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T.-I. Chikama, N. Takahashi, M. Wakuta, N. Nomi, Y. Ishida, R. Yanai, T. Nishida, T. Adachi, M. Enoki; Corneal Epithelial Disorder Associated With The Antineoplatic Drug S-1. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2354.
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S-1 is an oral antineoplastic drug that contains tegafur and has been shown to induce corneal disorders. To characterize the cellular changes in the corneal epithelium associated with S-1-induced keratopathy, we examined affected corneal epithelial cells by in vivo confocal microscopy and histopathologic analysis.
Three men and three women treated with S-1 participated in the study. The 12 eyes of the six subjects were evaluated with a confocal laser-scanning microscope, consisting of a Heidelberg Retina Tomograph II® attached to a Rostock Cornea Module ®(HRTII-RCM). Corneal epithelial debridement and histopathologic analysis of the specimens were performed for the five eyes of three subjects that were affected in the pupillary zone of the cornea.
Slitlamp examination revealed a local limbal abnormality characterized by abnormal epithelial invasion toward the central cornea in all 12 eyes. HRTII-RCM examination revealed an altered structure of the corneal epithelium with abnormal epithelial cells. Hematoxylin-eosin staining showed that each abnormal epithelial sheet lacked the stratified structure of the normal corneal epithelium. Immunofluorescence analysis of cytokeratins 12 and 4 revealed the presence of four types of cells-those positive for one, both, or neither of these proteins-in each lesion.
Four different phenotypes of cells were found in the corneal epithelium affected by S-1 administration. Cells lacking both cytokeratins 12 and 4 are likely undifferentiated cells, whereas those expressing cytokeratin 4 alone are likely conjunctival epithelial cells that entered the cornea through the limbus.
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