Retinal toxicity of intravitreal 5-fluorouracil in silicone-filled rabbit eyes.

Objective: To determine the retinal toxicity of 5-fluorouracil, by means of electroretinography and histopathology, at different doses in vitrectomized rabbit eyes injected with silicone oil.

Design: A pre-clinical experimental study.

Place And Duration Of Study: The Louisiana State University Eye Center and the Department of Ophthalmology at the Tulane University Health Sciences Center, between June 1999 and May 2002.

Materials And Methods: Thirty-two New Zealand albino rabbits were used for the study. One eye per animal was used. After vitrectomy, the eyes were injected with 1 ml of silicone oil and then randomly divided into 4 groups. Group 1 was intravitreally injected with 0.2 ml of normal saline; Group 2 was injected with 200 microg of 5-fluorouracil; Group 3 was injected with 400 microg of 5-fluorouracil and Group 4 was injected with 800 microg of 5-fluorouracil. Electroretinography (ERG) was performed before and 14 days after intravitreal injections. Retinal histological examinations were performed after the animals were euthanized at the end of the experiment to document any retinal toxicity.

Results: There was less than 15 % ERG decrease in the eyes injected with normal saline and 200 microg of 5-FU. Moderate postoperative ERG decrease (30-50%) was seen in the animals injected with 400 microg of 5-FU. Eyes injected with 800 microg of 5-FU Silicone oil showed severe postoperative ERG decrease (80-100%). Histological examinations of the enucleated eyes were consistent with ERG results. No retinal toxicity was observed in the eyes injected with saline and 200 microg of 5-FU. Moderate retinal damage was seen in the eyes injected with 400 microg of 5-FU. Severe retinal damage was seen in the eyes injected with 800 microg of 5-FU.

Conclusion: The results of this study suggest that doses lower than 2.5 mg of 5-FU are required for injection into silicone oil-filled vitrectomized rabbit eyes.