be the problem whose diagnostic study leads to the discovery and subsequent treatment of a connective tissue disease or a vasculitic disease. When scleritis is the only presenting complaint, diagnosis and therapy of the potentially lethal systemic disease are often delayed. In our series, scleritis was the Þrst manifestation of connective tissue disease or a vasculitic disease in 48 patients (10%). The most common diagnosis eventually discovered was granulomatosis with polyangiitis (Wegener) followed by relapsing polychondritis. Meticulous review of systems (with subsequent studies to pursue leads) was the most fruitful diagnostic endeavor for establishing a diagnosis. Evaluation of biopsed tissue, and laboratory or X-ray studies in the context of review of system Þndings, conÞrmed the initial diagnostic impressions.

Systemic disease association was found to be most common in the necrotizing anterior types of scleritis, either with inßammation (80%) and without inßammation (67%), followed by the diffuse anterior (36%), nodular anterior (30%), and posterior (19%) types (Table 4.4). Diffuse anterior scleritis with inßammation was found to be the most frequent subcategory in patients whose scleritis appeared as a Þrst manifestation of a systemic disease (81%).

Although gout has been reported with scleritis, the association in most cases is vague and indeÞnite [18, 21]. Because erythema nodosum is a sign of other underlying diseases, such as bacterial (streptococcal), mycobacterial (tuberculosis), and chlamydial (psittacosis) infections, sarcoidosis, arthritis associated to inßammatory bowel disease, and Beh•etÕs disease, we have not considered it as a separate diagnostic entity, unlike other authors [2, 5]. Likewise, because RaynaudÕs phenomenon is a vascular manifestation present in several connective tissue and vasculitic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and giant cell arteritis, we, unlike other authors [13], considered it as part of the primary systemic disease. Some patients with scleritis may give a past history of rheumatic heart disease, but the conditions have not been described as occurring at the same time [3].

4.2.6Complications of Scleritis

4.2.6.1 Keratopathy

Because corneal changes in scleritis appear as an extension of the adjacent scleral inßammation, the area most frequently involved is the corneal periphery. Peripheral corneal involvement may precede the onset of scleritis [143, 144]. The different patterns of corneal involvement are related to the severity and type of the scleral inßammation and they can be classiÞed, depending on whether or not thinning, inÞltration, or ulceration of the peripheral cornea occurs.

Peripheral Corneal Thinning

Peripheral corneal thinning is the most benign form of corneal involvement associated with scleritis. It is frequently associated with diffuse anterior scleritis and, although it may occur in young patients without any systemic condition, it is often found in middle-aged and elderly individuals with long-standing rheumatoid arthritis [2]. The peripheral cornea becomes grayish and thinned in one or more areas over a period of several years, eventually extending through the full circumference of the eye (Fig. 4.34). The gutter, usually about one-third thinner than the normal central cornea, does not extend more than 2 mm centrally and is not necessarily located in the same quadrant as the area of scleral inßammation. Because the central area remains unaffected, there is little effect on visual acuity. The epithelium remains intact throughout the thinning process, but vascularization, lipid deposition, and further opaciÞcation and thinning may eventually involve the edematous stroma. Deepening of the gutter may result in a progressive astigmatism that interferes with visual acuity. If some pain occurs, it is due to the scleral inßammation rather than the peripheral corneal thinning. Sometimes, the thinned cornea may progress to an area of ectasia. Spontaneous perforation is rare, although trauma can rupture the thin cornea. Peripheral corneal thinning may also occur without scleritis in patients with long-standing rheumatoid arthritis; [145Ð148] circumferential thinning with a well-demarcated central edge without lipid deposition and minimal vascularization resembles the

Fig. 4.34 Slit-lamp photomicrograph. Note the area in the inferior cornea of peripheral corneal thinning in this patient, who has had multiple bouts of diffuse anterior scleritis

Fig. 4.35 TerrienÕs marginal degeneration. Note the quiet eye, the area of corneal thinning in the superior 160¡ of the corneal periphery, and the lipid/protein deposits in the corneal stroma at the anterior border of the area of active thinning

appearance of an eye wearing a hard contact lens (Òcontact lensÓ cornea) [149].

The differential diagnosis of peripheral corneal thinning associated with scleritis includes TerrienÕs marginal degeneration (Fig. 4.35), pellucid marginal degeneration, and senile furrow degeneration (Table 4.10). All of these are slowly progressive, bilateral, and painless peripheral stromal thinning with intact epithelium. In all of these, there is rare loss of vision or central cornea involvement. Furthermore, in peripheral corneal thinning associated with scleritis and in TerrienÕs marginal degeneration, the peripheral gutter may have lipid deposition and vascularization. However, TerrienÕs marginal degeneration usually occurs superiorly and, although an atypical pterygium may be present in 20% of the cases, it is not associated with true scleritis [150, 151]. Peripheral corneal thinning associated with scleritis may account for some cases considered to be Òinßammatory TerrienÕs marginal corneal disease.Ó [152] Unlike peripheral corneal thinning associated with scleritis, pellucid marginal degeneration is a noninßammatory condition that affects only the inferior cornea and is not accompanied by lipid deposition or vascularization [153, 154]. Finally, in senile furrow degeneration, a peripheral corneal thinning of the clear interval between an arcus senilis and the limbus, there is neither vascularization and lipid inÞltration in the

narrow gutter (0.5 mm or less in width) nor adjacent scleral inßammation [155, 156]. Unlike peripheral corneal thinning associated with scleritis, TerrienÕs marginal degeneration, pellucid marginal degeneration, and senile furrow degeneration are not associated with any systemic disease.

Suppression of the scleral inßammation usually allows regression, but in some patients the defect remains. Lubrication or therapeutic soft contact lens may prove effective in some patients. In cases of astigmatic error, spectacles or rigid contact lens may be used, depending on the severity. Progression to a thinned, ectatic cornea may be treated by cyanoacrylate glue application with or without conjunctival resection or by excising the ectatic tissue and replacing it with an annular lamellar keratoplasty or with a conjunctival ßap.

Stromal Keratitis

Extension of the diffuse, nodular, or necrotizing scleral inßammation into the cornea may appear as isolated or multiple white or gray nummular midstromal opacities, which usually are in the periphery, although they can involve the central cornea. The opacities are usually in the same quadrant as the scleral inßammation; therefore, the corneal involvement in the diffuse type of scleritis is usually more extensive than in the nodular type. If the treatment for the scleritis is

delayed, the lesions may expand toward the center of the cornea and eventually coalesce so that large areas may become opaque and swollen, leading to an appearance resembling that of the sclera (ÒsclerosingÓ changes) (Fig. 4.36). Vessels may involve the superÞcial stroma, but they are always far behind the advancing edge of the opacity. Lipid deposition in the stromal opacities can be seen as crystalline deposits (Òcandy ßossÓ) [2].

The opacities may disappear completely with early and vigorous treatment of the scleral inßammation; more often, only partial regression occurs, leaving permanent changes that, if central, may require penetrating corneal grafting for visual restoration.

Peripheral Ulcerative Keratitis

The most severe form of keratitis associated with scleritis is PUK, a potentially devastating process in which the layers of the peripheral cornea are progressively destroyed, leaving the cornea so thin that it can easily perforate. The destructive

Fig. 4.36 Slit-lamp photomicrograph: peripheral sclerosing keratitis. Note the peripheral keratitis with associated neovascularization and opaciÞcation of the peripheral cornea in this patient, who has had chronic anterior scleritis

process, usually associated with necrotizing scleritis, begins as a gray, swollen, inÞltrated area adjacent to a region of scleral inßammation that in a few days may break down, leaving only some layers of deep stroma and/or DescemetÕs