its incidence in the general rheumatoid population [114]. Use of artiÞcial tear substitutes and punctal occlusion, initially with punctal plugs and then permanently with cautery, may be necessary adjunctive measures. Lid scrubs and hot compresses with or without systemic tetracyclines are indicated if there is meibomian gland dysfunction or blepharitis associated. The use of slow-release artiÞcial tear inserts without preservatives may provide continuous lubrication in the presence of some moisture. Topical cyclosporine (CsA) is the Þrst US Food and Drug Administration (FDA)- approved drug therapy for dry eye. The effect of this drug on inßammatory disease is due to its ability to inhibit T-cell-mediated inßammation by preventing the activation of CD 4-positive helper/ inducer T lymphocytes. Eyes treated with topical CsA have shown fewer apoptotic epithelial cells, decreased levels of the proapoptotic markers, and increased expression of the antiapoptotic factors. CsA signiÞcantly improved corneal ßuorescein staining, Schirmer scores, blurred vision, and dryness, and signiÞcantly increased conjunctival goblet cell density [115Ð120]. Occasionally, partial tarsorraphy may be required to decrease evaporation.

Scleritis

Rheumatoid arthritis is by far the most common systemic condition associated with scleritis. The reported incidence of RA in patients with scleritis ranges from 10 to 33% (Table 6.3) [114, 121Ð125]. Conversely, the reported incidence of scleritis in patients with RA ranges from 0.15 to 6.3% [114].

Rheumatoid scleritis is most common in the sixth decade of life, affects women more frequently than men, and is often bilateral [114, 123Ð126]. Diffuse anterior scleritis is the most frequent type of scleritis in patients with RA [114, 123]; however, cases of scleromalacia perforans anterior scleritis in which a systemic diagnosis can be ascribed, are almost exclusively due to RA [122]. Although posterior rheumatoid scleritis is uncommon, it is usually accompanied by diffuse anterior scleritis [114]. In our own series of 500 patients with scleritis, 32 patients had RA (6.4%). The mean age of our patients was 59 years (range, 19Ð80 years) and the scleritis was more common in women than in men (23 females and nine males). Twelve patients (37%) had bilateral scleritis. Diffuse anterior scleritis (81%) was the type most frequently encountered.

Although scleritis may be the initial sign of rheumatoid disease [125, 126], it usually presents in patients with long-standing RA, usually 13 or 14 years after the onset of arthritis [114, 127]. Patients with rheumatoid scleritis have more advanced joint disease and more extraarticular manifestations than do rheumatoid patients without scleritis [114, 121, 125, 127, 128]. Many of the extraarticular manifestations reßect an underlying rheumatoid vasculitis [129]. Although subcutaneous nodules appear in 20Ð30% of patients with classic RA, their presence increases to 50% in patients with rheumatoid scleritis [114]. Pulmonary disorders, such as pleural effusion, rheumatoid nodules of lung, and pneumonia, are more commonly present in patients with rheumatoid scleritis

than in rheumatoid patients without scleritis [114]. Cardiac manifestations, such as pericarditis [114, 129, 130], valvular disease [114, 125, 126], conduction abnormalities [114], and myocardial infarction [114, 129], have been described in association with rheumatoid scleritis. Myocardial ischemia is also more frequent in rheumatoid patients with scleritis [114]. Peripheral neuropathies, skin ulcers, and amyloidosis also have been described in rheumatoid patients with scleritis [114, 129].

Exacerbation of scleritis often occurs at times of increased activity of RA [121, 125, 127, 131, 132], and a progression from diffuse or nodular scleritis to necrotizing scleritis may indicate the onset of rheumatoid vasculitis elsewhere in the body [122]. Necrotizing scleritis also may appear after surgical trauma to the sclera. The mean time of presentation of scleritis in our series of 32 patients with rheumatoid scleritis was 16 years after the onset of arthritis. In two cases, scleritis was the initial manifestation whose study led to the diagnosis of RA. Many patients with rheumatoid scleritis had deforming joint disease and extraarticular RA manifestations. The most frequent extraarticular manifestations were subcutaneous nodules and skin vasculitic lesions. Other extraarticular manifestations included (1) pulmonary disorders, such as pleural effusion, pneumonia, and rheumatoid nodules of the lung;

(2) cardiac abnormalities, such as conduction defects, mitral valvular disease, myocardial infarction, and pericarditis; (3) neurologic involvement, such as carpal tunnel syndrome, sensory neuropathy, and sensorimotor neuropathy; (4) lymphadenopathy and non-HodgkinÕs lymphoma; (5) amyloidosis; (6) mild elevation of liver function tests; (7) gastrointestinal disorders, such as gastroduodenal ulcers in patients who had received long-term steroidal or nonsteroidal therapy; (8) kidney involvement secondary to gold treatment; and (9) bone abnormalities, such as osteoporosis in patients who had received long-term steroidal therapy. Necrotizing scleritis appeared an average of 16 weeks after ocular surgery in four patients with RA.

The prognosis for life is poorer in patients with RA complicated by scleritis when compared with RA patients without scleritis [114, 122, 125, 127Ð129]. Thirty-six to forty-Þve percent of

patients with rheumatoid scleritis will be dead within 3 years of the onset of scleritis unless immunosuppressive or biologic response modiÞer therapy is used. This compares to an 18% 3-year mortality in patients with RA without scleritis [114, 127]. Most causes of death are due to extraarticular RA vasculitic manifestations [122, 129]. Necrotizing scleritis is the type of scleritis most predictive of these deaths [122, 129].

Because the presence of necrotizing scleritis in RA may indicate an underlying potentially lethal systemic vasculitis, it is essential to detect both the ocular and systemic conditions as early as possible so that vigorous treatment can favorably alter not only the ocular, but also the life prognosis in these patients.

Scleral inßammation in RA may extend to the adjacent structures and may cause keratitis, anterior uveitis, glaucoma, cataract, retinal, choroidal,opticnervechanges,andmotilitydisturbances. Some of these complications may affect visual acuity. In our series of 32 patients with rheumatoid scleritis, a decrease in visual acuity (loss of vision equal or greater to two Snellen lines at the end of the follow-up period or vision equal to or worse than 20/80 at the Þrst examination) occurred in Þve patients (16%).

Keratitis

Corneal involvement associated with scleritis in patients with RA can be classiÞed depending on whether or not thinning, inÞltration, or ulceration of the cornea occurs. Peripheral corneal thinning, acute or sclerosing stromal keratitis, and PUK are the most common corneal abnormalities associated with rheumatoid scleritis (Fig. 6.6).

The reported incidence of keratitis associated with rheumatoid scleritis ranges from 36 to 43.5% [114, 127, 128]. In our series of 32 patients with rheumatoid scleritis, seven patients had keratitis (50%); of those, one patient had corneal thinning, two patients had acute stromal keratitis, and four patients had PUK. Keratitis in RA also may occur in the absence of adjacent scleritis [122, 133Ð139].

Anterior Uveitis

Anterior uveitis in RA is almost always caused by extension of scleral inßammation, but anterior uveitis in the absence of scleritis has no higher