RETROPERFUSION STUDIES OF THE AQUEOUS OUTFLOW SYSTEM .2. STUDIES IN HUMAN EYES

Purpose. To extend the retroperfusion technique to allow the delivery of drugs into Schlemm's canal in enucleated human eyes and to use this technique to gain insights into the function of the inner wall of Sch lemm's canal. Methods. Using our previously developed retroperfusion t echnique, the anterior chamber of enucleated human eyes was held at a small negative pressure (-0.75 mm Hg), and fluid was allowed to flow r etrograde from the limbal vessels, through the collector channels, and into Schlemm's canal. In this manner, the sulfhydryl agent N-ethyl ma leimide (NEM) or the fixative agent glutaraldehyde was delivered to th e inner wall of Schlemm's canal in normal and glaucomatous human eyes. Facility changes caused by retroperfusion were measured and correlate d with histologic studies of the inner wall of Schlemm's canal. Result s. Retroperfusion effectively delivers fluid fr-om the scleral surface into the lumen of Schlemm's canal. Retroperfusion with vehicle alone does not alter facility or change outflow pathway morphology. Retroper fusion with NEM causes an approximately 35% facility: increase and con comitant inner wall openings. Retroperfusion with glutaraldehyde in no rmal eyes and eyes with primary open-angle glaucoma causes a facility decrease of 53% and 64% respectively, and localized Fixation of the in ner wall Of Schlemm's canal, The magnitude of the facility changes cau sed by retroperfusion were similar to those seen using conventional fo rward perfusion of NEM and glutaraldehyde. Conclusions. Retroperfusion is a viable technique for the delivery of drugs or other agents into Schlemm's canal in enucleated human eyes. Retroperfusion-induced chang es in outflow facility are correlated strongly with morphologically ob served alterations in inner wall structure. The majority of outflow re sistance is localized to the inner wall of Schlemm's canal or the imme diately adjacent 1O-mu m region of the juxtacanlicular tissue in norma l eyes es and in eyes with primary open-angle glaucoma. Inner wall gia nt vacuoles and pores likely persist for sometime, even after fixation at zero or negative pressure.