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SAN FRANCISCO -- Inflammatory eye diseases remain perplexing and perhaps even scary to many rheumatologists, a New York consultant rheumatologist said here.

Non-uveitic ocular inflammatory diseases have numerous potential etiologies, and early recognition remains the key to successful management, Sergio Schwartzman, MD, of the Hospital for Special Surgery in New York City, said at the meeting. After recognizing a condition, rheumatologists can apply standard approaches to evaluation and management, he said.

"Rheumatologists are scared of the eyes. The eyes are enigmas to us. I've seen rheumatologists in the clinic completely ignore areas they're not familiar with. The eyes are one of those areas. We're afraid of the eye because it is such a vital organ. If you lose function in one of your joints, you're still going to be potentially independent, but if you lose your vision, you're going to be blind."

Acknowledging a multitude of challenging eye conditions, Schwartzman focused in his talk on strategies for recognition and management of two: scleritis and orbital inflammatory disease.

The two conditions have fairly prominent signs and symptoms. A patient with rheumatoid arthritis (RA) who complains of severe eye pain that interferes with sleep and has an associated eye nodule most likely has anterior nodular scleritis. Classic is one of the most common signs of orbital inflammatory disease.

The evaluation of a patient for suspected scleritis should take into account that the sclera is three-dimensional and that only the anterior sclera is visible. If a patient with RA or another inflammatory disease has severe eye pain unaccompanied by visible nodules, posterior scleritis is a potential diagnosis.

Distinguishing Features

A distinguishing feature of the sclera is its relative avascularity, said Schwartzman. Most of the blood supply comes from the outer covering, the episclera. The sclera is extensively innervated, which accounts for the severe pain associated with scleritis.

Several features distinguish episcleritis from scleritis. Episcleritis has an acute onset, associated with mild pain or discomfort, redness of the eye (localized or diffuse), no associated ocular symptoms other than watering and occasional photophobia, and can arise in one or both eyes.

Scleritis has a more gradual onset and is associated with severe, boring pain that often radiates to the forehead. The condition is predominantly unilateral, and patients more often have prominent symptoms, such as watering, photophobia, and gradual deterioration of vision.

Occasionally, patients have systemic symptoms, such as fever, vomiting, and headache. The condition may produce localized or generalized redness of the eye, and eye movement causes pain. Affected patients tend to have recurrent, symptomatic episodes.

Scleromalacia perforans, or necrotizing scleritis, is the most severe and threatening form of scleritis and can occur with few or no preceding symptoms. The inflammatory type is associated with severe pain. The eye may also exhibit discoloration, usually blue or gray.

"This is the most feared form of scleritis because it can lead to blindness," said Schwartzman.

Posterior scleritis can be either nodular or non-nodular, localized or diffuse. Redness of the eye in the absence of other signs or symptoms of anterior scleritis should prompt consideration of posterior scleritis, which requires aggressive treatment if confirmed.

Treatment Options

With regard to treatment, episodes of episcleritis usually respond to local therapy, such as lubricants and topical nonsteroidal anti-inflammatory drugs (NSAIDs). The same is not true of scleritis, said Schwartzman.

When an underlying systemic disease has been identified, effective treatment of the underlying condition is the first step in the treatment of associated scleritis. Initial treatment options for scleritis include topical steroids and NSAIDs.

Schwartzman reviewed findings from a "real world" study of 89 patients evaluated at a uveitis clinic, 31 of whom subsequently were found to have scleritis associated with an underlying inflammatory disease (most often RA). All but two of the patients eventually required systemic therapy.

No randomized, controlled studies have evaluated the treatment of scleritis associated with autoimmune or inflammatory diseases, said Schwartzman. Consequently, treatment has evolved to include most of the agents used for the underlying conditions: methotrexate, mycophenolate, azathioprine, cyclosporine, tacrolimus, cyclophosphamide (less commonly in the era of biologic therapy), infliximab (Remicade), and rituximab (Rituxan), among others.

With regard to biologic therapies, infliximab has been used most extensively and with considerable success. Adalimumab (Humira) and rituximab also have been used with good results. In general, etanercept (Enbrel) has not worked for autoimmune eye disease, said Schwartzman.

"Rituximab has become the drug to use in scleritis," he said. "It is now being studied fairly aggressively in both scleritis and autoimmune inflammatory disease."

Orbital Inflammatory Disease

Evaluation and management of orbital inflammatory disease is complicated by the multiple orbital sites that can be involved or affected by the disease process, said Schwartzman. Orbital muscles, orbital fat, the eyelid, and the lacrimal gland can be the primary site of involvement.

Potential symptoms include acute or recurrent pain, diplopia, and painful ophthalmoplegia. Other signs include proptosis, restricted eye movement, conjunctival vascular congestion and edema, eyelid erythema and swelling, impaired vision, elevated intraocular pressure, and intraocular scleritis, uveitis, or exudative retinal detachment. Patients may or may not have constitutional symptoms associated with the condition.

"My worry is about infection," Schwartzman said of the differential diagnosis. "If this presents in a patient with arthritis on steroids, you're not going to be jumping up and down to insist this is rheumatoid arthritis. The first thing you want to be sure of is that this is not infection."

A comprehensive laboratory analysis and a pathology evaluation are essential to rule out other potential causes of orbital inflammatory disease: lymphoma, melanoma, metastatic disease, and trauma, in addition to infection. Potential rheumatic causes include arteritis, thyroid disease, sarcoid disease, IgG4 disease, and granulomatosis with polyangiitis.

The standard approach to treatment includes high-dose steroids and remittive medications (particularly rituximab), said Schwartzman.

"The current trend in orthoinflammatory disease is to use rituximab as the first biologic agent."

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