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Everett F Magann,1 Julie R Whittington,1 John C Morrison2 ,†Suneet P Chauhan3 1Departments of Obstetrics and Gynecology of the University of Arkansas for the Medical Sciences, Little Rock, AR, USA; 2Department of Obstetrics and Gynecology of the University of Mississippi Medical Center, Jackson, MS, USA; 3Department of Obstetrics, Gynecology and Reproductive Sciences of the University of Texas Health Sciences Center at Houston, Houston, TX, USA†Dr John C. Morrison passed away on September 1, 2019Correspondence: Everett F MagannDepartment of Obstetrics and Gynecology of the University of Arkansas for the Medical Sciences, 4301 W. Markham St. Slot # 518, Little Rock, AR, 72205, USATel +1 501-686-8345Fax +1 501-526-7820Email efmagann@uams.eduAbstract: Actual AFV can be determined by a dye-dilution technique or be directly measured at cesarean. This allows investigators to correlate estimated and actual AFVs. Lessons learned by assessing the relationship of estimated to actual AFVs. 1) Ultrasound estimates normal actual AFVs well, but abnormal AFVs poorly. 2) Quantile regression is a better statistical methodology to create a normal AFV curve across pregnancy. 3) There is no difference in the accuracy of the subjective (visualization without measurements) compared with the objective (visualization with measurements) technique in identifying normal and abnormal AFVs. 4) Color Doppler use leads to the over-diagnosis of oligohydramnios. 5) Intravenous hydration increases actual AFVs. 6) The estimation of AFV can be done with the transducer held perpendicular to the floor or perpendicular to the uterine contour. 7) The single deepest pocket should be used for identifying low AFVs. 8) The AFI should be used for identifying high AFVs.Keywords: amniotic fluid volume, oligohydramnios, polyhydramnios, color Doppler, subjective assessment, objective assessment

In this study, we present a sensorless adaptive optics swept-source optical coherence tomographic angiography (sAO-SS-OCTA) imaging system for mice. Real-time graphics processing unit (GPU)-based OCTA image acquisition and processing software were applied to guide wavefront correction using a deformable mirror based on signal strength index (SSI) from both OCT and OCTA images. High-resolution OCTA images with aberrations corrected and contrast enhanced were successfully acquired. Fifty-degree field of view high-resolution montaged OCTA images were also acquired.

The objective of this study was to examine prior studies on maternal and neonatal outcomes with prophylactic compared with emergent blood transfusion in pregnant women with sickle cell disease. A review of the literature was performed. Twenty-one articles were identified and included in the analysis. A generalized linear mixed-effects model was used to analyze the outcomes. Pregnancy outcomes assessed were preeclampsia, pneumonia, pyelonephritis, pain crises, intrauterine growth restriction, neonatal death, perinatal death, and maternal mortality. Women who underwent emergent transfusion were more likely than women who underwent prophylactic transfusion to have the following adverse perinatal outcomes: preterm delivery (adjusted odds ratio [aOR 2.04], 95% confidence interval [CI] 1.14-3.63), pneumonia (aOR 2.98, 95% CI 1.44-6.15), pain crises (aOR 1.67, 95% CI 1.18-2.38), and perinatal death (aOR 1.84, 95% CI 1.06-3.07). Prophylactic transfusion should be reexamined as a potentially beneficial approach to the management of sickle cell disease in pregnancy.

To determine if there is a difference in the maternal and perinatal characteristics and outcomes of women undergoing a medically indicated labor induction and delivering vaginally compared to women in spontaneous labor delivering vaginally.This is a planned secondary analysis of previously published data with additional data collected for a case-control design. Maternal and perinatal characteristics and outcomes of women undergoing a medically indicated labor induction of labor and delivering vaginally were compared with the next woman who went into labor spontaneously and delivered vaginally.There were 1097 women in the medically indicated labor group and 1096 women in the spontaneous labor group. The medically indicated induction group was younger (Even with successful vaginal delivery of a medically indicated induction of labor, the risk for adverse outcomes remains elevated.

Purpose To simulate 24-2 visual field (VF) using optical coherence tomographic angiography (OCTA) for glaucoma evaluation. Design Cross-sectional study. Methods One eye each of 39 glaucoma and 31 age-matched normal participants was scanned using 4.5-mm OCTA scans centered on the disc. The peripapillary retinal nerve fiber layer plexus capillary density (NFLP-CD, %area) was measured. The NFLP-CD and 24-2 VF maps were divided into 8 corresponding sectors using an extension of Garway-Heath scheme. Results Sector NFLP-CD was transformed to a logarithmic dB scale and converted to sector simulated VF deviation maps. Comparing simulated and actual 24-2 VF maps, the worst sector was in the same or adjacent location in the same hemisphere 97% of the time. VF mean deviation (VF-MD) was simulated by NFLP mean deviation (NFLP-MD). The differences between NFLP-MD and VF-MD in early, moderate, and severe glaucoma stages were −0.9 ± 2.0, 0.9 ± 2.9, and 5.8 ± 3.2 dB. NFLP-MD had better (P = .015) between-visit reproducibility (0.63 dB pooled standard deviation) than VF-MD (1.03 dB). NFLP-MD had a significantly higher sensitivity than VF-MD (P Conclusions OCTA-based simulated VF agreed well with actual 24-2 VF in terms of both the location and severity of glaucoma damage, with the exception of severe glaucoma in which the simulation tended to underestimate severity. The NFLP-MD had better reproducibility than actual VF-MD and holds promise for improving glaucoma monitoring. The NFLP-MD had better diagnostic accuracy than both VF-MD and overall NFL thickness and may be useful for early glaucoma diagnosis.

PURPOSE: To detect plexus-specific peripapillary retinal perfusion defects in glaucoma using projection-resolved optical coherence tomography angiography (PR-OCTA). DESIGN: Prospective cross-sectional study. METHODS: One eye each of 45 perimetric glaucoma participants and 37 age-matched normal participants were scanned using 4.5-mm OCTA scans centered on the disc. The PR-OCTA algorithm removed flow projection artifacts in OCT angiograms. Five en face OCTA slabs were analyzed: nerve fiber layer plexus (NFLP), ganglion cell layer plexus (GCLP), superficial vascular complex (SVC = NFLP + GCLP), deep vascular complex (DVC), and all plexuses combined. Peripapillary retinal capillary density (CD) and vessel density (VD) were calculated using a reflectance-compensated algorithm. RESULTS: Focal capillary dropout could be visualized more clearly in the NFLP than the other slabs. The NFLP, SVC and all-plexus CD in the glaucoma group were significantly lower (P

Optical coherence tomography (OCT) is widely used in ophthalmic practice because it can visualize retinal structure and vasculature in vivo and 3-dimensionally (3D). Even though OCT procedures yield data volumes, clinicians typically interpret the 3D images using two-dimensional (2D) data subsets, such as cross-sectional scans or en face projections. Since a single OCT volume can contain hundreds of cross-sections (each of which must be processed with retinal layer segmentation to produce en face images), a thorough manual analysis of the complete OCT volume can be prohibitively time-consuming. Furthermore, 2D reductions of the full OCT volume may obscure relationships between disease progression and the (volumetric) location of pathology within the retina and can be prone to mis-segmentation artifacts. In this work, we propose a novel framework that can detect several retinal pathologies in three dimensions using structural and angiographic OCT. Our framework operates by detecting deviations in reflectance, angiography, and simulated perfusion from a percent depth normalized standard retina created by merging and averaging scans from healthy subjects. We show that these deviations from the standard retina can highlight multiple key features, while the depth normalization obviates the need to segment several retinal layers. We also construct a composite pathology index that measures average deviation from the standard retina in several categories (hypo- and hyper-reflectance, nonperfusion, presence of choroidal neovascularization, and thickness change) and show that this index correlates with DR severity. Requiring minimal retinal layer segmentation and being fully automated, this 3D framework has a strong potential to be integrated into commercial OCT systems and to benefit ophthalmology research and clinical care.

Diabetic kidney disease (DKD) develops in 1 in 3 people with type 2 diabetes (T2D) and is the leading cause of end-stage renal disease (ESRD). DKD currently costs the US healthcare system USD 50 billion annually. PromarkerD is a simple biomarker-based blood test that can predict future renal function decline in T2D patients who have no or mild existing DKD (eGFR >30). This study estimated the net savings to US payers from covering the PromarkerD test versus current standard of care (SOC). Model inputs included costs and frequency of testing, costs associated with changes to patient medication strategies, and cost-savings from slowed DKD progression and averted ESRD interventions (dialysis and kidney transplants). All estimates and inputs for the model were collected from recent peer-reviewed literature, established insurance payment rates, and PromarkerD clinical studies. Results showed that over ten years the net savings for US payers by adopting PromarkerD testing for T2D patients (KDIGO DKD category G1-3b) would exceed USD 14 billion and the equilibrium point (costs equal savings) can be achieved after two years. Primarily, savings arise from slower DKD stage progression, with contributions from delayed dialysis and transplants, and also from fewer unplanned dialyses. This economic study demonstrates that improved management of T2D patients through the use of early, accurate and cost-effective prognosis with the PromarkerD test could result in substantial savings to US payers in the treatment of DKD. Employing this alternative PromarkerD testing regime over the current SOC would enable early interventions for at-risk patients, thereby decreasing the need for expensive interventions such as dialysis and transplants, or unnecessary adoption of new therapeutic treatments. Disclosure W. Burchenal: Research Support; Self; Proteomics International. M. Datar: Research Support; Self; Proteomics International. K. E. Peters: Employee; Self; Proteomics International, Stock/Shareholder; Self; Proteomics International. G. C. Fernandez: Employee; Self; Proteomics International, Stock/Shareholder; Self; Proteomics International. J. C. Morrison: Consultant; Self; Proteomics International. R. J. Lipscombe: Employee; Self; Proteomics International.

The segmentation of en face retinal capillary angiograms from volumetric optical coherence tomographic angiography (OCTA) usually relies on retinal layer segmentation, which is time-consuming and error-prone. In this study, we developed a deep-learning-based method to segment vessels in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) directly from volumetric OCTA data. The method contains a three-dimensional convolutional neural network (CNN) for extracting distinct retinal layers, a custom projection module to generate three vascular plexuses from OCTA data, and three parallel CNNs to segment vasculature. Experimental results on OCTA data from rat eyes demonstrated the feasibility of the proposed method. This end-to-end network has the potential to simplify OCTA data processing on retinal vasculature segmentation. The main contribution of this study is that we propose a custom projection module to connect retinal layer segmentation and vasculature segmentation modules and automatically convert data from three to two dimensions, thus establishing an end-to-end method to segment three retinal capillary plexuses from volumetric OCTA without any human intervention.

Introduction Patch graft erosion and implant exposure is a known complication of glaucoma drainage device (GDD) surgery. Recently, electron beam (e-beam) irradiated corneal tissue ha s become available; however, limited data exist on the rates of erosion for e-beam irradiated corneal grafts compared to traditional scleral grafts after GDD surgery. Methods This retrospective study examines the records of 253 eyes from 225 adult subjects who underwent GDD surgery with either e-beam irradiated corneal or scleral grafts at the Casey Eye Institute by five surgeons between April 22, 2014 and October 11, 2017. Surgical procedures and the occurrence of graft erosion were determined using billing codes and verified by manual review of electronic health records. Results The average age at the time of surgery was 61.3 ± 17.5 years (n = 200) and 60.8 ± 16.8 years (n = 53) for the e-beam irradiated cornea and sclera groups, respectively. The average follow-up time post-surgery was 416 ± 345 days and 495 ± 343 days for the e-beam irradiated cornea and sclera groups, respectively. There were no statistically significant differences in sex, age, follow-up time, and glaucoma diagnosis between the groups; however, the e-beam irradiated cornea group was statistically more likely to have an Ahmed implant as compared to the sclera group. No erosion events were noted in either group. Conclusion e-Beam irradiated corneal grafts were used 3.8 times more frequently relative to scleral grafts, yet there were no cases of graft erosion in either group during the follow-up period.

Purpose We previously reported increased expression of cell proliferation and Jak-Stat pathway-related genes in chronic experimental glaucoma model optic nerve heads (ONH) with early, mild injury. Here, we confirm these observations by localizing, identifying, and quantifying ONH cellular proliferation and Jak-Stat pathway activation in this model. Methods Chronic intraocular pressure (IOP) elevation was achieved via outflow pathway sclerosis. After 5 weeks, ONH longitudinal sections were immunolabeled with proliferation and cell-type markers to determine nuclear densities in the anterior (unmyelinated) and transition (partially myelinated) ONH. Nuclear pStat3 labeling was used to detect Jak-Stat pathway activation. Nuclear density differences between control ONH (uninjected) and ONH with either early or advanced injury (determined by optic nerve injury grading) were identified by ANOVA. Results Advanced injury ONH had twice the nuclear density (P < 0.0001) of controls and significantly greater astrocyte density in anterior (P = 0.0001) and transition (P = 0.006) ONH regions. An increased optic nerve injury grade positively correlated with increased microglia/macrophage density in anterior and transition ONH (P < 0.0001, both). Oligodendroglial density was unaffected. In glaucoma model ONH, 80% of anterior and 66% of transition region proliferating cells were astrocytes. Nuclear pStat3 labeling significantly increased in early injury anterior ONH, and 95% colocalized with astrocytes. Conclusions Astrocytes account for the majority of proliferating cells, contributing to a doubled nuclear density in advanced injury ONH. Jak-Stat pathway activation is apparent in the early injury glaucoma model ONH. These data confirm dramatic astrocyte cell proliferation and early Jak-Stat pathway activation in ONH injured by elevated IOP.

We report the development of a 1300 nm swept-source optical coherence tomography (SS-OCT) system specifically designed to perform OCT imaging and optical microangiography (OMAG) in rat eyes in vivo and its use in evaluating the effects of intraocular pressure (IOP) elevation on ocular circulation. The swept laser is operated in single longitude mode with a 90 nm bandwidth centered at 1300 nm and 200 kHz A-line rate, providing remarkable sensitivity fall-off performance along the imaging depth, a larger field of view of 2.5 × 2.5 mm2 (approximately 35°), and more time-efficient imaging acquisition. The advantage of the SS-OCT/OMAG is highlighted by an increased imaging depth of the entire posterior thickness of optic nerve head (ONH) and its surrounding vascular anatomy, to include, for the first time in vivo, the vasculature at the scleral opening, allowing visualization of the circle of Zinn-Haller and posterior ciliary arteries (PCAs). Furthermore, the capillary-level resolution angiograms achieved at the retinal and choroidal layers over a larger field of view enable a significantly improved quantification of the response of vascular area density (VAD) to elevated IOP. The results indicate that reduction in perfusion of the choroid in response to elevated IOP is delayed compared to that seen in the retina; while choroidal VAD doesn't reach 50% of baseline until ~70 mmHg, the same effect is seen for the retinal VAD at ~60 mmHg. The superior image quality offered by SS-OCT may allow more comprehensive investigation of IOP-related ocular perfusion changes and their pathological roles in glaucomatous optic nerve damage.

OBJECTIVE To compare pregnancy outcomes in women with sickle cell disease from recent deliveries with a similar group delivered earlier. METHODS During a 12-year period (2005-2016), data from pregnant women with hemoglobin SS or SC were collected from three university medical centers and compared with earlier studies (1979-2003) involving similar patients. The primary endpoints were maternal complications during pregnancy and newborn outcomes. RESULTS There were 278 patients in the control group (1979-2003) compared with 150 patients in the study group (2005-2016). Women in the study group were older (P < 0.0001) and of less parity (P =0.0001), and complications of preterm delivery, preeclampsia, and having a transfusion were similar between the two groups (P = 0.45, 0.95, and 0.49, respectively). Pain crises were more common in the study group (P = 0.02) as was cesarean section (P < 0.0001), but there was a reduction in pulmonary complications (P = 0.0002). Maternal mortality was uncommon (control group [N=4] vs study group [N=3], P = 0.40). Newborn statistics revealed a similar gestational age at delivery (37 weeks), and the incidence of intrauterine growth restriction, as well as 5-minute Apgar score

Glaucoma is the second leading cause of blindness worldwide and is characterized by the death of retinal ganglion cells (RGCs), the cells that send vision information to the brain. Their axons exit the eye at the optic nerve head (ONH), the main site of damage in glaucoma. The importance of biomechanics in glaucoma is indicated by the fact that elevated intraocular pressure (IOP) is a causative risk factor for the disease. However, exactly how biomechanical insult leads to RGC death is not understood. Although rat models are widely used to study glaucoma, their ONH biomechanics have not been characterized in depth. Therefore, we aimed to do so through finite element (FE) modeling. Utilizing our previously described method, we constructed and analyzed ONH models with individual-specific geometry in which the sclera was modeled as a matrix reinforced with collagen fibers. We developed eight sets of scleral material parameters based on results from our previous inverse FE study and used them to simulate the effects of elevated IOP in eight model variants of each of seven rat ONHs. Within the optic nerve, highest strains were seen inferiorly, a pattern that was consistent across model geometries and model variants. In addition, changing the collagen fiber direction to be circumferential within the peripapillary sclera resulted in more pronounced decreases in strain than changing scleral stiffness. The results from this study can be used to interpret data from rat glaucoma studies to learn more about how biomechanics affects RGC pathogenesis in glaucoma.

Purpose: To evaluate nerve fiber layer (NFL) reflectance for glaucoma diagnosis. Methods: Participants were imaged with 4.5X4.5-mm volumetric disc scans using spectral-domain optical coherence tomography (OCT). The normalized NFL reflectance map was processed by an azimuthal filter to reduce directional reflectance bias due to variation of beam incidence angle. The peripapillary area of the map was divided into 160 superpixels. Average reflectance was the mean of superpixel reflectance. Low-reflectance superpixels were identified as those with NFL reflectance below the 5 percentile normative cutoff. Focal reflectance loss was measure by summing loss in low-reflectance superpixels. Results: Thirty-five normal, 30 pre-perimetric and 35 perimetric glaucoma participants were enrolled. Azimuthal filtering improved the repeatability of the normalized NFL reflectance, as measured by the pooled superpixel standard deviation (SD), from 0.73 to 0.57 dB (p, pages: 31; Tables: 6; Figures: 9

Assessing oxygen saturation (sO 2 ) remains challenging but is nonetheless necessary for understanding retinal metabolism. We and others previously achieved oximetry on major retinal vessels and measured the total retinal oxygen metabolic rate in rats using visible-light optical coherence tomography. Here we extend oximetry measurements to capillaries and investigate all three retinal vascular plexuses by amplifying and extracting the spectroscopic signal from each capillary segment under the guidance of optical coherence tomography (OCT) angiography. Using this approach, we measured capillary sO 2 in the retinal circulation in rats, demonstrated reproducibility of the results, validated the measurements in superficial capillaries with known perfusion pathways, and determined sO 2 responses to hypoxia and hyperoxia in the different retinal capillary beds. OCT capillary oximetry has the potential to provide new insights into the retinal circulation in the normal eye as well as in retinal vascular diseases.

We present how chamber background pressure affects energetic proton acceleration from an ultra-intense laser incident on a thin liquid target. A high-repetition-rate (100 Hz), 3.5 mJ laser with peak intensity of $$8 \times 10^{18}\,\text {Wcm}^{-2}$$ 8 × 10 18 Wcm - 2 impinged on a 450 nm sheet of flowing liquid ethylene glycol. For these parameters, we experimentally demonstrate a threshold in laser-to-proton conversion efficiency at background pressures $$< 8\,\text {Torr}$$ < 8 Torr , wherein the overall energy in ions $$>1\,\text {MeV}$$ > 1 MeV increases by an order of magnitude. Proton acceleration becomes increasingly efficient at lower background pressures and laser-to-proton conversion efficiency approaches a constant as the vacuum pressure decreases. We present two-dimensional particle-in-cell simulations and a charge neutralization model to support our experimental findings. Our experiment demonstrates that high vacuum is not required for energetic ion acceleration, which relaxes target debris requirements and facilitates applications of high-repetition rate laser-based proton accelerators.

Purpose MicroRNAs (miRNAs) are small, endogenous noncoding RNAs that have been detected in human aqueous humor (AH). Prior studies have pooled samples to obtain sufficient quantities for analysis or used next-generation sequencing. Here, we used PCR arrays with preamplification to identify and compare miRNAs from individual AH samples between patients with primary open-angle glaucoma (POAG) and normal controls. Methods AH was collected before cataract surgery from six stable, medically treated POAG patients and eight age-matched controls. Following reverse transcription and preamplification, individual patient samples were profiled on Taqman Low Density MicroRNA Array Cards. Differentially expressed miRNAs were stratified for fold changes larger than ±2 and for significance of P < 0.05. Significant Kyoto Encyclopedia of Genes and Genomes pathways influenced by the differentially expressed miRNAs were identified using the predicted target module of the miRWalk 2.0 database. Results This approach detected 181 discrete miRNAs, which were consistently expressed across all samples of both experimental groups. Significant up-regulation of miR-518d and miR-143, and significant down-regulation of miR-660, was observed in the AH of POAG patients compared with controls. These miRNAs were predicted to reduce cell proliferation and extracellular matrix remodeling, endocytosis, Wnt signaling, ubiquitin-mediated proteolysis, and adherens junction function. Conclusions This pilot study demonstrates that miRNA expression within the AH of POAG patients differs from age-matched controls. AH miRNAs exhibit potential as biomarkers of POAG, which merits further investigation in a larger case-controlled study. This technique provides a cost-effective and sensitive approach to assay miRNAs in individual patient samples without the need for pooling.

In this work, we develop a robust, extensible tool to automatically and accurately count retinal ganglion cell axons in optic nerve (ON) tissue images from various animal models of glaucoma. We adapted deep learning to regress pixelwise axon count density estimates, which were then integrated over the image area to determine axon counts. The tool, termed AxoNet, was trained and evaluated using a dataset containing images of ON regions randomly selected from whole cross sections of both control and damaged rat ONs and manually annotated for axon count and location. This rat-trained network was then applied to a separate dataset of non-human primate (NHP) ON images. AxoNet was compared to two existing automated axon counting tools, AxonMaster and AxonJ, using both datasets. AxoNet outperformed the existing tools on both the rat and NHP ON datasets as judged by mean absolute error, R2 values when regressing automated vs. manual counts, and Bland-Altman analysis. AxoNet does not rely on hand-crafted image features for axon recognition and is robust to variations in the extent of ON tissue damage, image quality, and species of mammal. Therefore, AxoNet is not species-specific and can be extended to quantify additional ON characteristics in glaucoma and potentially other neurodegenerative diseases.

We report on design and construction of a high nanosecond and picosecond contrast kHz dual chirp pulse amplification (DCPA) system with >15 mJ/pulse, pulse duration < 35 fs, for developing an efficient MeV ion acceleration and fast neutron source.

PURPOSE: To measure low perfusion areas (LPA) and focal perfusion loss (FPL) in the peripapillary retina using optical coherence tomographic angiography (OCTA) in glaucoma. DESIGN: Prospective observation study. PARTICIPANTS: Forty-seven primary open angle glaucoma (POAG) patients and 36 normal subjects were analyzed. METHODS: One eye of each subject was scanned using AngioVue 4.5-mm OCTA scan centered on the disc. En face nerve fiber layer plexus angiogram was generated. With the use of custom software, a capillary density map was obtained by computing the fraction of area occupied by flow pixels after low-pass filtering by local averaging 21×21 pixels. The low-perfusion map is defined by local capillary density below 0.5 percentile over a contiguous area above 98.5 percentile of the normal reference population. The LPA parameter is the cumulative area and FPL is the percent capillary density loss (relative to normal mean) integrated over the LPA. The retinal nerve fiber layer (NFL) thickness was measured from ONH scan on AngioVue. MAIN OUTCOME MEASURES: Peripapillary retinal LPA, FPL and NFL thickness. RESULTS: Among POAG patients, 3 had pre-perimetric glaucoma and 44 had perimetric glaucoma, with visual field (VF) mean deviation (MD) of −5.14 ± 4.25 dB. LPA was 3.40 ± 2.29 mm(2) in POAG and 0.11 ± 0.18 mm(2) among normal subjects (P < 0.001). FPL was 21.8 ± 17.0 % in POAG and 0.3 ± 0.7% in normal subjects (P < 0.001). The diagnostic accuracy as measured by the area under the receiver operating curve was 0.965 for both LPA and FPL, with sensitivity of 93.7% at 95% specificity. The repeatability as measured by intraclass correlation coefficient was 0.977 for LPA and 0.958 for FPL. FPL had an excellent correlation with VF MD (Spearman’s rho= −0.843) which was significantly (P = 0.008) better than the correlation between NFL thickness and VF MD (rho = 0.760). The hemispheric difference correlation between FPL and VF (Spearman’s rho=0.770) was significantly (P < 0.001) higher than the hemispheric difference correlation between LPA and VF (rho = 0.595). CONCLUSIONS: The low-perfusion map and the LPA and FPL parameters are able to assess the location and severity of focal glaucoma damage with good agreement with VF.

Defocusing, vignetting, and bulk motion degrade the image quality of optical coherence tomography angiography (OCTA) more significantly than structural OCT. The assessment of focus, alignment conditions, and stability of imaging subjects in commercially available OCTA systems are currently based on OCT signal quality alone, without knowledge of OCTA signal quality. This results in low yield rates for further quantification. In this Letter, we developed a novel OCTA platform based on a graphics processing unit (GPU) for a real-time, high refresh rate, B-san-by-B-scan split-spectrum amplitude-decorrelation angiography. The GPU provides a real-time display of both cross-sectional and en face images to assist operators during scan acquisition and ensure OCTA scan quality.

An adequately sized placenta at a suitable site with appropriate depth and centripetal progression of implantation are the major factors for optimal fetal development. The cytotrophoblasts surround the blastocyst fuses at the site of the uterine attachment. This forms a second layer of multinucleated syncytiotrophoblasts that constitutes the inner epithelial boundary of the chorionic villous against the intervillous space. In a normal pregnancy, extravillous cytotrophoblasts (EVT) invade and obstruct the spiral arteries and remodel them. Vacuoles in the syncytial cell layer fuse and develop the intervillous space. The inner cell mass (embryoblast) gives rise to the umbilical cord and the mesenchyme in the chorionic villi. Vasculogenesis starts with the formation of hemangioblastic cords in this mesenchyme. The trophoblastic cell columns anchor the placenta. A variety of molecular pathways participate in the placentation process. Placental morphogenesis occurs mainly through complex cellular interactions between the chorionic villous and the extravillous cytotrophoblasts. The formation of the normal structure of the chorionic villi, syncytiotrophoblast layer and vasculature is essential for placental function, hormone production, and regulation of fetal growth. At each stage of placental development, genetic variants, exposure to infection, poor vascular function, oxidative stress, or failure of normal development can all lead to abnormal formation resulting in the clinical complications of pregnancy such as fetal growth disorders, neonatal neurologic abnormalities, placental adhesions, and inflammatory problems as well as maternal disease such as preeclampsia.

Optical coherence tomographic angiography (OCTA) is a novel technology capable of imaging retinal vasculature three-dimensionally at capillary scale without the need to inject any extrinsic dye contrast. However, projection artifacts cause superficial retinal vascular patterns to be duplicated in deeper layers, thus interfering with the clean visualization of some retinal plexuses and vascular pathologies. Projection-resolved OCTA (PR-OCTA) uses post-processing algorithms to reduce projection artifacts. With PR-OCTA, it is now possible to resolve up to 4 distinct retinal vascular plexuses in the living human eye. The technology also allows us to detect and distinguish between various retinal and optic nerve diseases. For example, optic nerve diseases such as glaucoma primarily reduces the capillary density in the superficial vascular complex, which comprises the nerve fiber layer plexus and the ganglion cell layer plexus. Outer retinal diseases such as retinitis pigmentosa primarily reduce the capillary density in the deep vascular complex, which comprises the intermediate capillary plexus and the deep capillary plexus. Retinal vascular diseases such as diabetic retinopathy and vein occlusion affect all plexuses, but with different patterns of capillary loss and vascular malformations. PR-OCTA is also useful in distinguishing various types of choroidal neovascularization and monitoring their response to anti-angiogenic medications. In retinal angiomatous proliferation and macular telangiectasia type 2, PR-OCTA can trace the pathologic vascular extension into deeper layers as the disease progress through stages. Plexus-specific visualization and measurement of retinal vascular changes are improving our ability to diagnose, stage, monitor, and assess treatment response in a wide variety of optic nerve and retinal diseases. These applications will be further enhanced with the continuing improvement of the speed and resolution of the OCT platforms, as well as the development of software algorithms to reduce artifacts, improve image quality, and make quantitative measurements.

PURPOSE We investigated the feasibility of glaucoma detection by measuring retinal surface contour variability (RSCV) using optical coherence tomography (OCT). METHODS The peripapillary region in one eye of each participant was scanned over an 8 × 8 mm area with a swept source OCT prototype. The retinal surface contour was sampled at approximately 1.5- to 3.5-mm radius circles centered on the optic nerve head. The RSCV is defined as the average log value within a middle spatial frequency band of the Fourier transform to the elevation profile of the inner retinal surface. The spatial frequency band was optimized to distinguish glaucoma from normal. Nerve fiber layer thickness (NFLT) was sampled around a 1.7-mm radius circle. Glaucoma severity was assessed by automated static perimetry. RESULTS We enrolled 17 glaucomatous eyes and 17 healthy eyes. A great majority of the glaucoma group were in the early stage (visual field mean deviation average -2.48 ± 3.73 dB). Significant differences were found for RSCV between glaucoma and control eyes (P < 0.003) at all radii. The area under the receiver operating characteristic curve (AROC = 0.90) of RSCV was best at the 3.5-mm radius. This was not significantly better than NFLT (AROC = 0.84). With the 99% specificity, the glaucoma detection sensitivity was 53% for RSCV and 29% for NFLT (P = 0.13). CONCLUSIONS Retinal surface contour variability was significantly increased in glaucoma patients. The diagnostic accuracy of RSCV was equal to NFLT in early glaucoma. Since the RSCV detects small-scale focal damage and the average NFLT measures global damage, they provide different diagnostic information that may be synergistic.

PURPOSE: To characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG). METHODS: Unilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONHs with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons. RESULTS: Expansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (p < 0.0022), and in 7 of 8 EG eyes (p < 0.005). In at least 5 EG eyes, significant expansions (p < 0.005) in Bruch's membrane opening (BMO) (range 3-10%), the anterior and posterior scleral canal openings (8-21% and 5-21%, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11-30% and 8-41%, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (R = 0.768, p = 0.042). CONCLUSION: In the rat ONH, the optic nerve and surrounding BMO and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye. Supported in part by NIH grants R01EY011610 (CFB), R01EY10145 (JCM) and R01EY16866 (ECJ)) from the National Eye Institute, National Institutes of Health, Bethesda, Maryland; The Legacy Good Samaritan Foundation, Portland, Oregon; the Sears Trust for Biomedical Research, Mexico, Missouri; the Alcon Research Institute, Fort Worth, Texas; and an unrestricted grant from Research to Prevent Blindness.

The length of the third stage of labor is an important risk factor for postpartum hemorrhage (PPH). Current practice recommends manual placenta removal, if not delivered spontaneously, within 30 min. The review reexamines the evidence to determine the optimal length of the third stage of labor.A MEDLINE search that associated the length of the third stage of labor with the risk of PPH was undertaken.A retrospective cohort study revealed the risk of a PPH became significant at 10 min (odds ratio = 2.1, 95% confidence interval: 1.6-2.6), and had doubled by 20 min (odds ratio = 4.3, 95% confidence interval: 3.3-5.5). A receiver operator curve determined the optimal length of the third stage of labor to prevent PPH was 18 min. A follow up randomized controlled trial showed that hemodynamic compromise secondary to a PPH can be reduced with manual placenta removal at 10 compared to 15 min (6.4 versus 19.2%, p = 0.001).The time interval of 15 min may be a more appropriate time interval to recommend placental removal to prevent PPH.

In order to solve the partial differential equations that arise in the Hartree- Fock theory for diatomicmolecules and inmolecular theories that include electron correlation, one needs efficient methods for solving partial differential equations. In this article, we present numerical results for a two-variablemodel problem of the kind that arises when one solves the Hartree-Fock equations for a diatomic molecule. We compare results obtained using the spline collocation and domain decomposition methods with third-order Hermite splines to results obtained using the more-established finite difference approximation and the successive over-relaxation method. The theory of domain decomposition presented earlier is extended to treat regions that are divided into an arbitrary number of subregions by families of lines parallel to the two coordinate axes. While the domain decomposition method and the finite difference approach both yield results at the micro-Hartree level, the finite difference approach with a 9- point difference formula produces the same level of accuracy with fewer points. The domain decompositionmethod has the strength that it can be applied to problemswith a large number of grid points. The time required to solve a partial differential equation for a fine grid with a large number of points goes down as the number of partitions increases. The reason for this is that the length of time necessary for solving a set of linear equations in each subregion is very much dependent upon the number of equations. Even though a finer partition of the region has more subregions, the time for solving the set of linear equations in each subregion is very much smaller. This feature of the theory may well prove to be a decisive factor for solving the two-electron pair equation, which – for a diatomic molecule – involves solving partial differential equations with five independent variables. The domain decomposition theory also makes it possible to study complex molecules by dividing them into smaller fragments that are calculated independently. Since the domain decomposition approachmakes it possible to decompose the variable space into separate regions in which the equations are solved independently, this approach is well-suited to parallel computing.

Injection of hypertonic saline via episcleral veins toward the limbus in laboratory rats can produce elevated intraocular pressure (IOP) by sclerosis of aqueous humor outflow pathways. This article describes important anatomic characteristics of the rat optic nerve head (ONH) that make it an attractive animal model for human glaucoma, along with the anatomy of rat aqueous humor outflow on which this technique is based. The injection technique itself is also described, with the aid of a supplemental movie, including necessary equipment and specific tips to acquire this skill. Outcomes of a successful injection are presented, including IOP elevation and patterns of optic nerve injury. These concepts are then specifically considered in light of the use of this model to assess potential neuroprotective therapies. Advantages of the hypertonic saline model include a delayed and relatively gradual IOP elevation, likely reproduction of scleral and ONH stresses and strains that may be important in producing axonal injury, and its ability to be applied to any rat (and potentially mouse) strain, leaving the unmanipulated fellow eye as an internal control. Challenges include the demanding surgical skill required by the technique itself, a wide range of IOP response, and mild corneal clouding in some animals. However, meticulous application of the principles detailed in this article and practice will allow most researchers to attain this useful skill for studying cellular events of glaucomatous optic nerve damage.

In vivo high-resolution images are the most direct way to understand retinal function and diseases. Here we report the use of visible-light optical coherence tomography with volumetric registration and averaging to achieve cellular-level retinal structural imaging in a rat eye, covering the entire depth of the retina. Vitreous fibers, nerve fiber bundles, and vasculature were clearly revealed, as well as at least three laminar sublayers in the inner plexiform layer. We also successfully visualized ganglion cell somas in the ganglion cell layer, cells in the inner nuclear layer, and photoreceptors in the outer nuclear layer and ellipsoid zone. This technique provides, to the best of our knowledge, a new means to visualize the retina in vivo at a cellular resolution and may enable detection or discovery of cellular neuronal biomarkers to help better diagnose ocular disease.

Visible light optical coherence tomography (vis-OCT) is an emerging label-free and high-resolution 3-dimensional imaging technique that can provide retinal oximetry, angiography, and flowmetry in one modality. In this paper, we studied the organization of the arterial and venous retinal circulation in rats using vis-OCT. Arterioles were found predominantly in the superficial vascular plexus whereas veins tended to drain capillaries from the deep capillary plexus. After that, we determined the oxygen metabolic rate supported by retinal microcirculation by combining retinal vessel oxygen saturation and blood flow measurements. The ability to visualize and monitor retinal circulation organization and oxygen metabolism by vis-OCT may provide new opportunities for understanding the pathology of ocular diseases.

Oxidative stress is a consequence of reduction in the antioxidant capacity and excessive production of reactive oxygen and nitrogen species (ROS). Oxidative agents, which are overproduced due to ischemic-reperfusion injury in the placenta, may overwhelm the normal antioxidant activity. This imbalance is a key feature in the pathogenesis of preeclampsia. A decrease in glutathione peroxidase (GPX) activity is associated with the synthesis of vasoconstrictive eicosanoids such as F2-isoprostanes and thromboxane, which are known to be upregulated in preeclampsia. Biochemical markers of lipid peroxidation, such as malondialdehyde and F2-isoprostane in the placenta, are also increased. Adhesion molecules participate in the pathophysiology of preeclampsia by contributing to a reduced invasion by the trophoblast and increased vascular endothelial damage. Superoxide dismutase (SOD), catalase (CAT) and GPX play important roles counteracting oxidative stress. Other antioxidant factors participate in the etiology of preeclampsia. Levels of antioxidants such as Lycopene, Coenzyme 10, as well as some vitamins, are reduced in preeclamptic gestations.

Phase-based optical coherence tomography (OCT), such as OCT angiography (OCTA) and Doppler OCT, is sensitive to the confounding phase shift introduced by subject bulk motion. Traditional bulk motion compensation methods are limited by their accuracy and computing cost-effectiveness. In this Letter, to the best of our knowledge, we present a novel bulk motion compensation method for phase-based functional OCT. Bulk motion associated phase shift can be directly derived by solving its equation using a standard deviation of phase-based OCTA and Doppler OCT flow signals. This method was evaluated on rodent retinal images acquired by a prototype visible light OCT and human retinal images acquired by a commercial system. The image quality and computational speed were significantly improved, compared to two conventional phase compensation methods.

Accurate, quantitative assessment of retinal blood oxygen saturation (sO2 ) may provide a useful early indicator of pathophysiology in several ocular diseases. Here, with visible-light optical coherence tomography (OCT), we demonstrate an automated spectroscopic retinal oximetry algorithm to measure the sO2 within the retinal arteries (A-sO2 ) and veins (V-sO2 ) in rats by automatically detecting the vascular posterior boundary on cross-sectional structural OCT. The algorithm was validated in vitro with flow phantoms and in vivo in rats by comparing the sO2 results, respectively, to those obtained using a blood gas analyzer and pulse oximetry. We also investigated the response of oxygen extraction (A-V sO2 ), including inter-session reproducibility, at different inhaled oxygen concentrations.

Small molecule delivery to the optic nerve would allow for exploration of molecular and cellular pathways involved in normal physiology and optic neuropathies such as glaucoma, and provide a tool for screening therapeutics in animal models. We report a novel surgical method for small molecule drug delivery to the optic nerve head (ONH) in a rodent model. In proof-of-principle experiments, we delivered cytochalasin D (Cyt D; a filamentous actin inhibitor) to the junction of the superior optic nerve and globe in rats to target the actin-rich astrocytic cytoskeleton of the ONH. Cyt D delivery was quantified by liquid chromatography and mass spectrometry of isolated optic nerve tissue. One day after Cyt D delivery, anterior ONH filamentous actin bundle content was significantly reduced as assessed by fluorescent-tagged phalloidin labeling, relative to sham delivery. Anterior ONH nuclear counts and axon-specific beta-3 tubulin levels, as well as peripapillary retinal ganglion cell layer nuclear counts were not significantly altered after Cyt D delivery relative to sham delivery. Lastly, the surgical delivery technique caused minimal observable axon degeneration up to 10 days post-surgery. This small molecule delivery technique provides a new approach to studying optic neuropathies in in vivo rodent models.

The Hartree–Fock theory for diatomic molecules and a theoretical approach for performing many-body calculations are described. Using single-electron wave functions and energies produced by a numerical Hartree–Fock program, the Goldstone diagrams that arise in a perturbation expansion of the energy are evaluated by expressing the Goldstone diagrams in terms of pair functions that are the solution of first-order pair equations. The relevant pair equations are discretized and solved using the spline collocation method with a basis of third-order Hermite splines. Both the Hartree–Fock theory and many-body theory are more complex for diatomic molecules than they are for atoms. While the Hartree–Fock equations for atoms involve a single radial variable and the two-electron pair equation for atoms involve two radial variables, the Hartree–Fock equations for diatomic molecules involve two independent variables and the pair equation for diatomic molecules involves five independent variables. To deal with these problems of higher-dimensionality, we have developed numerical methods for dividing the variable space into smaller subregions in which the equations can be solved independently. This domain decomposition theory is described and numerical results are given for a single-electron model problem and for many-body calculations for diatomic molecules. Because the long-range goal of our work is to develop an extensive program for doing numerical coupled-cluster calculations on molecules, we will take special care to show how each part of our numerical approach is tested.

Glaucoma is the leading cause of irreversible blindness and involves the death of retinal ganglion cells (RGCs). Although biomechanics likely contributes to axonal injury within the optic nerve head (ONH), leading to RGC death, the pathways by which this occurs are not well understood. While rat models of glaucoma are well-suited for mechanistic studies, the anatomy of the rat ONH is different from the human, and the resulting differences in biomechanics have not been characterized. The aim of this study is to describe a methodology for building individual-specific finite element (FE) models of rat ONHs. This method was used to build three rat ONH FE models and compute the biomechanical environment within these ONHs. Initial results show that rat ONH strains are larger and more asymmetric than those seen in human ONH modeling studies. This method provides a framework for building additional models of normotensive and glaucomatous rat ONHs. Comparing model strain patterns with patterns of cellular response seen in studies using rat glaucoma models will help us to learn more about the link between biomechanics and glaucomatous cell death, which in turn may drive the development of novel therapies for glaucoma.

A reliable method of creating chronic elevation of intraocular pressure (IOP) in rodents is an important tool in reproducing and studying the mechanisms of optic nerve injury that occur in glaucoma. In addition, such a model could provide a valuable method for testing potential neuroprotective treatments. This paper outlines the basic methods for producing obstruction of aqueous humor outflow and IOP elevation by injecting hypertonic saline (a sclerosant) into the aqueous outflow pathway. This is one of several rodent glaucoma models in use today. In this method, a plastic ring is placed around the equator of the eye to restrict injected saline to the limbus. By inserting a small glass microneedle in an aqueous outflow vein in the episclera and injecting hypertonic saline toward the limbus, the saline is forced into Schlemm's canal and across the trabecular meshwork. The resultant inflammation and scarring of the anterior chamber angle occurs gradually, resulting in a rise in IOP after approximately 1 week. This article will describe the equipment necessary for producing this model and the steps of the technique itself.