Review Article | Published:

Therapy Insight: scleritis and its relationship to systemic autoimmune disease

Nature Clinical Practice Rheumatology volume 3, pages 219226 (2007) | Download Citation



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

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  1. 1.

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

  2. 2.

    and (1991) Progression of scleral disease. Ophthalmology 98: 467–471

  3. 3.

    et al. (1994) Severity of scleritis and episcleritis. Ophthalmology 101: 389–396

  4. 4.

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

  5. 5.

    and (1971) Scleritis and rheumatoid arthritis. Ann Rheum Dis 30: 343–347

  6. 6.

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

  7. 7.

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

  8. 8.

    and (1976) Scleritis and episcleritis. Br J Ophthalmol 60: 163–191

  9. 9.

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

  10. 10.

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

  11. 11.

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

  12. 12.

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

  13. 13.

    et al. (1995) Scleritis associated with systemic vasculitic diseases. Ophthalmology 102: 687–692

  14. 14.

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

  15. 15.

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

  16. 16.

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

  17. 17.

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

  18. 18.

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

  19. 19.

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

  20. 20.

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

  21. 21.

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

  22. 22.

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

  23. 23.

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

  24. 24.

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

  25. 25.

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

  26. 26.

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

  27. 27.

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

  28. 28.

    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

  29. 29.

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

  30. 30.

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

  31. 31.

    and (1993) Recognition of posterior scleritis and its treatment with indomethacin. Retina 13: 17–21

  32. 32.

    et al. (1993) An analysis of therapeutic decision for scleritis. Ophthalmology 100: 1372–1376

  33. 33.

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

  34. 34.

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

  35. 35.

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

  36. 36.

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

  37. 37.

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

  38. 38.

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

  39. 39.

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

  40. 40.

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

  41. 41.

    and (1989) Cyclosporin therapy for severe scleritis. Br J Ophthalmol 73: 743–746

  42. 42.

    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

  43. 43.

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

  44. 44.

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

  45. 45.

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

  46. 46.

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

  47. 47.

    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

  48. 48.

    and (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

  49. 49.

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

  50. 50.

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

  51. 51.

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

  52. 52.

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

  53. 53.

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

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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


  1. 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, and Chair of the Department of Rheumatology all at the Oregon Health & Science University, Portland, OR, USA.

    • Justine R Smith
    • , Friederike Mackensen
    •  & James T Rosenbaum


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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.

Corresponding author

Correspondence to Justine R Smith.

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