Inhibition of pseudomonal ulceration in rabbit corneas by a synthetic matrix metalloproteinase inhibitor.

PURPOSE: To evaluate the effect of the synthetic matrix metalloproteinase inhibitor, Galardin, on proteases produced by Pseudomonas aeruginosa (PA) and on a rabbit model of Pseudomonas keratitis. METHODS: Protease activities of culture broths from Pseudomonas strains PA-28 and W-186 were characterized in vitro by gelatin zymography and by digestion of Azocasein in the presence and absence of Galardin and the serine protease inhibitor, aprotinin. In a noninfectious in vivo experiment, sterile PA culture broth from W-186 was injected intrastromally into rabbit corneas that were treated topically with Galardin or vehicle, then evaluated clinically and histologically. In an infectious in vivo experiment, rabbit corneas were injected with washed PA-28, then treated topically with Galardin or vehicle and clinically scored. RESULTS: Gelatin zymography of culture broth from W-186 and PA-28 detected two proteases that were both inhibited by Galardin. Galardin reduced the digestion of Azocasein by both PA culture broths by 99%, whereas aprotinin did not significantly reduce the protease activity of PA-28 conditioned broth. Intrastromal injection of sterile W-186 culture broth caused rapid corneal destruction that was prevented by topical treatment with Galardin. Intrastromal injection of washed PA-28 bacteria resulted in progressive corneal melting that was significantly (P < 0.005) delayed, but ultimately not prevented, by topical treatment with Galardin. CONCLUSIONS: Pseudomonal protease activity in culture broth consisted predominantly of metalloproteinases and were effectively inhibited by Galardin in vitro. Topical treatment with Galardin prevented destruction of rabbit corneas by bacterial products present in culture broth, and it delayed corneal destruction after injection of PA bacteria. Galardin may be a useful adjuvant when corneal destruction proceeds despite prompt antibiotic treatment.

Temporary blindness in the TUR syndrome.

The TUR syndrome is a clinical disorder consisting of circulatory, gastrointestinal, and neurologic signs that are infrequently seen in some patients undergoing endoscopic surgery of the prostate gland with the use of nonconductive irrigating fluids. Several theories of its pathogenesis have been proposed. The condition may occasionally be associated with bilateral profound loss of vision. We report a patient with the TUR syndrome who suffered bilateral temporary blindness and speculate on the etiology of the visual loss and localization of the dysfunction along the visual pathway.

Giant cell astrocytoma of the retina in tuberous sclerosis.

The clinical and pathologic features of an unusual retinal glioma that was the only clinically overt manifestation of tuberous sclerosis in a 27-year-old woman are reported. The tumor was composed predominantly of large pleomorphic cells with glassy eosinophilic cytoplasm. Immunologic staining yielded positive results for gamma enolase, but not for glial fibrillary acid protein. The histologic and immunopathologic features of this tumor were essentially identical to the subependymal giant cell astrocytoma found in tuberous sclerosis. This case illustrates the large overlap in dysplastic astrocytic and neuronal differentiation that can occur in the retina of patients with tuberous sclerosis. Giant cell astrocytoma of the retina can be mistaken for a malignant tumor histologically by persons unfamiliar with this entity.