Glaucoma is a progressive optic neuropathy, characterized by the loss of retinal ganglion cells and its axons ultimately leading to loss of vision and subsequent irreversible blindness.1 Elevated intraocular pressure (IOP) is the only proven modifiable risk factor for the development and progression of glaucoma.2–5 Despite dedicated efforts to develop alternative therapies, reduction of IOP remains the current mainstay of glaucoma treatment. One important limitation in current glaucoma management is that IOP is normally only measured during office hours, usually by Goldmann applanation tonometry (GAT).6 Yet IOP varies throughout the circadian period.7–11 In addition to the absolute IOP level,12–16 IOP fluctuations,2,13,17–20 and in particular peak IOP levels have been identified as risk factors for progression of glaucoma.21–23 The role of IOP fluctuations in glaucoma pathogenesis remains controversial. Several studies have hypothesized that IOP fluctuation is an independent risk factor for glaucoma progression.24–28 In an experimental setting in non-human primates, mean and maximum IOP but not IOP variability were able to predict the rate of structural change.29 The same investigators also reported that IOP fluctuates by up to 10 mmHg within hours and between consecutive days in non-human primates.30 However, other studies have not supported the predictive role of IOP fluctuation. Retrospective post-hoc analyses of two prospective studies did not find such an association or had it disappear after accounting for other ocular or demographic parameters.31,32 Most importantly, these studies (with the exception of the Early Manifest Glaucoma Trial) only obtained single IOP measurements on the same day and calculated IOP fluctuation as the standard deviation of IOP at different visits. They are, therefore, not able to address the question of whether (24-hour) IOP fluctuations incur independent risk on glaucoma progression. Given the dynamic behavior of IOP, it may be clinically insufficient to rely on isolated IOP measurements only, in particular in patients with progression of glaucoma. Even the modest goal of obtaining representative diurnal (versus circadian) IOP profiles, our current methods seem to be insufficient. In one study, the likelihood of a single IOP measurement taken between 07:00–09:00 hours to reflect the daytime peak IOP was a mere 25 %.33 Other studies reported that 20–25 % of glaucoma patients who reached target IOP during isolated office measurements exhibited IOPs above the target level when submitted to a daytime IOP curve assessment.9,24 Patients with progressive visual field loss are more likely to have IOP peaks. Among patients presenting with IOP peaks during self-tonometry, 75 % had progressive glaucomatous disease compared with the patients without IOP peaks out of which only 25 % progressed.25 Compared with 24-hour IOP measurement curves, office hour IOP measurements did not correctly identify peak IOP in 80 % of patients with primary open angle glaucoma (POAG).10 These studies attest to the weak predictive value of office hour IOP measurements for detecting peak circadian IOP. In healthy and glaucomatous patients, IOP is higher than mean diurnal (daytime) IOP during the nocturnal period.26,27,34–36 The nocturnal IOP increase is in part due to increased episcleral venous pressure (EVP) and possibly to fluid redistribution, when assuming a recumbent position during sleep. Another study reported the variability in IOP pattern in patients with normal tension glaucoma, showing both daily and nocturnal acrophases.28 The dynamics and repeatability of the 24-hour IOP may indicate the existence of a circadian pattern, following the day/night light cycle. Preserved IOP patterns have been demonstrated in different species, including cats, rhesus macaques, and rabbits.29,30 A variety of hormones, through regulation of aqueous humor production and outflow, have a circadian rhythm and have been linked to circadian IOP patterns in rabbits.37 There also is a strong dependence of IOP on variable factors such as activity, posture, and emotions. Realini et al. in a series of studies found a fair to good reproducibility of repeated diurnal IOP measurements at two visits one week apart, both in healthy subjects (intraclass correlation coefficient [ICC] range 0.35–0.71) and in patients with POAG (ICC range 0.45–0.71).38,39 By contrast, another study reported a high daytime reproducibility of the IOP measurements (every three hours) on two consecutive days in patients with OAG and ocular hypertension (ICC range 0.80–0.86).40 In these studies, a lower than normal IOP reproducibility may in part be explained by the limited number of daytime IOP measurements. Current treatment strategies for glaucoma are frequently based on setting a target IOP range at which the development of further glaucomatous damage is assumed be prevented or reduced to a minimum.41,42 This target IOP is based on the patient’s past IOP levels, glaucomatous changes of the optic disc, visual field status, and, if available, the rates of structural and functional change. Despite an IOP that remains within the target range, a significant proportion of patients progress.20,43–47 Treatment strategies that rely solely on static IOP information do not account for the dynamic behavior of IOP and, therefore, have a limited predictive value for evaluating the risk for glaucoma progression.