Dose response of dexamethasone for the enhanced ocular hypotensive response to epinephrine in rabbits with prior dexamethasone treatment

We have previously shown that administration of epinephrine to the rabbit eye with dexamethasone pretreatment resulted in a significant decrease in intraocular pressure (IOP), compared to the use of epinephrine alone. Furthermore, this decrease in IOP is dose-dependent on epinephrine with the largest response of decrease of IOP occurring at the lower doses of epinephrine. We now extend this study to determine whether the decrease in IOP is dose-dependent on dexamethasone. Rabbit eyes were pretreated with five applications of topical dexamethasone or saline, administered at fifteen-minute intervals. Eyes were then treated with 0.005% epinephrine (0.01% epinephrine bitartrate). IOP was monitored for the next four hours. Different groups of rabbits received varying concentrations of dexamethasone base, from 0.0004% to 0.07% (dexamethasone phosphate), and a dose response curve was obtained. When compared to eyes treated with epinephrine alone, eyes pretreated with dexamethasone showed a significantly greater decrease in pressure at free base dexamethasone concentrations of 0.07%, 0.007% and 0.0007%, with the greatest difference at the 0.007% concentration (mean = 6.8 mm Hg). Similarly, the duration taken for the IOP to return to baseline levels was prolonged in the groups receiving dexamethasone pretreatment. The synergism between dexamethasone and epinephrine in lowering IOP may be a useful alternative in the treatment of ocular hypertension and glaucoma especially using a combination of a low dose of epinephrine with a low dose of dexamethasone.