AN INTRAVITREAL SUSTAINED-RELEASE TRIAMCINOLONE AND 5-FLUOROURACIL CODRUG IN THE TREATMENT OF EXPERIMENTAL PROLIFERATIVE VITREORETINOPATHY

Objective: To determine the efficacy and pharmacokinetics of an intrav itreal sustained-release triamcinolone acetonide and 5-fluorouracil (T A/5-FU) codrug in the treatment of experimental proliferative vitreore tinopathy (PVR). Methods: The therapeutic efficacy of the TA/5-FU codr ug was determined in a rabbit model that simulates human PVR. Intravit real levels of triamcinolone and 5-fluorouracil were measured at diffe rent time points and drug release in vitro was tested. Toxic effects w ere evaluated by electroretinograpy, clinical examination, and light m icroscopy. Results: Both the severity of PVR grade and the percentage of eyes with moderate or worse tractional detachment were significantl y less in eyes treated with the codrug. The therapeutic effect of the intravitreal codrug was paralleled by sustained intravitreal levels of triamcinolone and 5-fluorouracil. There were no drug related toxic ef fects evident on clinical or histopathologic examination of eyes conta ining the TA/S-FU codrug. Conclusions: The intravitreal sustained-rele ase TAI 5-FU codrug effectively inhibits the progression of PVR in a r abbit model that closely resembles PVR in humans. The TA/5-FU codrug m ay simultaneously target different components of the wound-healing res ponse.