The distance from the surface of the eye to the optic nerve is only about 2.5 cm, but within that short distance, an incredible diversity of tissue resides and almost any portion of that tissue could become inflamed. A rheumatologist should have a working knowledge of uveitis, keratitis, scleritis, episcleritis, conjunctivitis, optic neuritis, anterior ischemic optic neuropathy, dry eye, and orbital inflammation because rheumatologic diseases can be associated with inflammation in each of these areas and because managing a patient with one of these problems may require systemic immunosuppression, a form of treatment that is outside the expertise of the vast majority of ophthalmologists.

Essentials of Diagnosis

• Divided into anterior, intermediate, and posterior forms. Different disease entities are associated with different forms of uveitis.
  
• Panuveitis, the occurrence of anterior, intermediate, and posterior uveitis in the same patient, is particularly characteristic of Behçet disease and sarcoidosis.
  
• Management strategies vary according to whether the uveitis is anterior, intermediate, or posterior.

General Considerations

The uvea—the middle layer of the eye—includes the iris, ciliary body, and choroid. Anatomic subsets of uveitis can be defined: anterior uveitis (or iritis); iridocyclitis, when the ciliary body is inflamed along with the iris; intermediate uveitis (inflammation in the vitreous humor); posterior uveitis (involvement of the choroid or retina); and panuveitis, when the iris, vitreous, and retina all show evidence of inflammation. Uveitis can also be classified by etiology (Tables 67–1 and 67–2). A rheumatologist is usually essential in treating inflammation that is confined to the uveal tract or part of a systemic disease involving the uveal tract.

Clinical Findings

Uveitis has a variety of complications including cataract, glaucoma, posterior synechiae, macular edema, and retinal vasculitis. In an unpublished series, retinal vasculitis (Plate 51) was detected in one of every seven patients with uveitis, but retinal vasculitis does not have the same therapeutic implication as systemic vasculitis and patients with retinal vasculitis rarely have a systemic disease.

Treatment

Many patients with uveal inflammation can be treated with topical medications or by periocular or intraocular injections of glucocorticoids. Many ophthalmologists feel comfortable prescribing a short course of oral glucocorticoids. Glucocorticoid-sparing medications are generally indicated if the condition is not infectious or malignant, has not responded to local ophthalmic treatments listed earlier in this paragraph either due to lack of efficacy or lack of tolerance, and interferes with activities of daily living.

Commonly chosen glucocorticoid-sparing medications include methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine. A calcineurin antagonist such as cyclosporine or tacrolimus can be combined with an antimetabolite, offering greater efficacy than either medication alone but also posing greater risk. Although some groups advocate the use of an alkylating agent such as cyclophosphamide or chlorambucil, the author rarely uses medications in this class to treat uveitis.

The underlying diagnosis often plays a minor role in the selection of therapy. For example, about 30% of patients with uveitis in a referral clinic are labeled as having idiopathic disease, meaning that no specific etiology could be determined and it is presumably immune-mediated. Patients with idiopathic uveitis are often treated the same as a patient with sarcoid-associated uveitis or a patient with birdshot chorioretinopathy (Plate 52). A discussion about the nuances of therapy for specific forms of uveitis is beyond the scope of this chapter. However, methotrexate is used preferentially for children with juvenile idiopathic arthritis based on the experience using this medication in childhood. Vogt-Koyanagi-Harada syndrome (a form of uveitis characterized by bilateral anterior and posterior uveitis with serous retinal detachments and often eighth nerve disease and sterile meningitis) is generally treated with more sustained, relatively high-dose prednisone compared to other forms of uveitis. Behçet disease is especially responsive to infliximab, a drug that is sometimes instituted relatively soon in the approach to a patient with this diagnosis.

Although several oral or parenteral treatments for uveitis are currently undergoing clinical trials, no systemic immunomodulatory therapy has been approved. Of the biologic therapies, monoclonal antibodies to tumor necrosis factor (TNF) are the most widely used. Despite the lack of randomized, comparative efficacy data, the TNF therapies that are based on either chimeric or humanized monoclonal antibodies (eg, infliximab or adalimumab) are more consistently effective for eye disease than is etanercept, a soluble fusion protein. One prospective series using infliximab to treat various forms of uveitis found a 77% early response rate as well as a surprisingly high rate of toxicity. For example, drug-induced lupus develop in nearly 10% of the participants. Despite the efficacy, 52% of the initial participants did not continue infliximab therapy beyond 1 year.

Both infliximab and adalimumab are useful for patients with uveitis associated with juvenile idiopathic arthritis and an inadequate response to methotrexate. These children are more likely to experience sustained benefit with adalimumab rather than infliximab.

Uveitis, common among patients with ankylosing spondylitis, usually manifests itself as recurrent, unilateral, anterior disease (acute anterior uveitis). Several TNF inhibitors as well as sulfasalazine and possibly nonsteroidal anti-inflammatory drugs reduce the frequency of episodes of acute anterior uveitis in this setting. Paradoxically, TNF inhibition (especially etanercept use) sometimes appears to trigger uveitis.

Essentials of Diagnosis

• Erythema or a deep purplish hue of the sclera and intense pain are hallmarks of scleritis.
  
• There is a spectrum of disease severity, but scleritis can pose a vision-threatening complication of rheumatic diseases, particularly rheumatoid arthritis and granulomatosis with polyangiitis (GPA; formerly Wegener granulomatosis.)