PENETRATION INTO THE ANTERIOR-CHAMBER VIA THE CONJUNCTIVAL SCLERAL PATHWAY/

The importance of the conjunctival/scleral pathway as a route of entry into the ciliary body, and in particular uptake and depostion by vess els, was investigated. A constant concentration of methazolamide analo gs as well as 6-carboxyfluorescein (6-CB) and rhodamine B (RE) was mai ntained on either the cornea or the conjunctiva/sclera tissue, the lat ter excluding the cornea. The solutions were applied with the use of a cylindrical well affixed to the cornea of an anesthetized white rabbi t. After two hours, concentrations of drug or dye were measured in cor nea, aqueous humor or iris/ciliary body for both routes of entry. Conf ocal microscopy methods were used to determine reflected fluorescence images for 6-CB and RE. Carbonic anhydrase inhibition, partitioning, s olubility and intraocular pressure (IOP) measurements were also determ ined. Permeability calculations were estimated for drug diffusing agai nst aqueous now within the posterior chamber. The conjunctival/scleral route of entry produced higher iris/ciliary body concentrations for a ll compounds except for the lipophilic RE. Confocal microscopy results suggested that drug is gaining entry into the ciliary body through ve ssel uptake in the sclera. Following entry of drug into the conjunctiv al/scleral tissue, a significant portion enters scleral vessels and de posits within the ciliary body. Calculations are given that indicate t hat once drug penetrates the cornea it is highly unlikely drug diffuse s through the pupil against aqueous flow to enter the posterior chambe r and reach the ciliary body.