Purpose: The mechanism by which apraclonidine, an alpha(2)-adrenergic
agonist, lowers intraocular pressure (IOP) was evaluated in humans. Me
thods: In a randomized, double-masked, placebo-controlled study, 0.5%
apraclonidine was given topically twice daily for 1 week to one eye in
each of 21 ocular hypertensive volunteers. The other eye was treated
similarly with vehicle. Before and after 1 week of treatment, aqueous
flow, uveoscleral outflow, fluorophotometric outflow facility, intraoc
ular pressure, tonographic outflow facility, episcleral venous pressur
e, and outflow pressure were either directly measured or mathematicall
y calculated. Values were compared in treated versus contralateral con
trol eyes and on baseline versus day 8 of treatment. Results: When com
pared with both contralateral control eyes and baseline day, fluoropho
tometric outflow facility in the apraclonidine-treated eyes increased
by 0.09 to 0.10 mu l/minute/mmHg (P < 0.04), IOP decreased by 3.1 to 5
.2 mmHg (P < 0.0001), and outflow pressure decreased by 3.3 to 4.2 mmH
g (P < 0.0001). When compared with baseline day only, aqueous flow in
the apraclonidine-treated eyes decreased by 0.3 mu l/minute (P < 0.04)
, and episcleral venous pressure decreased by 1.0 mmHg (P < 0.001), Ep
iscleral venous pressure also decreased in the control eyes compared w
ith baseline day by 1.3 mmHg (P < 0.001). When compared with contralat
eral control eyes only, uveoscleral outflow in the apraclonidine-treat
ed eyes decreased by 0.47 mu l/minute (P < 0.03). Tonographic outflow
facility showed no change when compared with either contralateral cont
rol eyes or baseline values. Conclusions: The apraclonidine-induced re
duction in intraocular pressure was associated with an increase in flu
orophotometric outflow facility, decrease in aqueous flow and decrease
in episcleral venous pressure compared to baseline. The lack of a sig
nificant difference in aqueous flow and episcleral venous pressure bet
ween treated and contralateral control eyes may represent a contralate
ral drug effect.