It is well known that the rate of aqueous humor flow during the nocturnal/sleep period is about half the rate during the diurnal/wake period. This implies a 2:1 ratio for the daytime versus night-time rate of aqueous humor formation. With no other change occurring in aque-ous humor dynamics, the night-time intraocular pressure (IOP) should be significantly lower than the daytime IOP according to the Goldmann equation. During the past ten years, however, there have been in-creasing reports showing the contrary. The night-time IOP level has been reported to be higher than or closer to the daytime IOP in the same body position. In this article, Sit et al. (511) attempted to solve this riddle by employing well-established techniques to measure aqueous humor flow and outflow facility along with IOP in the middle of the diurnal/wake period and in the middle of the nocturnal/sleep period. They confirmed the 2:1 ratio of daytime versus night-time aqueous humor formation and the relatively small difference between the daytime and night-time IOP. Most importantly, change in the outflow facility was found to be insignificant, which failed to explain why the night-time IOP did not drop along with the night-time drop in aqueous humor formation.
Outflow resistance is not a major player in setting up the night-time IOPObviously, a major player for setting up the night-time IOP was missing. Using a sophisticated mathematical model, the authors hypothesized that a time-dependent and posture-independent change in episcleral venous pressure had to occur in order to reconcile daytime and night-time data in aqueous humor formation, outflow facility, and IOP. In clinical management of glaucoma, drugs are developed to lower IOP by a mechanism of reducing aqueous humor formation or increasing outflow facility. For a drug acting on aqueous humor formation, a significant night-time efficacy is not expected since aqueous formation is already very low. Recent studies also indicated that, for a drug acting on aqueous outflow, such as a prostaglandin analog, the night-time efficacy can be less than its daytime efficacy. This intricacy occurs possibly because the outflow resistance is not a major player in setting up the night-time IOP as shown in this article. None of the currently available IOP-lowering drug has a significant effect on episcleral venous pressure. The authors may have pointed out a new path for research should we consider a new IOP-lowering strategy at night using medication.