The effect of fluorouracil on the corneal endothelium
M. J. Mannis, E. H. Sweet and R. A. Lewis
Department of Ophthalmology, University of California, Davis, Sacramento 95616.
The utility of the antiproliferative agent fluorouracil has been
demonstrated recently in glaucoma-filtering surgery and in the management
of proliferative vitreoretinopathy after vitrectomy. Because of the
potential for contact with the corneal endothelium, its toxicity to the
endothelium is an important consideration. The effect of fluorouracil on
corneal endothelial integrity in an in vitro animal model was studied.
Freshly excised sheep corneal buttons were exposed to increasing
concentrations of fluorouracil for four hours and were subsequently
evaluated microscopically using vital staining with alizarin red and trypan
blue. Exposure to normal saline and chlorhexidine gluconate was used to
establish negative- and positive-staining controls. Corneal buttons exposed
to normal saline or to 1.0 mg/mL or less of fluorouracil had intact
endothelial monolayers that completely excluded trypan blue. Corneal
buttons exposed to chlorhexidine gluconate or to 10 mg/mL of fluorouracil,
however, had severely or totally disrupted endothelial monolayers in which
the remaining cells, if any, all had blue-staining nuclei. These results
suggest that the threshold concentration for fluorouracil toxicity to
corneal endothelium lies between 1 and 10 mg/mL when exposure time is four
hours.
