Ocular toxicity of fluorouracil after vitrectomy

Area of Science:

• Ophthalmology
• Toxicology
• Retinal Science

Background:

• Fluorouracil (5-FU) is an antimetabolite chemotherapy agent.
• Intraocular 5-FU use requires understanding its ocular toxicity profile.
• Lensectomy and vitrectomy create conditions for intraocular drug administration.

Purpose of the Study:

• To evaluate the retinal and corneal toxicity of varying fluorouracil (5-FU) dosages and frequencies in rabbit eyes post-lensectomy and vitrectomy.
• To determine dose-dependent reversibility of 5-FU ocular toxicity.
• To assess the therapeutic window for 5-FU's antiproliferative effects versus toxicity.

Main Methods:

• Rabbit eyes underwent lensectomy and vitrectomy.
• Group 1: 1.25 mg 5-FU every 12h for 4 days, then every 24h for 3 days.
• Group 2: 1.25 mg 5-FU every 24h for 7 days.
• Group 3: 0.5 mg 5-FU every 24h for 7 days.
• Evaluations included clinical observation, corneal opacity, electroretinography (ERG), and histology.

Main Results:

• Group 1 showed severe corneal opacity and retinal toxicity with no ERG recovery.
• Group 2 exhibited transient corneal opacity and partial ERG recovery.
• Group 3 (0.5 mg 5-FU) demonstrated no clinical, electrophysiologic, or histologic toxicity.
• Histology in Groups 1 & 2 showed photoreceptor outer segment and ribosome loss.
• Group 3 5-FU showed antiproliferative effects on retinal pigment epithelial cells.

Conclusions:

• Fluorouracil (5-FU) ocular toxicity is dose-dependent and frequency-dependent.
• A dosage of 0.5 mg 5-FU every 24 hours is well-tolerated in rabbit eyes post-surgery.
• This lower 5-FU dosage maintains antiproliferative efficacy with minimal toxicity, suggesting a potential therapeutic window.