Effects of daunomycin implants on filtering surgery outcomes in rabbits

To evaluate the effects of a novel daunomycin (DM) implant on intraocular pressure (IOP), bleb survival, and anterior segment complications when administered during filtering surgery on New Zealand White rabbits.

Implants were prepared by covalent coupling of DM to a high molecular weight hyaluronic acid (HA) and fabricated into solid implants containing 250, 65, and 25 microg of DM. Full thickness sclerostomies were performed, and rabbits received no implant (control), placebo implant containing HA, or an implant containing HA-DM conjugate at the time of surgery. Rabbits were then followed for 30 days to assess change in IOP, bleb survival, and anterior segment associated complications.

In vitro, the release of DM from the implants was a first order process with a half-life of 51 h. In control rabbits, rabbits receiving placebo implant, and rabbits receiving HADM (250 microg) 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 the control and placebo-implanted groups returned to preoperative levels. However, in rabbits receiving 250 microg 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 at these levels until studies were terminated on day 30. In control and placebo-implanted rabbits, bleb size started decreasing on day 1, and by day 7, no blebs were observed. In rabbits receiving 250 microg HA-DM implants, mean bleb survival time was greater than 30 days. The DM-induced reduction in IOP and enhanced bleb survival was dose-dependent. In rabbits receiving 65 microg of conjugated DM, lOPs were significantly reduced through day 30; however, at times beyond day 19 there was a gradual rise in mean IOP as filtering procedures in individual animals began to fail. Mean bleb survival time was greater than 30 days for implants containing 65 microg of conjugated DM. In rabbits receiving HA-DM implant containing 25 microg of DM, IOPs were not significantly different from preoperative levels beyond day 9, and no significant enhancement in bleb survival was observed in these animals. Comparison of HA-DM conjugated implants to those containing equal doses of free DM demonstrated that the mean IOP change at 30 days were similar; however, there was a reduction in anterior segment complications associated with the use of HA-DM conjugated implants.

This study provides evidence that the controlled release of DM when conjugated to HA can significantly improve the success of filtering procedures. The maintenance of ocular hypotension and bleb survival along with the reduction in anterior segment complications supports the idea that HA-DM conjugate will be more efficacious than the use of free DM in improving the success rate of filtering surgery.