Objective: To discourage fibrosis of the filtering bleb, 5 fluorouracil (5-FU) may be injected
after trabeculectomy. 5-FU is an antimetabolite that also can damage extraocular tissues at
concentrations as low as 0.5%. This study ascertained whether repeated injection of 5-FU has
toxic effects on intraocular structures.
Methods: After unilateral trabeculectomy in anesthetized New Zealand rabbits, 5-FU (5.0
mg/0.1 mL) was injected at the trabeculectomy site every 5 days for 15 days. Evaluation included
slit-lamp examination, confocal microscopy, and intraocular pressure (IOP). After sacrifice,
aqueous humor (AH) was drawn and eyes excised for scanning electron microscopy
(SEM) and light microscopy.
Results: The 5-FU injection not decrease IOP beyond trabeculectomy alone. Bleb height remained
constant, thickness increased, and vascularity decreased. No changes in cornea or anterior
segment were observed. No inflammation was observed in the bleb or surrounding tissues
by slit-lamp or histologic examination. Protein in AH increased from 0.6 ± 0.5 µg/mL at
baseline to 19.8 ± 4.4 µg/mL after trabeculectomy but only to 0.9 ± 0.6 µg/mL after trabeculectomy
plus 5-FU. Both in vivo confocal microscopy and SEM revealed deleterious effects
on corneal epithelial and endothelial cells with a minor shift toward smaller cells.
Conclusions: In this study 5-FU did not provoke an intraocular inflammatory response and
had minimal effect on extraocular structures. Changes in corneal epithelium and endothelium
detectable by confocal microscopy suggest a small toxic effect. These in vivo measurements
by confocal microscopy were confirmed by SEM. Repeated administration did not cause additional
cumulative toxic effects in the anterior segment. Therefore, multiple injections of 5-
FU into the filtering bleb pose minimal risk to intraocular structures.