Cytosine-arabinoside-induced keratopathy: a model of corneal proliferation kinetics

Aims: The use of the chemotherapeutic cytosine arabinoside (Ara-C) causes an ocular toxic reaction, characterized by aspecific keratopathy. We examined the pathway of the damaged cells by in vivo confocal microscopy. Methods: Prospective study of 11 patients with acute myeloic leukemia treated with high-dose Ara-C. Ten eyes developed fluorescein-negative punctate keratopathy, and were examined by slit lamp and in vivo confocal biomicroscopy at days 1, 3–4 and 9–14 after the beginning of ocular symptoms. Results: In vivo confocal microscopy revealed disseminated highly reflective granular irregular intraepithelial elements in the central cornea, which affected about 3% of epithelial cells. At day 1 of symptoms, these elements were present only in the basal epithelial layer (median 275.5/mm2), at days 3–4 they were mainly found in the basal (187.5/mm2) but also in the apical layers (96/mm2), at days 9–14 they mainly presented in more superficial layers (115/mm2 apically vs. 15.5/mm2 in the basal layers). Discussion: The intraepithelial distribution of cells with a granular cytosolic signal evolved over time, reflecting the migration of the necrotic basal cells to the wing cell layer and finally to apical epithelial layers. The desquamation of the necrotic cells is related to the resolution of symptoms, according to the period of the epithelial cell turnover. By confocal microscopy, we could follow the intraepithelial route of cells damaged by Ara-C in vivo.