Quantitative Trait Analysis of Timolol Response—A Combined Analysis

Abstract

Purpose: To determine the variations in the response of aqueous humor flow rate (flow) and intraocular pressure (IOP) in normal subjects treated with timolol.

Methods: The response of flow and IOP to timolol was studied in 92 normal participants (age 41.8 ± 16.0 years, 41% males). Fifty-three of these were studied in an inpatient setting to determine how their aqueous humor flow rate responded to timolol. Morning flow was assessed by fluorophotometry at baseline (no treatment) and after treatment with timolol 0.5%. Thirty-nine participants, who were part of a prospective, multicenter study, were evaluated for aqueous humor dynamic traits and IOP response to timolol. Outcome measures were the percent change in flow (∆ flow) and the percent change in IOP (∆ IOP). A treatment response, ∆ flow and ∆ IOP, of 15% or greater was considered clinically significant and designated a responder; conversely a response of less than 15% was considered as a “non-responder”. Treatment responses were analyzed by paired t-test.

Results: Flow decreased from 2.6 ± 0.8 µl/min (mean ± SD) to 1.7 ± 0.5 µl/min (p<0.0001) after timolol. ∆ Flow was 15% or more in 73/92 of subjects (79%) after treatment with timolol; the non-responder rate was 21%. IOP decreased from 13.7 ± 3.4 mmHg to 11.4 ± 3.6 mmHg (p<0.05) after timolol. ∆ IOP was 15% or more in 23/39 subjects (59%); the non-responder rate was 41%.

Conclusions: This combined analysis provides evidence of variation in the response of aqueous humor flow and IOP to timolol; flow rate does not respond in approximately 21% of the population and IOP does not respond in approximately 41%.The source of this variation could be other variables of aqueous humor dynamics expressed in the Goldmann equation or unidentified genetic or environmental factors. Additional analyses will determine the concordance between ∆ flow and ∆ IOP in response to timolol, will examine covariates of drug response, and will identify genetic factors that affect drug response.