Skip to main content

Update on the Treatment of Uveitis in Patients with Juvenile Idiopathic Arthritis: A Review

Abstract

Chronic uveitis is a common extra-articular manifestation of juvenile idiopathic arthritis. The classic clinical picture is one of chronic anterior uveitis, which usually remains asymptomatic until ocular complications arise. The risk of uveitis is increased in girls with an early onset of oligoarthritis and positive antinuclear antibodies. Even though the inflammation in patients with juvenile idiopathic arthritis is initially limited in the anterior part of the eye, chronic active inflammation may eventually cause significant damage to the posterior pole. Complications may include band keratopathy, cataract, secondary glaucoma, posterior synechiae, cystoid macular edema, and hypotony. The cooperation of ophthalmologists with rheumatologists may help define the best treatment plan. The ophthalmic therapeutic regimen includes topical corticosteroids and mydriatics, while in severe cases immunosuppressive and biological agents are introduced. Surgical management of complications might be needed.

This is a preview of subscription content, access via your institution.

References

  1. Ohm J. Bandfoermige Hornhauttruebung bei einem neunjaehrigen Maedchen und ihre Behandlung mit subconjunctivalen Jodkaliumeinspritzungen. Klin Monatsbl Augenheilkd. 1910;48:243–6.

    Google Scholar 

  2. Qian Y, Acharya NR. Juvenile idiopathic arthritis-associated uveitis. Curr Opin Ophthalmol. 2010;21:468–72.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sen ES, Dick AD, Ramanan AV. Uveitis associated with juvenile idiopathic arthritis. Nat Rev Rheumatol. 2015;11:338–48.

    CAS  Article  PubMed  Google Scholar 

  4. Foeldvari I. Ocular involvement in juvenile idiopathic arthritis: classification and treatment. Clin Rev Allergy Immunol. 2015;49:271–7.

    CAS  Article  PubMed  Google Scholar 

  5. Wells JM, Smith JR. Uveitis in juvenile idiopathic arthritis: recent therapeutic advances. Ophthalmic Res. 2015;54:124–7.

    CAS  Article  PubMed  Google Scholar 

  6. Petty RE, Southwood TR, Baum J, et al. Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997. J Rheumatol. 1998;25:1991–4.

    CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  8. Dana MR, Merayo-Lloves J, Schaumberg DA, Foster CS. Visual outcomes prognosticators in juvenile rheumatoid arthritis-associated uveitis. Ophthalmology. 1997;104:236–44.

    CAS  Article  PubMed  Google Scholar 

  9. Kanski JJ. Screening for uveitis in juvenile chronic arthritis. Br J Ophthalmol. 1989;73:225–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Deschenes J, Murray PI, Rao NA, Nussenblatt RB, International Uveitis Study Group. International Uveitis Study Group (IUSG): clinical classification of uveitis. Ocul Immunol Inflamm. 2008;16:1–2.

    Article  PubMed  Google Scholar 

  11. Andersson Gäre B. Juvenile arthritis—who gets it, where and when? A review of current data on incidence and prevalence. Clin Exp Rheumatol. 1999;17:367–74.

    Google Scholar 

  12. Clarke SL, Sen ES, Ramanan AV. Juvenile idiopathic arthritis-associated uveitis. Pediatr Rheumatol Online J. 2016;14:27.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bou R, Adán A, Borrás F, et al. Clinical management algorithm of uveitis associated with juvenile idiopathic arthritis: interdisciplinary panel consensus. Rheumatol Int. 2015;35:777–85.

    Article  PubMed  Google Scholar 

  14. Foster CS, Alter G, DeBarge LR, et al. Efficacy and safety of rimexolone 1% ophthalmic suspension vs 1% prednisolone acetate in the treatment of uveitis. Am J Ophthalmol. 1996;122:171–82.

    CAS  Article  PubMed  Google Scholar 

  15. Simonini G, Cantarini L, Bresci C, Lorusso M, Galeazzi M, Cimaz R. Current therapeutic approaches to autoimmune chronic uveitis in children. Autoimmun Rev. 2010;9:674–83.

    CAS  Article  PubMed  Google Scholar 

  16. Taylor SR, Tomkins-Netzer O, Joshi L, Morarji J, McLoone E, Lightman S. Dexamethasone implant in pediatric uveitis. Ophthalmology. 2012;119:2412.

    Article  PubMed  Google Scholar 

  17. Sella R, Oray M, Friling R, Umar L, Tugal-Tutkun I, Kramer M. Dexamethasone intravitreal implant (Ozurdex) for pediatric uveitis. Graefes Arch Clin Exp Ophthalmol. 2015;253:1777–82.

    CAS  Article  PubMed  Google Scholar 

  18. Pichi F, Nucci P, Baynes K, Lowder CY, Srivastava SK. Sustained-release dexamethasone intravitreal implant in juvenile idiopathic arthritis-related uveitis. Int Ophthalmol. 2017;37:221–8.

    Article  PubMed  Google Scholar 

  19. Vitale AT, Rodriguez A, Foster CS. Low-dose cyclosporin A therapy in treating chronic, noninfectious uveitis. Ophthalmology. 1996;103:365–73.

    CAS  Article  PubMed  Google Scholar 

  20. Foeldvari I, Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. J Rheumatol. 2005;32:362–5.

    CAS  PubMed  Google Scholar 

  21. Holland GN, Stiehm ER. Special considerations in the evaluation and management of uveitis in children. J Ophthalmol. 2003;135:867–78.

    Google Scholar 

  22. Foster CS. Diagnosis and treatment of juvenile idiopathic arthritis-associated uveitis. Curr Opin Ophthalmol. 2003;14:395–8.

    Article  PubMed  Google Scholar 

  23. Wentworth BA, Freitas-Neto CA, Foster CS. Management of pediatric uveitis. F1000Prime Rep. 2014;6:41.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Petty RE, Smith JR, Rosenbaum JT. Arthritis and uveitis in children: a pediatric rheumatology perspective. Am J Ophthalmol. 2003;135:879–84.

    Article  PubMed  Google Scholar 

  25. Levy-Clarke GA, Nussenblatt RB, Smith JA. Management of chronic pediatric uveitis. Cur Opin Ophthalmol. 2005;16:281–8.

    Article  Google Scholar 

  26. Simonini G, Paudyal P, Jones GT, Cimaz R, Macfarlane GJ. Current evidence of methotrexate efficacy in childhood chronic uveitis: a systematic review and meta-analysis approach. Rheumatology (Oxford). 2013;52:825–31.

    CAS  Article  Google Scholar 

  27. Kalinina Ayuso V, Rothova A, de Boer JH. Relapse rate of uveitis post-methotrexate treatment in juvenile idiopathic arthritis. Am J Ophthalmol. 2011;151:217–22.

    Article  PubMed  Google Scholar 

  28. Kostik MM, Gaidar EV, Hynnes AY, et al. Methotrexate treatment may prevent uveitis onset in patients with juvenile idiopathic arthritis: experiences and subgroup analysis in a cohort with frequent methotrexate use. Clin Exp Rheumatol. 2016;34:714–8.

    PubMed  Google Scholar 

  29. Samson CM, Waheed N, Baltatzis S, Foster CS. Methotrexate therapy for chronic noninfectious uveitis: analysis of a case series of 160 patients. Ophthalmology. 2001;108:1134–9.

    CAS  Article  PubMed  Google Scholar 

  30. Foeldvari I, Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. J Rheumatol. 2005;32:362–5.

    CAS  PubMed  Google Scholar 

  31. Tappeiner C, Schenck S, Niewerth M, Heiligenhaus A, Minden K, Klotsche J. Impact of antiinflammatory treatment on the onset of uveitis in juvenile idiopathic arthritis: longitudinal analysis from a nationwide pediatric rheumatology database. Arthritis Care Res (Hoboken). 2016;68:46–54.

    CAS  Article  Google Scholar 

  32. Tappeiner C, Roesel M, Heinz C, Michels H, Ganser G, Heiligenhaus A. Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis. Eye (Lond). 2009;23:1192–8.

    CAS  Article  Google Scholar 

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

    Article  Google Scholar 

  34. Amin RM, Miserocchi E, Thorne JE, Hornbeak D, Jabs DA, Zierhut M. Treatment options for juvenile idiopathic arthritis (JIA) associated uveitis. Ocul Immunol Inflamm. 2016;24:81–90.

    CAS  Article  PubMed  Google Scholar 

  35. Bichler J, Benseler SM, Krumrey-Langkammerer M, Haas JP, Hügle B. Leflunomide is associated with a higher flare rate compared to methotrexate in the treatment of chronic uveitis in juvenile idiopathic arthritis. Scand J Rheumatol. 2015;44:280–3.

    CAS  Article  PubMed  Google Scholar 

  36. Heiligenhaus A, Minden K, Föll D, Pleyer U. Uveitis in juvenile idiopathic arthritis. Dtsch Arztebl Int. 2015;112(6):92–100.

    PubMed  PubMed Central  Google Scholar 

  37. Vazquez-Cobian LB, Flynn T, Lehman JA. Adalimumab therapy for childhood uveitis. J Pediatr. 2006;149:572–5.

    CAS  Article  PubMed  Google Scholar 

  38. Biester S, Deuter C, Michels H, et al. Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol. 2007;91:319–24.

    Article  PubMed  Google Scholar 

  39. García-De-Vicuña C, Díaz-Llopis M, Salom D, et al. Usefulness of adalimumab in the treatment of refractory uveitis associated with juvenile idiopathic arthritis. Mediat Inflamm. 2013;2013:560632.

    Article  Google Scholar 

  40. Tambralli A, Beukelman T, Weiser P, Atkinson TP, Cron RQ, Stoll ML. High doses of infliximab in the management of juvenile idiopathic arthritis. J Rheumatol. 2013;40:1749–55.

    CAS  Article  PubMed  Google Scholar 

  41. Ruperto N, Lovell DJ, Quartier P, Paediatric Rheumatology International Trials Organization and the Pediatric Rheumatology Collaborative Study Group, et al. Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis. Arthritis Rheum. 2010;62:1792–802.

    CAS  Article  PubMed  Google Scholar 

  42. Birolo C, Zannin ME, Arsenyeva S, et al. Comparable efficacy of Abatacept used as first-line or second-line biological agent for severe juvenile idiopathic arthritis-related uveitis. J Rheumatol. 2016;43:2068–73.

    Article  PubMed  Google Scholar 

  43. Levy-Clarke G, Jabs DA, Read RW, Rosenbaum JT, Vitale A, Vangelder RN. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology. 2013;121:785–96.

    Article  PubMed  Google Scholar 

  44. Schmeling H, Horneff G. Etanercept and uveitis in patients with juvenile idiopathic arthritis. Rheumatology (Oxford). 2005;44:1008–11.

    CAS  Article  Google Scholar 

  45. Miserocchi E, Modorati G, Berchicci L, Pontikaki I, Meroni P, Gerloni V. Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis. Br J Ophthalmol. 2016;100:782–6.

    Article  PubMed  Google Scholar 

  46. Tappeiner C, Mesquida M, Adán A, et al. Evidence for tocilizumab as a treatment option in refractory uveitis associated with juvenile idiopathic arthritis. J Rheumatol. 2016;68:46–54.

    CAS  Google Scholar 

  47. Calvo-Río V, Santos-Gómez M, Calvo I, et al. Anti-interleukin-6 receptor tocilizumab for severe juvenile idiopathic arthritis-associated uveitis refractory to anti-tumor necrosis factor therapy: a multicenter study of twenty-five patients. Arthritis Rheumatol. 2017;69:668–75.

    Article  PubMed  Google Scholar 

  48. Lundvall A, Zetterström C. Cataract extraction and intraocular lens implantation in children with uveitis. Br J Ophthalmol. 2000;84:791–3.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  49. Probst LE, Holland EJ. Intraocular lens implantation in patients with juvenile rheumatoid arthritis. Am J Ophthalmol. 1996;122:161–70.

    CAS  Article  PubMed  Google Scholar 

  50. Välimäki J, Airaksinen PJ, Tuulonen A. Molteno implantation for secondary glaucoma in juvenile rheumatoid arthritis. Arch Ophthalmol. 1997;115:1253–6.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

No funding or sponsorship was received for the publication of this article. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. No assistance with medical writing or editing was received for this paper.

Disclosures

Ioannis Asproudis, Alexandra Tantou and Nikolaos Kozeis have nothing to disclose. Andreas Katsanos has received honorariums from Allergan, Novartis and Vianex and had congress and travel expenses covered by Vianex and Laboratoires Thea. Anastasios GP Konstas has received honorariums from (and is a consultant for) Alcon, Allergan, Mundipharma, and Santen and had congress and travel expenses covered by MSD/Vianex.

Compliance with Ethics Guidelines

This article is based on previously conducted studies, and does not involve any new studies of human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andreas Katsanos.

Additional information

Enhanced Content

To view enhanced content for this article go to http://www.medengine.com/Redeem/ACCCF06038A6065B.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Asproudis, I., Katsanos, A., Kozeis, N. et al. Update on the Treatment of Uveitis in Patients with Juvenile Idiopathic Arthritis: A Review. Adv Ther 34, 2558–2565 (2017). https://doi.org/10.1007/s12325-017-0635-3

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-017-0635-3

Keywords

  • Anti-TNF
  • Biological agents
  • DMARDS
  • Juvenile idiopathic arthritis
  • JIA
  • Methotrexate
  • Topical steroids
  • Uveitis