Investigators gather and evaluate day, night data on circadian patterns of aqueous humor dynamics

Key Points

Washington, DC-A study evaluating the circadian rhythm of aqueous humor dynamics reports that significant changes occur at night, at least in a middle-aged healthy population, reported Carol B. Toris, PhD, here at the annual meeting of the American Glaucoma Society.

The investigation included 30 individuals who were screened at an initial visit to confirm eligibility and then assessed at one day visit and one night visit 2 days later. The findings showed that at night compared with during the day, significant corneal thickening and decreases in aqueous flow, outflow facility, and seated IOP occurred. Uveoscleral outflow was unchanged.

"It is important to understand normal nocturnal changes in healthy eyes to identify abnormalities in eyes with elevated IOP," said Dr. Toris, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha. "These data now are being used for control values in ongoing studies evaluating aqueous humor dynamics in patients with ocular hypertension."

Measurements

Central corneal thickness was measured with an ultrasound pachymeter. In agreement with previous reports, mean corneal thickness increased significantly, from 560 µm during the day to 574 µm at night.

IOP was measured with a pneumatonometer. For measurements taken when patients were in a seated position, mean IOP was significantly less at night than during the day: 13.6 versus 15.9 mm Hg, respectively. Comparing measurements obtained with patients in habitual positions (seated during the day and supine at night), however, IOP measured at night was 18.5 mm Hg and significantly higher than the daytime IOP.

"In a study performed in enucleated rabbit eyes, we found that measured IOP was the same whether the tonometer probe was held horizontally or vertically," Dr. Toris said. "Therefore, we know that the postural differences in IOP at night are real and not an artifact of the measurement technique.

"We believe the reason that supine IOP is higher than seated IOP relates to postural changes in episcleral venous pressure," Dr. Toris continued.

Circadian changes in aqueous flow were evaluated by comparing data recorded with a fluorophotometer between 9 and 11 a.m. versus from 10 p.m. to 2 a.m. The analysis showed an approximate 50% decrease in aqueous flow rate from daytime to nighttime that was highly statistically significant.

Outflow facility measurements were obtained with both tonography and a fluorophotometric method. The results showed a significant decrease in outflow facility at night based on the tonographic data; this decrease was consistent with a previous report of young healthy subjects.

"The substantial reduction of aqueous flow at night is only partially offset by the reduction in outflow facility, and this may explain why seated IOP is lower at night than during the day," Dr. Toris said.

CAIs

No statistically significant difference was seen between the daytime and nocturnal values for outflow facility using the fluorophotometric assessment technique. Dr. Toris postulated that the discrepancy between the two assessment techniques could be explained by the use of a carbonic anhydrase inhibitor (CAI) in the fluorophotometric study. CAIs are used to reduce aqueous flow and IOP and allow calculation of outflow facility, which is the ratio of the change in flow to change in pressure.

"CAIs do not work well at night, at a time when aqueous flow already is suppressed," Dr. Toris said. "Therefore, we are looking for an alternate drug that will work well to modulate inflow during the day and at night, and then we would like to repeat this experiment."

The data from the tonographic and fluorophotometric methods also were used to calculate uveoscleral outflow using the modified Goldmann equation. No significant difference was found between the daytime and nighttime uveoscleral outflow values.