systemic disease
  • Iritis
  • HLA-B27
  • Pars planitis
  • Posterior uveitis
  • Panuveitis
  • Corticosteroid
  • Immunomodulatory therapy
  • Steroid implant