Practical Utility of Widefield OCT Angiography to Detect Retinal Neovascularization in Eyes with Proliferative Diabetic Retinopathy.

PURPOSE: To assess the real clinical utility of widefield OCT angiography (WF-OCTA) for detecting retinal neovascularization (RNV) in eyes with proliferative diabetic retinopathy (PDR). DESIGN: A retrospective cross sectional study. PARTICIPANTS: Consecutive eyes clinically suspected of PDR by physicians at a tertiary eye center between March 2021 and November 2022. METHODS: All eyes underwent ultrawidefield fluorescein angiography (UWF-FA) (California, Optos) and WF-OCTA (S1, Canon) with a 23 × 20 mm scan area. Two independent graders detected individual RNV lesions using UWF-FA and used them as the ground truth. Widefield OCT angiography images were first evaluated to determine whether the images successfully illustrated retinal vasculature, regardless of the image quality index or the presence of vitreous hemorrhage. The graders then identified the RNV lesions with WF-OCTA. We detected RNV by utilizing both the entire retinal slab, including flow signals in the retina, and the custom vitreoretinal interface slab, defined as flow signals from 20 µm below the internal limiting membrane (ILM) to 2000 µm above the ILM. We evaluated the applicability to real clinical practice by not correcting segmentation errors. MAIN OUTCOME MEASURES: The success rate of imaging and the detection rate of RNV using WF-OCTA. RESULTS: Initially, 69 consecutive patients who underwent UWF-FA were identified. Of these, 114 eyes from 57 (83%) patients underwent both UWF-FA and WF-OCTA. Of the 114 eyes, 108 (95%) produced gradable WF-OCTA images. Using UWF-FA, the graders identified 175 RNV lesions in 40 eyes. Widefield OCT angiography achieved a sensitivity of 95% and specificity of 88% for detecting eyes with RNV. At the level of individual RNV lesions, graders detected 156 RNV lesions with WF-OCTA, with 118 of these confirmed by UWF-FA (true positive). Among the 57 false-negative lesions, the primary causes were being out of the scan range (26 lesions) and segmentation errors (21 lesions). CONCLUSIONS: Widefield OCT angiography imaging had a high success rate, achieving a sensitivity of 95% and a specificity of 88% for detecting eyes with RNV in a real clinical setting. Despite a 67% detection rate for individual RNV lesions, WF-OCTA may serve as a valuable noninvasive method for RNV detection in eyes with diabetic retinopathy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Greater Impact of Paternal, Compared to Maternal, Hereditary Background on Depressive-Like Behavior in Wistar Kyoto Rats with Different Amino Acid Metabolism in the Pup Brain.

In the pathogenesis of depression, heredity is believed to be a major factor. However, the mechanism by which heredity contributes to the onset of depression is not fully understood. Wistar Kyoto (WKY) rats have been used as an animal model for depression because of their increased depression-like behavior compared to Wistar (WIS) rats. In the present study, pups crossbred from WKY × WIS rats were used to evaluate locomotor activity in an open field test (OFT) and depression-like behavior in a forced swimming test (FST), with a focus on amino acid metabolism. Pups in the WKY♂ × WKY♀ group showed lower locomotor activity in the OFT and higher depression-like behavior in the FST than those in the WIS♂ × WIS♀ group. In addition, multiple regression analysis showed that the paternal strain had a greater effect than the maternal strain on locomotor activity and depression-like behavior in OFT and FST, respectively. Several amino acids in the brainstem, hippocampus, and striatum were significantly decreased through the influence of the WKY paternal strain, but not the WKY maternal strain. Based on these data from comparing WKY and WIS rats, we hypothesize that the hereditary effects of the WKY paternal strain on behavioral tests are partially caused by dysregulation of the amino acid metabolism in the brain.

Dysregulated metabolism and behaviors by disrupting gut microbiota in prenatal and neonatal mice.

The live microbiota ecosystem in the intestine plays a critical role in maintaining the normal physiological and psychological functions in both animals and human beings. However, the chronic effect of microbiota disturbances during prenatal and neonatal developing periods on animal's health remains less studied. In the current study, pregnant ICR mice were fed with an antibiotic diet (7-g nebacitin [bacitracin-neomycin sulphate 2:1]/kg standard diet) from day 14 of conception, and their offspring were provided with the same diet till the termination of the experiments. Dams treated with antibiotics showed increased body weight along with enlarged gut. Antibiotic-treated offspring revealed decreased bodyweight, increased food, water, and sucrose intake. Administration of antibiotics affected corticosterone responsivity to acute 20 min restraint challenge in male pups. In behavior tests, female pups showed decreased movement in open field while male pups revealed decreased latency to open arms in elevated plus maze test and immobility time in tail suspension test. Together, these results suggested that early antibiotic exposure may impact on the food intake, body weight gain, and emotional behavior regulation in mice.

Effects of Baerveldt Glaucoma Implant Surgery on Corneal Endothelial Cells of Patients with No History of Trabeculectomy.

PURPOSE: Persistent corneal edema is a serious potential complication of Baerveldt glaucoma implant (BGI) surgery. A trabeculectomy reduces the density of corneal endothelial cells. We investigated the effect of BGI surgery on corneal endothelial cells of patients with no history of trabeculectomy. METHODS: We retrospectively analyzed 85 eyes of 85 patients who underwent BGI surgery and were followed-up for ≥12 months. We used new criteria for surgical failure. We defined persistent corneal edema or needed additional surgery for changing the tube position due to remarkable reduction in corneal endothelial cells as failure. We compared surgical outcomes with new criteria and the rates of corneal endothelial cell density (ECD) loss after BGI surgery between the anterior chamber insertion (AC) group (n=23) and vitreous cavity insertion (VC) group (n=63). RESULTS: The mean pre-operative ECD values of the AC and VC groups were not significantly different at 2309 ± 498 and 2204 ± 556 (p=0.426). The ECD reduction rate in the AC group was significantly faster than in the VC group. The mean post-operative IOP values significantly decreased in both groups. However, the VC group's surgical outcomes were significantly better than the AC group's (p=0.0241) with the new criteria. CONCLUSION: The mean of ECD did not decrease significantly after BGI surgery in VC group patients with no history of trabeculectomy. BGI surgery insertion to the vitreous cavity was safe and had much less effect on the ECD decrease compared to insertion to the anterior chamber.

Differences in free amino acid concentrations in milk between Wistar and Wistar Kyoto rats.

Wistar Kyoto (WKY) rats, an animal depression model, display abnormal behaviors such as hypoactivity and depression-like behavior compared with Wistar (WIS) rats as a control. A previous study confirmed a dysfunction of amino acid metabolism in the brain of WKY rats compared with that of WIS rats. At the neonatal stage, free amino acids in milk are important nutrients because they act as immediate nutrients for offspring and may affect later health and behavior of the offspring. Therefore, the present study aimed to investigate free amino acid concentrations in milk and the relationships between free amino acid concentrations in milk and plasma in WIS and WKY rats. The concentrations of ten of the determined free amino acids in milk were significantly higher, but only L-methionine was significantly lower, in WKY rats. Six free amino acids had significantly higher concentrations in colostrum and two free amino acids had higher concentrations in matured milk. Free amino acid concentrations in plasma changed by both genetic background and lactation stage; however, the patterns of change in most free amino acid concentrations except for taurine in plasma were similar between WIS and WKY rats. The transport ratio of free amino acids from plasma to milk was not similar among the free amino acids tested, and each free amino acid was influenced by the genetic background and/or the type of milk.

Decreased stress-induced depression-like behavior in lactating rats is associated with changes in the hypothalamic-pituitary-adrenal axis, brain monoamines, and brain amino acid metabolism.

Depression-like behavior during lactation may relate to changes in the hypothalamic-pituitary-adrenal (HPA) axis, brain monoamines, and brain amino acid metabolism. This study investigated how the behavior, HPA axis activity, brain monoamines, and brain free amino acid metabolism of rats were changed by stress or lactation period. Rats were separated into four groups: (1) control lactating (n = 6), (2) stress lactating (n = 6), (3) control virgin (n = 7), and (4) stress virgin (n = 7) and restrained for 30 min a total of ten times (once every other day) from postnatal day (PND) 1. Depression-like behavior in the forced swimming test (FST) on PND 10 and concentration of corticosterone in plasma, as well as monoamines and L-amino acids including ß-alanine, γ-aminobutyric acid, cystathionine, 3-methyl-histidine and taurine in the prefrontal cortex and hypothalamus on PND 19 were measured. The plasma corticosterone concentration, measured just after restraint stress, was significantly higher in the stress groups, versus the control groups, but there were no significant differences between control and stress lactating groups. Depression-like behavior (immobility) in the FST was significantly lower in the lactating groups, versus the virgin groups. Stress enhanced dopamine and glutamate, and decreased threonine and glycine concentrations in the hypothalamus. In addition, 3-methoxy-4-hydroxyphenylglycol (MHPG), threonine and ornithine concentrations in the prefrontal cortex were significantly higher in the lactating groups compared with the virgin groups. Changes in plasma corticosterone concentration, monoamine, and amino acid metabolism may relate to stress-induced depression-like behavior in lactating rats. Lay summary This study revealed that reduced depression-like behavior in lactating, relative to virgin rats, was associated with changes in monoamine and amino acid metabolism in the prefrontal cortex of the brain. In addition, the effect of stress on monoamine and amino acid metabolism is prominently observed in the hypothalamus and may be related to neuroendocrine stress axis activity and secretion of corticosterone. This study suggested that stress-induced depression-like behavior may be associated with several changes in the stress axis, brain monoamines, and brain amino acid metabolism. These parameters were associated with attenuated depression-like behavior in lactating rats.