Postoperative Corneal Melt Workup
- Author: Arun Verma, MD; Chief Editor: Hampton Roy, Sr, MD more...
Impression cytology to detect conjunctivalization for diagnosing stem cell deficiency. Identifying the underlying cause is as important as making the diagnosis of the perforation. In trauma, the history often is sufficient to make the diagnosis. In infections, laboratory confirmation is important, and scraping and culture are often essential.
At times, corneal biopsy may be necessary and may be part of the definitive treatment of the perforation, with the excised cornea at keratoplasty being used to make the diagnosis.
External ocular examination including evaluation of lid function and anatomy, testing of corneal sensation, and evaluation of tear function may help to establish the etiologic diagnosis.
In noninfectious inflammatory corneal melting, an evaluation for systemic inflammatory disease may be necessary.
Tests to rule out collagen vascular disease
The erythrocyte sedimentation rate may be elevated in cases of orbital inflammation, but this should bring to mind the possibility of a concurrent systemic disease such as one of the collagen vascular diseases.
Circulating immune complexes may deposit in the limbal vasculature, triggering complement activation, influx of inflammatory cells, and release of enzymes and mediators. The result is a limbal vasculitis; the subsequent loss of vascular integrity facilitates leakage of inflammatory cells and mediators into the peripheral cornea. Immune complexes may leak into the peripheral cornea as well, sparking complement activation, especially with the increased concentration of C1 in the peripheral cornea. Also, it is possible that autoantibodies to corneal epithelial and/or stromal antigen may arrive via the limbal vasculature or via the tear film and play a role. T cells and activated macrophages have been found in active rheumatoid arthritis associated corneal melts, suggesting cell-mediated mechanisms. Collagenase produced by the adjacent conjunctiva and keratocytes and polymorphonuclear leukocytes (PMNs) in the cornea promote stromal dissolution.
In a reported case of postoperative corneal melt, light microscopy revealed a thickened corneal epithelium with an irregular Bowman layer and mild infiltration of the superficial stroma with inflammatory cells, mostly lymphocytes but some PMNs. The adjacent conjunctiva also showed some infiltration by lymphocytes. Immunohistochemistry showed expression of class II antigens on less than 25% of corneal epithelial cells and keratocytes compared with 75-100% of cells in a Mooren ulcer specimen. Less than 5% of lymphocytes were B cells, versus 25-50% in the Mooren specimen. Also, T-cell numbers were much lower in the corneal melt cases; the ratio of helper T cells to suppressor/cytotoxic T cells was 1:1, compared with 2.4:1 for the Mooren sample.
Since all the collagen vascular diseases are basically immune complex diseases, there would be finding of circulating immune complexes. There is great variability from disease to disease in the frequency of positive immune-complex assays. In some diseases, such as systemic lupus erythematosus (SLE), there is a high frequency of positive immune-complex assays. In others, the frequency of positive assays may be much lower.
Examination of tissues using immunofluorescent techniques to detect immune deposits is also important in establishing the diagnosis of immune-complex disease. Immune complexes deposited in tissues may be evanescent. In fact, it has been suggested that the levels of serum C4 and C3 are the most sensitive indexes of disease activity of SLE.
Other tests may suggest indirectly the presence of immune-complex disease. For example, the finding of immunoglobulin M (IgM) cryoprecipitates suggests the presence of immune complexes. The presence of antinuclear antibodies suggests autoimmunity, as does the presence of a number of tissue-component–specific antibodies. Similarly, the presence of specific antigen such as hepatitis-B surface antigen in the circulation together with appropriate clinical symptoms may suggest an immune-complex disease. Many patients with these diseases have an elevated erythrocyte sedimentation rate.
In SLE, the presence of characteristic antibodies such as anti-DNA, anti-Sm, and anti-RNP confirms the diagnosis of SLE. Antinuclear antibodies are the best screening tests. High serum levels of antinuclear antibodies anti-DNA and low levels of complement usually reflect disease activity.
Serum levels of cryoglobulins or other immune complexes occasionally correlate with disease activity. Total functional hemolytic complement (CH50) levels are the most sensitive measure of complement activation. Quantitative levels of C3 and C4 are widely available. Hematologic abnormalities are common and include anemia (usually normochromic, normocytic but occasionally hemolytic), leucopenia, lymphopenia, and thrombocytopenia. In some patients, the Westergren erythrocyte sedimentation rate correlates with disease activity. Urinalysis and serum creatinine should be measured periodically in these patients.
In patients with rheumatoid arthritis, no tests are specific, but, rheumatoid factors, which are autoantibodies reactive with Fc portion of immunoglobulin G (IgG), are found in more than two thirds of the patients. Widely used tests detect IgM rheumatoid factors.
Rheumatoid factor is present in about 75% of patients with Sjögren syndrome even when symptoms of arthritis are absent. Antinuclear antibodies are present in about 70% of patients, and a positive lupus erythematosus (LE) cell test occurs in about 25% of patients. Two antinuclear antibodies, SS-A and SS-B, usually are associated with Sjögren syndrome. SS-B antibodies are found in up to 70% of patients and are fairly specific for the diagnosis of this disease. SS-A antibodies are found in up to 14% of patients. There is a high incidence of antibodies against Epstein-Barr virus nuclear antigen and human leukocyte antigen Dw3 (HLA-Dw3).
Collagen vascular diseases such as rheumatoid arthritis, polyarteritis nodosa, and Wegener granulomatosis can be associated with sterile peripheral corneal melting ulceration, either with or without adjacent scleritis. The pathophysiology of such ulceration undoubtedly is linked to the underlying autoimmune mechanisms of each of these diseases and is probably similar for all. This is supported clinically by the fact that those patients with rheumatoid arthritis who develop necrotizing scleritis or peripheral ulcerative keratitis have an increased mortality rate because of systemic vasculitis.
Histologic findings include loss of limbal stem cells and stromal cells.
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