Scleritis almost always requires treatment with systemic medications. Important considerations in the formulation of a therapeutic plan include accurate classification of scleritis type and identification of concomitant local or systemic disease, the exclusion of possible infectious etiologies, and the potential for medication related toxicity and/or possible drug interactions.
The first line of treatment for patients with noninfectious diffuse or nodular scleritis not associated with an underlying systemic vasculitis is oral NSAIDs, with or without the use of topical corticosteroids. A treatment response is usually evident within 2 to 3 weeks of commencing therapy and sequential trials of various NSAIDs may be necessary in order to find which agent is most effective. Again, the selective COX-2 inhibitors are advantageous in cases where adverse gastrointestinal side effects or drug interactions might otherwise limit treatment. Patients with associated conditions such as gout, rosacea, or atopy require specific treatment of the underlying disease.
Therapeutic failure with oral NSAIDs requires the addition or substitution of systemic corticosteroids, commencing at high doses (prednisone 1 to 1.5 mg/kg/day), with subsequent taper and discontinuation as soon as is possible while maintaining clinical remission with or without continued NSAIDs. Typically, a slow and steady taper (10 mg per week) is commenced once scleral inflammation has been controlled (usually within 7 to 14 days) until a dose of 20 mg/day of prednisone is reached. The dose may be further reduced by smaller decrements (2.5 to 5 mg per week) or an alternate dosage schedule may be employed in patients in whom a slower taper is anticipated in an effort to reduce steroid-associated side effects. Alternatively, intravenous, high-dose methylprednisolone (1 g/day for 3 days, usually administered in divided doses, as 250 mg q 6 hours or 500 mg q 12 hours), alone or in conjunction with other immunosuppressive agents, has been shown safe and effective for the induction of disease remission in patients with severe scleritis. This approach obviates some of the potential side effects associated with prolonged, high-dose oral corticosteroid therapy.
Periocular injections of corticosteroids have been reported to be safe and effective, both adjunctively and as primary therapy, in the treatment of various forms of nonnecrotizing scleritis; however, their use is controversial due to concerns surrounding the potential exacerbation of scleral melting and/or scleral perforation. Recent reports support a potential role for subconjunctival injection of triamcinolone acetonide in selected cases of nonnecrotizing anterior scleritis, especially where systemic therapy is either not desired or poorly tolerated.
Immunosuppressive therapy is indicated in patients with severe scleritis who have failed to respond to high-dose oral or intravenous corticosteroids or in whom unacceptably high doses of systemic corticosteroids are necessary to achieve inflammatory control. In the latter case, the addition of immunosuppressive therapy is said to be “steroid sparing,” allowing lower doses of each medication to be used in an effort to achieve inflammatory quiescence while minimizing the side-effects of either agent used as monotherapy at higher doses. Immunosuppressive medications which have been successful in the treatment of scleritis include methotrexate, azathioprine, cyclophosphamide, mycophenolate mofetil, daclizumab, infliximab, and rituximab. Typically these drugs are commenced together with oral corticosteroids, as a response to therapy may take up to 3 weeks, with the latter being tapered and discontinued as described above.
The scleritis associated with an underlying systemic vasculitis requires systemic immunosuppressive therapy at the outset, typically with cyclophosphamide (1 to 3 mg/Kg/day) supplemented with systemic prednisone. This therapy is directed not only in an effort to control scleral inflammation, but also for the treatment of the underlying systemic vasculitis, which, if left untreated, carries a significantly high mortality, especially for patients with Wegener granulomatosis and polyarteritis nodosa. A similar therapeutic strategy may be extended to patients with noninfectious necrotizing scleritis associated with other underlying systemic vasculitic or connective tissue disease conditions such as rheumatoid arthritis or relapsing polychondritis. A “hand in glove” collaboration between the ophthalmologist and chemotherapist (an oncologist, hematologist, or rheumatologist) works most effectively for patients requiring these medications.
Patients with diffuse or nodular scleritis, not associated with underlying systemic vasculitic disease, who have failed therapy with NSAIDs and/or systemic corticosteroids, may be treated with a variety of other immunomodulatory agents. Methotrexate (7.5 to 15 mg orally or 15 mg intramuscularly or subcutaneously once weekly), together with folic acid (1 mg daily) is probably the best initial choice as it is both efficacious and steroid sparing in the treatment of scleritis and has a favorable side effect profile and lower oncogenic potential as compared to cytotoxic drugs (cyclophosphamide and chlorambucil). Oral azathioprine (1 to 2 mg/kg daily), while less effective as monotherapy than other immunosuppressive agents in controlling severe scleritis, is most frequently used in conjunction with systemic corticosteroids as a steroid-sparing agent and is generally well tolerated. Similarly, oral mycophenolate mofetil (1 g twice daily) may be most useful as a steroid-sparing agent in patients with controlled scleral disease rather than as adjunctive therapy in patients with severe active scleritis requiring additional immunosuppressive therapy. Infliximab, a tumor necrosis factor alpha (TNF-α) inhibitor, has been shown to be effective and safe in the management of refractory scleritis when conventional immunosuppression has failed (Figures 10a, 10b). Daclizumab (humanized immunoglobulin G monoclonal antibody that specifically binds CD25 of the human interleukin-2 receptor that is expressed on activated T lymphocytes) and rituximab (anti-CD20B cell monoclonal antibody) have also been shown to be successful in the treatment of refractory scleritis.