Preclinical safety evaluation of subconjunctival methotrexate in the rabbit model.

PURPOSE: To assess the safety of subconjunctival methotrexate in New Zealand White rabbits.

METHODS

The New Zealand white rabbits received subconjunctival injections of methotrexate in the right eye with amounts of 400, 800, 1600, and 3200 μg. Slit lamp biomicroscopy and corneal fluorescein staining were used to assess the anterior segment of the eye. Vitreous haze and fundus abnormalities were evaluated using slit lamp indirect ophthalmoscopy. The intraocular pressure was measured using a rebound tonometer. After 30 days of methotrexate administration, the rabbits were sacrificed, and their eyeballs were enucleated for histological analysis.

RESULTS

Upon examination, no obvious changes were observed in the anterior and posterior segments of the eye. The intraocular pressure levels of the injected eye, prior to and after injections, did not show any significant difference. Furthermore, the ocular tissue displayed no signs of histological alterations.

CONCLUSION

Methotrexate injected via the subconjunctival route (up to 3200 μg) was found to be safe and well-tolerated in the rabbit model. However, future investigations are required to assess the pharmacokinetics and therapeutic efficacy in the disease-specific animal model.