Flow of aqueous humor in humans [The Friedenwald Lecture]

Based on clinical experiments with fluorophotometry, several observations can be made about aqueous flow through the chambers of the human eye. 1. The rate of flow is 2.75 +/- 0.63 microliters/min in normal subjects, as derived from measurements averaged during normal office hours. The normal range (95%) is 1.8 to 4.3 microliters/min. 2. There is a circadian rhythm of flow, with the highest rates during morning hours, slightly lower rates during afternoon hours, and rates during sleep that are approximately one half of those during the morning. The hormonal basis for this rhythm is unknown, but it is known to be present in both eyes of persons with unilateral Horner's syndrome. 3. A slight decline of the rate occurs after age 10 yr--3.2% per decade. There is no significant difference in aqueous flow between men and women. 4. Of the hundreds of drugs that are used clinically, most are unlikely to have a significant effect on aqueous flow. Exceptions are the beta-adrenergic agonists that, under certain circumstances, are able to increase flow, the corticosteroids that may have a stimulating effect on flow, and three classes of drugs that have therapeutically useful suppressing effects on flow: carbonic-anhydrase inhibitors, beta-adrenergic antagonists, and alpha 2-selective adrenergic agonists. 5. Timolol, which has a remarkably consistent suppressing effect on flow during the day, has no effect on the flow of sleeping subjects. By contrast, acetazolamide and apraclonidine are able to reduce the flow of sleeping subjects. 6. Acute doses of beta-adrenergic antagonists and alpha 2-agonists are not additive, but beta-adrenergic antagonists and carbonic-anhydrase inhibitors are partly additive. 7. The eye adapts partly to the chronic use of timolol and recovers from its effects when it is discontinued. 8. The rate of disappearance of the effect of beta-adrenergic antagonists is longer for the noncardioselective agents, such as timolol and levobunolol, but is relatively short for the cardioselective agent, betaxolol. 9. The rate of aqueous flow is insensitive to moderate changes of intraocular pressure. Clinical studies can provide suggestive leads for more basic investigations or test specific hypotheses. Biochemical, biologic, and pharmacologic approaches in simpler, more controlled experimental conditions are necessary to determine the fundamental processes that bring about aqueous formation in the living eye. The combination of many disciplines (eg, studying molecules, cells, tissues, organs, and the intact living system) has the best chance of furthering our understanding of the aqueous circulation.