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In a previous study, pretreatment of rabbit eyes with echothiophate iodide prevented the ocular hypotensive effect of dipivefrin. The present masked study, using inpatient volunteers and nurse-administered drops, investigated whether a similar antagonism of action occurred in human beings. Eight volunteers received 0.25% echothiophate iodide twice a day in both eyes for three weeks. During the second week of therapy, one eye also received 0.25% dipivefrin twice a day and the contralateral eye received 2% epinephrine hydrochloride twice a day. During the third week of therapy, the eyes receiving dipivefrin and epinephrine were reversed. In four volunteers, dipivefrin plus echothiophate produced a significantly greater reduction in intraocular pressure than epinephrine plus echothiophate. As a group the eight eyes treated with dipivefrin plus echothiophate had significantly lower IOPs than the eyes treated with epinephrine plus echothiophate during the second week of therapy. Epinephrine plus echothiophate was never superior to dipivefrin plus echothiophate. Dipivefrin seemed to be effective during combination therapy with echothiophate.

A study was undertaken to determine whether the antiesterase activity of echothiophate iodide would prevent the conversion of dipivefrin to epinephrine. Dipivefrin was administered singly and in combination with echothiophate to 24 adult rabbits. Administration of dipivefrin lowered the intraocular pressure (IOP) 8 +/- 1 mm Hg (P less than .001). When echothiophate was given before and concomitant with dipivefrin, there was no further decrease in IOP compared with that produced by echothiophate alone (5 +/- 1 mm Hg). Addition of epinephrine to eyes receiving dipivefrin plus echothiophate resulted in a significant additional decrease in IOP of 4 +/- 1 mm Hg (P less than .001). When echothiophate was given after dipivefrin had lowered the IOP and both drugs were continued, the IOP rose to baseline levels. These results fit the theory that the esterase converting dipivefrin to epinephrine is inactivated by cholinesterase inhibitors. The clinical use of cholinesterase inhibitors and dipivefrin may be contraindicated.

A time-course study was performed on the intraocular pressure response of pigmented rabbit eyes. Dipivefrin administration produced in initial hypertensive phase lasting less than two hours followed by a prolonged hypotensive phase. Echothiophate iodide therapy produced a more pronounced and prolonged hypertensive response; there was no hypotensive phase. Administration of echothiophate plus dipivefrin resulted in a hypertensive phase similar to that from echothiophate alone; as previously reported, this combination was not followed by a hypotensive phase. The alpha-blocker phentolamine mesylate prevented the echothiophate-induced hypertension. When dipivefrin was administered with echothiophate plus phentolamine, there was an immediate hypotensive effect. It was concluded that the hypertensive effect of echothiophate in pigmented rabbit eyes may mask the hypotensive action of dipivefrin. This, rather than an echothiophate-induced inhibition of esterases, may explain why combination therapy with these drugs seemed ineffective.

Fifty-four subjects with initial intraocular pressures under 20 mm Hg received a different commercial corticosteroid ester of prednisolone or dexamethasone in each eye for three to six weeks. Compliance was controlled. The intraocular pressure responses of the two eyes of a subject were similar. It was concluded that the absorptions of all four corticosteroids were in excess of the minimum amounts needed to maximally elevate pressure. Subjects complained that prednisolone acetate was irritating. Corticosteroid-induced uveitis developed in 3% (3) of the eyes.

In age-, race-, and sex-matched groups, the relative abilities of medrysone, fluorometholone, and dexamethasone phosphate to elevate intraocular pressure were compared in a masked manner. Compliance was controlled by drops being given by nursing personnel. The 18 male hospitalized volunteers received commercial preparations of one of the corticosteroids to each eye four times a day for six weeks. The relative ability of medrysone, fluorometholone, and dexamethasone phosphate to raise IOP was 1, 4, and 7.6, respectively.