Do injections of 5-fluorouracil after trabeculectomy have toxic effects on the anterior segment?
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 microg/mL at baseline to 19.8 +/- 4.4 microg/mL after trabeculectomy but only to 0.9 +/- 0.6 microg/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.
Lattanzio
F A
FA
Thomas R. Lee Center for Ocular Pharmacology, Eastern Virginia Medical School, Norfolk, VA 23501, USA. lattanfa@evms.edu
Sheppard
J D
JD
Allen
R C
RC
Baynham
S
S
Samuel
P
P
Samudre
S
S
D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D000963:Antimetabolites / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D001082:Aqueous Humor / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D015552:Injections, Intralesional; D007429:Intraocular Pressure / Q000187:drug effects*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D011506:Proteins / Q000032:analysis; D011817:Rabbits; D014130:Trabeculectomy; D014945:Wound Healing / Q000187:drug effects
D000963:Antimetabolites; D011506:Proteins; D005472:Fluorouracil