FOCAL SCLERAL PERMEABILITY ENHANCED BY COLLAGENASE DIGESTION - EXPERIMENTAL-MODEL OF ENZYMATIC SCLEROSTOMY

Purpose: The purpose of this study is to demonstrate that restricted a pplication of clostridial collagenase to the animal sclerolimbal area produces increased tissue permeability in vitro and results in a lasti ng significant decrease in the intraocular pressure (IOP) in vivo. Met hods: A special miniature device was developed to apply the carefully characterized enzyme to a small (l-mm diameter) and defined sclerolimb al area isolated from the surrounding tissue. The device was applied t o the rabbit limbus for 4 hours and then removed. The enzyme was inact ivated and washed out with an inhibitory solution. The IOP was measure d by pneumotonometry, and the treated tissue was investigated by light and electron microscopy. Application and removal of the drug-delivery microapplicator was performed under topical anesthesia. Results: Enzy matic degradation propagated without lateral spreading and reached at least two thirds of tissue width. Results of histologic examination of the treated area showed a thin tissue, characterized by degraded and disorganized collagen fibers, which were sharply separated from the in tact fibers in the untreated area. This was sufficient to cause a tenf old increase in the basic transscleral flow in vitro, and a significan t, relatively long-lasting (> 30 days) lowering of the mean IOP in 15 albino rabbits. In the first IO-day period after treatment, the IOP wa s reduced by 40%, and during the rest of the follow-up the IOP remaine d lowered by more than 20% (P > 0.0001) without any adjuvant treatment . Conclusion: Despite the small size of the collagenase-affected tissu e, the evacuation rate of the aqueous humor was sufficient to cause a significant and relatively longlasting lowering of IOP in rabbits. Thi s mild treatment, performed under topical anesthesia, might present th e basis for the development of an ambulatory treatment of human glauco ma.