A new poly(ortho ester)-based drug delivery system as an adjunct treatmentin filtering surgery

PURPOSE. Pharmacologic modulation of wound healing after glaucoma filtering surgery remains a major clinical challenge in ophthalmology. Poly(ortho es ter) (POE) is a bioerodible and biocompatible viscous polymer potentially u seful as a sustained drug delivery system that allows the frequency of intr aocular injections to be reduced. The purpose of this study was to determin e the efficacy of POE containing a precise amount of 5-fluorouracil (5-FU) in an experimental model of filtering surgery in the rabbit. METHODS. Trabeculectomy was performed in pigmented rabbit eyes. An ointment like formulation of POE containing 1% wt/wt 5-FU was injected subconjunctiv ally at the site of surgery, during the procedure. Intraocular pressure (IO P), bleb persistence, and ocular inflammatory reaction were monitored until postoperative day 30. Quantitative analysis of 5-FU was performed in the a nterior chamber. Histologic analysis was used to assess the appearance of t he filtering fistula and the polymer's biocompatibility. RESULTS. The decrease in IOP from baseline and the persistence of the filte ring bleb were significantly more marked in the 5-FU-treated eyes during po stoperative days 9 through 28. Corneal toxicity triggered by 5-FU was signi ficantly lower in the group that received 5-FU in POE compared with a 5-FU tamponade. Histopathologic evaluation showed that POE was well tolerated, a nd no fibrosis occurred in eyes treated with POE containing 5-FU. CONCLUSIONS. In this rabbit model of trabeculectomy, the formulation based on POE and containing a precise amount of 5-FU reduced IOP and prolonged bl eb persistence in a way similar to the conventional method of a 5-FU tampon ade, while significantly reducing 5-FU toxicity.