Importance: Nasolacrimal occlusion (NLO) is effective in reducing systemic absorption of eye drop medication but it is difficult and often performed poorly.We propose an alternative easier and equally effective technique. Background: To test the effectiveness of systemic absorption, we evaluated plasma concentration and ocular effects after topically administered timolol and compared to NLO. Design: Cross-over trial carried out in Capital Eye Specialist, Wellington.Participants: A total of 21 subjects over 18 years without contraindications for topical beta-blocker medication and not using systemic beta-blockers. Methods: During three clinic visits separated by at least one week, alternative approaches to reduce systemic eye drop absorption were tested. These were: (a) nasolacrimal (punctal) occlusion for 5 min, (b) tissue press method or (c) no intervention. Timolol plasma levels were measured 1 h after drop application. At each visit, baseline measurement of blood pressure, heart rate and intraocular pressure (IOP) were performed, and repeated 1 h after timolol 0.5% eye drop application. Main Outcome Measures: Comparison of timolol plasma concentration after each intervention. Secondary outcome measurements included effects on blood pressure, heart rate and IOP. Results: Plasma timolol concentrations after tissue press method and NLO were significantly lower than those without intervention. Comparing tissue press method to NLO, there were no significant differences in plasma levels of timolol, blood pressure, heart rate or IOP. Conclusion and Relevance: The tissue press method is equally effective as NLO in reducing systemic absorption of timolol. It is also easier and faster to administer. K E Y W O R D Sglaucoma, glaucoma medication, side effect, timolol

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Eyes treated with a topical betablocker may exhibit the phenomenon of longterm drift, leading to loss of intraocular pressure control. It has been suggested that discontinuation of the betablocker may restore sensitivity to betablocker therapy, and that this phenomenon might be enhanced by the administration of an adrenergic agonist during this holiday period. This study was set up to examine further this hypothesis. Nine patients with ocular hypertension receiving treatment with timolol were entered into the study. Timolol was discontinued then re-started after four weeks of treatment with dipivefrin. This treatment cycle was repeated after a further four weeks. IOP was measured every two weeks. Re-introduction of timolol was associated with a significant lowering of IOP at two weeks (3.2 mmHg in the first cycle, p < 0.01, 3.4 mmHg in the second cycle, p < 0.01). Discontinuation of timolol and treatment with dipivefrin was not associated with a significant change in IOP.

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