Analyzing Intraocular Pressures Outside Clinic Hours to Understand Variations in Glaucoma Drug Response

Abstract

Purpose : To analyze 24-hour intraocular pressure (IOP) in primary open-angle glaucoma or ocular hypertensive patients on treatment with timolol and latanoprost and during washout in the Eye Dynamics and Engineering Network Aqueous Humor Dynamics clinical trial (NCT04412096).

Methods : Subjects measured IOP at least 6 times per day/night with rebound tonometry during 1 week at baseline (untreated), 1 week on timolol or latanoprost, weekly intervals during washout, and 1 week switched to the second medication. Cosinor analysis was used to model 24-hour IOP as a chronobiological dataset. Mesor (Midline Estimating Statistic Of Rhythm), or rhythmic mean, was determined using single-component cosinor regression. Kruskal-Wallis ANOVA tests with post-hoc Dunn’s test were used for comparing mesors from the different test periods.

Results : Twenty-one subjects (60.3 ± 8.1 years; 13 females; 8 males) were included with enrollment continuing. Latanoprost and timolol reduced mesor IOP by 2.5 mmHg (p = 0.0007) and 1.8 mmHg (p = 0.008), respectively. Mesor IOP did not change from baseline compared to 6 weeks of washout (Fig 1). Mesor IOP did not change compared to baseline during any week of latanoprost washout, i.e., latanoprost returned to baseline within one week of washout. Mesor IOP was below baseline for the first week of timolol washout only, i.e., timolol returned to baseline two weeks after washout began (p = 0.026). To examine whether cosinor was an appropriate model, the zero-amplitude test, which gives the probability of the best fitting cosine curve with no amplitude, was applied. This analysis found 75% (79/107) of the cosine curves had p-values < 0.05, indicating a cosine curve is a good fit. A greater number of IOPs was associated with a better fitting cosine curve.

Conclusions : One week treatment with latanoprost or timolol both reduced mesor IOP. The IOP-lowering effects of timolol persisted longer than latanoprost during one week of washout but not later. Cosinor is a good model for 24-hour changes in IOP if patients collect >5 diurnal measurements.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Figure 1. Change in mesor IOP compared to baseline during treatment with latanoprost, timolol, and six weeks of washout from latanoprost (LW) and timolol (TW). The black line at zero indicates no change from baseline. Latanoprost and timolol mesor IOP change was significantly lower compared to washout.