The effect of oral dexamethasone on the circadian rhythm of aqueous humor flow in humans

Purpose. To determine if the circadian rhythm of plasma corticosteroid activity is necessary for the circadian rhythm of aqueous humor flow to occur in humans. Methods. Twenty normal volunteers were recruited for this randomized, double-masked, placebo-controlled study. Oral dexamethasone was given at a dose of 0.5 mg every 6 hours; this is equivalent to more than two times the normal 24-hour endogenous adrenal corticosteroid production. This dosage schedule will maintain a relatively constant level of corticosteroid action throughout a 24-hour period. Topical fluorescein and a scanning fluorophotometer were used to measure the rate of aqueous humor flow. Subjects were studied on two separate days. On one study day, the subject took 0.5 mg of dexamethasone every 6 hours; on the other study day, the same subject took a placebo every 6 hours. Results. During the morning, aqueous flow was 4.06 ± 0.70 μl/min (mean ± SD) in subjects taking dexamethasone and 3.82 ± 0.85 in subjects taking a placebo. This 6% higher dexamethasone flow was not significant (P = 0.10). During the afternoon, aqueous flow was 3.83 ± 0.78 in subjects taking dexamethasone and 3.52 ± 0.77 in subjects taking a placebo. This 9% higher dexamethasone flow was statistically significant (P = 0.02). The nighttime aqueous flow was 1.38 ± 0.45 in subjects taking dexamethasone and 1.43 ± 0.34 in subjects taking the placebo. There was not a significant difference between placebo and dexamethasone during the night (P = 0.40). On each day, intraocular pressure was measured at 8:00 AM, 4:00 PM, and 6:00 AM. When comparing dexamethasone to placebo, no significant difference was observed in any of the intraocular pressures. Conclusions. The study is interpreted as showing that the reduction of aqueous humor flow during sleep can occur in the absence of a comparable fall in plasma corticosteroid activity.