EFFECTS OF DAUNOMYCIN IMPLANTS ON FILTERING SURGERY OUTCOMES IN RABBITS

Purpose. To evaluate the effects of a novel daunomycin (DM) implant on intraocular pressure (IOP), bleb survival, and anterior segment compl ications when administered during filtering surgery on New Zealand Whi te rabbits. Methods. implants were prepared by covalent coupling of DM to a high molecular weight hyaluronic acid (HA) and fabricated into s olid implants containing 250, 65, and 25 mu g of DM. Full thickness sc lerostomies were performed, and rabbits received no implant (control), placebo implant containing HA, or an implant containing HA-DM conjuga te at the time of surgery, Rabbits were then followed for 30 days to a ssess change in IOP, bleb survival, and anterior segment associated co mplications. Results. In vitro, the release of DM from the implants wa s a first order process with a half-life of 51 h, In control rabbits, rabbits receiving placebo implant, and rabbits receiving HA-DM (250 mu g) implants, the mean IOPs on day 3 were 11.1 +/- 1.6, 10.8 +/- 2.7, and 14 +/- 0.98 mm of Hg, respectively. On days 5 through 9, IOP in th e control and placebo-implanted groups returned to preoperative levels . However, in rabbits receiving 250 mu g of conjugated DM, mean IOP on day 7 was reduced from preoperative levels by 11.8 +/- 3.2 mm of Hg ( P < 0.05). This reduction In IOP was significantly different (P < 0.05 ) from both control and placebo implant groups, and IOPs remained sit these levels until studies were terminated on day 30. In control and p lacebo-implanted rabbits, bleb size started decreasing on day 1, and b y day 7, no blebs were observed. In rabbits receiving 250 mu g HA-DM i mplants, mean bleb survival time was greater than 30 days. The DM-indu ced reduction In IOP and enhanced bleb survival was dose-dependent. In rabbits receiving 65 pg of conjugated DM, IOPs were significantly red uced through day 30; however, at times beyond day 19 there was a gradu al rise in mean IOP as filtering procedures in individual animals bega n to fail. Mean bleb survival time was greater than 30 days for implan ts containing 65 mu g of conjugated DM. In rabbits receiving HA-DM imp lant containing 25 mu g of DM, IOPs were not significantly different f rom preoperative levels beyond day 9, and no significant enhancement i n bleb survival was observed in these animals. Comparison of HA-DM con jugated implants to those containing equal doses of Free DM demonstrat ed that the mean IOP change at 30 days were similar; however, there wa s a reduction in anterior segment complications associated with the us e of HA-DM conjugated implants. Conclusions. This study provides evide nce that the controlled release of DM when conjugated to HA can signif icantly improve the success of filtering procedures. The maintenance o f ocular hypotension and bleb survival along with the reduction in ant erior segment complications supports the idea that HA-DM conjugate wil l be more efficacious than die use of free DM in Improving the success rate of filtering surgery.