Goldmann's equation and clinical measures of aqueous dynamics.

Goldmann's equation has served for over 50 years as an adequate description of aqueous humor dynamics for clinical applications. Recent advances in therapeutics for glaucoma have made it necessary to revise the equation and to reinterpret the meanings of its parameters.

Effect of ibopamine on aqueous humor production in normotensive humans.

PURPOSE: Ibopamine is a prodrug of epinine (deoxyepinephrine) that exhibits activity at dopaminergic and adrenergic receptors. Topical ocular application has been shown to cause mydriasis without cycloplegia and to increase the rate of aqueous humor flow in normotensive human eyes. Mydriasis can interfere with the measurement of aqueous flow. In this study ibopamine's effect on aqueous humor production was measured while making allowance for the potential artifact caused by its mydriatic effect. METHODS: The effects of topical ibopamine on pupillary diameter, aqueous humor flow measured by fluorophotometry, and intraocular pressure were studied in 24 healthy, blue-eyed humans. Ibopamine was administered with and without the alpha-adrenergic antagonist dapiprazole, and its effects were compared with those of tropicamide, with and without dapiprazole in a double-masked, randomized, crossover design. RESULTS: Ibopamine dilated the pupil from a diameter of 3.7 +/- 0.64 (mean +/- SD, n=24) to 7.7 +/- 0.70 mm. Ibopamine, during its peak mydriasis, was associated with a very large increase in the rate of clearance of topically applied fluorescein from the cornea and anterior chamber, an effect that was not associated with tropicamide during its peak mydriasis. The mydriatic effect of ibopamine was completely blocked by dapiprazole, and the increase in fluorescein clearance was partially blocked. When mydriasis was blocked, ibopamine increased fluorescein clearance by 13% (P<0.0001), which was interpreted as an increased rate of aqueous humor production. Compared with placebo and with the tropicamide control, ibopamine decreased intraocular pressure, despite its stimulation of aqueous humor flow. CONCLUSIONS: Ibopamine is in a specific class of drug, along with pilocarpine, epinephrine, and bimatoprost that in humans increases the rate of aqueous humor flow as measured by fluorophotometry. This effect is partly responsible for its ability to increase intraocular pressure in persons suspected to have abnormally low aqueous humor outflow facility. The transient apparent doubling of aqueous humor flow, measured by fluorescein clearance after administration of ibopamine is an artifact of increased fluorescein clearance through the dilated pupil while accommodation is active.

Targeting outflow facility in glaucoma management.

Glaucoma is often characterized by decreased pressure-sensitive aqueous outflow through the trabecular meshwork. This defect in pressure-sensitive aqueous outflow is evident from the low tonographic facility of outflow ("C") measured in many patients. The impairment in outflow facility causes the high intraocular pressure (IOP) and large diurnal IOP fluctuations often found in glaucoma. Because large diurnal IOP fluctuations have been shown to be a risk factor for glaucomatous progression, IOP-lowering therapy should aim to achieve a low, stable IOP. Pressure-sensitive aqueous outflow helps prevent and dampen pressure spikes; thus, drugs that enhance outflow facility, in particular, may stabilize as well as lower IOP. Outflow facility is an attractive target for glaucoma treatment because enhancing outflow facility tends to restore the self-regulating tendency of IOP. Older drugs such as the cholinergic pilocarpine and the catecholamine epinephrine act primarily by improving outflow facility. This action is also important for the recently introduced prostamide, bimatoprost, as well as for the prostaglandin prodrug, latanoprost. Realization of the importance of facility of outflow in lowering and stabilizing IOP will stimulate additional research into the mechanism of action of ocular hypotensive agents and will help optimize the medical treatment of glaucoma.

Pupillary response to four concentrations of pilocarpine in normal subjects: application to testing for Adie tonic pupil.

PURPOSE: To determine the amount of pupillary constriction to four different concentrations of pilocarpine in normal human subjects and to determine if pupillary constriction correlates with bioavailability of the instilled concentrations. The amount of pupillary constriction to dilute pilocarpine is utilized as a diagnostic test for Adie tonic pupil as distinguished from a normal pupil response. DESIGN: Twenty healthy volunteers had automated binocular infrared pupillography in the dark after instillation of four different concentrations of dilute pilocarpine. Ocular penetration of eye drops was also assessed using 2% fluorescein sodium as a tracer. METHODS: Prospective institutional double-masked study of both eyes of twenty healthy volunteers, ten with brown irides, ten with blue irides, between the ages of 20-40 years. RESULTS: A pilocarpine dose-dependent curve showed decreased pupil size within 15 minutes, peaking at 30-60 minutes. No difference was noted between right and left eyes, iris color, or corneal permeability. CONCLUSIONS: Normal pupils constrict to dilute concentrations of pilocarpine (0.25% or 0.125%), but constrict insignificantly to concentrations of 0.0313% or 0.0625%. Pupil constriction with 0.0625% pilocarpine should distinguish an Adie pupil from normal. This confirms the utility of this simple office diagnostic procedure.