Anterior chamber depth in mice is controlled by several quantitative trait loci.

Anterior chamber depth (ACD) is a quantitative trait associated with primary angle closure glaucoma (PACG). Although ACD is highly heritable, known genetic variations explain a small fraction of the phenotypic variability. The purpose of this study was to identify additional ACD-influencing loci using strains of mice. Cohorts of 86 N2 and 111 F2 mice were generated from crosses between recombinant inbred BXD24/TyJ and wild-derived CAST/EiJ mice. Using anterior chamber optical coherence tomography, mice were phenotyped at 10-12 weeks of age, genotyped based on 93 genome-wide SNPs, and subjected to quantitative trait locus (QTL) analysis. In an analysis of ACD among all mice, six loci passed the significance threshold of p = 0.05 and persisted after multiple regression analysis. These were on chromosomes 6, 7, 11, 12, 15 and 17 (named Acdq6, Acdq7, Acdq11, Acdq12, Acdq15, and Acdq17, respectively). Our findings demonstrate a quantitative multi-genic pattern of ACD inheritance in mice and identify six previously unrecognized ACD-influencing loci. We have taken a unique approach to studying the anterior chamber depth phenotype by using mice as genetic tool to examine this continuously distributed trait.

Immediate and cumulative effects of upper-body isometric exercise on the cornea and anterior segment of the human eye.

Objectives: The execution of isometric resistance training has demonstrated to cause changes in the ocular physiology. The morphology of the cornea and anterior chamber is of paramount importance in the prevention and management of several ocular diseases, and thus, understating the impact of performing isometric exercise on the eye physiology may allow a better management of these ocular conditions. We aimed to determine the short-term effects of 2-minutes upper-body isometric effort at two different intensities on corneal and anterior eye morphology. Methods: Eighteen healthy young adults performed a 2-minutes isometric biceps-curl exercise against two loads relative to their maximum strength capacity (high-intensity and low-intensity) in a randomized manner. An Oculus Pentacam was used to measure the corneal morphology and anterior chamber parameters in both experimental conditions at baseline, during the isometric effort (after 30, 60, 90 and 120 seconds), and after 30 and 120 seconds of passive recovery. Results: We found that isometric effort causes an increase in pupil size (P < 0.001), and a decrease in the iridocorneal angle (P = 0.005), anterior chamber volume (P < 0.001) and K-flat (P < 0.001) during isometric effort, with these effects being more accentuated in high-intensity condition (P < 0.005 in all cases).Performing 2-minutes upper-body isometric effort did not alter anterior chamber depth, central corneal thickness, corneal volume, and K-steep (P > 0.05 in all cases). Conclusions: Our data exhibit that performing 2-minutes of upper-body isometric exercise modifies several parameters of the corneal morphology and anterior eye biometrics, with these changes being greater for the high-intensity exercise condition. The findings of this study may be of relevance for the prevention and management of corneal ectasias and glaucoma.

Índices biométricos oculares en vietnamitas de 46 a 65 años de edad / Ocular biometric indices in Vietnamese 46 to 65 years of age

Introducción: La longitud axial ocular, la profundidad de la cámara anterior y el grosor corneal central, son tres índices biométricos oculares importantes. Estas medidas son útiles para mostrar los cambios en la población vietnamita con presbicia. Objetivos: Determinar los índices biométricos oculares, longitud axial ocular, profundidad de la cámara anterior y espesor corneal central, en población vietnamita y evaluar la correlación entre ellos y con la edad y el sexo. Métodos: Se realizó un estudio transversal en población vietnamita, con edad de 46 a 65 años. Se recogieron los datos de longitud axial ocular, profundidad de la cámara anterior y grosor corneal central. Se utilizaron la prueba t de Student y ANOVA para comparar las medias de los índices, agrupados por edad y sexo. La relación entre los índices biométricos oculares fue probada mediante la correlación de Pearson, con un nivel de significación de p < 0,05. Resultados: Se analizaron 390 ojos de 195 personas. La longitud media del eje ocular fue 23,13 ± 0,66 mm, la profundidad de la cámara anterior, 3,15 ± 0,36 mm, el grosor corneal central, 529,15 ± 30,57 µm. Los tres índices biométricos disminuyeron con la edad y fueron mayores en los hombres (p < 0,05). La longitud del eje ocular tuvo relación positiva con la profundidad de la cámara anterior (r = 0,411 y p < 0,001) y el espesor corneal central (r = 0,141 y p < 0,001). No hubo relación entre la profundidad de la cámara anterior y el grosor corneal central (r = 0,039 y p = 0,44). Conclusión: Los tres índices biométricos oculares disminuyeron con la edad y fueron mayores en los hombres. La longitud del eje ocular se relacionó con la profundidad de la cámara anterior y el grosor de la córnea central(AU)

Introduction: Ocular axial length, anterior chamber depth and central corneal thickness are three important ocular biometric indices. These measurements are useful to show changes in the Vietnamese population with presbyopia. Objectives: To determine the ocular biometric indices, ocular axial length, anterior chamber depth and central corneal thickness, in Vietnamese population and evaluate the correlation between these indices. Methods: A cross-sectional study was carried out in a Vietnamese population, aged 46 to 65 years. Data on ocular axial length, anterior chamber depth and central corneal thickness were collected. The Student's t test and ANOVA were used to compare the means of the indices, grouped by age and sex. The relationship between the ocular biometric indices was tested using Pearson's correlation, with a significance level of p <0.05. Results: 390 eyes of 195 people were analyzed. The mean length of the ocular axis was 23.13 ± 0.66 mm, the depth of the anterior chamber, 3.15 ± 0.36 mm, and the central corneal thickness, 529.15 ± 30.57 µm. The three biometric indices decreased with age and were higher in men (p <0.05). The length of the ocular axis had a positive relationship with the depth of the anterior chamber (r = 0.411 and p <0.001) and the central corneal thickness (r = 0.141 and p <0.001). There was no relationship between anterior chamber depth and central corneal thickness (r = 0.039 and p = 0.44). Conclusion: Three ocular biometric indices decreased with age and were higher in men. The length of the ocular axis was related to the depth of the anterior chamber and the thickness of the central cornea(AU)

In vivo MRI evaluation of early postnatal development in normal and impaired rat eyes.

This study employed in vivo 7-T magnetic resonance imaging (MRI) to evaluate the postnatal ocular growth patterns under normal development or neonatal impairments in Sprague-Dawley rats. Using T2-weighted imaging on healthy rats from postnatal day (P) 1 (newborn) to P60 (adult), the volumes of the anterior chamber and posterior chamber (ACPC), lens, and vitreous humor increased logistically with ACPC expanding by 33-fold and the others by fivefold. Intravitreal potassium dichromate injection at P1, P7, and P14 led to T1-weighted signal enhancement in the developing retina by 188-289%. Upon unilateral hypoxic-ischemic encephalopathy at P7, monocular deprivation at P15, and monocular enucleation at P1, T2-weighted imaging of the adult rats showed decreased ocular volumes to different extents. In summary, in vivo high-field MRI allows for non-invasive evaluation of early postnatal development in the normal and impaired rat eyes. Chromium-enhanced MRI appeared effective in examining the developing retina before natural eyelid opening at P14 with relevance to lipid metabolism. The reduced ocular volumes upon neonatal visual impairments provided evidence to the emerging problems of why some impaired visual outcomes cannot be solely predicted by neurological assessments and suggested the need to look into both the eye and the brain under such conditions.

Eye lymphatic defects induced by bone morphogenetic protein 9 deficiency have no functional consequences on intraocular pressure.

Aqueous humor drainage is essential for the regulation of intraocular pressure (IOP), a major risk factor for glaucoma. The Schlemm's canal and the non-conventional uveoscleral pathway are known to drain aqueous humor from the eye anterior chamber. It has recently been reported that lymphatic vessels are involved in this process, and that the Schlemm's canal responds to some lymphatic regulators. We have previously shown a critical role for bone morphogenetic protein 9 (BMP9) in lymphatic vessel maturation and valve formation, with repercussions in drainage efficiency. Here, we imaged eye lymphatic vessels and analyzed the consequences of Bmp9 (Gdf2) gene invalidation. A network of lymphatic vessel hyaluronan receptor 1 (LYVE-1)-positive lymphatic vessels was observed in the corneolimbus and the conjunctiva. In contrast, LYVE-1-positive cells present in the ciliary bodies were belonging to the macrophage lineage. Although enlarged conjunctival lymphatic trunks and a reduced valve number were observed in Bmp9-KO mice, there were no morphological differences in the Schlemm's canal compared to wild type animals. Moreover, there were no functional consequences on IOP in both basal control conditions and after laser-induced ocular hypertonia. Thus, the BMP9-activated signaling pathway does not constitute a wise target for new glaucoma therapeutic strategies.

Diurnal Cycle of Translaminar Pressure in Nonhuman Primates Quantified With Continuous Wireless Telemetry.

Purpose: Recent retrospective clinical studies and animal experiments have suggested that cerebrospinal fluid pressure (CSFP) is important in glaucoma pathogenesis. Intraocular pressure (IOP) and CSFP are the driving components of the translaminar pressure (TLP), which directly effects the optic nerve head. This study measured the diurnal cycle of TLP using continuous wireless telemetry in nonhuman primates (NHPs), a common animal model of glaucoma. Methods: We have developed an implantable wireless telemetry system based on a small piezoelectric pressure transducer with low drift. Unilateral IOP was measured in the anterior chamber of the eye, and intracranial pressure (ICP, a surrogate measure of CSFP) was measured in the brain parenchyma in four awake, behaving NHPs for periods of 22 to 281 days. IOP and ICP telemetry transducers were calibrated with direct pressure measurements in the eye (every 2 weeks) and brain (monthly). TLP was quantified in real time as IOP-ICP, and hourly means of IOP, ICP, and TLP were analyzed. Results: Results show that mean ICP is significantly higher by an average of 4.8 ± 0.8 mmHg during sleeping hours in NHPs (P < 0.01). IOP showed a small but significant nocturnal elevation in two of four animals despite NHPs sleeping upright (P < 0.05). TLP was significantly lower during sleep (7.1 ± 0.6 mmHg; P < 0.01) than when the animals were awake and active (11.0 ± 0.9 mmHg), driven primarily by the large increase in ICP during sleep. Conclusions: The 56% increase in TLP during waking hours in NHPs matches the increase in TLP due to postural change from supine to upright reported previously in humans.

Intraocular pressure and axial length changes during altitude acclimatization from Beijing to Lhasa.

PURPOSE: To investigate changes in intraocular pressure (IOP) and axial length (AL) on the ascent to high altitude from Beijing to Lhasa. PATIENTS AND METHODS: Twenty volunteers (17 men, 3 women) who had been sent to work in Lhasa, Tibet for more than 6 months were enrolled. One of their journeys from Beijing to Lhasa was chosen as the time for the examination. IOP, AL, corneal curvature (K), and blood pressure (BP) were measured in Beijing (altitude 43 m) and Lhasa (altitude 3658 m). Their first examination was conducted at least 1 day before arriving in Lhasa and the second examination after they had stayed in Lhasa for 7 days. The data from the highland and lowland examinations were analyzed with a paired-sample T test and Pearson's correlation coefficient was calculated for the association between IOP and average BP. RESULTS: The mean IOP was 12.65±2.34 mmHg in Beijing and 14.85±3.1 mmHg in Lhasa. The mean AL was 24.61±1.50mm in Beijing, and 24.98±1.45 mm in Lhasa. The IOP and AL showed a significant elevation in highland compared with lowland (P<0.05). The mean K was 43.58±2.25 D in Beijing and 43.56±2.21 D in Lhasa and no significant difference was found in this study (P>0.05). A positive correlation between variance of IOP and ACD was found (r = 0.475, P<0.05) and no correlation between IOP and average BP was noted. CONCLUSIONS: High altitude may lead to a small but significant change in IOP and axial length. However, the shape of the corneal surface was not influenced by the hypobaric and hypoxic conditions.

Validation of the Icare® TONOVET plus rebound tonometer in normal rabbit eyes.

To determine the accuracy and precision of the Icare® TONOVET Plus rebound tonometer for measuring intraocular pressure (IOP) in normal rabbit eyes, as well as compare it to three other commercially available tonometers: the Icare® TONOVET (TV01), Tono-Pen Vet™, and Tono-Pen AVIA Vet™. The anterior chambers of both eyes of three New Zealand White rabbits were cannulated, post-mortem. IOP was measured using each of the above four tonometers at manometric pressures ranging between 5 mmHg and 70 mmHg. Data were analyzed by linear regression, ANOVA, and Bland-Altman plots. A p-value of ≤0.05 was considered significant for all statistical tests. IOP values obtained with the TONOVET Plus (in 'lapine' mode) were significantly closer to manometric IOP than those obtained with the other tonometers tested. The TV01 (in 'd' dog setting) and Tono-Pen AVIA Vet™ were significantly more accurate compared to the Tono-Pen Vet™. All tonometers had high levels of precision, though the TONOVET Plus and TV01 were significantly more precise compared to the Tono-Pen AVIA Vet™. All tonometers tended to underestimate IOP, particularly at high pressures, however the TONOVET Plus was highly correlated with manometric IOP in the clinically relevant range of 5-50 mmHg. The TONOVET Plus is an appropriate choice of instrument for measuring IOP in rabbit eyes in both research and clinical settings.

Comparison of the trabecular meshwork length between open and closed angle with evaluation of the scleral spur location.

This study analysed the trabecular meshwork (TM) length in open and closed angle patients and presented a better method for locating the scleral spur using Schwalbe's line method in anterior segment optical coherence tomography (AS-OCT). Patients who underwent AS-OCT at Yonsei University Gangnam Severance Hospital we enrolled; 58 and 57 open and closed angle eyes, respectively. We measured the distance from the scleral spur to Schwalbe's line as the TM length and compared it between open and closed angle patients, and to previous studies. TM length was applied to locate the scleral spur using Schwalbe's line method. Mean TM lengths were 811 ± 83 µm and 575 ± 96 µm in the open and closed angle groups, respectively (p < 0.001). Comparing the actual TM heights using Schwalbe's line method with an updated reference distance significantly increased accuracy to locate the scleral spur (open: 811 µm, closed: 575 µm) when compared with the 1000 µm reference distance (p < 0.001). TM length was significantly different between open and closed angle patients. Further, the reference distance for Schwalbe's line method should be distinguished according to open and closed angle eyes in order that the scleral spur can be located properly.

Inflammatory cytokines in highly myopic eyes.

Currently, myopic retinopathy is the most common irreversible blinding disease but its pathophysiology is not completely clear. A cross-sectional, observational study was conducted in a single center to analyze aqueous samples from highly myopic eyes (axial length >25 mm, n = 92) and ametropic or mild myopic eyes (n = 88) for inflammatory cytokines. Vascular endothelial growth factor (VEGF), Interleukin 6 (IL-6), and matrix metalloproteinase-2 (MMP-2) were measured using an enzyme-linked immunosorbent assay. IL-6 and MMP-2 were significantly higher in the highly myopic eyes than in the non-high myopic eyes (IL-6: 11.90 vs. 4.38 pg/mL, p < 0.0001; MMP-2: 13.10 vs. 8.82 ng/mL, p = 0.0003) while adjusting for age, gender, and intraocular pressure. There was a significant positive association between levels of IL-6 and MMP-2 in aqueous humor and the axial lengths of the eye globes (IL-6, ß = 0.065, p < 0.0001, n = 134; MMP-2, ß = 0.097, p < 0.0001, n = 131). Conversely, VEGF in aqueous humor was significantly lower in the highly myopic eyes than in the non-high myopic eyes (45.56 vs. 96.90 pg/mL, p < 0.0001, n = 153) while age, gender, and intraocular pressure were adjusted. The results suggest that low-grade intraocular inflammation may play an important role in the development and progression of high myopia and myopic retinopathy.

Effect of pupil dilation on biometric measurements and intraocular lens power calculations in schoolchildren.

PURPOSE: To investigate the effect of pupil dilation on ocular biometric parameters and intraocular lens (IOL) power calculation in schoolchildren using the Lenstar LS 900. METHODS: One hundred forty eyes of 140 healthy schoolchildren were included in the analysis. Axial length (AL), central corneal thickness (CCT), aqueous depth (AD), anterior chamber depth (ACD), lens thickness (LT), flat keratometry (K), steep K, astigmatism, white-to-white (WTW), and iris/pupil barycenter distance were measured, before and after pupil dilation. Anterior segment length (ASL) was defined as the sum of ACD and LT, and lens position (LP) was defined as ACD plus half of the LT. The relative lens position (RLP) was defined as LP divided by AL. IOL power was calculated using the eight formulas (Hill-RBF, Barrett, Haigis, Hoffer Q, Holladay, Olsen, SRK II, and SRK/T) integrated in the Lenstar LS 900. Parameters before and after pupil dilation were compared. RESULTS: AL, AD, ACD, LT, ASL, LP, RLP, flat K, iris barycenter distance, pupil barycenter distance, and PD differed significantly after pupil dilation (P < 0.001 in all cases), as compared to before dilation. The Olsen formula demonstrated significant differences in the magnitude of astigmatism (P = 0.010) and IOL power (P = 0.003) after pupil dilation. Using the different formulas, 23.6-40.7% of participants had IOL power changes of more than 0.50 diopters, while 0.7-1.4% had IOL changes of more than 1.0 diopter after pupil dilation. CONCLUSIONS: Dilated and undilated pupil size affected the Lenstar LS 900 measurement of some ocular biometric parameters, and pupil dilation led to IOL power changes exceeding 0.50 diopters with a high percentage (from 23.6% to 40.7%) in schoolchildren, which should be noticed in clinical practice.

Effects of sustained daily latanoprost application on anterior chamber anatomy and physiology in mice.

Latanoprost is a common glaucoma medication. Here, we study longitudinal effects of sustained latanoprost treatment on intraocular pressure (IOP) in C57BL/6J mice, as well as two potential side-effects, changes in iris pigmentation and central corneal thickness (CCT). Male C57BL/6J mice were treated daily for 16 weeks with latanoprost. Control mice were treated on the same schedule with the preservative used with latanoprost, benzalkonium chloride (BAK), or handled, without ocular treatments. IOP and CCT were studied at pre-treatment, 2 "early" time points, and 2 "late" time points; slit-lamp analysis performed at a late time point; and expression of corneal and iridial candidate genes analyzed at the end of the experiment. Latanoprost lowered IOP short, but not long-term. Sustained application of BAK consistently resulted in significant corneal thinning, whereas sustained treatment with latanoprost resulted in smaller and less consistent changes. Neither treatment affected iris pigmentation, corneal matrix metalloprotease expression or iridial pigment-related genes expression. In summary, latanoprost initially lowered IOP in C57BL/6J mice, but became less effective with sustained treatment, likely due to physiological adaptation. These results identify a new resource for studying changes in responsiveness associated with long-term treatment with latanoprost and highlight detrimental effects of commonly used preservative BAK.

Changes in the parameters of the anterior segment of the eye in pregnant women - literature review.

The physiology of pregnancy is a curious issue for specialists from different branches of medicine and science. In this systematic review, the attention was focused on changes in eyes during pregnancy and confinement. To summarise and systematize actual knowledge in eyes' changes during pregnancy, publications from years 2011-2017 were analysed. Stud-ies about parameters of corneal endothelial cells, corneal biomechanical parameters, keratometric variables, intraocular pressure and biometry of the anterior chamber were compared. The conducted studies demonstrated the unambiguous character of changes only in case of intraocular pressure, which decreased during the II and III trimesters of pregnancy. Inconsistent study methods and low number of examined patients did not enable to draw explicit conclusions in context of other parameters of the anterior segment of the eye in pregnant women. It is indicated to perform further studies on a representative and homogeneous group of female patients.

A generalised porous medium approach to study thermo-fluid dynamics in human eyes.

The present work describes the application of the generalised porous medium model to study heat and fluid flow in healthy and glaucomatous eyes of different subject specimens, considering the presence of ocular cavities and porous tissues. The 2D computational model, implemented into the open-source software OpenFOAM, has been verified against benchmark data for mixed convection in domains partially filled with a porous medium. The verified model has been employed to simulate the thermo-fluid dynamic phenomena occurring in the anterior section of four patient-specific human eyes, considering the presence of anterior chamber (AC), trabecular meshwork (TM), Schlemm's canal (SC), and collector channels (CC). The computational domains of the eye are extracted from tomographic images. The dependence of TM porosity and permeability on intraocular pressure (IOP) has been analysed in detail, and the differences between healthy and glaucomatous eye conditions have been highlighted, proving that the different physiological conditions of patients have a significant influence on the thermo-fluid dynamic phenomena. The influence of different eye positions (supine and standing) on thermo-fluid dynamic variables has been also investigated: results are presented in terms of velocity, pressure, temperature, friction coefficient and local Nusselt number. The results clearly indicate that porosity and permeability of TM are two important parameters that affect eye pressure distribution. Graphical abstract Velocity contours and vectors for healthy eyes (top) and glaucomatous eyes (bottom) for standing position.

Distribution of Anterior Chamber Parameters in Normal Chinese Children and the Associated Factors.

PURPOSE: To describe the distribution of anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) and establish the associated factors in the pediatric population in Shanghai, China. MATERIALS AND METHODS: In this cross-sectional study, children aged 6 to 18 years from 9 primary and middle schools in Shanghai were enrolled. The Pentacam Scheimpflug camera was used to measure anterior eye chamber parameters. The distribution of ACD, ACV, ACA, and their associations with age, sex, body mass index, cycloplegic refractive error, axial length, intraocular pressure, and other parameters were analyzed. RESULTS: A total of 1321 children were included, with a mean age of 9.65±2.95 years. The mean ACA, ACD, and ACV values were 37.95±7.96 degrees, 3.22±0.23 mm and 194.89±28.95 mm, respectively, and were higher in boys than in girls. ACV and ACD had similar growth trend curves with age, whereas ACA was stable. Overall, 5% of the tested children had ACA values ≤24.91 degrees. Greater ACV, deeper ACD, shorter pupil diameter, shorter axial length, and thinner apex corneal thickness were the independent factors associated with wider ACA (R=13.0%, P<0.001). CONCLUSIONS: As one of diagnostic indicators of angle closure, ACA was stable with age. The results of this study should improve the current understanding of the distribution of anterior chamber parameters and the main factors affecting their variation.

Pregnancy and the eye. Changes in morphology of the cornea and the anterior chamber of the eye in pregnant woman.

OBJECTIVES: The main goal of the study was to determine whether uncomplicated pregnancy and natural labor exert influence on the cornea and the anterior chamber of the eye. MATERIAL AND METHODS: The study included 114 eyes of 57 women in age of 21-35 years old. Only patients in the physiological pregnancy and giving natural birth were recruited into study. Prospective observative examination was performed. Patients were diagnosed twice: in 36 HBD and 6 weeks after labor. Using the Scheimpflug camera (Pentacam system) the following parameters were assessed: central corneal thickness (CCT), keratometric parameters: flat (K1) and steep (K2), astigmatism value and axis, anterior chamber depth (ACD), anterior chamber volume (ACV) and anterior chamber angle (ACA). The statistical analysis was carried out in the StatSoft Statistica 13 program. RESULTS: CCT value is greater in the third trimester than in 6th week after the labour. ACD and ACA values are higher in 36 HBD than in the post-partum period but the difference is not statistically important (p > 0.05). K1, K2, cylindrical refraction error, axis of cylindrical refraction error do not change. CONCLUSIONS: Authors claim that it is the result from an increase in water retention in the corneal stroma as a response to hormonal changes. The plasticity of the anterior chamber seen before delivery can be a natural adaptive mechanism of the female body, which counteracts the excessive increase in intraocular pressure in the second stage of delivery.

Flow in the anterior chamber of the eye with an implanted iris-fixated artificial lens.

Flow in the aqueous humour that fills the anterior chamber of the eye occurs in response to the production and drainage of the aqueous humour, and also due to buoyancy effects produced by thermal gradients. Phakic intraocular lenses are manufactured lenses that are surgically inserted in the eyes of patients to correct refractive errors. Their presence has a dramatic effect on the circulation of the aqueous humour, resulting a very different flow in the anterior chamber, the effects of which have not been extensively investigated. In this article we use a simplified mathematical model to analyse the flow, in order to assess the effect of the implanted lens on the pressure drop required to drive the flow and also on the wall shear stress experienced by the corneal endothelial cells and the cells of the iris. A high pressure drop could result in an increased risk of glaucoma, whilst raised shear stress on the cornea could result in a reduction in the density of endothelial cells there, and on the iris it could result in the detachment of pigment cells, which block the outflow of the eye, also leading to glaucoma. Our results confirm those of previous fully numerical studies, and show that, although the presence of the lens causes significant differences in the flow topology and direction, the typical magnitudes of the shear stress are not significantly changed from the natural case. Our semi-analytical solution allows us to perform a thorough study of the dependence of the results on the controlling parameters and also to understand the basic physical mechanisms underlying flow characteristics.

Ocular anatomic changes for different accommodative demands using swept-source optical coherence tomography: a pilot study.

PURPOSE: The purpose of our study was to assess the changes in ocular parameters for different accommodative demands using a new optical biometer based on swept-source optical coherence tomography (SS-OCT). METHODS: Seven subjects were included in this pilot study, and only one eye per participant was analyzed. Each eye was measured six times with the optical biometer IOLMaster 700 (Carl Zeiss Meditec, Jena, Germany). As this instrument is not able to change the vergence of the stimulus, to enable measurements at different accommodative states, a tilted first-surface mirror attached to the optical biometer was used to place the fixation stimulus at different vergences. Measurements were taken on the right eye of the subject while the left eye was looking through the mirror. Central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), axial length (AL), white-to-white (WTW) distance and keratometric readings were evaluated for three different accommodative states: 0.0 diopters (D), 1.5 D, and 3.0 D. RESULTS: No statistically significant differences were found for CCT, AL, WTW, K1 and K2 between the three accommodative states. As expected, changing the accommodative condition did not change CCT, AL, WTW, and keratometric outcomes. Nevertheless, statistically significant differences between the accommodative states were found for ACD and LT measurements. In addition, variations in ACD correlated linearly with variations in LT (R2 ≥ 0.99) when changing the vergence of the optotype. CONCLUSION: A practical methodology to assess the changes in ocular parameters for different accommodative demands using the IOLMaster 700 based on SS-OCT has been described. Statistically significant changes that have been found that agree well with previous reports.

Anterior chamber perfusion versus posterior chamber perfusion does not influence measurement of aqueous outflow facility in living mice by constant flow infusion.

Mice are now routinely utilized in studies of aqueous humor outflow dynamics. In particular, conventional aqueous outflow facility (C) is routinely measured via perfusion of the aqueous chamber by a number of laboratories. However, in mouse eyes perfused ex-vivo, values for C are variable depending upon whether the perfusate is introduced into the posterior chamber (PC) versus the anterior chamber (AC). Perfusion via the AC leads to posterior bowing of the iris, and traction on the iris root/scleral spur, which may increase C. Perfusion via the PC does not yield this effect. But the equivalent situation in living mice has not been investigated. We sought to determine whether AC versus PC perfusion of the living mouse eye may lead to different values for C. All experiments were conducted in C57BL/6J mice (all ♀) between the ages of 20 and 30 weeks. Mice were divided into groups of 3-4 animals each. In all groups, both eyes were perfused. C was measured in groups 1 and 2 by constant flow infusion (from a 50 µL microsyringe) via needle placement in the AC, and in the PC, respectively. To investigate the effect of ciliary muscle (CM) tone on C, groups 3 and 4 were perfused live via the AC or PC with tropicamide (muscarinic receptor antagonist) added to the perfusate at a concentration of 100 µM. To investigate immediate effect of euthanasia, groups 5 and 6 were perfused 15-30 min after death via the AC or PC. To investigate the effect of CM tone on C immediately following euthanasia, groups 7 and 8 were perfused 15-30 min after death via the AC or PC with tropicamide added to the perfusate at a concentration of 100 µM. C in Groups 1 (AC perfusion) and 2 (PC perfusion) was computed to be 19.5 ± 0.8 versus 21.0 ± 2.1 nL/min/mmHg, respectively (mean ± SEM, p > 0.4, not significantly different). In live animals in which tropicamide was present in the perfusate, C in Group 3 (AC perfusion) was significantly greater than C in Group 4 (PC perfusion) (22.0 ± 4.0 versus 14.0 ± 2.0 nL/min/mmHg, respectively, p = 0.0021). In animals immediately following death, C in groups 5 (AC perfusion) and 6 (PC perfusion) was computed to be 21.2 ± 2.0 versus 22.8 ± 1.4 nL/min/mmHg, respectively (mean ± SEM, p = 0.1196, not significantly different). In dead animals in which tropicamide was present in the perfusate, C in group 7 (AC perfusion) was greater than C in group 8 (PC perfusion) (20.6 ± 1.4 versus 14.2 ± 2.6 nL/min/mmHg, respectively, p < 0.0001). C in eyes in situ in living mice or euthanized animals within 15-30 min post mortem is not significantly different when measured via AC perfusion or PC perfusion. In eyes of live or freshly euthanized mice, C is greater when measured via AC versus PC perfusion when tropicamide (a mydriatic and cycloplegic agent) is present in the perfusate.

Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm's Canal Endothelia.

The juxtacanalicular connective tissue of the trabecular meshwork together with inner wall endothelium of Schlemm's canal (SC) provide the bulk of resistance to aqueous outflow from the anterior chamber. Endothelial cells lining SC elaborate tight junctions (TJs), down-regulation of which may widen paracellular spaces between cells, allowing greater fluid outflow. We observed significant increase in paracellular permeability following siRNA-mediated suppression of TJ transcripts, claudin-11, zonula-occludens-1 (ZO-1) and tricellulin in human SC endothelial monolayers. In mice claudin-11 was not detected, but intracameral injection of siRNAs targeting ZO-1 and tricellulin increased outflow facility significantly. Structural qualitative and quantitative analysis of SC inner wall by transmission electron microscopy revealed significantly more open clefts between endothelial cells treated with targeting, as opposed to non-targeting siRNA. These data substantiate the concept that the continuity of SC endothelium is an important determinant of outflow resistance, and suggest that SC endothelial TJs represent a specific target for enhancement of aqueous movement through the conventional outflow system.