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Comment by Paul Kaufman on:

46409 Aqueous humor dynamics during the day and night in volunteers with ocular hypertension, Fan S; Hejkal JJ; Gulati V et al., Archives of Ophthalmology, 2011; 129: 1162-1166

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The aqueous humor dynamics team at the University of Nebraska have recently reported the results of a prospective evaluation of circadian aqueous humor dynamics in subjects with ocular hypertension. In summary, they found that sitting intraocular pressure (IOP) was lower, but supine IOP higher at night than during the day; that both aqueous flow and uveoscleral outflow were reduced in the nocturnal period compared to the diurnal period; and that outflow facility remained unchanged from daytime to night-time. Of note, this latter finding is in contrast with published reports that outflow facility is lower at night than during the day in healthy volunteers.The investigators surmise that perhaps outflow facility is already reduced in ocular hypertensive eyes and thus does not undergo further nocturnal reduction. There are a few methodological issues that warrant commentary. First is their patient sample. By investigating the aqueous humor dynamics of ocular hypertensive eyes, the team has hypothesized that eyes with IOP above nor-mal might have altered dynamics compared to normotensive eyes. To explore this hypothesis, their sample should be definitively ocular hypertensive and clearly different from healthy normal subjects. Yet they defined ocular hypertension as IOP above 20 mmHg on two historical occasions with normal optic nerves and visual fields. This is a fairly liberal definition, as the normal range of IOP is customarily taken to be 10-21 mmHg. In fact, the mean daytime IOP of their cohort, after washout of any IOP-lowering medications, was 21.3 ± 3.5 mmHg, suggesting that their cohort was, on average, ocular hypertensive by the very smallest of margins. This is not what I consider to be clinical ocular hypertension, and it is difficult to generalize their findings to the typical practitioner's ocular hypertensive patient population. More robust eligibility criteria (say, IOP above 21 mmHg after washout) might have yielded a more definitively ocular hypertensive sample. Second is the group's approach to measuring episcleral venous pressure (ESVP). To satisfy the Goldmann equation, all measurable parameters must be determined in order to calculate the unmeasurable uveoscleral outflow term. Thus, to compare daytime versus nighttime aqueous humor dynamics, all parameters must be measured (or, less robustly, estimated) at both times. The research group did measure ESVP in the daytime but not in the nighttime, instead estimating nighttime ESVP (based on daytime values) from prior studies of ESVP circadian behavior by subtracting 2 mmHg from daytime seated values and adding 1.5 mmHg to daytime supine values. This approach assumes a con-served circadian ESVP pattern (which has not been established) and also assumes that every eye's ESVP is altered by an identical and predictable amount at night compared to day, which is not established and is entirely unlikely.As a consequence, the calculated uveoscleral outflow rates at night reported in this study must be interpreted with caution.

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