AimsTo determine the influence of prostaglandin analogues (PGAs) on corneal biomechanical properties in patients undergoing chronic treatment for primary open-angle glaucoma (POAG).MethodsProspective, interventional case–control study. 70 eyes from 35 patients with POAG on chronic PGA therapy were recruited. One eye per patient underwent PGA cessation for 6 weeks while the contralateral eye continued to receive the treatment. Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOP) (IOPcc), central corneal thickness (CCT) and Goldmann tonometry (Haag-Streit AG, Koeniz, Switzerland) IOP (IOPGAT) were measured at baseline (visit 1), 6 weeks after PGA cessation (visit 2) and 6 weeks after PGAs reinitiation (visit 3) and were analysed using a linear mixed-effect model. The discrepancy between IOPcc and IOPGAT was defined as IOP bias (IOPcc—IOPGAT).ResultsBaseline characteristics were comparable between the two groups. In the study eyes, significant increases (p<0.0001) were detected at visit 2 in CH (9.0±1.8 vs 10.3±1.7 mm Hg), CRF (10.5±2.1 vs 11.7±2.1 mm Hg), CCT (541.8±43.2 vs 551.9±41.9 μm) and IOPGAT (15.4±3.0 vs 18.4±3.8 mm Hg). IOP bias in this group was significantly lowered at visit 2 (p<0.0001). These effects were reversed at visit 3. The control eyes did not demonstrate any significant changes over the study period.ConclusionTopical PGAs induce reversible reduction in CH, CRF and CCT in patients with POAG. These changes contribute to underestimation of the IOP measured by Goldmann applanation tonometry and warrant caution when assessing response to treatment.Trial registration numberNCT02388360, Results.