Aqueous Humor Dynamics Research Articles

Comparative Human Aqueous Dynamics Study between Black and White Subjects with Glaucoma

To compare the baseline aqueous humor dynamics in white Caucasians and patients of African origin with previously untreated primary open-angle glaucoma (POAG) or ocular hypertension (OHT). Ninety-one participants were enrolled in this prospective, observational controlled study: 34 black subjects with POAG or OHT, 32 white Caucasian participants with POAG or OHT, and 12 black and 13 white healthy volunteers as the controls. All aqueous humor parameters were taken between 9 AM and 12 noon on the same day. Intraocular pressure (IOP) was measured by pneumatonometer; morning aqueous humor flow rate was measured by fluorophotometry and trabecular outflow facility by electronic Schiøtz tonography. Uveoscleral outflow was calculated by using Goldmann's equation with assumed episcleral venous pressure of 8, 9, 10, and 11 mm Hg. Differences among groups were analyzed with parametric and nonparametric tests and the relationship between aqueous dynamics parameters were evaluated with linear regression analyses. The POAG/OHT groups had similar IOP (white, 24.6 ± 3.0 mm Hg; black, 24.3 ± 4.0 mm Hg; comparison by Holm's sequential Bonferroni method (HBonf): P(HBonf) = 0.51), outflow facility (white, 0.13 ± 0.09 μL/min/mm Hg; black, 0.13 ± 0.07 μL/min/mm Hg; P(HBonf) = 0.87), aqueous flow (white, 2.36 ± 0.63 μL/min; black, 2.35 ± 0.53 μL/min; P(HBonf) = 0.95), and uveoscleral outflow (white, 0.42 ± 1.59 μL/min; black, 0.58 ± 1.17 μL/min; P(HBonf) = 1.78). POAG/OHT groups had significantly higher IOP and lower outflow facility than their healthy counterparts (P < 0.01). Black participants had significant thinner corneas (540 ± 37 μm vs. 564 ± 36 μm) than those of white participants (P = 0.002). The aqueous humor dynamics of black African and white Caucasian patients with POAG or OHT have no significant differences. However, the significantly thinner corneas of the black patients may be masking potential differences in outflow facility and IOP measurements between the racial groups.

ENOS, a Pressure-Dependent Regulator of Intraocular Pressure

Pathology in the primary drainage pathway for aqueous humor in the eye is responsible for ocular hypertension, the only treatable risk factor in patients with glaucoma. Unfortunately, the mechanisms that regulate pressure-dependent drainage of aqueous humor and thus intraocular pressure (IOP) are unknown. To better understand one possible underlying molecular factor that regulates IOP, nitric oxide (NO), pressure-dependent drainage in transgenic mice overexpressing endothelial NO synthase (eNOS) was studied. IOP was measured by rebound tonometry in mice, and pressure versus flow data were measured by ex vivo perfusion at multiple pressures between 8 and 45 mm Hg, using mock AH ±100 μM L-NAME. A subset of eyes was examined histologically using standard techniques or was assayed for fusion protein expression by Western blot analysis. IOP was lower (9.6 ± 2.7 vs. 11.4 ± 2.5 mm Hg; mean ± SD; P = 0.04) and pressure-dependent drainage was higher (0.0154 ± 0.006 vs. 0.0066 ± 0.0009 μL/min/mm Hg; P = 0.002) in the transgenic mice than in the wild-type animals; however, pressure-independent drainage was unaffected. The NOS inhibitor L-NAME normalized pressure-dependent drainage in transgenic animals. For IOP >35 mm Hg, the slope of the pressure-flow curve in wild-type mice increased to match that seen in transgenic mice. Shear stress in the pressure-dependent pathway at elevated pressures was calculated to be in a range known to affect eNOS expression and activity in vascular endothelia. Endothelial NOS overexpression lowers IOP by increasing pressure-dependent drainage in the mouse eye. Data are consistent with NO's having a mechanoregulatory role in aqueous humor dynamics, with eNOS induction at elevated IOPs leading to increased pressure-dependent outflow.

Topical application of 0.005% latanoprost increases episcleral venous pressure in normal dogs

Episcleral venous pressure (EVP) has an important role in intraocular pressure (IOP) homeostasis and accounts for more than 70% of the IOP in the normal dog. A frequently used species in glaucoma research is the normotensive dog especially when evaluating the efficacy of prostaglandin analogues and prostamides; however, aqueous humor dynamic studies in normal dogs are lacking, and the effect of 0.005% latanoprost on canine EVP is not known. We sought to determine the effects to the EVP of topically applied 0.005% latanoprost in the normotensive beagle dog. Female beagle dogs (n = 14) were used and each had a normal ophthalmic examination on study entry. EVP was determined using a standard episcleral venomanometer. Animals were dosed in one eye with 0.005% latanoprost, and the effects on EVP were compared with the averaged baseline EVP's determined in the predosing phase and the fellow nondosed eye. The Mixed Model Repeated Measures method was used to analyze the EVP data. During the dosing phase of the study with topical 0.005% latanoprost, the mean EVPs of dosed eyes were significantly higher than that of nondosed eyes (P < 0.0001). The increase in EVP in the dog with exposure to topical 0.005% latanoprost has not been observed in other species that have been studied, such as in the mouse and in humans, where the drug had no significant effect on the EVP. This response may be unique to dogs and suggests that dogs may not fully mimic human aqueous humor dynamics with topical 0.005% latanoprost. Although frequently performed in human studies, EVP should not be regarded to be a constant value in aqueous humor dynamic studies in the normal beagle dog.

The effect of topical administration of sildenafil in acute ocular hypertension model in rabbits.

Background: Nitric oxide ( NO) is a physiological mediator of many processes in the eye including regulation of aqueous humor dynamics. Compounds acting via NO dependent mechanisms may enhance aqueous humor outflow and reduce intraocular pressure (IOP) .Objective: Sildenafil a cGMP specific phosphodiesterase 5inhibitor that potentiates NO production and increases cyclic GMP is tested in this study for its effects on intraocular pressure in an acute ocular hypertension model in rabbits.Materials and methods: Newzealand albino rabbits of either sex weighing 2–2.5 Kg , were used in this study. Sildenafil was prepared in a vehicle of phosphate buffer and diluted to the required strength of 0.5%. Intraocular pressure (IOP ) was measured after 45 seconds of one drop of proparacaine topical anesthesia by using schiotz indentation tonometer. Basal IOP was obtained for both eyes using 12 rabbits .One drop of sildenafil (0.5%) was then topically instilled in the left eye while the right eye received the vehicle and served as a control. After 30 minutes of drug and vehicle administration the IOP was measured in both eyes and acute ocular hypertension was induced by the administration of 15ml/kg 5% glucose. The IOP was then recorded every 15 min for 180 minutes.Results: Topical 0.5% sildenafil administration had no effect on the basal IOP levels. However sildenafil significantly (p &lt; 0.05) attenuated the acute rise in IOP induced by 5% glucose infusion. The IOP levels returned to their basal values in shorter time with sildenafil compared to the controlConclusion: Topical sildenafil pretreatment reduces IOP in acutely induced intraocular hypertension.

Microanatomy of the anterior uveoscleral outflow pathway in normal and primary open‐angle glaucomatous dogs

To compare the morphology of the uveoscleral (US) outflow pathway in normal and glaucomatous canines. 10 normal beagles, 10 beagles with inherited primary open-angle glaucoma, 4 cocker spaniels with spontaneous glaucoma. Formalin-preserved globes were sectioned tangentially and sagittally and treated with H&E, Masson's trichrome, or elastin stains or analyzed by immunohistochemistry to visualize smooth muscle actin. Tissues associated with the US pathway were observed and compared using light microscopy. Tangentially oriented sections clearly revealed spaces for the transport of aqueous humor at the junction of the posterior iridocorneal angle (ICA) and anterior ciliary body musculature (CBM). Within the external anterior-most of the US pathway, the supraciliary space, distinct connective tissue cords and smooth muscle pegs fastened the ciliary body to the adjacent sclera. Compared to normal controls, glaucomatous eyes developed a robust scleral elastic sheath at the junction between the posterior ICA and the anterior CBM. In advanced glaucomatous beagles and cocker spaniels, a large amount of melanophores were seen in the US pathway and surrounding vasculature. Within the C8M of glaucomatous specimens, the smooth muscle bundles appeared fewer and separated by elastic-rich ECM. Structures of the US pathway changed little with age. The anterior portion of the canine US pathway is well defined and appears to be altered little with age. However with glaucoma, changes of the US pathway were associated with its the elastic components, as well as the accumulation of melanophores. Collectively, these changes may have an effect on US outflow and, subsequently, aqueous humor dynamics.

Aqueous Humor Dynamics During the Day and Night in Volunteers With Ocular Hypertension

To evaluate the differences in aqueous humor dynamics between nighttime and daytime in participants with ocular hypertension. Thirty participants (mean [SD] age, 59.2 [11.1] years) with ocular hypertension were enrolled in the study, which included 1 daytime and 1 nighttime visit. During each visit, measurements included central cornea thickness by ultrasound pachymetry, intraocular pressure (IOP) by pneumatonometry, aqueous flow by fluorophotometry, outflow facility by tonography, and blood pressure by sphygmomanometry. Uveoscleral outflow was calculated using the Goldmann equation. Daytime measurements were made only of episcleral venous pressure by venomanometry, anterior chamber depth by A-scan, and outflow facility by fluorophotometry. Repeated-measures analysis of variance and 2-tailed t tests were used for statistical comparisons. Compared with daytime seated IOP (21.3 [3.5] mm Hg), nighttime seated IOP (17.2 [3.7] mm Hg) was reduced (P < .001) and nighttime supine IOP (22.7 [4.6] mm Hg) was increased (P = .03). Central cornea thickness was increased at night from 570 (39) μm to 585 (46) μm (P < .001). There was a 48% nocturnal reduction in aqueous flow from 2.13 (0.71) μL/min during the day to 1.11 (0.38) μL/min at night (P < .001). Uveoscleral outflow was significantly reduced (P = .03) by 0.61 μL/min at night when using supine IOP, tonographic outflow facility, and episcleral venous pressure adjusted for postural changes in the Goldmann equation. All other measurements had no significant changes. Significant ocular changes occur at night in individuals with ocular hypertension, including a reduction in seated IOP but an increase in habitual IOP, thickening of the cornea, and decreases in aqueous flow and uveoscleral outflow. Outflow facility does not change significantly at nighttime.

Ghrelin expression in the rat’s eye

AbstractPurpose The purpose of this study was to evaluate the ghrelin’s ocular tissue distribution in the adult rat’s eye and to confirm previously reported data, describing the identification of ghrelin’s mRNA in the iris posterior epithelium and in the ciliary body non pigmented epithelium.Methods Adult Wistar rats were sacrificed through an intraperitoneal injection of sodium pentobarbital and both eyes were immediately enucleated and processed for cryostat sections and indirect immunofluorescence protocol. Slides were incubated with anti‐ghrelin, anti‐histone H3 (positive control) and with 2% NGS (negative control) at 4ºC for 48 hours and then with secondary antibody containing a fluorescent tag during 1 hour. After incubation slides were examined under a fluorescence microscope.Results We observed immunolocalization of ghrelin in the rat’s ciliary body epithelium. Its major label was in the inner part of that epithelium facing to the stroma of the ciliary processes. This peptide was not localized in the posterior segment, naamely in the retinal pigmented epithelium.Conclusion Ghrelin is locally produced in the eye, mainly in the ciliary processes. Based on these findings, we can conclude that this peptide may play a role as a local regulator of the aqueous humor dynamics and ciliary muscle kinetics.

Investigation of the liquid in‐ and outflow parameters of the human eye using a modified strategy of the mechanical loading test

AbstractPurpose To obtain an additional information about the status of the inflow and outflow systems of the eye from ophthalmologic procedures based on static loading, with further application to diagnostics.Methods The standard method, based on static load application, for the estimation of parameters characterizing the aqueous humor dynamics was supplemented with an unloading test. After a four‐minute stationary mechanical loading by a Schiøtz tonometer, the load was removed and IOP was measured in a discrete regime for up to 20 min using the same tonometer. Clinical measurements were carried out on glaucoma (13) and non‐glaucoma (4) patients. The data obtained were processed using our mathematical model that represents the eyeball as an elastic water‐filled shell whose inner volume is regulated by dynamic balance between the liquid inflow and outflow and is assumed to be a function of IOP and the elastic and geometric characteristics of the system.Results The most important result is a strong difference between two characteristic times: the time that characterizes the rate of pressure fall under load and the time that characterizes the rate of pressure recovery after removing the load. The characteristic time is directly related with the outflow facility. The difference varies in different groups of patients. The results can be understood within the assumption of nonlinear IOP dependence of the outflow facility coefficient.Conclusion The modified mechanical loading test is a useful tool for investigating the biomechanical behavior of glaucoma and non‐glaucoma eyes. Our preliminary results give grounds to expect that the effect revealed may be applied to diagnostics.

A novel method for computerized measurement of episcleral venous pressure in humans

Episcleral venous pressure (EVP) is an important determinant of intraocular pressure (IOP) and can be estimated by the pressure required to compress an episcleral vein. However, the lack of objective measurement endpoints makes EVP measurements in humans uncertain. To address this issue, we developed a new method to measure EVP objectively and reproducibly, and demonstrated its utility on a group of normal subjects. Our system for pressure chamber based venomanometry included a computer-controlled motor drive to increase pressure automatically, a transducer to record pressure, and a high-definition video camera to record vein collapse. Pressure measurements were synchronized with the video stream to determine the pressure required to collapse the vein to a specific pre-determined degree. This system was used to measure EVP in 10 eyes from 5 young healthy volunteers. Episcleral veins were selected in each of 4 quadrants. EVP was calculated to be the pressure in the chamber that compressed the vein by 0% (by back-projection), 10% or 50% as determined by using image analysis of the video stream. For this group of subjects, mean EVP was 6.3 ± 2.8 mmHg (mean ± SD, n = 40 measurements), 7.0 ± 2.6 mmHg, and 9.6 ± 2.6 mmHg using the 0%, 10% and 50% reduction endpoints, respectively. Pressures and standard deviations determined from these endpoints were significantly different from each other ( p < 0.001). Coefficients of variation between right and left eyes were12.7%, 10.2%, and 6.8% using the 0%, 10% and 50% endpoints, respectively. Based on previous research and theoretical considerations, the 0% endpoint is assumed to provide the most accurate estimate of baseline EVP, and can only be estimated by analyzing the brightness profiles of the vessels in the video stream. Objective measurement of EVP is important for understanding normal aqueous humor dynamics and its changes in disease states and with therapies. EVP has typically been assumed to be constant because of the lack of a convenient means of its measurement. This new method provides a precise means to assess EVP based on specific endpoints of vessel collapse, and enables, for the first time, objective and non-invasive measurements of EVP changes.

Aqueous Humor Dynamics During the Day and Night in Healthy Mature Volunteers

To investigate the daytime vs nighttime differences in intraocular pressure (IOP), aqueous humor dynamics, central cornea thickness, and blood pressure among a cohort of healthy volunteers. Thirty healthy volunteers (mean [SD] age, 57.0 [8.6] years) were enrolled in the study. Individuals underwent 1 daytime visit and 1 nighttime visit for the measurement of aqueous humor dynamics. Measurements included IOP by pneumatonometry, aqueous flow by fluorophotometry, outflow facility by fluorophotometry and tonography, uveoscleral outflow by mathematical calculation, central cornea thickness by pachymetry, and blood pressure by sphygmomanometry. Results between visits were compared by appropriate t test. Dependence of the pneumatonometer probe results on position was tested in enucleated rabbit eyes at set pressures and probe positions. Compared with daytime seated IOP, nighttime seated IOP was reduced by 16%, whereas nighttime supine IOP was increased by 17% (P < .001 for both). The IOP changes were independent of the pneumatonometer probe position. Central cornea thickness was increased at nighttime from a mean (SD) of 560 (37) μm to a mean (SD) of 574 (37) μm (P < .001). Compared with daytime aqueous flow, nighttime aqueous flow was reduced by 49% (P < .001). During the night, fluorophotometric outflow facility was reduced by 45% (P = .05), and tonographic outflow facility was reduced by 17% (P < .01). Uveoscleral outflow at night was decreased when calculated using tonographic outflow facility but not fluorophotometric outflow facility in the Goldmann equation. All other measurements were unchanged. Significant changes in aqueous humor dynamics at night in healthy mature humans include reductions in aqueous flow, outflow facility, and possibly uveoscleral outflow. Nocturnal changes in IOP are independent of the pneumatonometer probe position and are dependent on an individual's posture during the measurement.

Correlations between Parameters of Aqueous Humor Dynamics and the Influence of Central Corneal Thickness

The individual parameters of aqueous humor dynamics may influence each other to maintain intraocular pressure (IOP) homeostasis. Central corneal thickness (CCT) is known to be associated with onset and progression of glaucoma and can potentially influence the individual parameters of aqueous humor dynamics that maintain IOP. This study investigates the correlation between parameters of aqueous humor dynamics and the influence of CCT in healthy volunteers and compares it with the correlations seen in patients with ocular hypertension. Aqueous humor dynamics (aqueous flow, outflow facility, and uveoscleral outflow), IOP, and pachymetry data from 94 healthy ocular normotensive (ONT) volunteers and 63 ocular hypertensive (OHT) patients was analyzed retrospectively. Linear correlations between individual aqueous humor dynamics parameters and pachymetry were evaluated using scatter plots and the Spearman correlation coefficient where appropriate. In both groups, a significant (P < 0.05) negative correlation was found between corneal thickness and aqueous flow (ONT, R(2) = 0.14; OHT, R(2) = 0.10) and between corneal thickness and uveoscleral outflow (ONT and OHT, R(2) = 0.10). A significant (P < 0.05) positive correlation was found between aqueous flow and outflow facility (ONT, R (2) = 0.24; OHT, R(2) = 0.10). In healthy controls, but not OHT patients, a significant (P < 0.001) positive correlation was found between aqueous flow and uveoscleral outflow (R(2) = 0.15). Thicker corneas may be associated with lower aqueous production and lower uveoscleral outflow. The interplay between parameters of aqueous humor dynamics suggests possible autoregulatory mechanisms in the eye. OHT may differ from ONT subjects in their inability to increase the uveoscleral outflow with increases in aqueous inflow.

Assessment of Aqueous Humor Dynamics in the Mouse by a Novel Method of Constant-Flow Infusion

To characterize a technique that concurrently assesses all aqueous humor hydrodynamic parameters in mouse eyes. Mouse outflow facility (C) was determined by multiple flow-rate infusion and episcleral venous pressure (Pe) measured by manometry. The animals were then euthanatized, eliminating aqueous formation rate (Fin) and Pe. C was determined again (C(dead)) while uveoscleral outflow (Fu(dead)) and Fin were deduced. To assess whether Fu(dead) would remain the same as Fu(live), the animals were perfused with FITC-dextran and Fu determined. The effects of IOP-lowering drugs on the parameters of aqueous hydrodynamics were also evaluated. Under the conditions tested, Fu(live) (0.012 ± 0.003 μL/min) was not different from Fu(dead) (0.015 ± 0.003 μL/min; P = 0.472). In anesthetized mice, IOP = 11.4 ± 0.2 mm Hg (mean ± SEM, n = 8), C = 0.018 ± 0.0006 μL/min/mm Hg, Pe = 5.4 ± 0.2 mm Hg, Fin = 0.14 ± 0.0007 μL/min, and Fu = 0.029 ± 0.005 μL/min. C(dead) was not different from C (P = 0.317). Latanoprost reduced IOP by increasing C by 0.009 ± 0.0003 μL/min/mm Hg (P < 0.001), without affecting Fin or Fu. Betaxolol reduced Fin by 0.075 ± 0.021 μL/min (P = 0.009). Brimonidine increased C by 0.005 ± 0.0005 μL/min/mm Hg (P < 0.001) and Fu by 0.013 ± 0.003 μL/min (P = 0.007). In this study, a unique technique was developed to concurrently assess IOP, C, Pe, Fin, and Fu in the mouse eye. This experimental approach should be useful to evaluate effects of pharmacologic agents or genetic manipulations on aqueous humor dynamics in mice and other animal models.

Pharmacotherapies for Glaucoma

Glaucoma is a group of progressive optic neuropathies in which the axons in the optic nerve are injured, retinal ganglion cell numbers are reduced and vision is gradually and permanently lost. The only approved and effective way to treat glaucoma is to reduce the intraocular pressure (IOP). This is usually accomplished by surgical and/or pharmacological means. Drugs designed to reduce IOP target one or more of the parameters that maintain it. These parameters (collectively known as aqueous humor dynamics) are the production rate of aqueous humor, the pressure in the episcleral veins and the drainage of aqueous humor through the trabecular or uveoscleral outflow pathways. Intraocular pressure lowering drugs can be classified as inflow or outflow depending on whether they reduce aqueous humor inflow into the anterior chamber or improve aqueous humor outflow from the anterior chamber. Inflow drugs, like β adrenergic antagonists and carbonic anhydrase inhibitors, reduce the rate of aqueous humor production. Outflow drugs, like prostaglandin analogs, cholinergic agonists and sympathomimetics, increase the rate of drainage through the uveoscleral outflow pathway and/or increase the facility of outflow through the trabecular meshwork. Some drugs have mixed inflow/outflow effects. This review summarizes the pharmacological treatments for glaucoma in use today and some new drugs showing potential for use in the future.

Aqueous humor dynamics in inbred rhesus monkeys with naturally occurring ocular hypertension

This study evaluates aqueous humor dynamics in rhesus monkeys from the University of Florida inbred colony with ocular normotension and naturally occurring ocular hypertension. Eight monkeys with untreated intraocular pressures (IOPs) of less than 18 mmHg in one eye (ONT group) and seven with untreated IOPs of greater than or equal to 18 mmHg in one eye (OHT group) were included in the study. Assessments included central cornea thickness by ultrasound pachymetry, IOP by tonometry, aqueous flow and outflow facility by fluorophotometry, and uveoscleral outflow by mathematical calculation. Animals were sedated with ketamine for all measurements. Values from the two eyes of each animal were averaged, with the exception of one animal that had only one good eye. Comparisons between groups were made by Student’s two-tailed unpaired t-tests. Compared to the ONT group, the OHT group had higher IOPs at all times measured (4:00 PM the day before the study, 21.2 ± 6.5 versus 14.4 ± 1.5 mmHg, p = 0.01; 9:00 AM the day of the study, 20.7 ± 6.6 versus 14.8 ± 1.2 mmHg, p = 0.03; 11:00 AM the day of the study, 16.0 ± 1.6 versus 13.3 ± 2.9 mmHg, p = 0.05) and lower aqueous flow (2.12 ± 0.40 versus 4.54 ± 1.11 μl/min, p = 0.0001), outflow facility (0.17 ± 0.10 versus 0.33 ± 0.07 μl/min/mmHg, p = 0.01) and uveoscleral outflow ( p < 0.05). The elevated IOP in inbred Florida rhesus monkeys is a result of significantly reduced outflow facility and uveoscleral outflow. These animals also have slower aqueous flow than the ONT animals which does not contribute to the higher IOP.

Aqueous Humor Dynamics: A Review~!2010-03-03~!2010-06-17~!2010-09-02~!

Glaucoma is a family of optic neuropathies which cause irreversible but potentially preventable vision loss. Vision loss in most forms of glaucoma is related to elevated IOP with subsequent injury to the optic nerve. Secretion of aqueous humor and regulation of its outflow are physiologically important processes for maintaining IOP in the normal range. Thus, understanding the complex mechanisms that regulate aqueous humor circulation is essential for management of glaucoma. The two main structures related to aqueous humor dynamics are the ciliary body and the trabecular meshwork (TM). Three mechanisms are involved in aqueous humor formation: diffusion, ultrafiltration and active secretion. Active secretion is the major contributor to aqueous humor formation. The aqueous humor flow in humans follows a circadian rhythm, being higher in the morning than at night. The aqueous humor leaves the eye by passive flow via two pathways - the trabecular meshwork and the uveoscleral pathway. In humans, 75% of the resistance to aqueous humor outflow is localized within the TM with the juxtacanalicular portion of the TM being the main site of outflow resistance. Glycosaminoglycan deposition in the TM extracellular matrix (ECM) has been suggested to be responsible for increased outflow resistance at this specific site whereas others have suggested deposition of proteins, such as cochlin, obstruct the aqueous humor outflow through the TM. The uveoscleral outflow pathway is relatively independent of the intraocular pressure and the proportion of aqueous humor exiting the eye via the uveoscleral pathway decreases with age.

Aqueous Humor Dynamics in Pigment Dispersion Syndrome

To assess aqueous humor dynamics in pigment dispersion syndrome (PDS). Four groups of age-matched participants included 2 experimental groups with PDS (PDS with ocular hypertension [PDS-OHT], 17 eyes; PDS without ocular hypertension [PDS-ONT], 18 eyes) and 2 control groups without PDS (OHT, 18 eyes; ONT, 18 eyes). Assessments included intraocular pressure measured by pneumatonometry, episcleral venous pressure by venomanometry, aqueous flow and outflow facility by fluorophotometry, corneal thickness and anterior chamber depth by pachymetry, and uveoscleral outflow by mathematical calculation. Comparisons were made by analysis of variance and 2-tailed unpaired t tests. The PDS-OHT group had higher intraocular pressures than the ONT and PDS-ONT groups (P < .001) and higher episcleral venous pressure (P = .04) and lower outflow facility (P = .01) than the ONT group. Anterior chamber volume was larger in the PDS-OHT group than in the other groups (P < .05 for all). No other comparisons between the PDS-OHT group and the other groups yielded statistically significant differences at a significance level of less than .05. The elevated intraocular pressure in PDS is caused by reduced outflow facility. This differs from OHT without PDS, in which reductions in uveoscleral outflow and outflow facility have been reported.

Mathematical model for biomechanical estimation of the data obtained in ophthalmologic procedures based on the application of a static load to the human eye.

Abstract Purpose To develop a mathematical model that makes it possible to analyze the interaction of various mechanical factors involved in the intraocular pressure formation and to apply it to processing the results of ophthalmologic procedures based on static load application. Methods The mathematical model that represents the eyeball as an elastic water‐filled shell is constructed. The intraocular volume is regulated by a dynamic balance between the liquid inflow (aqueous humor secretion) and outflow (drainage from the eye through the trabecular meshwork and the uveoscleral pathways) and assumed to be a function of the intraocular pressure and the elastic and geometric characteristics of the system. The effect of the hydrodynamic conditions in the blood vessels and osmotic pressure differences is taken into account. Results The model was tested, using clinical measurement data, for different hypotheses concerning the dependence of the outflow and inflow resistances on the intraocular pressure, the effect of the plasma proteins on the intraocular pressure formation, etc. Applying the model to processing standard clinical tests, we can obtain an additional parameter characterizing the aqueous humor dynamics. Conclusion The model developed is a useful tool for analyzing, by comparing with experimental data, a possible role of different mechanisms in mass transfer processes in the eye. In particular, the hydrodynamic in‐ and outflow characteristics can be estimated from the change with time of the tonometric pressure under an applied load. The general form of the model makes it possible to take, if necessary, additional effects into account.

Duration of Anesthesia Affects Intraocular Pressure, But Not Outflow Facility in Mice

Purpose: The study of aqueous humor dynamics (AHD) in mice is becoming more prevalent as more strains with elevated intraocular pressure (IOP) are developed. High IOP is usually associated with reduced outflow facility making this one of the more important AHD parameters to evaluate. Ocular measurements in mice require anesthesia that has profound effects on IOP but unknown effects on outflow facility. This study evaluates the effects of anesthesia duration and latanoprost treatment on outflow facility and IOP in BALB/c mice.Methods: IOPs were measured in conscious and anesthetized mice by tonometry. Outflow facility was evaluated in 15-min intervals at three pressure levels over two 45-min periods. Comparisons were made between latanoprost-treated eyes and untreated contralateral eyes. To determine the effect of anesthesia duration on IOP, a microneedle method was used to follow IOP for 120 min in separate mice.Results: IOP was 9.7 ± 0.3 mmHg (mean ± SEM) in conscious mice and 7.1 ± 0.02 within 10 min of anesthesia initiation (p < 0.01). IOP changed significantly between but not within assessment periods. IOP at 75 min was significantly (p = 0.004) reduced compared to IOP at 15 min after initial anesthesia. In control eyes, outflow facility did not change between the two 45-min assessment periods during the 120 min test (p = 0.80). In latanoprost-treated eyes, outflow facility increased compared with control eyes during both assessment periods (p = 0.03). A test of filters in series with known resistance found that the method was sensitive enough to detect a change in outflow facility of 0.001 μl/min/mmHg.Conclusions: Administration of ketamine/xylazine anesthesia for 120 min did not alter outflow facility or lessen the effect of latanoprost on outflow facility in mice as determined by a new analysis system. Accurate IOP measurements must be made within minutes of anesthesia administration but outflow facility measurements can be made with less haste.

Efficacy and Mechanisms of Intraocular Pressure Reduction With Latanoprost and Timolol in Participants With Ocular Hypertension: A Comparison of 1 and 6 Weeks of Treatment

To investigate whether the intraocular pressure (IOP) reduction and mechanism of action of timolol and latanoprost change between 1 and 6 weeks of treatment. Thirty participants on no ocular medications completed this double-masked, 6-visit, crossover study. At each visit IOP was determined by pneumatonometry, aqueous flow by fluorophotometry, and outflow facility by fluorophotometry and tonography. Separate values of uveoscleral outflow were calculated using the Goldmann equation, an episcleral venous pressure of 11 mm Hg, and each of the 2 outflow facility values. In a randomized fashion, both eyes were treated for 6 weeks with latanoprost 0.005% once daily or timolol 0.5% twice daily. Measurements were repeated at 1 and 6 weeks of dosing. After 6 weeks of washout, the second drug was administered in a crossover manner. One and 6 weeks of treatment were compared with appropriate baselines using 1-way analyses of variance (ANOVA). Timolol reduced aqueous flow by 27% at week 1 (P<0.001) and 16% at week 6 (P=0.03). Latanoprost increased uveoscleral outflow several fold at each visit (P<0.05). Neither drug altered outflow facility. Neither drug showed a detectable change in aqueous humor dynamics at week 6 compared with week 1. Both drugs significantly (P<0.001) reduced IOP at 1 and 6 weeks of treatment. Timolol and latanoprost significantly reduce IOP by different mechanisms. Timolol reduces aqueous flow whereas latanoprost increases uveoscleral outflow. Continued treatment with timolol or latanoprost for 6 weeks did not alter effects on aqueous humor dynamics. Outflow facility changes sometimes reported with prostaglandin analogues were not detected in this study.

Evaluation of anterior segment parameter changes using the Pentacam after uneventful phacoemulsification

This study set out to evaluate the influences of uneventful phacoemulsification on the anterior segment parameters obtained with the Pentacam rotating Scheimpflug camera and intraocular pressure (IOP). A total of 42 eyes of 34 patients (26 men, eight women) were evaluated preoperatively, and at 1, 3 and 6 months postoperatively with the Pentacam. Intraocular pressure was measured with the Goldmann applanation tonometer. The non-parametric paired t-test was used to compare preoperative and 1-, 3- and 6-month postoperative measurements of anterior chamber depth (ACD), anterior chamber volume (ACV), anterior chamber angle (ACA) width, central corneal thickness (CCT), the central 3-, 5- and 7-mm corneal volume (CV), pupil size, and IOP. Pearson's correlation test was used to evaluate the relationships between IOP and ACD, ACV and ACA width. The differences between ACD, ACV, ACA and IOP values taken preoperatively and those taken postoperatively at 1, 3 and 6 months were statistically significant (p<0.05). The differences between CCT, central 3-, 5- and 7-mm CV, and pupil size measurements taken preoperatively and those taken postoperatively at 1, 3 and 6 months were not statistically significant (p>0.05). The decrease in IOP was not correlated with the changes in ACD, ACV and ACA (p>0.05). Uneventful phacoemulsification significantly reduced IOP, increased ACD and ACV, and widened the ACA. However, alterations in CV, CCT and pupil size values were not statistically significant. Alterations in ACD, ACV, ACA and IOP remain stable after the first month of surgery.