The Acute Effect of Exercise Type and Timing on Ambulatory Blood Pressure and Intra-Ocular Pressure in Individuals With Glaucoma: Protocol for Two Randomized Crossover Trials

Objective: Uncontrolled blood pressure (BP) and increased blood pressure variability (BPV) are associated with worse cardiovascular outcomes and progression to blindness in patients with primary open angle glaucoma (POAG). Exercise could be a promising non-pharmacological therapy to improve BP control. However, its safety, effectiveness, and optimal timing have not been systematically evaluated in patients with POAG. We aim to evaluate the acute effect of different types and timings of exercise on 24-hour ambulatory BP and intra-ocular pressure (IOP) in patients with POAG and elevated BP or hypertension. Design and method: This study, embedded within the ACHIEVE-project (Advancing Cardiovascular and Ocular Health in Eye Patients: Effectiveness and Mechanisms of Exercise) will deliver two monocentric, single-blinded, prospective randomized controlled crossover trials (Figure 1). Sixty patients with POAG and elevated BP or hypertension (Table 1) will be recruited and allocated to either a morning (08:00–11:00) or evening (17:00–20:00) trial (n=30 per trial). Participants will complete three single experimental exercise sessions: one isometric wall squat session, one high intensity interval session and one moderate continuous session, along with one seated control session in random order in a period of maximum eight weeks, with a minimum one-week washout between sessions. Efficacy outcomes include 24-hour ambulatory BP profiles and BPV indices (dipping status, morning BP surge, and average real variability), evaluated over the 24-hour period following each session. Safety will be assessed through direct and indirect indicators, including immediate post-exercise IOP measurements and evaluation of nocturnal BP patterns. Results: We hypothesize that all exercise sessions will induce post-exercise hypotension, with the largest and most sustained BP reduction following high-intensity aerobic exercise performed in the morning. Exercise is hypothesized to be safe irrespective of timing or modality, with sessions not inducing significant increases in IOP or marked nocturnal dipping (‘extreme dipping’) patterns on 24-hour ambulatory BP. Recruitment is scheduled to begin in April 2026. Conclusions: ACHIEVE will provide much-needed evidence on the safety, efficacy, and optimal timing of exercise, thereby informing the design of subsequent chronic intervention studies and supporting future implementation of exercise therapy to improve BP control in patients with POAG.