BACKGROUND:The aim of this article was to study the circadian intraocular pressure (IOP)-related effects of ocular hypotensive medications using a contact lens sensor (CLS). DESIGN:This is a university-based prospective, randomized, crossover trial. PARTICIPANTS:A total of 23 patients with primary open-angle glaucoma participated. METHODS:Patients underwent ambulatory recording of IOP-related patterns for 24 h in one eye during 3 monthly sessions using a CLS. Patients were untreated in session 1 (S1), were randomized to one of four classes of glaucoma drops for S2 and had a prostaglandin analogue add-on for S3. MAIN OUTCOME MEASURES:Changes in IOP-related patterns were defined using (i) slopes from wake/sitting to sleep/supine; (ii) cosinor rhythmometry modelling; and (iii) area under receiver operating curve (AUC) of sleep period. RESULTS:Mean patient age was 63.8 ± 11.8 years. Positive linear slopes were seen from wake/sitting to sleep/supine at S1 (17.1 ± 14.2 mVeq/h) and S2 (5.5 ± 23.9 mVeq/h) and negative slopes at S3 (-1.9 ± 29.4 mVeq/h) (S1-S2, P = 0.01; S1-S3, P = 0.02). In the prostaglandin group, slopes changed significantly with introduction of drops (S1-S2, P < 0.024), whereas they did not in a mixed group combining the three other classes (S1-S2, P = 0.060). Overall, cosinor amplitudes were 98.4 ± 46.5 mVeq (S1), 113.0 ± 35.6 mVeq (S2) and 109.6 ± 58.3 mVeq (S3) (S1-S2, P = 0.23; S1-S3, P = 0.66; S2-S3, P = 0.93). AUC were 91.8 ± 63.0 mVeq (S1), 76.3 ± 102.7 mVeq (S2) and 19.9 ± 135.8 mVeq (S3). Differences between sessions were not statistically significant (S1-S2, P = 0.541; S1-S3, P = 0.083; S2-S3, P = 0.092). CONCLUSIONS:Prostaglandin analogues, but not other medications, seem to flatten the IOP-related increase at transition of the wake/sitting to the sleep/supine period, but do not seem to have an effect on acrophase and amplitude.