Increasing evidence shows that the 24-hour, day-and-night pattern of human intraocular pressure (IOP) does not follow the 24-hour pattern of aqueous humor flow. Changes in other parameters in aqueous humor dynamics must be responsible. Fan et al. present an interesting study on this research topic with a very rich dataset in untreated patients with ocular hypertension. While techniques employed to study the parameters of aqueous humor dynamics are not new and probably the best available, each technique has an inherent difference in measurement precision and reliability. The study result onaqueous humor flow showing an approximately 50% reduction at night is in line with reports in the literature. The result on outflow facility determined by tonography can be reliable with experienced researchers, but others may argue that performing tonography is more of an art than science. The most challenging is the determination of uveoscleral outflow by mathematical calculations derived from aqueous humor flow, outflow facility, and an imprecise measurement of episcleral venous pressure. It should also be reminded that habitual body positions during the day and at night are different. However, techniques for studying aqueous humor dynamics often require a fixed body position; a seated position for determining aqueous humor flow and a supine position for tonography. There may be other time-dependent ocular parameters that can affect 24-hour IOP pattern. For example, there is a question whether or not aqueous humor volume remains constant throughout 24 hours. Is it possible that aqueous humor volume becomes smaller at night due to a nighttime corneal swelling in the direction of corneal endothelium? The answer may provide additional clues for why the nighttime IOP does not follow the nighttime pattern of aqueous humor flow. Until we have much improved techniques for measuring aqueous humor outflow, particularly the uveoscleral outflow, and episcleral venous pressure, the door is still open for other players entering the arena to explain the 24-hour IOP pattern.
The IOP difference between the ocular hypertension patients and normotensive individuals is associated with outflow facility, not uveoscleral outflow
Despite the overall techniques being far from ideal, results from the present study do provide useful information of what may cause the elevated IOP in the ocular hypertension patients. To better appreciate this point of view, one should evaluate the present study together with a comparative study on volunteers with normal IOP under similar experimental conditions and using the same techniques (Arch Ophthalmol 2011; 129: 269-275). The most significant difference in the results between these two studies is the day and night change pattern of outflow facility, not uveoscleral outflow. Therefore, the IOP difference between the ocular hypertension patients and normotensive individuals is associated with outflow facility, not uveoscleral out-flow. This very much expected outcome affirms the unmet need to develop a more effective and tolerable medication to treat elevated IOP by the mechanism of action on outflow facility.