Serial administration of adrenergic antagonist and agonist ("pulsatile therapy") reduces the incidence of long-term drift to timolol in humans

Abstract

Purpose: To test whether the incidence of long-term drift to timolol can be reduced by a "pulsatile" treatment (6 months timolol-2 months dipivefrin).

Methods: In a randomized clinical trial, 100 consecutive subjects with ocular hypertension or high-tension primary open-angle glaucoma in at least one eye were randomly assigned to either group A, which was administered timolol 0.5% twice a day (b.i.d.), or to group B, which was administered timolol 0.5% b.i.d. (6 months) alternated with 0.1% dipivefrin b.i.d. (2 months). Diurnal intraocular pressure (IOP) was measured at recruitment, 1 month later during timolol administration ("reference value"), and every 6 months in group A or at the end of each pulse in group B. In bilateral cases, the right eye only was considered for the analysis. Length of follow-up was 54 months. Long-term drift was diagnosed if the IOP on timolol increased by at least 5 mm Hg over the reference value and was followed by a </ = 2mm Hg increase after withdrawing timolol for 2 weeks.

Results: Reference values were comparable in both groups (16.4+/-1.2 mm Hg in group A, 15.9+/-1.7 mm Hg in group B). Eleven subjects (four in group A and seven in group B) did not complete follow-up because IOP increased >5 mm Hg in the study eye without detectable drift to the beta-blocker. The actual 54-month incidence of long-term drift was 45% (21/46) in group A versus 7% (3/43) in group B (P<0.01). In group B, IOP was always higher during dipivefrin pulse than on timolol (paired samples t-test, P<0.01). However, dipivefrin proved more effective through follow-up; IOP was 21.1+/-1.2 mm Hg at month 8 (first "pulse") and 18.6+/-0.95 mm Hg at month 48 (last "pulse") (paired samples t-test, P<0.01).

Conclusions: Serial administration of adrenergic antagonist and agonist can reduce the incidence of long-term drift to the beta-blockade in ocular hypertension and primary open angle glaucoma.