Aqueous Humor Dynamics Research Articles

Glutathione Modulates Hydrogen Sulfide Release and the Ocular Hypotensive Action of Diallyl Polysulfide Compounds.

Hydrogen sulfide (H2S) is an endogenous transmitter with the potential to regulate aqueous humor dynamics and protect retinal neurons from degeneration. The aim of the present study was two-fold: (a) to evaluate the release of H2S from two polysulfides, diallyl disulfide (DADS), and diallyl trisulfide (DATS); and (b) to investigate their ocular hypotensive actions in normotensive male and female rabbits in the presence and absence of GSH. H2S was quantified hourly for up to 6 h using a H2S-Biosensor (World Precision Instruments, Sarasota, Fl). Intraocular pressure (IOP) was assessed in normotensive New Zealand Albino rabbits using a pneumotonometer (model 30 classic; Reichert Ophthalmic Instruments, Depew, NY, USA). In the presence of GSH, there was an increase in the in vitro release of H2S produced by DADS and DATS. Both DADS and DATS also caused a dose-dependent reduction in IOP in male and female rabbits, in both treated and untreated eyes. For instance, in male animals, the presence of GSH (3% and 5%) significantly (p < 0.05, n = 5) enhanced the ocular hypotensive action of DADS (2%) and DATS (2%) from 14.02 ± 2.89% to 18.67 ± 5.6% and from 16.22 ± 3.48 to 23.62 ± 5.79%, respectively. GSH enhanced both H2S release and ocular hypotensive action of the polysulfides in a manner that was dependent on the number of sulfur atoms present in each polysulfide. Furthermore, female animals were less sensitive to the IOP-lowering action of the polysulfides, when compared to their male counterparts.

The aqueous humour dynamics in primary angle closure disease: a computational study

PurposeTo create a computational fluid dynamics (CFD) model of ocular anterior segment for primary angle closure diseases (PACD) and assess the aqueous humour (AH) dynamics in different angle closure ranges...

Effect of Ambient Lighting on Intraocular Pressure Rhythms in Rats.

The purpose of this study was to determine the effects of ambient lighting on intraocular pressure (IOP) rhythmicity and variability. IOP was continuously recorded by wireless telemetry from rats under light/dark (LD), dark/light (DL), asymmetric (6L18D and 18D6L), constant dark (DD), and constant light (LL) cycles. In some DD experiments, 1-hour light pulses were presented at varying times. IOP rhythmicity and variability were respectively quantified via cosinor analysis and peak detection algorithms that identified transient and sustained fluctuations. Rat IOP peaked at night and troughed during the day with LD amplitude of 8.7 ± 3.4mm Hg. Rhythmicity persisted in DD and LL with a free-running period of 24.1 ± 0.3 and 25.2 ± 0.4 hours, respectively. Peak-to-trough amplitude was approximately 60% smaller in LL, often disappeared after 1 to 2 weeks as daytime IOP drifted 2.6 ± 1.5mm Hg higher, and returned to approximately 60% larger in LD. Rhythmicity was similarly impacted but resynchronized to DL over 4 to 6days. Rhythmicity was unaltered by short photoperiods (6L18D), but the nocturnal IOP elevation was markedly shortened by long photoperiods (18L6D) and temporarily lowered to daytime levels by light pulses during the subjective night. Transient and sustained event rate, amplitude, interval, and energy content were nearly identical in LD, DD, and LL. Aqueous humor dynamics of rat eyes are intrinsically configured to set IOP at daytime levels. Circadian clock input modulates these dynamics to elevate IOP at night. Light at night blocks this input, sending IOP back to daytime levels. Effects of abnormal lighting on IOP rhythmicity may contribute to pressure-related ocular neuropathies.

Nicotinamide: Bright Potential in Glaucoma Management.

Glaucoma is a major cause of incurable ocular morbidity and poses significant challenges in its management due to the limited treatment options and potential adverse effects. Nicotinamide, a naturally occurring diet-rich nutrient, has emerged as a promising therapeutic agent for glaucoma, offering neuroprotective effects and the potential modulation of intraocular pressure (IOP) regulation pathways. This comprehensive review sought to analyze the current literature on nicotinamide in glaucoma management, exploring its mechanisms of action, efficacy, and safety profile. A systematic search of the PubMed database was conducted to identify relevant records on the therapeutic actions of nicotinamide in ocular hypertension and glaucoma. Publications evaluating nicotinamide's effects on retinal ganglion cells (RGCs), optic nerve function, IOP regulation, and neuroinflammatory pathways were included. The literature review revealed the preclinical evidence supporting nicotinamide's neuroprotective effects on RGCs, the preservation of optic nerve integrity, and the modulation of glaucoma-associated neuroinflammation. Additionally, nicotinamide may exert IOP-lowering effects through its influence on ocular blood flow and aqueous humor dynamics. Nicotinamide holds promise as a novel therapeutic approach in glaucoma management, offering potential neuroprotective and IOP-lowering effects. The authors recommend more research to determine the nicotinamide efficacy, safe dosing parameters, and any long-term safety concerns in glaucoma patients.

In vivo quantification of anterior and posterior chamber volumes in mice: implications for aqueous humor dynamics.

Aqueous humor inflow rate, a key parameter influencing aqueous humor dynamics, is typically measured by fluorophotometery. Analyzing fluorophotometric data depends, inter alia, on the volume of aqueous humor in the anterior, but not the posterior, chamber. Previous fluorophotometric studies of aqueous inflow rate in mice have assumed the ratio of anterior:posterior volumes in mice to be similar to those in humans. Our goal was to measure anterior and posterior chamber volumes in mice to facilitate better estimates of aqueous inflow rates. We used standard near-infrared optical coherence tomography (OCT) and robotic visible-light OCT (vis-OCT) to visualize, reconstruct and quantify the volumes of the anterior and posterior chambers of the mouse eye in vivo. We used histology and micro-CT scans to validate relevant landmarks from ex vivo tissues to facilitate in vivo measurement. Posterior chamber volume is 1.1 times the anterior chamber volume in BALB/cAnNCrl mice, i.e. the anterior chamber constitutes about 47% of the total aqueous humor volume, which is very dissimilar to the situation in humans. Anterior chamber volumes in 2-month-old BALB/cAnNCrl and 7-month-old C57BL6/J mice were 1.55 ± 0.36 μL (n=10) and 2.41 ± 0.29 μL (n=8), respectively. This implies that previous studies likely over-estimated aqueous inflow rate by approximately two-fold. It is necessary to reassess previously reported estimates of aqueous inflow rates, and thus aqueous humor dynamics in the mouse. For example, we now estimate that only 0-15% of aqueous humor drains via the pressure-independent (unconventional) route, similar to that seen in humans and monkeys.

The TGFβ Induced MicroRNAome of the Trabecular Meshwork.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGFβ affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-β1 and -β2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFβ-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

The Factors Affecting the Stability of IOP Homeostasis.

Shear-induced nitric oxide (NO) production by Schlemm's canal (SC) endothelial cells provides a fast, IOP-sensitive feedback signal that normally contributes to IOP homeostasis. Our goal was to analyze the response of this homeostatic system under constant flow perfusion (as occurs in vivo) vs. constant pressure perfusion (as typical for laboratory perfusions). A mathematical model of aqueous humor dynamics, including shear-mediated NO signaling, was formulated and analyzed for stability. The model includes Goldmann's equation, accounting for proximal and distal outflow resistance, and describes how elevated IOP causes narrowing of SC lumen that increases the shear stress on SC cells. Elevated shear stress stimulates NO production, which acts to reduce outflow resistance and relax trabecular meshwork cells to decrease trabecular meshwork stiffness, affecting the SC luminal caliber. During constant flow perfusion, the outflow system is typically stable, returning to baseline IOP after a perturbation. In contrast, during constant pressure perfusion, the outflow system can become unstable and exhibit a time-dependent change in outflow resistance that diverges from baseline. The stability of shear mediated IOP homeostasis is predicted to differ critically between constant flow vs. constant pressure perfusion. Because outflow facility is typically measured at a constant pressure in the laboratory, this instability may contribute to the characteristic time-dependent increase in outflow facility, known as washout, observed in many nonhuman species. Studies of IOP homeostasis should consider how the outflow system may respond differently under constant pressure vs. constant flow perfusion.

Effect of a fixed combination of ripasudil and brimonidine on aqueous humor dynamics in mice

Ripasudil–brimonidine fixed-dose combination (K-232) simultaneously targets three different intraocular pressure (IOP) lowering mechanisms, increasing trabecular meshwork outflow and uveoscleral outflow, and reducing aqueous humor production Vascularly, ripasudil induces transient vasodilation, brimonidine transient vasoconstriction. Investigating effects on IOP, aqueous dynamics, and EVP in mice eyes by microneedle and constant-pressure perfusion methods, and on cytoskeletal and fibrotic proteins changes in HTM cells by a gel contraction assay and immunocytochemistry. Ripasudil, K-232, and brimonidine droplets significantly reduced IOP at 30 min, with K-232 sustaining the effect at 60 min. For EVP, only K-232 exhibited reduced EVP until 60 min after instillation. In vitro, ripasudil inhibited gel contractility and TGFβ2-induced fibrotic changes, whereas brimonidine did not. K-232 significantly lowered IOPs in mice by combining the effects of ripasudil and brimonidine. Brimonidine alone also showed IOP reductions with enhanced outflow facility, and the drug did not interfere with the effects of ripasudil on the trabecular meshwork outflow; K-232 and ripasudil alone both significantly lowered the EVP and enhanced outflow facility, demonstrating that K-232 efficiently reduces IOPs.

NCX 470 Reduces Intraocular Pressure More Effectively Than Lumigan in Dogs and Enhances Conventional and Uveoscleral Outflow in Non-Human Primates and Human Trabecular Meshwork/Schlemm's Canal Constructs.

Purpose: To determine NCX 470 (0.1%) and Lumigan® (bimatoprost ophthalmic solution, 0.01%-LUM) intraocular pressure (IOP)-lowering activity after single or repeated (5 days) dosing along with changes in aqueous humor (AH) dynamics. Methods: Ocular hypotensive activity of NCX 470 and LUM was compared with vehicle (VEH) in Beagle dogs using TonoVet®. Non-human primates (NHP) and bioengineered three-dimensional (3D) human Trabecular Meshwork/Schlemm's Canal (HTM/HSC™) constructs exposed to transforming growth factor-β2 (TGFβ2) were used to monitor NCX 470 and LUM-induced changes in AH dynamics. Results: NCX 470 (30 μL/eye) showed greater IOP reduction compared with LUM (30 μL/eye) following single AM dosing [maximum change from baseline (CFBmax) = -1.39 ± 0.52, -6.33 ± 0.73, and -3.89 ± 0.66 mmHg (mean ± standard error of the mean) for VEH, NCX 470, and LUM, respectively]. Likewise, repeated 5 days daily dosing of NCX 470 resulted in lower IOP than LUM across the duration of the study (average IOP decrease across tests was -0.45 ± 0.22, -6.06 ± 0.15, and -3.60 ± 0.22 mmHg for VEH, NCX 470, and LUM, respectively). NCX 470 increased outflow facility (Cfl) in vivo in NHP (CflVEH = 0.37 ± 0.09 μL/min/mmHg and CflNCX470 = 0.64 ± 0.17 μL/min/mmHg) as well as in vitro (CHTM/HSC) in HTM/HSC constructs (CHTM/HSC_VEH = 0.47 ± 0.02 μL/min/mm2/mmHg and CHTM/HSC_NCX470 = 0.76 ± 0.03 μL/min/mm2/mmHg). In addition, NCX 470 increased uveoscleral outflow (FuVEH = 0.62 ± 0.26 μL/min and FuNCX470 = 1.53 ± 0.39 μL/min with episcleral venous pressure of 15 mmHg) leaving unaltered aqueous flow (AHFVEH = 2.03 ± 0.22 μL/min and AHFNCX470 = 1.93 ± 0.31 μL/min) in NHP. Conclusions: NCX 470 elicits greater IOP reduction than LUM following single or repeated dosing. Data in NHP and 3D-HTM/HSC constructs suggest that changes in Cfl and Fu account for the robust IOP-lowering effect of NCX 470.

Simulation of gravity- and pump-driven perfusion techniques for measuring outflow facility of ex vivo and in vivo eyes.

Aqueous humor dynamics are commonly assessed by infusing fluid into the eye and measuring intraocular pressure (IOP). From the pressure-flow relationship, conventional outflow facility is estimated to study glaucomatous processes that lower facility or identify therapeutics that enhance facility in hopes of restoring healthy IOP levels. The relative merits and limitations of constant flow (CF), gravity-driven constant pressure (CPg), and pump-driven constant pressure (CPp) infusion techniques were explored via simulations of a lumped parameter viscoelastic model of the eye. Model parameter values were based on published perfusion system properties and outflow facility data from rodents. Step increases in pressure or flow were simulated without and with IOP noise recorded from enucleated eyes, anesthetized animals, and conscious animals. Steady-state response levels were determined using published window and ratio criteria. Model simulations show that all perfusion techniques estimate facility accurately and that ocular fluid dynamics set a hard limit on how fast measurements can be taken. This limit can be approached with CPg and CPp systems by increasing their gain but not with CF systems, which invariably take longest to settle. Facility experiment duration is further lengthened by inclusion of IOP noise, and data filtering is needed for steady-state detection with in vivo noise. The ratio criterion was particularly affected because noise in the flow data is amplified by the higher gain of CPg and CPp systems. A recursive regression method is introduced, which can ignore large transient IOP fluctuations that interfere with steady-state detection by fitting incoming data to the viscoelastic eye model. The fitting method greatly speeds up data collection without loss of accuracy, which could enable outflow facility measurements in conscious animals. The model may be generalized to study response dynamics to fluid infusion in other viscoelastic compartments of the body and model insights extended to optimize experiment design.

EFFICACY AND SAFETY OF RHO KINASE INHIBITOR EYEDROPS FOR THE TREATMENT OF OPEN-ANGLE GLAUCOMA AND OCULAR HYPERTENSION: A LITERATURE REVIEW

Introduction: Reduction of intraocular pressure (IOP) is the only proven method to treat glaucoma. Studies on aqueous humor dynamics have contributed to our understanding of aqueous outflow mechanisms that have led to the discovery of new drugs from Rho Kinase Inhibitors (RKI). Aims: To evaluate the efficacy and safety of RKI for treating open-angle glaucoma (OAG) and ocular hypertension (OHT). Methods: Literature searching was conducted through PubMed, ScienceDirect, Google Scholar, and Springer Link. Search terms included: “Open Angle Glaucoma”, “Ocular Hypertension”, and “Rho Kinase Inhibitors”, which provides for Netarsudil (AR-13530), Ripasudil (K-115)" or any relevant synonym. Validity was assessed using version 2 of the Cochrane risk of bias tool for randomized trials (RoB 2). Efficacy was evaluated by reported mean change IOP from baseline. Safety was assessed by adverse events experienced during the treatment course. Results: Eight randomized clinical trial studies fulfilled our inclusion criteria (four studies using Netarsudil 0.02% and four using FCNL as the primary treatment). IOP reduction from Netarsudil 0.02% was not inferior to Timolol 0.5%. Meanwhile, IOP reduction from FCNL class was statistically superior to its active component alone. The most common adverse events of Netarsudil 0.02% and FCNL were conjunctival hyperemia, cornea verticillate, and conjunctival hemorrhage. FCNL showed additional adverse events of site hyperemia and pain. Conclusion: Netarsudil 0.02% and FCNL can be reliable IOP control medications. The adverse events were tolerable.

The Effect of Scleral Buckle Surgery on Tonographic Outflow Facility, Positional Intraocular Pressure, and Ocular Biomechanics

To investigate the invivo effect of scleral buckle surgery on ocular biomechanics and aqueous humor dynamics. Prospective observational cross-sectional study. Nine patients with unilateral 360 degree encircling scleral buckles without vitrectomy for rhegmatogenous retinal detachments, between 3 and 39 months postoperative. All measurements were performed in both eyes of all participants. Intraocular pressure (IOP) was measured in the seated and supine positions using pneumatonometry. Outflow facility was measured using 2-minute weighted pneumatonography. Ocular rigidity coefficient was determined from the Friedenwald equations based on the difference in IOP with and without a weighted tonometer tip. The percentage change in IOP upon transitioning from seated to supine was calculated. Measurements for buckled and nonbuckled eyes were compared using paired Student t test of means. Sitting and supine IOP and percentage difference between the 2 positions; outflow facility; ocular rigidity coefficient. Seated IOP was similar between buckled and nonbuckled eyes (16.1 ± 2.5 vs. 16.7 ± 2.7 mmHg; P= 0.5) whereas supine IOP was lower in buckled eyes compared with nonbuckled eyes (18.7 ± 2.6 vs. 21.3 ± 2.5 mmHg; P= 0.008). The percentage increase in IOP upon change in body position from seated to supine was greater in nonbuckled eyes (17.4 ± 9.4% vs. 27.6 ± 9.5%; P= 0.005). Ocular rigidity coefficient was lower in buckled (9.9× 10-3 ± 1.4× 10-3 μL-1) vs. nonbuckled eyes (14.4× 10-3 ± 3.1× 10-3 μL-1; P= 0.006). Outflow facility was not significantly different in buckled and nonbuckled eyes. Scleral buckling decreases ocular rigidity but does not affect outflow facility. This change in ocular biomechanics likely results in the attenuated IOP change from seated to supine position. Decreased ocular rigidity may also reduce IOP fluctuations and potentially reduce the risk for glaucoma progression. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Short-Term Effect of Micropulse Transscleral Laser Therapy on Intraocular Pressure in Untreated Fellow Eyes of Glaucoma Patients: Preliminary Results.

It has been observed that an intraocular pressure (IOP) altering intervention in one eye is followed by a consensual response in the untreated fellow eye. The underlying mechanisms remain unclear. Involvement of neuronal, cytokine, and hormonal regulation of aqueous humor dynamics, as well as improved treatment adherence or systemic absorption of topically administered medical compounds, have been suggested. Our aim was to investigate the short-term effects of unilateral micropulse transscleral laser therapy on IOP in the fellow eye. All medical records of glaucoma patients who underwent micropulse transscleral laser therapy in a tertiary referral center between May 2019 and February 2023 were collected and analyzed. We found a significant reduction in IOP in the treated eyes, indicating successful treatment. In the fellow eyes, despite not having changed any of the pharmacological IOP-reducing therapies, a significant reduction in IOP from 17.0 ± 5.1 mmHg to 13.5 ± 4.4 mmHg (p < 0.01) was observed. This reduction was, however, short-term and reached statistical significance on the first postoperative day only. Our findings support the concept of consensual inter-eye responses to unilateral IOP changes. Further research is warranted to elucidate the mechanisms underlying this phenomenon.

Numerical simulation of aqueous flow in a novel posterior chamber phakic intraocular lens versus its counterparts

Phakic intraocular lenses (pIOLs), particularly posterior chamber pIOLs, are becoming important for patients with high myopia and thin corneas. By phakic intraocular, we mean the ocular environmental conditions, where the natural lens is unremoved. A new posterior chamber pIOL, the sine wave phakic refractive lens (SW-PRL), is in the development stage, and its aqueous humor (AH) dynamics and the effects of intraocular geometry on the flow characteristics are not well understood. To analyze the adaptability and functionality of SW-PRL, a comparison study is made with its counterparts, the posterior chamber phakic refractive lens (PC-PRL), PC-PRL combined with peripheral iridotomy [PC-PRL(PI)], and implantable collamer lens with a central hole (ICL V4c). The result demonstrates that SW-PRL has a positive effect on AH flow circulation. Interestingly, there is a relationship between a posterior chamber flow and the type of pIOLs with vault variation. With an increase in vault, the flow between the lens and pIOLs slowed down after ICL V4C implantation but accelerated after PC-PRL (PI) implantation with little change after SW-PRL implantation. On the rear surface of the iris, the wall shear stress (WSS) was lower for PC-PRL(PI), SW-PRL, and ICL V4c (5.6 × 10−4, 6 × 10−3, and 8.2 × 10−3 Pa, respectively) compared to the PC-PRL (0.14 Pa), and on the front surface of lens, the WSS was lower for PC-PRL and SW-PRL (1.16 × 10−5 and 9.7 × 10−6 Pa, respectively) compared to the ICL V4c (8.2 × 10−4 Pa). WSS on the cornea surface was similar for each pIOL. These might provide a fresh viewpoint on the clinical decision of different intraocular lenses.

Intraocular pressure variation from ocular compression in low and high myopia

ABSTRACT Clinical relevance Change in intraocular pressure during acute ocular compression is related to aqueous humour dynamics. Monitoring intraocular pressure (IOP) change throughout ocular compression has potential to evaluate aqueous outflow facilities. Background Recent studies have monitored lamina cribrosa deformation using optical coherence tomography during ocular compression. IOP was measured only once immediately after ocular compression. This study aimed to evaluate IOP changes during and after ocular compression and compare the differences between low and high myopia. Methods Two groups of young, healthy adults were age-matched and underwent ocular compression. IOP was measured at baseline and monitored during a 2-min ocular compression followed by a 10-min recovery phase. Rebound tonometry was used and applied at 30-s intervals. Results Thirty low and 30 high myopes (60 right eyes) were included in the study. They had similar baseline IOP at 14.9 mmHg. IOP was elevated to 21.7 ± 3.8 mmHg and 22.3 ± 4.2 mmHg for the low and high myopic group, respectively (p = 0.877). Low myopes had faster IOP decay during ocular compression at −3.24 mmHg/min than high myopes at −2.58 mmHg/min (p = 0.0528). The IOP dropped below the baseline level after the release of the compressive force. Low myopes had IOP that returned to baseline levels faster (at 360 s) than high myopes (at 510 s). Conclusion Measuring IOP once immediately after ocular compression could under-estimate the effect of IOP elevation during ocular compression. Further studies are required regarding IOP changes from ocular compression in aqueous humour dynamics.

Morphological and biomechanical analyses of the human healthy and glaucomatous aqueous outflow pathway: Imaging-to-modeling

Background and objectiveIntraocular pressure (IOP) is maintained via a dynamic balance between the production of aqueous humor and its drainage through the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm's canal (SC) endothelium of the conventional outflow pathway. Primary open angle glaucoma (POAG) is often associated with IOP elevation that occurs due to an abnormally high outflow resistance across the outflow pathway. Outflow tissues are viscoelastic and actively interact with aqueous humor dynamics through a two-way fluid-structure interaction coupling. While glaucoma affects the morphology and stiffness of the outflow tissues, their biomechanics and hydrodynamics in glaucoma eyes remain largely unknown. This research aims to develop an image-to-model method allowing the biomechanics and hydrodynamics of the conventional aqueous outflow pathway to be studied. MethodsWe used a combination of X-ray computed tomography and scanning electron microscopy to reconstruct high-fidelity, eye-specific, 3D microstructural finite element models of the healthy and glaucoma outflow tissues in cellularized and decellularized conditions. The viscoelastic TM/JCT/SC complex finite element models with embedded viscoelastic beam elements were subjected to a physiological IOP load boundary; the stresses/strains and the flow state were calculated using fluid-structure interaction and computational fluid dynamics. ResultsBased on the resultant hydrodynamics parameters across the outflow pathway, the primary site of outflow resistance in healthy eyes was in the JCT and immediate vicinity of the SC inner wall, while the majority of the outflow resistance in the glaucoma eyes occurred in the TM. The TM and JCT in the glaucoma eyes showed 1.32-fold and 1.13-fold larger beam thickness and smaller trabecular space size (2.24-fold and 1.50-fold) compared to the healthy eyes. ConclusionsCharacterizing the accurate morphology of the outflow tissues may significantly contribute to constructing more accurate, robust, and reliable models, that can eventually help to better understand the dynamic IOP regulation, hydrodynamics of the aqueous humor, and outflow resistance dynamic in the human eyes. This model demonstrates proof of concept for determining changes to outflow resistance in healthy and glaucomatous tissues and thus may be utilized in larger cohorts of donor tissues where disease specificity, race, age, and gender of the eye donors may be accounted for.

A GPU accelerated study of aqueous humor dynamics in human eyes using the lattice Boltzmann method.

In this paper, we presented a 3D human eyes aqueous humor (AH) dynamics model, and additionally, designed and optimized it using GPU technology. First, the feasibility of the model is demonstrated through validation. Then, the effect of different factors on AH flow was investigated using the validated model. The experimental results showed that AH flow more rapidly when standing than supine; the intraocular temperature has the greatest effect on AH flow compared to other factors; the AH secretion rate and trabecular meshwork (TM) permeability had a greater effect on intraocular pressure (IOP). Corneal indentation and ovoid anterior chamber (AC) can also affect AH flow. Finally, the PartSparse algorithm based GPU can save more than 50% of the memory consumption and achieves a performance of 1491.29 MLUPS and a Speedup of 837.61 times.

The Effect of Intraocular Pressure Load Boundary on the Biomechanics of the Human Conventional Aqueous Outflow Pathway.

Aqueous humor outflow resistance in the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and Schlemm's canal (SC) endothelium of the conventional outflow pathway actively contribute to intraocular pressure (IOP) regulation. Outflow resistance is actively affected by the dynamic outflow pressure gradient across the TM, JCT, and SC inner wall tissues. The resistance effect implies the presence of a fluid-structure interaction (FSI) coupling between the outflow tissues and the aqueous humor. However, the biomechanical interactions between viscoelastic outflow tissues and aqueous humor dynamics are largely unknown. A 3D microstructural finite element (FE) model of a healthy human eye TM/JCT/SC complex was constructed with elastic and viscoelastic material properties for the bulk extracellular matrix and embedded elastic cable elements. The FE models were subjected to both idealized and a physiologic IOP load boundary using the FSI method. The elastic material model for both the idealized and physiologic IOP load boundary at equal IOPs showed similar stresses and strains in the outflow tissues as well as pressure in the aqueous humor. However, outflow tissues with viscoelastic material properties were sensitive to the IOP load rate, resulting in different mechanical and hydrodynamic responses in the tissues and aqueous humor. Transient IOP fluctuations may cause a relatively large IOP difference of ~20 mmHg in a very short time frame of ~0.1 s, resulting in a rate stiffening in the outflow tissues. Rate stiffening reduces strains and causes a rate-dependent pressure gradient across the outflow tissues. Thus, the results suggest it is necessary to use a viscoelastic material model in outflow tissues that includes the important role of IOP load rate.

Geometric Modeling of Human Eyes Based on OCT Image of Anterior Segment and Its Application

The aqueous humor flowing in the human eye plays a very important role in maintaining the normal physiological function of the human eye. Once the outflow of aqueous humor is blocked, it will lead to the increase of intraocular pressure, which will lead to glaucoma and other ophthalmic diseases. Therefore, it is of great significance to study the aqueous humor dynamics mechanism of human eyes to explore the physiological structure of human eyes, the pathogenesis and treatment of ophthalmic diseases. In previous studies, most of the geometric models of anterior segment of human eye hydrodynamics are ideal simplified models based on the anatomical data of human eyes, so the simulated results may deviate from the actual situation. In this paper, the OCT image of anterior segment is denoised and segmented by using image processing technology. At the same time, combined with the conventional data of human anatomy, the geometric model of anterior segment is reconstructed, which is closer to the real human eye and has personalized characteristics. On this basis, the flow of aqueous humor in normal eyes was simulated and studied, and the vortex in iris recess was found. The results show that this method can reflect the aqueous humor flow in real eyes more accurately.

Eye Dynamics and Engineering Network Consortium: Baseline Characteristics of a Randomized Trial in Healthy Adults

To improve understanding of intraocular pressure (IOP) and its variance, this project identifies systemic and ocular characteristics of healthy eyes of adult volunteers including IOP variation, ocular biometrics, and aqueous humor dynamics (AHDs). These data serve as baseline controls for further studies from the Eye Dynamics and Engineering Network (EDEN) Consortium. Multicenter open-label clinical trial in healthy adults randomized to 1 week treatment with 2 approved glaucoma drugs in a crossover design. Among 135 healthy participants, 122 participants (aged 55.2 ± 8.8 years; 92 females, 30 males) completed the protocol. Participants from the University of Michigan, Mayo Clinic, and University of Nebraska Medical Center underwent measurements of ocular biometrics, AHD, and IOP using 4 tonometers. Intraocular pressure data during 3 study visits without glaucoma medications were used in the analysis. The PhenX Toolkit survey acquired standardized data on medical history, surgical history, medications, smoking and alcohol exposures, and physical measures. The variability of IOP measurements within eyes was assessed as visit-to-visit IOP variation, within-visit IOP variation, and within-visit positional IOP variation. The concordance (or correlation) between eyes was also assessed. Average positional change of > 4.7 mmHg was detected with a range of 0.5-11.0 mmHg. Pearson correlation of IOP between eyes within a visit was 0.87 (95% confidence interval [CI], 0.82-0.91) for Goldmann applanation tonometry, 0.91 (95% CI, 0.88-0.94) for Icare rebound tonometry, and 0.91 (95% CI, 0.88-0.94) for pneumatonometry. There was a 4% to 12% asymmetric fluctuation of 3 mmHg or more between eyes between visits using rebound tonometry, 9% with Goldmann applanation tonometry, and 3% to 4% by pneumotonometry. The coefficient of variation between visits for the same eye ranged from 11.2% to 12.9% for pneumatonometry, from 13.6% to 17.4% for rebound tonometry, and 15.8% to 16.2% for Goldmann applanation tonometry. The current study from the EDEN Consortium describes measurement methods and data analyses with emphasis on IOP variability. Future papers will focus on changes in ocular biometrics and AHD with timolol or latanoprost treatment. Proprietary or commercial disclosure may be found after the references.