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Ferroelectricity is demonstrated for the first time in Si(100)/SiO2/TiN/HfO2-ZrO2/TiN stack using pulsed laser deposition (PLD) and the effects of temperatures, partial oxygen pressures, and thickness for the stabilization of the ferroelectric phase were mapped. Thin films deposited at a higher temperature and a higher oxygen partial pressure have a higher thickness, demonstrating a better ferroelectric response with ~12 μC/cm2 remnant polarization, a leakage current of 10−7 A (at 8 V) and endurance > 1011 cycles indicative of an orthorhombic crystal phase. In contrast, thin films deposited at lower temperatures and pressures does not exhibit ferroelectric behavior. These films can be attributed to having a dominant monoclinic phase, having lower grain size and increased leakage current. Finally, the effects of ZrO2 as top and bottom layer were also investigated which showed that ZrO2 as the top layer provided better mechanical confinement for stabilizing the orthorhombic phase instead of as the bottom layer.

The purpose of this study was to assess ocular coat mechanical behavior using controlled ocular microvolumetric injections (MVI) of 15 µL of balanced salt solution (BSS) infused over 1 second into the anterior chamber (AC) via a syringe pump.Intraocular pressure (IOP) was continuously recorded at 200 Hz with a validated implantable IOP telemetry system in 7 eyes of 7 male rhesus macaques (nonhuman primates [NHPs]) during 5 MVIs in a series at native (3 trials), 15 and 20 mm Hg baseline IOPs, repeated in 2 to 5 sessions at least 2 weeks apart. Ocular rigidity coefficients (K) and ocular pulse volume (PV) were calculated for each trial. Data were averaged across sessions within eyes; PV was analyzed with a three-level nested ANOVA, and parameter relationships were analyzed with Pearson Correlation and linear regression.After MVI at native baseline IOP of 10.4 ± 1.6 mm Hg, IOP increased by 9.1 ± 2.8 mm Hg (∆IOP) at a 9.6 ± 2.7 mm Hg/s slope, ocular pulse amplitude (OPA) was 0.70 ± 0.13 mm Hg on average; the average K was 0.042 ± 0.010 µL-1 and average PV was 1.16 ± 0.43 µL. PV varied significantly between trials, days, and eyes (P ≤ 0.05). OPA was significantly correlated with K at native IOP: Pearson coefficients ranged from 0.71 to 0.83 (P ≤ 0.05) and R2 ranged from 0.50 to 0.69 (P ≤ 0.05) during the first trial.The MVI-driven ∆IOP and slope can be used to assess ocular coat mechanical behavior and measure ocular rigidity.Importantly, OPA at native IOP is correlated with ocular rigidity despite the significant variability in PV between heartbeats.

Scleral crosslinking using genipin has been identified as a promising treatment approach for myopia control. The efficacy of genipin to alter biomechanical properties of the sclera has been shown in several animal models of myopia but its safety profile remains unclear. In this safety study, we aim to investigate the effect of scleral crosslinking using retrobulbar injections of genipin on retinal structure and function at genipin doses that were shown to be effective in slowing myopia progression in juvenile tree shrews. To this end, three or five retrobulbar injections of genipin at 0 mM (sham), 10 mM, or 20 mM were performed in one eye every other day. Form deprivation myopia was induced in the injected eye. We evaluated retinal function using full-field electroretinography and retinal structure using in vivo optical coherence tomography imaging and ex vivo histology. The optical coherence tomography results revealed significant thinning of the peripapillary retinal nerve fiber layer in all genipin treated groups including the lowest dose group, which showed no significant treatment effect in slowing myopia progression. In contrast, inducing form deprivation myopia alone and in combination with sham injections caused no obvious thinning of the retinal nerve fiber layer. Electroretinography results showed a significant desensitizing shift of the b-wave semi-saturation constant in the sham group and the second highest genipin dose group, and a significant reduction in b-wave maxima in the two highest genipin dose groups. The ex vivo histology revealed noticeable degeneration of photoreceptors and retinal pigment epithelium in one of two investigated eyes of the highest genipin dose group. While scleral crosslinking using genipin may still be a feasible treatment option for myopia control, our results suggest that repeated retrobulbar injections of genipin at 10 mM or higher are not safe in tree shrews. An adequate and sustained delivery strategy of genipin at lower concentrations will be needed to achieve a safe and effective scleral crosslinking treatment for myopia control in tree shrews. Caution should be taken if the proposed treatment approach is translated to humans.

Intraocular pressure (IOP) remains the only modifiable risk factor for glaucoma progression. Our previous discovery that stimulation of nuclei within the hypothalamus can modulate IOP, intracranial pressure (ICP), and translaminar pressure difference (TLPD) fluctuations led us to investigate this pathway further. Our purpose was to determine the role of orexin neurons, primarily located in the dorsomedial hypothalamus (DMH) and perifornical (PeF) regions of the hypothalamus, in modulating these pressures.Sprague Dawley rats were pretreated systemically with a dual orexin receptor antagonist (DORA-12) at 30 mg/Kg (n = 8), 10 mg/Kg (n = 8), or vehicle control (n = 8). The IOP, ICP, heart rate (HR), and mean arterial pressure (MAP) were recorded prior to and following excitation of the DMH/PeF using microinjection of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline methiodide (BMI).Administration of the DORA at 30 mg/Kg significantly attenuated peak IOP by 5.2 ± 3.6 mm Hg (P = 0.007). During the peak response period (8-40 minutes), the area under the curve (AUC) for the 30 mg/Kg DORA cohort was significantly lower than the control cohort during the same period (P = 0.04). IOP responses for peak AUC versus DORA dose, from 0 to 30 mg/Kg, were linear (R2 = 0.18, P = 0.04). The ICP responses during the peak response period (4-16 minutes) versus DORA dose were also linear (R2 = 0.24, P = 0.014). Pretreatment with DORA significantly decreased AUC for the TLPD following stimulation of the DMH/PeF (10 mg/kg, P = 0.045 and 30 mg/kg, P = 0.015).DORAs have the potential to attenuate asynchronous changes in IOP and in ICP and to lessen the extent of TLPDs that may result from central nervous system (CNS) activation.

Myopia and glaucoma are both increasing in prevalence and are linked by an unknown mechanism as many epidemiologic studies have identified moderate to high myopia as an independent risk factor for glaucoma. Myopia and glaucoma are both chronic conditions that lead to connective tissue remodeling within the sclera and optic nerve head. The mechanobiology underlying connective tissue remodeling differs substantially between both diseases, with different homeostatic control mechanisms. In this article, we discuss similarities and differences between connective tissue remodeling in myopia and glaucoma; selected multi-scale mechanisms that are thought to underlie connective tissue remodeling in both conditions; how asymmetric remodeling of the optic nerve head may predispose a myopic eye for pathological remodeling and glaucoma; and how neural tissue deformations may accumulate throughout both pathologies and increase the risk for mechanical insult of retinal ganglion cell axons.

Introduction: Microscopic details about retinal conditions can provide insight into pathological mechanisms, but these are ordinarily difficult to obtain in situ. We demonstrate how high-resolution imaging and optical modeling can be combined to reveal morphological features of a macular microcyst, offering insight into microcyst formation. Objective: To use adaptive optics scanning laser ophthalmoscopic (AOSLO) images to track a transient retinal microcyst and derive its 3-dimensional shape. Methods: A series of AOSLO images were gathered before, during, and after a transient retinal microcyst developed in an otherwise normal healthy 26-year-old male subject. Optical coherence tomography (OCT) independently confirmed the location of the microcyst. Optical modeling was conducted to quantify the lensing effect of the optically uniform microcyst and to determine its 3-dimensional shape. Increment threshold sensitivity, targeted within and around the microcyst, was tested to see if cone photoreceptor function was affected. Results: A transient microcyst appeared as a 50 µm diameter circle in AOSLO images, localized to the inner nuclear layer. Based on image distortion of the photoreceptor mosaic, optical modeling suggests that the microcyst had the shape of an aspherical lens, distinguishable from a spherical, cylindrical, or elliptical shape, indicative of an edematous expansion of laminar tissue. The microcyst spontaneously resolved about 30 days after first discovery. No changes to the photoreceptor mosaic ensued from the presence of the microcyst, and functional testing of the photoreceptors below the microcyst indicated no loss of light sensitivity. Conclusions: Microcysts have been associated with numerous subtypes of optic nerve degeneration, including multiple sclerosis and various inherited neuropathies. This microcyst appeared in a healthy individual and resolved without intervention. Lensing effects can be used to determine microcyst shape, which cannot be resolved by OCT imaging, and to help infer etiology.

Hydrus microstent (HMS) implantation at the time of cataract surgery appears to be cost-effective in mild-to-moderate glaucoma. However, long-term follow-up is essential for a full assessment of device performance, safety and cost-effectiveness.The aim was to assess the societal cost-utility to the US Medicare system of implanting HMS with cataract surgery versus cataract surgery alone in patients with open-angle glaucoma.Markov model cohort of patients with mild-to-moderate open-angle glaucoma and visually significant cataract.Patients received HMS during cataract surgery versus cataract surgery alone, in a deterministic model over a 2-year horizon using TreeAge software. Both arms received additional ocular hypotensive agents to control intraocular pressure. Treatment effect of HMS was measured as mean number of ocular hypotensive medications and intraocular pressure, which directly impacted transition probabilities. Health states included the Hodapp-Parrish-Anderson glaucoma stages (mild, moderate, advanced, blind) and death. One-way sensitivity and probabilistic sensitivity analyses were conducted on device efficacy and longer time horizons.At 2 years, HMS with cataract surgery in mild glaucoma had an incremental cost-utility ratio of USD 38,346.43 per utility gained, compared with cataract surgery alone. Probabilistic sensitivity analysis was cost-effective in 61.4% of iterations for HMS+cataract surgery. The probability of side-effects with eye drops, utility decrement with side-effects, cost of the HMS and real-world efficacy rate had the greatest impact on model outcomes. HMS must be 85.60% as effective as published data to maintain cost-effectiveness at a willingness-to-pay threshold of USD 50,000. The incremental cost-utility ratio of HMS with cataract surgery in moderate glaucoma was USD 42,895.38.HMS implantation during cataract surgery appears to be cost-effective for patients with mild-to-moderate glaucoma. Nevertheless, more long-term safety and efficacy data are required.

Purpose To find genetic contributions to glaucoma in African Americans. Design Cross-sectional, case-control study. Participants One thousand eight hundred seventy-five primary open-angle glaucoma (POAG) patients and 1709 controls, self-identified as being of African descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGES) III and Wake Forest School of Medicine. Methods MegaChip genotypes were imputed to Thousand Genomes data. Association of single nucleotide polymorphisms (SNPs) with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by receiver operator characteristic curves (ROC-AUCs). Main Outcome Measures Primary open-angle glaucoma defined by visual field loss without other nonocular conditions (n = 1875). Advanced POAG was defined by age-based mean deviation of visual field (n = 946). Results Eighteen million two hundred eighty-one thousand nine hundred twenty SNPs met imputation quality of r2 > 0.7 and minor allele frequency > 0.005. Association of a novel locus, EN04, was observed for advanced POAG (rs185815146 β, 0.36; standard error, 0.065; P Conclusions A novel association with advanced POAG in the EN04 locus was identified putatively in persons of AD. In addition to this finding, this genome-wide association study in POAG patients of AD contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine mapping of regions because of shorter average LD (FNDC3B). Although not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.

PURPOSE:To describe the study protocol and baseline characteristics of the African Descent and Glaucoma Evaluation Study (ADAGES) III. DESIGN:Cross-sectional, case-control study. PARTICIPANTS:Three thousand two hundred sixty-six glaucoma patients and control participants without glaucoma of African or European descent were recruited from 5 study centers in different regions of the United States. METHODS:Individuals of African descent (AD) and European descent (ED) with primary open-angle glaucoma (POAG) and control participants completed a detailed demographic and medical history interview. Standardized height, weight, and blood pressure measurements were obtained. Saliva and blood samples to provide serum, plasma, DNA, and RNA were collected for standardized processing. Visual fields, stereoscopic disc photographs, and details of the ophthalmic examination were obtained and transferred to the University of California, San Diego, Data Coordinating Center for standardized processing and quality review. MAIN OUTCOME MEASURES:Participant gender, age, race, body mass index, blood pressure, history of smoking and alcohol use in POAG patients and control participants were described. Ophthalmic measures included intraocular pressure, visual field mean deviation, central corneal thickness, glaucoma medication use, or past glaucoma surgery. Ocular conditions, including diabetic retinopathy, age-related macular degeneration, and past cataract surgery, were recorded. RESULTS:The 3266 ADAGES III study participants in this report include 2146 AD POAG patients, 695 ED POAG patients, 198 AD control participants, and 227 ED control participants. The AD POAG patients and control participants were significantly younger (both, 67.4 years) than ED POAG patients and control participants (73.4 and 70.2 years, respectively). After adjusting for age, AD POAG patients had different phenotypic characteristics compared with ED POAG patients, including higher intraocular pressure, worse visual acuity and visual field mean deviation, and thinner corneas (all P < 0.001). Family history of glaucoma did not differ between AD and ED POAG patients. CONCLUSIONS:With its large sample size, extensive specimen collection, and deep phenotyping of AD and ED glaucoma patients and control participants from different regions in the United States, the ADAGES III genomics study will address gaps in our knowledge of the genetics of POAG in this high-risk population.

The optimal approach for continuous measurement of intraocular pressure (IOP), including pressure transducer location and measurement frequency, is currently unknown. This study assessed the capability of extraocular (EO) and intraocular (IO) pressure transducers, using different IOP sampling rates and duty cycles, to characterize IOP dynamics. Transient IOP fluctuations were measured and quantified in 7 eyes of 4 male rhesus macaques (NHPs) using the Konigsberg EO system (continuous at 500 Hz), 12 eyes of 8 NHPs with the Stellar EO system and 16 eyes of 12 NHPs with the Stellar IO system (both measure at 200 Hz for 15 s of every 150 s period). IOP transducers were calibrated bi-weekly via anterior chamber manometry. Linear mixed effects models assessed the differences in the hourly transient IOP impulse, and transient IOP fluctuation frequency and magnitude between systems and transducer placements (EO versus IO). All systems measured 8000–12,000 and 5000–6500 transient IOP fluctuations per hour > 0.6 mmHg, representing 8–16% and 4–8% of the total IOP energy the eye must withstand during waking and sleeping hours, respectively. Differences between sampling frequency/duty cycle and transducer placement were statistically significant (p

Nonarteritic anterior ischemic optic neuropathy (NAION) has been associated with a thickened choroid at the optic nerve head (ONH). Here, we use computational modeling to better understand how choroidal expansion and choroidal geometry influence tissue deformation within the ONH relative to intraocular pressure (IOP) and intracranial pressure (ICP) effects.Using a model of the posterior eye that included the sclera, peripapillary sclera, annular ring, pia mater, dura mater, neural tissues, Bruch's membrane, choroid, and lamina cribrosa, we examined how varying material properties of ocular tissues influenced ONH deformations under physiological and supra-physiological, or "pathological," conditions. We considered choroidal expansion (c. 35 µL of expansion), elevated IOP (30 mm Hg), and elevated ICP (20 mm Hg), and calculated peak strains in the ONH relative to a baseline condition representing an individual in the upright position.Supra-physiological choroidal expansion had the largest impact on strains in the prelaminar neural tissue. In addition, compared to a tapered choroid, a "blunt" choroid insertion at the ONH resulted in higher strains. Elevated IOP and ICP caused the highest strains within the lamina cribrosa and retrolaminar neural tissue, respectively.Acute choroidal expansion caused large deformations of the ONH and these deformations were impacted by choroid geometry. These results are consistent with the concept that compartment syndrome due to the choroid geometry and/or expansion at the ONH contributes to NAION. Prolonged deformations due to supra-physiological loading may induce a mechanobiological response or ischemia, highlighting the potential impact of choroidal expansion on biomechanical strains in the ONH.

Purpose Recent retrospective clinical studies and animal experiments have suggested that cerebrospinal fluid pressure (CSFP) is important in glaucoma, acting through the translaminar pressure (TLP = IOP - CSFP), which directly affects the optic nerve head. In this study, IOP and intracranial pressure (ICP; a surrogate of CSFP) were measured at various body positions to quantify the determinants of TLP. Methods We have developed an implantable wireless pressure telemetry system based on a small piezoelectric sensor with low temporal drift. Telemetry transducers were placed in the anterior chamber to measure IOP and in the brain parenchyma at eye height to measure ICP. IOP was calibrated against anterior cannulation manometry, and ICP/CSFP was calibrated against an intraparenchymal Codman ICP Express microsensor. We measured IOP, ICP, and TLP = IOP - ICP continuously at 200 Hz in three male nonhuman primates (NHPs) in three trials; pressures were then averaged for 30 seconds per body position. Relative change of IOP, ICP, and TLP from the supine (baseline) position to the seated, standing, and inverted positions were quantified. Results TLP changed significantly and instantaneously from the supine to seated (+14 mm Hg), supine to standing (+13 mm Hg) and supine to inverted (-12 mm Hg) positions (P < 0.05). There was no significant TLP change for supine to prone. ICP showed greater relative change than IOP. Conclusions TLP change due to body position change is driven more by ICP/CSFP than IOP. IOP, ICP, and TLP variability, coupled with telemetry, should allow us to test the hypotheses that IOP, ICP, or TLP fluctuations contribute independently to glaucoma onset or progression.

We propose an empirical distortion correction approach for optical coherence tomography (OCT) devices that use a fan-scanning pattern to image the posterior eye segment. Two types of reference markers were used to empirically estimate the distortion correction approach in tree shrew eyes: retinal curvature from MRI images and implanted glass beads of known diameter. Performance was tested by correcting distorted images of the optic nerve head. In small animal eyes, our purposed method effectively reduced nonlinear distortions compared to a linear scaling method. No commercial posterior segment OCT provides anatomically correct images, which may bias the 3D interpretation of these scans. Our method can effectively reduce such bias.

Purpose Rodent and primate models are commonly used in glaucoma research; however, both have their limitations. The tree shrew (Tupaia belangeri) is an emerging animal model for glaucoma research owing in part to having a human-like optic nerve head anatomy, specifically a collagenous load-bearing lamina. However, the anterior segment anatomy and function have not been extensively studied in the tree shrew. Thus, the purpose of this study was to provide the first detailed examination of the anterior segment anatomy and aqueous outflow facility in the tree shrew. Methods Aqueous outflow dynamics were measured in five ostensibly normal eyes from three tree shrews using the iPerfusion system over a range of pressures. Gross histological assessment and immunohistochemistry were performed to characterize anterior segment anatomy and to localize several key molecules related to aqueous outflow. Results Anterior segment anatomy in tree shrews is similar to humans, demonstrating a scleral spur, a multilayered trabecular meshwork and a circular Schlemm's canal with a single lumen. Average outflow facility was 0.193 µL/min/mm Hg (95% confidence interval, 0.153–0.244), and was stable over time. Outflow facility was more similar between contralateral eyes (approximately 5% average difference) than between eyes of different animals. No significant dependence of outflow facility on time or pressure was detected (pressure–flow nonlinearity parameter of 0.01 (95% % confidence interval, −0.29 to 0.31 CI µL/min/mm Hg). Conclusions These studies lend support to the usefulness of the tree shrew as a novel animal model in anterior segment glaucoma and pharmacology research. The tree shrew's cost, load-bearing collagenous lamina cribrosa, and lack of washout or anterior chamber deepening provides a distinct experimental and anatomic advantage over the current rodent and nonhuman primate models used for translational research.

Thin films of Ga2O3 and its alloys open the possibility of ultrawide bandgap heterostructure device designs that includes HEMT, quantum well UV optoelectronics, wide bandgap spintronics, high resistive buffer layers for FET and electrocatalytic applications. In this paper, (Ga1-xFex)2O3 (for x = 0.0–0.50) thin film alloys as a function of growth temperatures (450–750 °C) and partial oxygen pressures (10-1 −10-6 torr) grown using pulsed laser deposition are reported. The results suggest that, with the increase of Fe content at a fixed growth temperature and pressure, the bandgap decreases (4.93 to 3.43 eV and 4.39 to 2.25 eV for direct and indirect, respectively) due to a change in the Fe oxidation states as the Fe composition is increased from 0 to 50%. Density functional theory calculations also show a reduction in the bandgap of the alloy as the Fe content increases with the formation of a localized band of states close to the conduction band. Fe content, ≥ 40% in the alloy leads a phase change in the crystal structure with the formation of a gamma phase, also corroborated by theoretical calculations. Finally, room temperature ferromagnetic property was observed in thin films with the introduction of Fe into the Ga2O3 lattice.

Importance While 6-month data are available regarding spaceflight-associated neuro-ocular syndrome, manned missions for 1 year and beyond are planned, warranting evaluation for spaceflight-associated neuro-ocular syndrome beyond 6 months. Objective To determine if the manifestation of spaceflight-associated neuro-ocular syndrome worsens during International Space Station missions exceeding the present 4- to 6-month duration. Design, Setting, and Participants The One-Year Mission Study used quantitative imaging modalities to investigate changes in ocular structure in 2 crew members who completed a 1-year–long spaceflight mission. This study investigated the ocular structure of crew members before, during, and after their mission on the International Space Station. Two crew members participated in this study from March 2015 to September 2016. Analysis began in March 2015 and ended in May 2020. Exposures Crew members were tested before, during, and up to 1 year after spaceflight. Main Outcomes and Measures This study compares ocular changes (peripapillary retinal edema, axial length, anterior chamber depth, and refraction) in two 1-year spaceflight mission crew members with cohort crew members from a 6-month mission (n = 11). Minimum rim width (the shortest distance between Bruch membrane opening and the internal limiting membrane) and peripapillary total retinal thickness were measured using optical coherence tomography. Results Both crew members were men. Minimum rim width and total retinal thickness increased in both participants throughout the duration of spaceflight exposure to the maximal observed change from preflight (minimum rim width: participant 1, 561 [+149 from preflight] μm at flight day 270; participant 2, 539 [+56 from preflight] μm at flight day 270; total retinal thickness: participant 1, 547 [+135 from preflight] μm at flight day 90; participant 2, 528 [+45 from preflight] μm at flight day 210). Changes in peripapillary choroid engorgement, axial length, and anterior chamber depth appeared similar between the 1-year mission participants and a 6-month mission cohort. Conclusions and Relevance This report documents the late development of mild optic disc edema in 1 crew member and the progressive development of choroidal folds and optic disc edema in another crew member over the duration of 1 year in low Earth orbit aboard the International Space Station. Previous reports characterized the ocular risk associated with 4 to 6 months of spaceflight. As future spaceflight missions are planned to increase in duration and extend beyond low Earth orbit, further observation of astronaut ocular health on spaceflight missions longer than 6 months in duration may be warranted.

Purpose: Cerebrospinal fluid pressure (CSFp) changes are involved or implicated in various ocular conditions including glaucoma, idiopathic intracranial hypertension, and visual impairment and intracranial pressure syndrome. However, little is known about the effects of CSFp on lamina cribrosa and retrolaminar neural tissue (RLNT) biomechanics, potentially important in these conditions. Our goal was to use an experimental approach to visualize and quantify the deformation of these tissues as CSFp increased.\ud\udMethods: The posterior eye and RLNT of porcine eyes (n = 3) were imaged using synchrotron radiation phase-contrast micro-computed tomography (PC μCT) at an intraocular pressure of 15 mm Hg and CSFps of 4, 10, 20, and 30 mm Hg. Scans of each tissue region were acquired at each CSFp step and analyzed using digital volume correlation to determine 3-dimensional tissue deformations.\ud\udResults: Elevating CSFp increased the strain in the lamina cribrosa and RLNT of all three specimens, with the largest strains occurring in the RLNT. Relative to the baseline CSFp of 4 mm Hg, at 30 mm Hg, the lamina cribrosa experienced a mean first and third principal strain of 4.4% and −3.5%, respectively. The corresponding values for the RLNT were 9.5% and −9.1%.\ud\udConclusions: CSFp has a significant impact on the strain distributions within the lamina cribrosa and, more prominently, within the RLNT. Elevations in CSFp were positively correlated with increasing deformations in each region and may play a role in ocular pathologies linked to changes in CSFp.

Many experiments have documented the response of intraocular pressure (IOP) to postural change. External forces caused by gravitational orientation change produce a dynamic response that is encountered every day during normal activities. Tilting the body at a small downward angle is also relevant to studying the effects of hypogravity (spaceflight), including ocular changes. We examined data from 36 independent datasets from 30 articles on IOP response to postural change, representing a total population of 821 subjects (≥1173 eyes) with widely varying initial and final postures. We confirmed that IOP was well predicted by a simple quantity, namely the hydrostatic pressure at the level of the eye, although the dependence was complex (nonlinear). Our results show that posturally induced IOP change can be explained by hydrostatic forcing plus an autoregulatory contribution that is dependent on hydrostatic effects. This study represents data from thousands of IOP measurements and provides insight for future studies that consider postural change in relation to ocular physiology, intraocular pressure, ocular blood flow and aqueous humor dynamics.

Spontaneous retinal venous pulsations (SRVPs), pulsations of branches of the central retinal vein, are affected by intraocular pressure (IOP) and intracranial pressure (ICP) and thus convey potentially-useful information about ICP. However, the exact relationship between SRVPs, IOP, and ICP is unknown. It is not easily feasible to study this relationship in humans, necessitating the use of an animal model. We here propose tree shrews as a suitable animal model to study the complex relationship between SRVPs, IOP, and ICP. Tree shrew SRVP incidence was determined in a population of animals. Following validation of a modified IOP control system to accurately and quickly control IOP, IOP and/or ICP were manipulated in two tree shrews with SRVPs and the effects on SRVP properties were quantified. SRVPs were present in 75% of tree shrews at physiologic IOP and ICP. Altering IOP or ICP produced changes in tree shrew SRVP properties; specifically, increasing IOP caused SRVP amplitude to increase, while increasing ICP caused SRVP amplitude to decrease. In addition, a higher IOP was necessary to generate SRVPs at a higher ICP than at a lower ICP. SRVPs occur with a similar incidence in tree shrews as in humans, and tree shrew SRVPs are affected by changes in IOP and ICP in a manner qualitatively similar to that reported in humans. In view of anatomic similarities, tree shrews are a promising animal model system to further study the complex relationship between SRVPs, IOP, and ICP.

To describe the first known case of Bacteroides spp. related blebitis, keratitis, and endophthalmitis following uncomplicated trabeculectomy.This was a case report and literature review.A 63-year-old immunocompetent white male underwent uncomplicated trabeculectomy of his right eye. Two weeks later, a blebitis with adjacent keratitis was diagnosed, progressing over several days to endophthalmitis despite hourly topical fortified antibiotic therapy. Although gram stain and culture of the bleb surface, a conjunctival suture, the aqueous humor, and the vitreous were negative, topical real-time quantitative polymerase chain reaction testing disclosed the presence of Bacteroides spp. Following treatment with topical and intravitreal clindamycin and intravenous meropenem, all clinical evidence of infection resolved. Best spectacle-corrected visual acuity improved to 20/25 (0.8) subsequent to combined cataract extraction, intraocular lens implantation, and pars plana vitrectomy for persistent vitreous debris.Bacteroides may be a rare cause of postoperative blebitis, keratitis, and endophthalmitis. A favorable outcome may be attained, provided that an accurate diagnosis and effective treatment can be provided, which may be facilitated by real-time quantitative polymerase chain reaction in select cases.

Purpose To evaluate the effect of scleral crosslinking (SXL) on slowing experimental progressive myopia in tree shrew eyes using sub-Tenon's injections of genipin (GEN) at different concentrations and number of injections. Methods Three or five sub-Tenon's injections of GEN at 0 mM (sham), 10 mM, or 20 mM were performed in one eye every other day starting at 18 days of visual experience. Form deprivation (FD) myopia was induced in the injected eye between 24 and 35 days of visual experience; the fellow eye served as control. Tree shrews were randomly assigned to five experimental groups: FD (n = 8); FD + 5 × sham injections (n = 6); FD + 3 × GEN injections at 10 mM (n = 6) and 20 mM (n = 6); and FD + 5 × GEN injections at 20 mM (n = 6). Refractive state and ocular dimensions were measured daily. Results Compared with the FD group, the sham-injected group showed a transient effect on slowing vitreous chamber elongation. With increasing GEN dose, SXL had an increasing treatment effect on slowing vitreous chamber elongation and myopia progression. In addition, SXL led to a dose-dependent shortening of the aqueous chamber depth and corneal thickening. Lens thickening was observed in the group with the highest concentration. Conclusions We have shown that SXL using GEN can slow axial elongation and myopia progression in tree shrews. The extent of this treatment effect was dose dependent. Several unexpected effects were observed (corneal thickening, decrease of the anterior chamber depth, and lens thickening), which require further optimization of the GEN delivery approach before clinical consideration. Translational relevance The results of this preclinical study suggest that scleral crosslinking using genipin can slow myopia progression.

Purpose Recent retrospective clinical and animal studies suggest that cerebrospinal fluid pressure (CSFP) is important in glaucoma pathogenesis. Intraocular pressure (IOP) and CSFP are the driving components of translaminar pressure (TLP = IOP – CSFP), which acts across the lamina cribrosa (LC) thickness to create the translaminar pressure gradient (TLPG = TLP/LC thickness). Methods We developed an implantable wireless telemetry system based on a small piezoelectric sensor with low temporal drift. IOP, measured in the anterior chamber, and intracranial pressure (ICP), measured in the brain parenchyma (as a surrogate for CSFP) were measured at 200 Hz in three male rhesus macaques (nonhuman primates, NHPs) on a 10% duty cycle (15 seconds of every 150-second period). Three-dimensional LC thickness was autosegmented as the mean thickness of the visible hyperreflective band in 48 radial spectral-domain optical coherence tomography b-scans centered on the optic nerve head. Results Results indicated the rank order of IOP, ICP, TLP, and TLPG for waking, sleeping, and 24-hour periods averaged across all days. NHP 150110 had the highest IOP and ICP in all periods; however, it had the lowest TLPG in all periods due to its relatively thick LC. The other two NHPs showed similar shifts in the rank order of possible glaucoma risk factors. Conclusions IOP is the only modifiable and readily measurable pressure-based risk factor for glaucoma. However, other potential risk factors such as ICP, TLP, and TLPG, as well as their rank-order patterns, differed compared to IOP across subjects, demonstrating that a comprehensive view of relevant risk factors is warranted. Translational Relevance Future studies should consider including CSFP, TLP, and TLPG in addition to IOP as potential risk factors when assessing eye-specific glaucoma susceptibility.

Visual impairment and intracranial pressure (VIIP) syndrome is characterized by a number of permanent ophthalmic changes, including loss of visual function. It occurs in some astronauts during long-duration spaceflight missions. Thus, understanding the pathophysiology of VIIP is currently a major priority in space medicine research. It is hypothesized that maladaptive remodeling of the optic nerve sheath (ONS), in response to microgravity-induced elevations in intracranial pressure (ICP), contributes to VIIP. However, little is known about ONS biomechanics. In this study, we developed a custom mechanical testing system that allowed for unconfined lengthening, twisting, and circumferential distension of the porcine ONS during inflation and axial loading. Data were fit to a four-fiber family constitutive equation to extract material and structural parameters. Inflation testing showed a characteristic “cross-over point” in the pressure–diameter curves under different axial loads in all samples that were tested; the cross-over pressure was $$10.3 \pm 0.95$$ mmHg ( $$\hbox {mean} \pm \hbox {SEM}$$ ). Large sample-to-sample variations were observed in the circumferential strain, while only modest variations were observed in the circumferential stress. Multiphoton microscopy revealed that the collagen fibers of the ONS were primarily oriented axially when the tissue was loaded. The existence of this cross-over behavior is expected to be neuroprotective, as it would avoid optic nerve compression during routine changes in gaze angle, so long as ICP was within the normal range. Including these observations into computational models of VIIP will help provide insight into the pathophysiology of VIIP and could help identify risk factors and potential interventions.

Purpose To characterize ocular perfusion pressure (OPP) fluctuations with continuous telemetry over 24-hour periods across multiple days in nonhuman primates (NHPs) to test the hypotheses that OPP differs among NHPs and that the diurnal cycle of OPP is characterized by low OPP during sleep. Methods We have developed and validated two implantable radiotelemetry systems that allow continuous measurement of intraocular pressure (IOP), arterial blood pressure (BP), and OPP up to 500 Hz. OPP was measured unilaterally in 12 male NHPs for periods of 38 to 412 days. IOP transducers were calibrated directly via anterior chamber manometry, and OPP was calculated continuously as central retinal artery BP minus IOP. OPP data were corrected for signal drift between calibrations and averaged hourly. Results OPP varied widely among animals, with daily averages ranging from ∼47 to 65 mm Hg. In eight of 12 NHPs, OPP was significantly lower during sleep compared to waking hours. In three animals, the diurnal cycle was reversed and OPP was significantly higher during sleep (P < 0.05), and one NHP showed no diurnal cycle. Day-to-day OPP variability within NHPs was the largest source of overall OPP variability, even larger than the differences between NHPs. Average daily OPP showed an unexplained ∼32-day cyclic pattern in most NHPs. Conclusions Average OPP varied widely and exhibited differing diurnal cycles in NHPs, a finding that matches those of prior patient studies and indicates that OPP studies in the NHP model are appropriate. Infrequent snapshot measurements of either IOP or BP are insufficient to capture true IOP, BP, and OPP and their fluctuations.

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.

PURPOSE: To describe the study protocol and baseline characteristics of the “African Descent and Glaucoma Evaluation Study (ADAGES) III: Contribution of Genotype to Glaucoma phenotype in African Americans”. DESIGN: Cross-sectional, case-control study PARTICIPANTS: There were 3266 glaucoma patients and controls without glaucoma of African or European descent recruited from five study centers in different regions of the United States. METHODS: Individuals of African descent (AD) and European descent (ED) with primary open angle glaucoma (POAG) and control subjects completed a detailed demographic and medical history interview. Standardized height, weight and blood pressure measurements were obtained. Saliva and blood samples to provide serum, plasma, DNA and RNA were collected for standardized processing. Visual fields, stereoscopic disc photographs, and details of the ophthalmic examination were obtained and transferred to the University of California-San Diego Data Coordinating Center for standardized processing and quality review. MAIN OUTCOME MEASURES: Participant gender, age, race, body mass index, blood pressure, history of smoking and alcohol use in POAG patients and controls are described. Ophthalmic measures included intraocular pressure, visual field mean deviation, central corneal thickness, glaucoma medication use or past glaucoma surgery. Ocular conditions including diabetic retinopathy, age-related macular degeneration and past cataract surgery were recorded. RESULTS: The 3266 ADAGES III study participants in this report include 2146 AD POAG patients, 695 ED POAG patients, 198 AD controls and 227 ED controls. AD POAG patients and controls were significantly younger (both 67.4 years) than ED POAG patients and controls (73.4 and 70.2 years, respectively). After adjusting for age, AD POAG patients had different phenotypic characteristics compared to ED POAG patients, including higher intraocular pressure, worse visual acuity and visual field mean deviation, and thinner corneas (all p

Purpose To study the effect and time course of body position changes on IOP in nonhuman primates. Methods We recorded continuous bilateral IOP measurements with a wireless telemetry implant in three rhesus macaques in seven different body positions. IOP measurements were acquired in the seated-upright, standing, prone, supine, right and left lateral decubitus positions (LDPs), and head-down inverted positions. Continuous IOP was recorded for 90 seconds in each position before returning to a supine reference position until IOP stabilized; measurements were averaged after IOP stabilized at each position. Results Head-down inversion increased IOP an average of 8.9 mm Hg, compared to the supine reference. In the LDP, IOP decreased an average of 0.5 mm Hg in the nondependent eye (i.e., the higher eye), while the fellow dependent (i.e., lower) eye increased an average of 0.5 mm Hg, compared to supine reference. Standing and seated positions decreased IOP 1.5 and 2.2 mm Hg, respectively, compared with supine reference. IOP changes occurred within 4 to 15 seconds of a body position change, and timing was affected by the speed at which body position was changed. Compared to the IOP in the supine position, the IOP in the inverted, prone, and seated positions was significantly different (P = 0.0313 for all). The IOP in the standing position was not statistically different from the IOP in the supine position (P = 0.094). In addition, the IOP was significantly different between the nondependent eye and the dependent eye in the LDPs compared to the supine position (P = 0.0313). Conclusions Body position has a significant effect on IOP and those changes persist over time.

Exposure to microgravity causes a bulk fluid shift toward the head, with concomitant changes in blood volume/pressure, and intraocular pressure (IOP). These and other factors, such as intracranial pressure (ICP) changes, are suspected to be involved in the degradation of visual function and ocular anatomical changes exhibited by some astronauts. This is a significant health concern. Here, we describe a lumped-parameter numerical model to simulate volume/pressure alterations in the eye during gravitational changes. The model includes the effects of blood and aqueous humor dynamics, ICP, and IOP-dependent ocular compliance. It is formulated as a series of coupled differential equations and was validated against four existing data sets on parabolic flight, body inversion, and head-down tilt (HDT). The model accurately predicted acute IOP changes in parabolic flight and HDT, and was satisfactory for the more extreme case of inversion. The short-term response to the changing gravitational field was dominated by ocular blood pressures and compliance, while longer-term responses were more dependent on aqueous humor dynamics. ICP had a negligible effect on acute IOP changes. This relatively simple numerical model shows promising predictive capability. To extend the model to more chronic conditions, additional data on longer-term autoregulation of blood and aqueous humor dynamics are needed.NEW & NOTEWORTHY A significant percentage of astronauts present anatomical changes in the posterior eye tissues after spaceflight. Hypothesized increases in ocular blood volume and intracranial pressure (ICP) in space have been considered to be likely factors. In this work, we provide a novel numerical model of the eye that incorporates ocular hemodynamics, gravitational forces, and ICP changes. We find that changes in ocular hemodynamics govern the response of intraocular pressure during acute gravitational change.

This paper presents a minimally invasive implantable pressure sensing transponder for continuous wireless monitoring of intraocular pressure (IOP). The transponder is designed to make the implantation surgery simple while still measuring the true IOP through direct hydraulic contact with the intraocular space. Furthermore, when IOP monitoring is complete, the design allows physicians to easily retrieve the transponder. The device consists of three main components: 1) a hypodermic needle (30 gauge) that penetrates the sclera through pars plana and establishes direct access to the vitreous space of the eye; 2) a micromachined capacitive pressure sensor connected to the needle back-end; and 3) a flexible polyimide coil connected to the capacitor forming a parallel LC circuit whose resonant frequency is a function of IOP. Most parts of the sensor sit externally on the sclera and only the needle penetrates inside the vitreous space. In vitro tests show a sensitivity of 15 kHz/mmHg with approximately 1-mmHg resolution. One month in vivo implants in rabbits confirm biocompatibility and functionality of the device.

Background Although the hypothalamic orexin system is known to regulate appetitive behaviors and promote wakefulness and arousal (Sakurai, 2007 [56] ), this system may also be important in adaptive and pathological anxiety/stress responses (Suzuki et al., 2005 [4]). In a recent study, we demonstrated that CSF orexin levels were significantly higher in patients experiencing panic attacks compared to non-panicking depressed subjects (Johnson et al., 2010 [9]). Furthermore, genetically silencing orexin synthesis or blocking orexin 1 receptors attenuated lactate-induced panic in an animal model of panic disorder. Therefore, in the present study, we tested if orexin (ORX) modulates panic responses and brain pathways activated by two different panicogenic drugs. Methods We conducted a series of pharmacological, behavioral, physiological and immunohistochemical experiments to study the modulation by the orexinergic inputs of anxiety behaviors, autonomic responses, and activation of brain pathways elicited by systemic injections of anxiogenic/panicogenic drugs in rats. Results We show that systemic injections of two different anxiogenic/panicogenic drugs (FG-7142, an inverse agonist at the benzodiazepine site of the GABA A receptor, and caffeine, a nonselective competitive adenosine receptor antagonist) increased c-Fos induction in a specific subset of orexin neurons located in the dorsomedial/perifornical (DMH/PeF) but not the lateral hypothalamus. Pretreating rats with an orexin 1 receptor antagonist attenuated the FG-7142-induced anxiety-like behaviors, increased heart rate, and neuronal activation in key panic pathways, including subregions of the central nucleus of the amygdala, bed nucleus of the stria terminalis, periaqueductal gray and in the rostroventrolateral medulla. Conclusion Overall, the data here suggest that the ORX neurons in the DMH/PeF region are critical to eliciting coordinated panic responses and that ORX1 receptor antagonists constitute a potential novel treatment strategy for panic and related anxiety disorders. The neural pathways through which ORX1 receptor antagonists attenuate panic responses involve the extended amygdala, periaqueductal gray, and medullary autonomic centers.

Purpose To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging. Design Cross-sectional study. Participants A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics. Methods Subjects were imaged using spectral domain optical coherence tomography (SD OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the Age-Related Eye Disease Study (AREDS) 9-step scale. Criteria for SDD presence were identification on ≥1 en face modality plus SD OCT or on ≥2 en face modalities if absent on SD OCT. Subretinal drusenoid deposits were considered present at the person level if present in 1 or both eyes. Main Outcome Measures Prevalence of SDD in participants with and without AMD. Results Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, P = 0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD ( P Conclusions Subretinal drusenoid deposits are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and increases with age, and its retinal topography including peripapillary involvement resembles that of rod photoreceptors. Consensus on SDD detection methods is recommended to advance our knowledge of this lesion and its clinical and biologic significance.

The N-type voltage-gated calcium channel (Cav 2.2) has gained immense prominence in the treatment of chronic pain. While decreased channel function is ultimately anti-nociceptive, directly targeting the channel can lead to multiple adverse side effects. Targeting modulators of channel activity may facilitate improved analgesic properties associated with channel block and a broader therapeutic window. A novel interaction between Cav 2.2 and collapsin response mediator protein 2 (CRMP-2) positively regulates channel function by increasing surface trafficking. We recently identified a CRMP-2 peptide (TAT-CBD3), which effectively blocks this interaction, reduces or completely reverses pain behavior in a number of inflammatory and neuropathic models. Importantly, TAT-CBD3 did not produce many of the typical side effects often observed with Cav 2.2 inhibitors. Notably chronic pain mechanisms offer unique challenges as they often encompass a mix of both neuropathic and inflammatory elements, whereby inflammation likely causes damage to the neuron leading to neuropathic pain, and neuronal injury may produce inflammatory reactions. To this end, we sought to further disseminate the ability of TAT-CBD3 to alter behavioral outcomes in two additional rodent pain models. While we observed that TAT-CBD3 reversed mechanical hypersensitivity associated with a model of chronic inflammatory pain due to lysophosphotidylcholine-induced sciatic nerve focal demyelination (LPC), injury to the tibial nerve (TNI) failed to respond to drug treatment. Moreover, a single amino acid mutation within the CBD3 sequence demonstrated amplified Cav 2.2 binding and dramatically increased efficacy in an animal model of migraine. Taken together, TAT-CBD3 potentially represents a novel class of therapeutics targeting channel regulation as opposed to the channel itself.

To study the health profiles and behavioral differences between primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients.Confidential mail survey of ICD-9 defined POAG (n = 277) and NTG (n = 116) patients was carried out to collect information regarding age, gender, height, weight, waist circumference, blood pressure (BP), medications [prescription (Rx) and over the counter (OTC)], education, and the Short Health Anxiety Inventory (SHAI).NTG patients (59/116) were significantly more likely to respond to the survey than POAG patients (43/277), p = 0.0001, and to have obtained college level education (70% vs. 42%), p = 0.003. Body weight, waist circumference, body mass index, systolic BP, pulse pressure, and ratio of prescription medications to OTC medications were significantly lower in the NTG group (p 0.0001). The SHAI score, mean age, and diastolic BP were not different between the two groups. A subgroup analysis of college-educated patients in both groups revealed persisting significant differences in waist circumference, systolic BP, and ratio of Rx to OTC medications.NTG patients do not have significantly greater health anxiety than POAG patients. NTG patients are more likely to have lower BMI, systolic BP, and ratio of Rx to OTC medications than POAG patients. The pilot nature of this study limits generalizability of these findings. Larger studies confirming these findings and elucidating the role of refractive error and medical history on such differences are needed.

Purpose Choroid geometry and swelling have been proposed to contribute to ocular pathologies. Thus, it is important to understand how the choroid may impact the optic nerve head (ONH) biomechanical environment. We developed a finite element model to study how acute choroidal swelling and choroid geometry affect ONH deformation. Methods We developed two geometric models of the ONH: one with a "blunt" choroidal insertion and another with a "tapered" choroid insertion. We examined how choroidal volume changes (2.1-14.2 μL, estimated to occur during the ocular pulse) impact biomechanical strain in three tissue regions: the prelaminar neural tissue, lamina cribrosa, and retrolaminar neural tissue. Then, we performed a sensitivity analysis to understand how variation in ONH pressures, tissue material properties, and choroidal swelling influenced the peak tissue strains. Results Choroidal swelling in the blunt choroid geometry had a large impact on the strains in the prelaminar neural tissue, with magnitudes comparable to those expected to occur due to an IOP of 30 mm Hg. Choroidal swelling in the tapered choroid geometry also affected strains but to a lesser extent compared to the blunt geometry. A sensitivity analysis confirmed that choroidal swelling was more influential on prelaminar neural tissue strains in the blunt choroid geometry. Conclusions Choroid anatomy and swelling can interact to play an important role in prelaminar neural tissue deformation. These findings suggest that the choroid may play an important, and previously unappreciated, role in ONH biomechanics, and motivate additional research to better define the in vivo effects of choroidal volume change.

Purpose Primates and rodents are used widely as animal models of glaucoma, but each has significant limitations. Researchers need additional animal models that closely resemble the relevant anatomy and pathologic features of the human disease to more quickly advance research. We validate a novel glaucoma animal model in tree shrews (Tupaia belangeri). Methods Experimental glaucoma was induced in adult tree shrews (n = 8) by injecting 50 μL of a 25 mg/mL ferromagnetic bead solution into the anterior chamber. Beads were directed into the iridocorneal angle with a magnet to impede aqueous outflow. Animals were followed for 3 months with weekly IOP measurements and biweekly spectral domain optical coherence tomography (SD-OCT) images of the optic nerve head. Histopathology of the optic nerve and optic nerve axon counts were completed at the end of the study. Results The 12-week average mean IOP was 22.7 ± 3.6 and 8.6 ± 2.9 mm Hg in the treated and control eyes, respectively. Longitudinal analysis showed significant retinal nerve fiber layer (RNFL) thinning throughout the study. Axon counts were significantly reduced (59.7%) in treated versus control eyes. SD-OCT imaging showed cupping and posterior displacement of the lamina cribrosa in glaucomatous eyes. RNFL thickness and optic nerve axon counts were reduced consistent with IOP elevation. Optic nerves demonstrated histopathology consistent with glaucomatous optic neuropathy. Conclusions Tree shrews with experimental glaucoma show key pathologic characteristics of the human disease. The tree shrew model of glaucoma has the potential to help researchers accelerate our understanding of glaucoma pathophysiology.

Pathologic changes in intracranial pressure (ICP) are commonly observed in a variety of medical conditions, including traumatic brain injury, stroke, brain tumors, and glaucoma. However, current ICP measurement techniques are invasive, requiring a lumbar puncture or surgical insertion of a cannula into the cerebrospinal fluid (CSF)-filled ventricles of the brain. A potential alternative approach to ICP measurement leverages the unique anatomy of the central retinal vein, which is exposed to both intraocular pressure (IOP) and ICP as it travels inside the eye and through the optic nerve; manipulating IOP while observing changes in the natural pulsations of the central retinal vein could potentially provide an accurate, indirect measure of ICP. As a step toward implementing this technique, we describe the design, fabrication, and characterization of a system that is capable of manipulating IOP in vivo with

Glaucoma, a leading cause of blindness worldwide, can be detected using retinal thicknesses from spectral-domain optical coherence tomography (SD-OCT) scans of the macula. We calculate the desired thickness maps as the distance between the inner-limiting membrane (ILM) and retinal pigmented epithelium (RPE) of the retina. To delineate these two layers, we use a set of two deformable open surfaces that are driven by intensity contrast, while preserving their shape and topology properties, i.e. local surface smoothness and inter-surface distance smoothness. To evaluate our method, qualified graders manually segmented 30 random sections from 20 OCT image stacks, in triplicate; we make comparisons with obtained ground-truth and the clinically tested Heidelberg Spectralis segmentation. We show the superiority of our method with respect to accuracy and average execution time (∼7 secs), validating it as a clinical tool.

Emotional stress provokes a stereotyped pattern of autonomic and endocrine changes that is highly conserved across diverse mammalian species. Nearly 50 years ago, a specific region of the hypothalamus, the hypothalamic defense area, was defined by the discovery that electrical stimulation in this area evoked changes that replicated this pattern. Attention later shifted to the hypothalamic paraventricular nucleus (PVN) owing to (1) elucidation of its role as the final common pathway mediating activation of the hypothalamic-pituitary-adrenal (HPA) axis, a defining feature of the stress response and (2) the finding that the PVN was the principal location of hypothalamic neurons that project directly to spinal autonomic regions. Consequently, a primary role for the PVN as the hypothalamic center integrating the autonomic and endocrine response to stress was inferred. However, our findings indicate that neurons in the nearby dorsomedial hypothalamus (DMH)--a region originally included in the hypothalamic defense area--and not in the PVN play a key role in the cardiovascular changes associated with emotional or exteroceptive stress. Indeed, excitation of neurons in the parvocellular PVN and consequent recruitment of the HPA axis that occurs in exteroceptive stress is also signaled from the DMH. Thus, the DMH may represent a higher order hypothalamic center responsible for integrating autonomic, endocrine and even behavioral responses to emotional stress.