Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Therapy Insight: scleritis and its relationship to systemic autoimmune disease

Nature Clinical Practice Rheumatology volume 3, pages 219–226 (2007)Cite this article

Abstract

The term scleritis describes a chronic inflammation that involves the outermost coat and skeleton of the eye. Disease can be isolated to the eye, but in up to half of affected individuals it occurs in the context of an immune-mediated systemic inflammatory condition, such as rheumatoid arthritis or Wegener's granulomatosis. Although uncommon, scleritis is often extremely painful, can lead to vision-threatening complications (and involvement of other ocular tissues), and is considered to confer an increased risk of mortality in patients with rheumatoid arthritis. Pathogenic mechanisms in scleritis are poorly understood, but enzymatic degradation of collagen fibrils by resident cells and infiltrating leukocytes seems to be a key feature. Several forms of inflammation can be distinguished histologically; interestingly, although the disease typically presents with engorgement of scleral vessels, vasculitis is not universally present at the microscopic level. Although some patients with scleritis respond well to treatment with NSAIDs, aggressive systemic therapy is often required to obtain a favorable outcome, particularly when systemic disease coexists. The mainstay of treatment is oral prednisone, but this agent is usually combined with a steroid-sparing immunosuppressive drug. New therapies presently under investigation for scleritis include local corticosteroid injections and various biologic agents.

Key Points

  • The hallmark symptom of scleritis is pain; examination of the eye typically reveals ocular redness due to engorged scleral vessels

  • Classification of scleritis into clinical subtypes is helpful to guide management, and predict both prognosis and the presence of associated systemic disease

  • Anterior scleritis, which is much more common than posterior scleritis, must be differentiated from other forms of 'red eye', such as conjunctivitis, episcleritis, corneal abrasions or ulcerations, acute anterior uveitis, and acute angle-closure glaucoma

  • Most cases of scleritis are immune-mediated, and in up to a half of patients a systemic disease (such as rheumatoid arthritis or Wegener's granulomatosis) coexists with the eye condition

  • Patients with non-necrotizing forms of scleritis might respond to prompt treatment with oral NSAIDs; if the scleritis does not improve, or when the inflammation is necrotizing or associated with a systemic vasculitis, more aggressive treatment than NSAID therapy with prednisone and/or corticosteroid-sparing agents is necessary

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Diagrammatic representation of the eye shown in cross section
Figure 2: Images that illustrate the subtypes of scleritis
Figure 3: Photomicrographs of sections of scleral tissue stained with hematoxylin and eosin that show zonal necrotizing granulomatous inflammation in a patient with rheumatoid arthritis (A), and diffuse (nonzonal) nongranulomatous inflammation in a patient with 'idiopathic scleritis' (B)

Similar content being viewed by others

References

  1. Akpek EK et al. (2004) Evaluation of patients with scleritis for systemic disease. Ophthalmology 111: 501–506

    Article  Google Scholar 

  2. Tuft SJ and Watson PG (1991) Progression of scleral disease. Ophthalmology 98: 467–471

    Article  CAS  Google Scholar 

  3. Sainz de la Maza M et al. (1994) Severity of scleritis and episcleritis. Ophthalmology 101: 389–396

    Article  CAS  Google Scholar 

  4. McGavin DD et al. (1976) Episcleritis and scleritis. A study of their clinical manifestations and association with rheumatoid arthritis. Br J Ophthalmol 60: 192–226

    Article  CAS  Google Scholar 

  5. Jayson MI and Jones DE (1971) Scleritis and rheumatoid arthritis. Ann Rheum Dis 30: 343–347

    Article  CAS  Google Scholar 

  6. Smith JL (1957) Ocular complications of rheumatic fever and rheumatoid arthritis. Am J Ophthalmol 43 (Pt 1): 575–582

    Article  Google Scholar 

  7. Watson PG et al. (1968) Episcleritis and scleritis. I. Br J Ophthalmol 52: 278–279

    Article  CAS  Google Scholar 

  8. Watson PG and Hayreh SS (1976) Scleritis and episcleritis. Br J Ophthalmol 60: 163–191

    Article  CAS  Google Scholar 

  9. Watson PG (1980) The diagnosis and management of scleritis. Ophthalmology 87: 716–720

    Article  CAS  Google Scholar 

  10. Sainz de la Maza M et al. (1994) Scleritis associated with rheumatoid arthritis and with other systemic immune-mediated diseases. Ophthalmology 101: 1281–1286

    Article  CAS  Google Scholar 

  11. McCluskey PJ et al. (1999) Posterior scleritis: clinical features, systemic associations, and outcome in a large series of patients. Ophthalmology 106: 2380–2386

    Article  CAS  Google Scholar 

  12. Jabs DA et al. (2000) Episcleritis and scleritis: clinical features and treatment results. Am J Ophthalmol 130: 469–476

    Article  CAS  Google Scholar 

  13. Sainz de la Maza M et al. (1995) Scleritis associated with systemic vasculitic diseases. Ophthalmology 102: 687–692

    Article  CAS  Google Scholar 

  14. Hemady R et al. (1992) Six cases of scleritis associated with systemic infection. Am J Ophthalmol 114: 55–62

    Article  CAS  Google Scholar 

  15. Livir-Rallatos C et al. (1998) Recurrent nodular scleritis associated with varicella zoster virus. Am J Ophthalmol 126: 594–597

    Article  CAS  Google Scholar 

  16. Lee GA et al. (2002) Acanthamoeba sclerokeratitis: treatment with systemic immunosuppression. Ophthalmology 109: 1178–1182

    Article  Google Scholar 

  17. Macarol V and Fraunfelder FT (1994) Pamidronate disodium and possible ocular adverse drug reactions. Am J Ophthalmol 118: 220–224

    Article  CAS  Google Scholar 

  18. Zamir E et al. (2001) Self-inflicted anterior scleritis. Ophthalmology 108: 192–195

    Article  CAS  Google Scholar 

  19. O'Donoghue E et al. (1992) Surgically induced necrotising sclerokeratitis (SINS)—precipitating factors and response to treatment. Br J Ophthalmol 76: 17–21

    Article  CAS  Google Scholar 

  20. Dorey SE et al. (2002) Orbital lymphoma misdiagnosed as scleritis. Ophthalmology 109: 2347–2350

    Article  Google Scholar 

  21. Yap EY et al. (1992) Scleritis as an initial manifestation of choroidal malignant melanoma. Ophthalmology 99: 1693–1697

    Article  CAS  Google Scholar 

  22. Soukiasian SH et al. (1992) Diagnostic value of anti-neutrophil cytoplasmic antibodies in scleritis associated with Wegener's granulomatosis. Ophthalmology 99: 125–132

    Article  CAS  Google Scholar 

  23. Hembry RM et al. (1979) Experimental model for scleritis. Arch Ophthalmol 97: 1337–1340

    Article  CAS  Google Scholar 

  24. Fong LP et al. (1991) Immunopathology of scleritis. Ophthalmology 98: 472–479

    Article  CAS  Google Scholar 

  25. Young RD and Watson PG (1984) Microscopical studies of necrotising scleritis. I. Cellular aspects. Br J Ophthalmol 68: 770–780

    Article  CAS  Google Scholar 

  26. Rao NA et al. (1985) Necrotizing scleritis. A clinico-pathologic study of 41 cases. Ophthalmology 92: 1542–1549

    Article  CAS  Google Scholar 

  27. Young RD and Watson PG (1984) Microscopical studies of necrotising scleritis. II. Collagen degradation in the scleral stroma. Br J Ophthalmol 68: 781–789

    Article  CAS  Google Scholar 

  28. Di Girolamo N et al. (1997) Increased expression of matrix metalloproteinases in vivo in scleritis tissue and in vitro in cultured human scleral fibroblasts. Am J Pathol 150: 653–666

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Riono WP et al. (1999) Scleritis: a clinicopathologic study of 55 cases. Ophthalmology 106: 1328–1333

    Article  CAS  Google Scholar 

  30. Erhardt CC et al. (1989) Factors predicting a poor life prognosis in rheumatoid arthritis: an eight year prospective study. Ann Rheum Dis 48: 7–13

    Article  CAS  Google Scholar 

  31. Rosenbaum JT and Robertson JE Jr (1993) Recognition of posterior scleritis and its treatment with indomethacin. Retina 13: 17–21

    Article  CAS  Google Scholar 

  32. Sainz de la Maza M et al. (1993) An analysis of therapeutic decision for scleritis. Ophthalmology 100: 1372–1376

    Article  CAS  Google Scholar 

  33. Bauer AM et al. (2005) Celecoxib, a selective inhibitor of cyclooxygenase 2 for therapy of diffuse anterior scleritis. Am J Ophthalmol 139: 1086–1089

    Article  CAS  Google Scholar 

  34. Spiegel BM et al. (2005) Minimizing complications from nonsteroidal antiinflammatory drugs: cost-effectiveness of competing strategies in varying risk groups. Arthritis Rheum 53: 185–197

    Article  Google Scholar 

  35. Messmer EM and Foster CS (1995) Destructive corneal and scleral disease associated with rheumatoid arthritis. Medical and surgical management. Cornea 14: 408–417

    Article  CAS  Google Scholar 

  36. Kaplan-Messas A et al. (2003) Methotrexate as a first-line corticosteroid-sparing therapy in a cohort of uveitis and scleritis. Ocul Immunol Inflamm 11: 131–139

    Article  CAS  Google Scholar 

  37. Shah SS et al. (1992) Low-dose methotrexate therapy for ocular inflammatory disease. Ophthalmology 99: 1419–1423

    Article  CAS  Google Scholar 

  38. Sen HN et al. (2003) Mycophenolate mofetil for the treatment of scleritis. Ophthalmology 110: 1750–1755

    Article  Google Scholar 

  39. Thorne JE et al. (2005) Mycophenolate mofetil therapy for inflammatory eye disease. Ophthalmology 112: 1472–1477

    Article  Google Scholar 

  40. Hakin KN et al. (1991) Use of cyclosporin in the management of steroid dependent non-necrotising scleritis. Br J Ophthalmol 75: 340–341

    Article  CAS  Google Scholar 

  41. Wakefield D and McCluskey P (1989) Cyclosporin therapy for severe scleritis. Br J Ophthalmol 73: 743–746

    Article  CAS  Google Scholar 

  42. Langford CA et al. (2003) Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener's granulomatosis: extended follow-up and rate of relapse. Am J Med 114: 463–469

    Article  CAS  Google Scholar 

  43. Stone JH (2002) Polyarteritis nodosa. JAMA 288: 1632–1639

    Article  Google Scholar 

  44. Albini TA et al. (2005) Evaluation of subconjunctival triamcinolone for nonnecrotizing anterior scleritis. Ophthalmology 112: 1814–1820

    Article  Google Scholar 

  45. Sen HN et al. (2005) Subconjunctival corticosteroid injection for the treatment of non-necrotising anterior scleritis. Br J Ophthalmol 89: 917–918

    Article  CAS  Google Scholar 

  46. Tu EY et al. (1995) Therapy of nonnecrotizing anterior scleritis with subconjunctival corticosteroid injection. Ophthalmology 102: 718–724

    Article  CAS  Google Scholar 

  47. Smith JR 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  Google Scholar 

  48. El-Shabrawi Y and Hermann J (2005) Anti-TNF alpha therapy in chronic necrotizing scleritis resistant to standard immunomodulatory therapy in a patient with Wegener's granulomatosis. Eye 19: 1017–1018

    Article  CAS  Google Scholar 

  49. Cazabon S et al. (2005) The successful use of infliximab in resistant relapsing polychondritis and associated scleritis. Eye 19: 222–224

    Article  CAS  Google Scholar 

  50. Murphy CC et al. (2004) Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis. Ophthalmology 111: 352–356

    Article  Google Scholar 

  51. Papaliodis GN et al. (2003) Treatment of ocular inflammatory disorders with daclizumab. Ophthalmology 110: 786–789

    Article  Google Scholar 

  52. Ahmadi-Simab K et al. (2005) Successful treatment of refractory anterior scleritis in primary Sjogren's syndrome with rituximab. Ann Rheum Dis 64: 1087–1088

    Article  CAS  Google Scholar 

  53. Cheung CM et al. (2005) Successful treatment of Wegener's granulomatosis associated scleritis with rituximab. Br J Ophthalmol 89: 1542

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are supported in part by Research to Prevent Blindness (Senior Scholar Award to JT Rosenbaum and Career Development Award to JR Smith) and the Rosenfeld Family Fund. The authors gratefully acknowledge Dr Narsing Rao, MD (Doheny Eye Institute, University of Southern California, Los Angeles), who provided the images in Figure 3.

Author information

Authors and Affiliations

  1. and Chair of the Department of Rheumatology all at the Oregon Health & Science University, JR Smith is Associate Professor of Ophthalmology and Cell & Developmental Biology, F Mackensen is a previous Uveitis Fellow and JT Rosenbaum is the Edward Rosenbaum Professor of Inflammation Research, Professor of Medicine, Ophthalmology and Cell & Developmental Biology, Portland, OR, USA.,

    Justine R Smith, Friederike Mackensen & James T Rosenbaum

Authors
  1. Justine R Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Friederike Mackensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James T Rosenbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Justine R Smith.

Ethics declarations

Competing interests

Dr Smith receives support for clinical trials from Centocor and Allergan, with support from Abbott and Genentech currently pending. Dr Mackensen declared no competing interests. Dr Rosenbaum is a consultant for Novartis, Medarex and Bristol Myers. He receives support for clinical trials from Centocor and Allergan, with support from Abbott, Genentech and Amgen currently pending.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, J., Mackensen, F. & Rosenbaum, J. Therapy Insight: scleritis and its relationship to systemic autoimmune disease. Nat Rev Rheumatol 3, 219–226 (2007). https://doi.org/10.1038/ncprheum0454

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncprheum0454

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing