The patient in this issue has scleritis secondary to systemic rheumatologic disease.

The sclera is a dense, poorly vascularized connective tissue structure composed of collagen, elastin, proteoglycans and glycoproteins. Various inflammatory and noninflammatory processes can result in inflammatory conditions that manifest as episcleritis and scleritis.1-4

Rheumatoid arthritis (RA) can affect almost all ocular structures, including the sclera and cornea together (sclerosing keratitis) or the sclera alone (scleritis). For example, patients who have RA and noninfectious corneal inflammation may present with complaints of foreign-body sensation, dryness, photophobia, soreness and blurred vision.

Patients who have RA may also develop peripheral corneal thinning without infiltration or an overlying epithelial defect. This condition, also known as marginal furrow degeneration, presents as a relatively quiet eye, with minimal infiltration and associated neovascularization. This benign condition results from a slowly progressive resorption of peripheral corneal tissue.

Acute onset of stromal infiltration and/or opacity associated with stromal edema may occur with or without an overlying epithelial defect. The opacity may gradually resolve to leave an area of superficial vascularization and stromal thinning.1-4

The pathology of paracentral sclerocorneal rheumatoid melting involves infiltration by monocytes, macrophages and T-cells, as well as immunoglobulin deposition.1-4 Interleukin-1 and tumor necrosis factor-alpha are local cytokines that induce production of collagenase and protease, which play a role in corneal ulceration. Adjacent episcleritis or scleritis is common in rheumatoid-associated keratitis.1-4

Scleritis proper is a rare condition. Most scleral inflammation is noninfectious, though infection is possible. On rare occasions, tuberculosis may be the cause of scleral nodules.

Histopathology shows granulomatous or nongranulomatous inflammation, vasculitis, and scleral necrosis. Antigen-antibody complexes and T cells appear to play a role. Of the patients who present with scleritis, 50% appear to have no underlying systemic disease, while the other 50% harbor a connective tissue disorder.1

Scleral inflammation may cause structural damage to the eye. Scleral translucency and thinning regularly occur. Scleritis adjacent to the cornea may be associated with focal or diffuse keratitis. Focal keratitis may manifest as a ring infiltrate at the limbus, without the peripheral clear zone that is seen with staphylococcal marginal infiltrates.1,4

Inflammatory cells may block scleral emissary vessels, resulting in elevated episcleral venous pressure and hence elevated IOP. Ciliary body detachment adjacent to areas of active scleritis may cause angle closure as the lens-iris diaphragm rotates anteriorly.

Topical corticosteroids may also induce an elevation in IOP. Accompanying uveitis may be responsible for glaucoma if the trabecular meshwork becomes clogged with inflammatory cells and debris.1-4

To work up a patient who has active scleritis, evaluate the patient for evidence of vasculitis, connective tissue disease and infection. Appropriate laboratory tests might include erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), antinuclear antibody (ANA), fluorescent treponemal antibody absorption (FTA-ABS), a complete blood count (CBC), urinalysis, a chest radiograph and an antineutrophil cytoplasmic antibody (ANCA) test.1-4 (For more on these tests, see A Review of Lab Tests for Uveitis, March 2004.) Additional testing might include sodium fluorescein staining to rule out corneal melting and vitreous examination to rule out pars planitis.

Episcleritis is the most difficult differential diagnostic challenge in patients who have scleritis, with differentiating features similar to scleritis but on a smaller scale. Episcleral inflammation produces injection of the conjunctiva, anterior chamber reaction (cell and flare), pain, photophobia, lacrimation, pain upon ocular movement and in some cases, depending on the amount of keratic precipitate, decreased vision. When a systemic cause is uncovered, episcleritis is considered to be on the continuum of scleritis. Episcleritis that is secondary to antigen antibody response (allergic/immune etiology) is often unilateral and focal in presentation. When it is bilateral, it is typically asymmetric with a scaled-down proportion of the same symptoms.   

Most patients who have active scleritis require systemic and topical therapy. We placed this patient on oral prednisone, which we tapered as follows: 60mg(day one), 40mg (days two and three), and 20mg (days four to six). We also prescribed atropine 1% bid and ketorolac qid. She felt better within 48 hours. We referred her to a rheumatologist for systemic management.

Topical nonsteroidal anti-inflammatory drugs such as diclofenac and ketorolac may offer some benefit to patients who have mild episcleritis, but these are of minimal or no benefit for true scleritis. Topical corticosteroids seldom have any marked beneficial anti-inflammatory effect in cases of true scleritis, although they may help treat secondary uveitis.1,5

Administer oral NSAIDs as the first line of treatment in patients with mild and moderately severe scleritis. Indomethacin 50mg tid or, in the sustained-release form, 75mg bid is effective. Other nonsteroidal agents that appear to work well are piroxicam, ibuprofen, naproxen, tolmetin and sulindac. Etodolac, a newer NSAID, may cause fewer gastrointestinal side effects than other agents. Gastrointestinal problems and kidney damage from long-term therapy can all occur. Patients who take NSAIDs may require other medications to prevent or treat gastrointestinal side effects.1  These oral medications have stood the test of time, serving as a mainstay for more severe systemic inflammatory conditions such as arthritis. They are effective medications in cases of ocular inflammation as well.  

Oral corticosteroids usually are required for patients who have moderately severe to severe scleritis.1 Begin with about 1mg/kg/day of prednisone. In severe cases, doses up to 1.5mg/kg/day may be required. Slowly taper the prednisone to a best-tolerated dose. Some patients require daily prednisone for six months to a year, perhaps longer.1-4

Other possible treatments:

Pulse intravenous methylprednisolone. Doses of 0.5g to 1g have been used for some patients who have severe scleritis.1

Methotrexate or azathioprine. Low-dose methotrexate (7.5mg to 15mg weekly) has been reported to be of benefit in reducing or eliminating the need for prednisone in patients who have scleritis. Azathioprine at a dose of 1.5mg/kg to 2mg/kg/day also may reduce or eliminate the need for corticosteroids. However, both these agents can cause hepatic and hematological problems.

Cyclophosphamide or chlorambucil.. Cyclophosphamide works more rapidly (frequently within a few days to a week) than chlorambucil, which has a slower onset. Giving the drug once a week or once a month may be less toxic than daily oral cyclophosphamide, although it may be less effective. Pulse I.V. cyclophosphamide also has been used in severe sight- or life-threatening disease.1-4 Realize that cyclophosphamide has the added risk of hemorrhagic cystitis.

Cyclosporine. This agent  apparently interferes with interleukin-2, has shown some success in treating scleritis. However, it is quite toxic.3

Patients with this type of anterior segment inflammation must be closely monitored. Producing a plan with a regimen that works takes time and titration. Decompensation can come quickly resulting in keratolysis (corneal melting) which can incur permanent visual disability.    

1. Goldstein DA, Tessler HH. Conjunctival and corneal degenerations; Salzmanns corneal degeneration. In: Yanoff M, Duker JS. Ophthalmology. Philadelphia: Mosby, 1999:

2. Hamideh F, Prete PE. Ophthalmologic manifestations of rheumatic diseases. Semin Arthritis Rheum 2001 Feb;30(4):217-41.

3. Rosenbaum JT, Becker MD, Smith JR. Toward new therapies for ocular inflammation. Arch Soc Esp Oftalmol 2000 Aug;75(8):511-4.

4. Daniell MD, Dart JK, Lightman S. Use of cyclosporin in the treatment of steroid resistant post-keratoplasty atopic sclerokeratitis. Br J Ophthalmol 2001 Jan;85(1):91-2.

5. Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and scleritis: clinical features and treatment results. Am J Ophthalmol 2000 Oct;130(4):469-76.

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Vol. No: 141:05Issue: 5/15/04