Applying cosinor to characterize glaucoma drug washout on IOP measured by iCare HOME

Abstract

Purpose : Current glaucoma management to assess intraocular pressure (IOP) is typically measured during clinic, but our knowledge of IOP variability outside of office hours is limited, particularly when changing glaucoma medications. When treatment is not effective, it’s unclear how long IOP takes to return to baseline. Using iCare HOME tonometry, our purpose was to assess glaucoma medication washout using a chronobiological method that accounts for rhythmicity.

Methods : Participants (9 male, 6 female) were on average 59 ± 8.2 (1 SD) years old with either ocular hypertension or open-angle glaucoma and enrolled in a multicenter, prospective, randomized crossover trial of latanoprost and timolol (ClinicalTrials.gov Identifier NCT04412096) as part of Eye Dynamics and Engineering Network 2 (EDEN2). Participants were instructed to use iCare HOME to measure IOP at least 6 times a day over four periods: at baseline, after starting 1^st treatment, during a 6-week washout, and after starting 2^nd treatment. Drug washout was defined as the time period in weeks needed for IOP circadian rhythm to return to baseline, as measured by MESOR and acrophase (Figure 1). IOPs at time points were tested by ANOVA (p > 0.05). 24-hour IOPs were analyzed by cosinor fits with kronos in R.

Results : To date, 30 participants completed EDEN2, and 15 (10 latanoprost, 5 timolol) had sufficient 24-hour IOP data for cosinor analysis. Average MESOR was 20.85 ± 1.27 mmHg (95% CI) at baseline, 18.01 ± 1.18 on latanoprost, and 18.25 ± 1.04 on timolol. Mean washout was 3.3 ± 1.1 weeks (95% CI) for latanoprost and 4.8 ± 0.7 for timolol (Table 1).

Conclusions : Based on preliminary data from EDEN2, 24-hour cosinor modeling indicates high variability in latanoprost washout period after short-term treatment, possibly earlier latanoprost washout than previously described, and longer washout for timolol compared to latanoprost. By using cosinor modeling on iCare HOME tonometry data, clinicians may add time as a dimension in the evaluation of drug washout. The significance of this approach will begin to fill the knowledge gap on IOP variance under treatment and improve our understanding of the duration of drug effect after stopping therapy.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Figure 1. Key cosinor terms.

 

Table 1. Summary of number of participants returning to baseline IOP during each week of washout following cessation of latanoprost (n = 10) and timolol (n = 5) treatments.