Antiproliferative Effect of Retinoic Acid in Intravitreous Silicone Oil in an Animal Model of Proliferative Vitreoretinopathy

Purpose: To evaluate, in vitro, the solubility and stability of all-trans RA in silicone oil (SiO) and, in vivo, the stability and the antiproliferative effect of all-trans RA in SiO on an experimental model of PVR.

Methods: The solubility and stability of RA in SiO, in vitro and in vivo, were evaluated by HPLC. Rabbits underwent unilateral gas-compression vitrectomy and gas-SiO exchange. Rabbits received 10 micrograms (n = 17), 5 micrograms (n = 11), and 2 micrograms (n = 9) of all-trans RA in SiO, and SiO only (n = 12). All rabbits received an intravitreous injection of 150,000 fibroblasts.

Results: RA is stable in SiO in vitro, but some isomerization from all-trans to 13-cis was observed under light exposure. In vivo, after 1 week, trace amounts of RA in SiO were observed in the controls and in the experimental animals, suggesting a steady state between the release of RA from the SiO and from the retina to the SiO. The rate of fractional retinal detachment was significantly lower in the animals that received 10 and 5 micrograms of RA than in the controls (P < 0.05). No statistical differences were found between the eyes treated with 10 and 5 micrograms of RA. Eyes that received 2 micrograms of RA showed no difference from the control group.

Conclusions: The in vivo data suggest that retinoic acid might be useful as an antiproliferative agent in human eyes.