Ocular complications associated with rheumatoid arthritis

This review covers common ocular complications (related to the eyes) associated with rheumatoid arthritis and provides an overview of available therapies.

Complications of rheumatoid arthritis (RA) include inflammation of various parts of the eye, including scleritis (inflammation of the white part, or sclera) and peripheral ulcerative keratitis (inflammation of the the transparent front part of the eye, or cornea). RA is the leading cause of these two severe conditions, which can rapidly progress to irreversible eye damage and blindness. In addition, research suggests that ocular complications are suggestive of disease prognosis and are associated with an increased risk of mortality due to their association with additional inflammatory complications. This review provides an overview of ocular inflammatory complications in patients with RA with focus on current available therapies.

Episcleritis is a mild and benign inflammation of the superficial layers of the sclera. Episcleritis occurs in 0.17 to 3.7% of RA patients, and causes red eyes, often described as ‘salmon pink’ in color, with no visual loss and no ocular pain. Episcleritis does not usually progress to more severe forms of ocular inflammation, and may resolve spontaneously without treatment.  Treatment of episcleritis can include the local application of corticosteroid eye drops to accel­erate resolution and alleviate bothering symptoms. In a study of 18 patients with episcleritis, 17% of the patients displayed spontaneous resolution without treatment, 50% responded well to local corticosteroid treatment and 17% required additional oral anti-inflammatory treat­ment.

Scleritis is a more severe inflammation of the sclera, and is estimated to affect 0.2 to 6.3% of all patients with RA.  Scleritis is much more common in women than in men, with women account­ing for 70% of cases, and is observed principally in patients between the ages of 30 and 60 years.  In contrast with episcleritis, scleritis manifests princi­pally as severe eye pain that does not respond to pain relieving drugs, and may be accompanied by tearing and visual disturbances. Scleritis can lead to visual loss due to potential com­plications, including peripheral ulcerative keratitis, necrotizing scleritis (death of the sclera tissue) and perforation of the ocular globe.

Peripheral ulcerative keratitis (PUK), a severe inflammatory condition of cornea, affects approximately 3% of RA patients. The incidence of PUK has decreased over recent years, possibly because of improved treatments for RA. PUK can arise as a complication of scleritis or inde­pendently of this condition. In the largest published study of patients with scleritis, comprising 500 patients, PUK was observed in 7.4% of simple scleritis cases, but in 35% of necrotizing scleritis cases. Commonly, signs of widespread inflammation of the blood vessels (referred to as vasculitis) are reported in the month follow­ing the onset of PUK, significantly increasing the risk of mortality. Therefore, the occurrence of PUK marks a turning point in the course of RA, now requiring intensive medical therapy.

Due to a limited number of properly designed studies investigating the treatment of scleritis or PUK among RA patients, there are no guidelines con­cerning the optimal management of these inflammatory ocular complications.

The initial treatment of scleritis and PUK is currently based on a combination of systemic corticosteroids treat­ment (steroids given orally or intravenously) and immunosuppressant therapy (drugs that suppress the the immune system and reduce inflammation). 

Cyclophosphamide is the most commonly used immunosuppressant, particularly since most patients with RA are already receiving another immunosuppressant (methotrexate) at the time of PUK or scleritis diagnosis. The beneficial effect of combining corticosteroids and cyclo­phosphamide for the treatment of ocular inflammation associated with RA has been demonstrated in several studies. One study including 34 RA patients with necrotizing scleritis and/or PUK demonstrated a significantly lower 10-year mortality rate among patients receiving a combination of an immunosuppressant and corticosteroids compared to those treated with corticosteroids alone (6% versus 53%). In addition, none of the patients treated with combined therapy suffered progression of eye damage, compared to 76% of patients treated with corticosteroids alone. Overall, response to treatment is observed in 83% of cases of necrotizing scleritis or PUK.

In less severe forms of scleritis, or if corticosteroid therapy is not optional (due to resistance or adverse effects), other immunosuppressant agents such as methotrexate (MTX, Trexall, Rheumatrex), azathioprine (Imuran, Azasan) and mycophenolate mofetil (Cellcept) may be prescribed.

Biological therapies which suppress inflammation, such as infliximab (Remicade) or rituximab (Rituxan), might also have a role in the treatment RA-associated ocular inflammations. Although no large controlled studies have been reported, infliximab has demonstrated good results in the treatment of PUK in small retrospective studies (looks backwards and examine the outcome of a specific exposure, such as therapy), and rituximab has demonstrated good results in the treatment of both PUK and scleritis in isolated case studies. This review suggests that infliximab or rituximab should be initiated in the treatment of PUK or severe scleritis after the failure of cyclophosphamide treatment.