glycerin-preserved full-thickness human donor sclera is then cut to size, using this template. The graft is secured with 10Ð0 nylon sutures to the edges of the resention site and the knots are buried. Conjunctiva is pulled down over the graft whenever enough tissue is present and is sutured with 8Ð0 Vicryl.

5.4Summary

Histopathologically, most cases of episcleritis and diffuse or nodular scleritis show chronic, nongranulomatous inßammation with lymphocytes and plasma cells, vascular dilatation, and edema. By contrast, most cases of necrotizing scleritis show chronic granulomatous inßammation with epithelioid cells, multinucleated giant cells, lymphocytes, plasma cells, and less often neutrophils, along with inßammatory microangiopathy. Mast cells and eosinophils can sometimes be seen in the granuloma and around vessels. T lymphocyte subset and surface glycoprotein studies in necrotizing scleritis show a predominance of macrophages and T lymphocytes, with a high T helper/T suppressor ratio, and a marked increase in HLA-DR glycoproteins. These Þndings suggest an underlying cell-medi- ated reaction (type IV hypersensitivity reaction) in which the tissue injury is the result of macrophage and lymphocyte immune interaction and enzyme liberation with subsequent extracellular matrix component degradation.

Comparison of extracellular matrix components between normal and necrotizing scleritis specimens shows a decrease in dermatan sulfate and chondroitin sulfate without obvious differences collagen types I, III, V, and VI; these Þndings suggest that proteoglycans may be the Þrst extracellular matrix components to be degraded in necrotizing scleritis.

The presence of inßammatory microangiopathy in many of the diffuse and nodular recurrent scleritis specimens and most of the necrotizing scleritis specimens suggests an underlying immune complex reaction (type III hypersensitivity reaction), in which the vascular injury is the result of antigenÐantibody conjugation within

and outside the vessel wall, with subsequent activation of complement.

Demonstration of necrotizing vasculitis with or without granulomas in biopsy material of involved extraocular tissues conÞrms the diagnosis of systemic vasculitic diseases in patients with compatible multisystem clinical Þndings. Inßammatory microangiopathy in scleral or conjunctival specimens from patients with scleritis further strengthens the concept of an underlying vasculitic disease. Because noninfectious necrotizing scleritis is highly associated with the presence of inßammatory microangiopathy, scleral, and/or conjunctival biopsy is not necessary to prove a vasculitic process. The presence of necrotizing scleritis should be regarded as an ominous sign because it indicates an ocular and probably a systemic vasculitic process that should be treated with high dosage of corticosteroids or other immunosuppressive drugs. Because noninfectious recurrent diffuse or nodular scleritis is less highly associated with inßammatory microangiopathy, scleral biopsy may be helpful in detecting a local and systemic vasculitic process that should be treated with a high dosage of corticosteroids or other immunosuppressive drugs.

Pathological detection of granulomas with or without inßammatory microangiopathy in scleral and/or conjunctival specimens conÞrms the diagnosis of granulomatosis with polyangiitis (Wegener) in a patient with necrotizing, diffuse, or nodular scleritis with complete and, especially, limited clinical features, particularly if ANCA testing is borderline or low positive. Pathological detection of granulomas with or without inßammatory microangiopathy in sclera and/or conjunctival specimens conÞrms the diagnosis of the highly limited form of granulomatosis with polyangiitis (Wegener) in a patient with necrotizing, diffuse, or nodular scleritis and positive ANCA testing. In the absence of granulomas in sclera and/or conjunctival specimens, a positive ANCA test in a patient with necrotizing, diffuse, or nodular scleritis is suggestive of highly limited granulomatosis with polyangiitis (Wegener), although not diagnostic. In the absence of positive ANCA testing, the presence of granulomas without systemic clinical features does not

support the diagnosis of granulomatosis with polyangiitis (Wegener).

In infectious scleritis, stainings and cultures of scleral scrapings may demonstrate the microorganism implicated. However, when scrapings are negative, analysis of conjunctival and scleral specimens by histopathological (stainings and cultures), tissue homogenization (culture or cell culture lines), and indirect immunoßuorescence (antimicrobe antibodies) techniques may be important for microbe isolation.

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