title: Slow release of the antimetabolite 5-fluorouracil (5-FU) from modified Baerveldt glaucoma drains to prolong drain function.
abstract: Drainage devices are routinely placed in the eyes of patients with glaucoma to reduce intraocular pressure (IOP) by providing controlled outflow of fluid (aqueous humor) via a filtering bleb. However, the natural wound healing response often interferes with fluid outflow by thickening the walls of the bleb over time, so that these devices rarely remain functional for more than 5 years. We investigated the use of controlled release of an antimetabolite, 5-fluorouracil (5-FU), within glaucoma drains to determine if the wound healing response could be reduced and the useful life span of the device increased. Collagen plugs containing 1.125 mg of 5-FU were placed in the silicone tubes of modified Baerveldt glaucoma drains. Eight drains with 5-FU and eight drains without 5-FU were implanted in one eye each of 16 New Zealand white rabbits: the contralateral eyes served as unoperated controls. Results were evaluated in terms of IOP, fibrous capsule thickness, macrophage density. and presence of type III collagen surrounding the drain plate, 3 and 6 months after implantation. In general, eyes implanted with antimetabolite-containing drains demonstrated significantly lower values for all evaluated parameters at 3 months and lower or equal values at 6 months, compared with the eyes not receiving 5-FU and the unoperated controls, indicating improved IOP-lowering function, reduced bleb wall thickness, and earlier achievement of a steady-state wound healing response. All eyes remained healthy throughout the 6-month duration of the study with no cytotoxicity complications in any of the eyes. Thus, biodegradable plugs placed within the silicone tubes of glaucoma drains can safely deliver 5-FU to filtering blebs over time, which could prolong the functional life of the bleb by decreasing the thickness of the anterior fibrous capsule and permitting sufficient fluid outflow to reduce IOP to physiological levels.
authors.affiliation: LSU Eye Center Louisiana State University Health Sciences Center, New Orleans 70112, USA. jjacob@lsuhsc.edu
authors.forename: J T
authors.initials: JT
authors.lastname: Jacob
authors.forename: O J
authors.initials: OJ
authors.lastname: Lacour
authors.forename: C F
authors.initials: CF
authors.lastname: Burgoyne
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage*; D001672:Biocompatible Materials; D003094:Collagen; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005472:Fluorouracil / Q000008:administration & dosage*; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D020327:Glaucoma Drainage Implants; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008422:Materials Testing; D011817:Rabbits
chemical_list: D000963:Antimetabolites; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004343:Drug Implants; D003094:Collagen; D005472:Fluorouracil