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.

Effect of squalamine on iris neovascularization in monkeys.

PURPOSE: To investigate the effect of squalamine, an antiangiogenic aminosterol, in an experimental model of iris neovascularization. METHODS: Iris neovascularization was created in cynomolgus monkeys by occluding retinal veins with an argon laser and inducing persistent hypotony with a central corneal suture. Twenty-four eyes were treated in three groups. In Group 1, four eyes were injected intravitreally with 3 microg/0.1 mL squalamine and four eyes with balanced saline solution (controls) immediately after vein occlusion (day 1); injections were repeated every 3 days for 3 weeks. In Group 2, 1 mg/kg squalamine was administered with intravenous infusion in dextrose 5% in four animals; four control animals received only dextrose. Infusions began on day 1 and were repeated every 3 days for 3 weeks. In Group 3, after development of iris neovascularization on day 7, 1 mg/kg squalamine was injected systemically in four animals; four control animals received dextrose 5%. Monkeys were examined by slit-lamp biomicroscopy and underwent color photography and fluorescein angiography. RESULTS: Group 1: All eyes, treated and control, developed intense and persistent rubeosis iridis. Group 2: Two of the four treated eyes in this group developed minimal iris neovascularization; the other two had no iris neovascularization. All four control eyes developed intense, persistent iris neovascularization. Group 3: All eyes developed extensive rubeosis iridis; iris neovascularization regressed in all four treated eyes after squalamine injections. Two of four treated eyes retained minimal iris neovascularization; two showed complete regression of rubeosis iridis. Rubeosis iridis completely regressed in two of the four control eyes; the remaining two control eyes had intense, persistent iris neovascularization. CONCLUSIONS: Intravitreally injected squalamine did not affect the development of iris neovascularization; however, systemic squalamine injection inhibited the development of iris neovascularization and caused partial regression of new vessels in a primate model.