ABSTRACT
OBJECTIVE: To determine whether the altered hormonal milieu of pregnancy is associated with changes in the dynamics of aqueous humor formation and drainage. DESIGN: Nineteen women were studied during each trimester of a single pregnancy and post partum. Measures of aqueous dynamics included intraocular pressure, aqueous flow, facility of outflow, aqueous flare, and corneal thickness. RESULTS: Pregnancy was associated with relatively lower intraocular pressure, reduced aqueous flare, increased corneal thickness, and increased aqueous outflow facility. Aqueous flow was unchanged. The progesterone level increased during pregnancy and decreased during the postpartum period. The beta-human chorionic gonadotropin level was highest during the first trimester. The progesterone level, but not the beta-human chorionic gonadotropin level, was correlated with intraocular pressure, aqueous flare, and corneal thickness. The change in aqueous outflow facility that accompanied pregnancy could not be correlated directly to changes in beta-human chorionic gonadotropin or progesterone concentrations. CONCLUSIONS: Aqueous flow remains constant during and after pregnancy, but intraocular pressure decreases during pregnancy due to an increase in the outflow facility. The changes in aqueous dynamics are consistent with the hypothesis that excess progesterone during pregnancy blocks the ocular hypertensive effect of endogenous corticosteroids. However, we were unable to find a statistically significant correlation when a direct comparison between the observed changes in outflow facility and the observed changes in the progesterone level was made, perhaps because of intersubject variability of these changes. The changes in intraocular pressure and outflow facility could have been due to one of many other changes in pregnancy that were not measured.
Subject(s)
Aqueous Humor/metabolism , Chorionic Gonadotropin/blood , Pregnancy/physiology , Progesterone/blood , Adult , Cornea/physiology , Female , Humans , Intraocular PressureABSTRACT
OBJECTIVE: To study the effects of a topically applied prostaglandin F2 alpha analogue, PhXA41 (Latanoprost; 13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-isopropyl ester), on aqueous dynamics in the human eye. DESIGN: A randomized, double-masked study was carried out on 20 normal and 20 ocular hypertensive humans. One eye of each subject was treated with 0.006% PhXA41, while the contralateral eye received placebo twice daily for 5 days. MAIN OUTCOME: Compared with placebo, PhXA41 reduced intraocular pressure in both groups by approximately 20%. RESULTS: Tonographic facility of outflow was increased 24% in the normal group and 30% in the ocular hypertensive group; no changes were observed in the rates of aqueous humor flow in either group. The changes in tonographic facility were insufficient to fully explain the ocular hypotensive effect of the drug, suggesting that PhXA41 enhances outflow via the uveoscleral pathway. The suitability of fluorophotometry as a measure of flow was confirmed by three methods of comparing blood-aqueous barrier permeability: polarization of cameral fluorescence, intensity of backscattered light from the anterior chamber (flare), and cameral fluorescence after oral administration of fluorescein sodium. All of these measured parameters were normal, suggesting that this compound has no clinically significant effects on the blood-aqueous barrier or on the accuracy of fluorophotometry. PhXA41 was well tolerated in both groups. Only four of 40 subjects reported a transient foreign-body sensation, and only one of 40 subjects was observed to have greater than moderate conjunctival hyperemia. Most subjects had no symptoms and no measurable hyperemia. CONCLUSIONS: These results suggest that PhXA41 is a potentially useful ocular hypotensive agent that enhances the egress of aqueous humor via both major outflow pathways. The relative lack of ocular side effects in this study further suggests that this agent has promise for the treatment of chronic glaucoma.
Subject(s)
Aqueous Humor/metabolism , Dinoprost/analogs & derivatives , Ocular Hypertension/drug therapy , Prostaglandins F, Synthetic/administration & dosage , Biological Transport, Active , Cell Membrane Permeability , Double-Blind Method , Drug Tolerance , Fluorophotometry , Humans , Intraocular Pressure/drug effects , Latanoprost , Ocular Hypertension/metabolism , Ocular Hypertension/physiopathology , Ophthalmic Solutions , Prostaglandins F, Synthetic/adverse effects , Prostaglandins F, Synthetic/pharmacokineticsABSTRACT
Diffusion of fluorescein between the plasma and anterior chamber has been considered a one-step process with transfer coefficient kd. However, after systemic administration, fluorescein enters the anterior chamber by a different kinetic than this simple model predicts. In this study we added to the model another compartment, the 'iris', between the plasma and anterior chamber. When fluorescein diffuses into the anterior chamber, it must cross two barriers, one between plasma and iris with coefficient ki.ip, and one between iris and anterior chamber with coefficient ki.ia. Fluorescein was measured in the anterior chamber after intravenous injection and was compared to fluorescein concentration calculated by using both kinetic models, the three-compartment model (iris, anterior chamber, and cornea) and the two-compartment model (anterior chamber and cornea). Transfer coefficients were determined by the method of least squares in 12 pigmented rabbits and two groups of six human subjects measured in two previous fluorophotometry studies. In all subjects except one, the three-compartment model matched the data better than the two-compartment model. In a second experiment, diffusion of fluorescein out of the anterior chamber was studied in 15 pigmented rabbits. Diffusional loss was determined from the relative clearances of rhodamine-labeled dextran, a large molecule that left only by bulk outflow, and fluorescein that was cleared by diffusion and outflow. The upper 95% confidence limit of diffusional clearance was less than 11% of total clearance in anesthetized rabbits.
