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Therapy Insight: scleritis and its relationship to systemic autoimmune disease

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

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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)

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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.

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Correspondence to Justine R Smith.

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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.

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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

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