BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade.

Aims: Retinal ischemia/reperfusion (I/R) injury is implicated in the etiology of various ocular disorders. Prior research has demonstrated that bone marrow tyrosine kinase on chromosome X (BMX) contributes to the advancement of ischemic disease and inflammatory reactions. Consequently, the current investigation aims to evaluate BMX's impact on retinal I/R injury and clarify its implied mechanism of action. Main methods: This study utilized male and female systemic BMX knockout (BMX-/-) mice to conduct experiments. The utilization of Western blot assay and immunofluorescence labeling techniques was employed to investigate variations in the expression of protein and tissue localization. Histomorphological changes were observed through H&E staining and SD-OCT examination. Visual function changes were assessed through electrophysiological experiments. Furthermore, apoptosis in the retina was identified using the TUNEL assay, as well as the ELISA technique, which has been utilized to determine the inflammatory factors level. Key findings: Our investigation results revealed that the knockdown of BMX did not yield a significant effect on mouse retina. In mice, BMX knockdown mitigated the negative impact of I/R injury on retinal tissue structure and visual function. BMX knockdown effectively reduced apoptosis, suppressed inflammatory responses, and decreased inflammatory factors subsequent to I/R injury. The outcomes of the current investigation revealed that BMX knockdown partially protected the retina through downregulating phosphorylation of AKT/ERK/STAT3 pathway. Significance: Our investigation showed that BMX-/- reduces AKT, ERK, and STAT3 phosphorylation, reducing apoptosis and inflammation. Thus, this strategy protected the retina from structural and functional damage after I/R injury.

Setanaxib mitigates oxidative damage following retinal ischemia-reperfusion via NOX1 and NOX4 inhibition in retinal ganglion cells.

Glaucoma, a prevalent cause of permanent visual impairment worldwide, is characterized by the progressive degeneration of retinal ganglion cells (RGCs). NADPH oxidase (NOX) 1 and NOX4 are pivotal nodes in various retinal diseases. Setanaxib, a potent and highly selective inhibitor of NOX1 and NOX4, can impede the progression of various diseases. This study investigated the efficacy of setanaxib in ameliorating retinal ischemia-reperfusion (I/R) injury and elucidated its underlying mechanisms. The model of retinal I/R induced by acute intraocular hypertension and the oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary RGCs were established. By suppressing NOX1 and NOX4 expression in RGCs, setanaxib mitigated I/R-induced retinal neuronal loss, structural disruption, and dysfunction. Setanaxib reduced TUNEL-positive cells, upregulated Bcl-2, and inhibited Bax, Bad, and cleaved-caspase-3 overexpression after I/R injury in vitro and in vivo. Moreover, setanaxib also significantly reduced cellular senescence, as demonstrated by downregulating SA-ß-gal-positive and p16-INK4a expression. Furthermore, setanaxib significantly suppressed ROS production, Hif-1α and FOXO1 upregulation, and NRF2 downregulation in damaged RGCs. These findings highlight that the setanaxib effectively inhibited NOX1 and NOX4, thereby regulating ROS production and redox signal activation. This inhibition further prevents the activation of apoptosis and senescence related factors in RGCs, ultimately protecting them against retinal I/R injury. Consequently, setanaxib exhibits promising potential as a therapeutic intervention for glaucoma.

Effect of high-frequency oscillation on reduction of atelectasis in perioperative patients: a prospective randomized controlled study.

BACKGROUND: Atelectasis affects approximately 90% of anaesthetized patients, with laparoscopic surgery and pneumoperitoneum reported to exacerbate this condition. High-frequency oscillation therapy applies continuous positive pressure pulses to oscillate the airway, creating a pressure difference in small airways obstructed by secretions. This process helps reduce peak airway pressure, open small airways, and decrease atelectasis incidence, while also facilitating respiratory tract clearance. This study examines the efficacy of high-frequency oscillation on reduction of atelectasis in laparoscopic cholecystectomy (LC) patients under general anaesthesia, evaluated using lung ultrasound. METHODS: Sixty-four patients undergoing laparoscopic cholecystectomy were randomly divided into a control group and a high-frequency oscillation (HFO) group. Both groups underwent total intravenous anaesthesia under invasive arterial monitoring. The HFO group received a 10-minute continuous high-frequency oscillation therapy during surgery, while the control group received no intervention. Lung ultrasound evaluations were performed three times: five minutes post-intubation (T1), at the end of the surgery (T2), and before leaving the Post-Anaesthesia Care Unit (PACU; T3). Blood gas analysis was performed twice: prior to induction with no oxygen supply and before PACU discharge (oxygen supply off). RESULTS: The HFO group displayed a significantly lower incidence of atelectasis at T3 (57.5% vs. 90.3%, OR 6.88, 95%CI (1.74 to 27.24)) compared to the control group. Moreover, the HFO group's PaO2 levels remained consistent with baseline levels before PACU discharge, unlike the control group. Although there was no significant difference in LUS scores between the groups at T1 (8.56 ± 0.15 vs. 8.19 ± 0.18, p = 0.1090), the HFO group had considerably lower scores at T2 (13.41 ± 0.17 vs.7.59 ± 0.17, p < 0.01) and T3 (13.72 ± 0.14 vs.7.25 ± 0.21, p < 0.01). CONCLUSION: Our study indicates that high-frequency oscillation effectively reduces atelectasis in patients undergoing laparoscopic cholecystectomy. Additionally, it can mitigate the decline in oxygen partial pressure associated with atelectasis.

Association of glyphosate exposure with multiple adverse outcomes and potential mediators.

Glyphosate (GLY) is a widely used herbicide with potential adverse effects on public health. However, the current epidemiological evidence is limited. This study aimed to investigate the potential associations between exposure to GLY and multiple health outcomes. The data on urine GLY concentration and nine health outcomes, including type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease (CVD), obesity, chronic kidney disease (CKD), hepatic steatosis, cancers, chronic obstructive pulmonary disease (COPD), and neurodegenerative diseases (NGDs), were extracted from NHANES (2013-2016). The associations between GLY exposure and each health outcome were estimated using reverse-scale Cox regression and logistic regression. Furthermore, mediation analysis was conducted to identify potential mediators in the significant associations. The dose-response relationships between GLY exposure with health outcomes and potential mediators were analyzed using restricted cubic spline (RCS) regression. The findings of the study revealed that individuals with higher urinary concentrations of GLY had a higher likelihood of having T2DM, hypertension, CVD and obesity (p < 0.001, p = 0.005, p < 0.001 and p = 0.005, respectively). In the reverse-scale Cox regression, a notable association was solely discerned between exposure to GLY and the risk of T2DM (adjusted HR = 1.22, 95% CI: 1.10, 1.36). Consistent outcomes were also obtained via logistic regression analysis, wherein the adjusted OR and 95% CI for T2DM were determined to be 1.30 (1.12, 1.52). Moreover, the present investigation identified serum high-density lipoprotein cholesterol (HDL) as a mediator in this association, with a mediating effect of 7.14% (p = 0.040). This mediating effect was further substantiated by RCS regression, wherein significant dose-response associations were observed between GLY exposure and an increased risk of T2DM (p = 0.002) and reduced levels of HDL (p = 0.001). Collectively, these findings imply an association between GLY exposure and an increased risk of T2DM in the general adult population.

Association between co-exposure to phenols, phthalates, and polycyclic aromatic hydrocarbons with the risk of frailty.

The phenomenon of population aging has brought forth the challenge of frailty. Nevertheless, the contribution of environmental exposure to frailty remains ambiguous. Our objective was to investigate the association between phenols, phthalates (PAEs), and polycyclic aromatic hydrocarbons (PAHs) with frailty. We constructed a 48-item frailty index using data from the National Health and Nutrition Examination Survey (NHANES). The exposure levels of 20 organic contaminants were obtained from the survey circle between 2005 and 2016. The association between individual organic contaminants and the frailty index was assessed using negative binomial regression models. The combined effect of organic contaminants was examined using weighted quantile sum (WQS) regression. Dose-response patterns were modeled using generalized additive models (GAMs). Additionally, an interpretable machine learning approach was employed to develop a predictive model for the frailty index. A total of 1566 participants were included in the analysis. Positive associations were observed between exposure to MIB, P02, ECP, MBP, MHH, MOH, MZP, MC1, and P01 with the frailty index. WQS regression analysis revealed a significant increase in the frailty index with higher levels of the mixture of organic contaminants (aOR, 1.12; 95% CI, 1.05-1.20; p < 0.001), with MIB, ECP, COP, MBP, P02, and P01 identified as the major contributors. Dose-response relationships were observed between MIB, ECP, MBP, P02, and P01 exposure with an increased risk of frailty (both with p < 0.05). The developed predictive model based on organic contaminants exposure demonstrated high performance, with an R2 of 0.9634 and 0.9611 in the training and testing sets, respectively. Furthermore, the predictive model suggested potential synergistic effects in the MIB-MBP and P01-P02 pairs. Taken together, these findings suggest a significant association between exposure to phthalates and PAHs with an increased susceptibility to frailty.

Identification of dietary components in association with abdominal aortic calcification.

The precise impact of dietary components on vascular health remains incompletely understood. To identify the dietary components and their associations with abdominal aortic calcification (AAC), the data from NHANES was employed in this cross-sectional study. The LASSO method and logistic regression were utilized to identify dietary components that exhibited the strongest association with AAC. Grouped WQS regression analysis was employed to evaluate the combined effects of dietary components on AAC. Furthermore, principal component analysis was employed to identify the primary dietary patterns in the study population. The present analysis included 1862 participants, from whom information on 35 dietary macro- and micronutrient components was obtained through 24-hour dietary recall interviews. The assessment of AAC was performed utilizing dual-energy X-ray absorptiometry. The LASSO method identified 10 dietary components that were associated with AAC. Total protein, total fiber, vitamin A, and ß-cryptoxanthin exhibited a negative association with AAC. Compared to the first quartile, the adjusted odds ratios (95% CIs) for the highest quartile were 0.59 (0.38, 0.93), 0.63 (0.42, 0.93), 0.59 (0.41, 0.84), and 0.68 (0.48, 0.94), respectively. Grouped WQS regression demonstrated a positive association between the lipid group and AAC (aOR: 1.29; 95% CI: 1.12, 1.50), while the proteins and phytochemical group exhibited a negative association with AAC (aOR: 0.69; 95% CI: 0.58, 0.82). For the dietary pattern analysis, high adherence to the plant-based pattern (aOR: 0.62; 95% CI: 0.44, 0.88) was associated with a lower risk of AAC, whereas the caffeine and theobromine pattern (aOR: 1.73; 95% CI: 1.25, 2.41) was associated with a higher risk of AAC. The findings of this study indicate that adopting a dietary pattern characterized by high levels of protein and plant-based foods, as well as reduced levels of fat, may offers potential advantages for the prevention of AAC.

Effects of heavy metal exposure on hypertension: A machine learning modeling approach.

Heavy metal exposure is a common risk factor for hypertension. To develop an interpretable predictive machine learning (ML) model for hypertension based on levels of heavy metal exposure, data from the NHANES (2003-2016) were employed. Random forest (RF), support vector machine (SVM), decision tree (DT), multilayer perceptron (MLP), ridge regression (RR), AdaBoost (AB), gradient boosting decision tree (GBDT), voting classifier (VC), and K-nearest neighbour (KNN) algorithms were utilized to generate an optimal predictive model for hypertension. Three interpretable methods, the permutation feature importance analysis, partial dependence plot (PDP), and Shapley additive explanations (SHAP) methods, were integrated into a pipeline and embedded in ML for model interpretation. A total of 9005 eligible individuals were randomly allocated into two distinct sets for predictive model training and validation. The results showed that among the predictive models, the RF model demonstrated the highest performance, achieving an accuracy rate of 77.40% in the validation set. The AUC and F1 score for the model were 0.84 and 0.76, respectively. Blood Pb, urinary Cd, urinary Tl, and urinary Co levels were identified as the main influencers of hypertension, and their contribution weights were 0.0504 ± 0.0482, 0.0389 ± 0.0256, 0.0307 ± 0.0179, and 0.0296 ± 0.0162, respectively. Blood Pb (0.55-2.93 µg/dL) and urinary Cd (0.06-0.15 µg/L) levels exhibited the most pronounced upwards trend with the risk of hypertension within a specific value range, while urinary Tl (0.06-0.26 µg/L) and urinary Co (0.02-0.32 µg/L) levels demonstrated a declining trend with hypertension. The findings on the synergistic effects indicated that Pb and Cd were the primary determinants of hypertension. Our findings underscore the predictive value of heavy metals for hypertension. By utilizing interpretable methods, we discerned that Pb, Cd, Tl, and Co emerged as noteworthy contributors within the predictive model.

Inhibition of NOX4 with GLX351322 alleviates acute ocular hypertension-induced retinal inflammation and injury by suppressing ROS mediated redox-sensitive factors activation.

Reactive oxygen species (ROS) overproduction plays an essential role in the etiology of ischemic/hypoxic retinopathy caused by acute glaucoma. NADPH oxidase (NOX) 4 was discovered as one of the main sources of ROS in glaucoma. However, the role and potential mechanisms of NOX4 in acute glaucoma have not been fully elucidated. Therefore, the current study aims to investigate the NOX4 inhibitor GLX351322 that targets NOX4 inhibition in acute ocular hypertension (AOH)-induced retinal ischemia/hypoxia injury in mice. Herein, NOX4 was highly expressed in AOH retinas, particularly the retinal ganglion cell layer (GCL). Importantly, the NOX4 inhibitor GLX351322 reduced ROS overproduction, inhibited inflammatory factor release, suppressed glial cell activation and hyperplasia, inhibited leukocyte infiltration, reduced retinal cell senescence and apoptosis in damaged areas, reduced retinal degeneration and improved retinal function. This neuroprotective effect is at least partially associated with mediated redox-sensitive factor (HIF-1α, NF-κB, and MAPKs) pathways by NOX4-derived ROS overproduction. These results suggest that inhibition of NOX4 with GLX351322 attenuated AOH-induced retinal inflammation, cellular senescence, and apoptosis by inhibiting the activation of the redox-sensitive factor pathway mediated by ROS overproduction, thereby protecting retinal structure and function. Targeted inhibition of NOX4 is expected to be a new idea in the treatment of acute glaucoma.

A Hybrid System for Automatic Identification of Corneal Layers on In Vivo Confocal Microscopy Images.

Purpose: Accurate identification of corneal layers with in vivo confocal microscopy (IVCM) is essential for the correct assessment of corneal lesions. This project aims to obtain a reliable automated identification of corneal layers from IVCM images. Methods: A total of 7957 IVCM images were included for model training and testing. Scanning depth information and pixel information of IVCM images were used to build the classification system. Firstly, two base classifiers based on convolutional neural networks and K-nearest neighbors were constructed. Second, two hybrid strategies, namely weighted voting method and light gradient boosting machine (LightGBM) algorithm were used to fuse the results from the two base classifiers and obtain the final classification. Finally, the confidence of prediction results was stratified to help find out model errors. Results: Both two hybrid systems outperformed the two base classifiers. The weighted area under the curve, weighted precision, weighted recall, and weighted F1 score were 0.9841, 0.9096, 0.9145, and 0.9111 for weighted voting hybrid system, and were 0.9794, 0.9039, 0.9055, and 0.9034 for the light gradient boosting machine stacking hybrid system, respectively. More than one-half of the misclassified samples were found using the confidence stratification method. Conclusions: The proposed hybrid approach could effectively integrate the scanning depth and pixel information of IVCM images, allowing for the accurate identification of corneal layers for grossly normal IVCM images. The confidence stratification approach was useful to find out misclassification of the system. Translational Relevance: The proposed hybrid approach lays important groundwork for the automatic identification of the corneal layer for IVCM images.

An artificial intelligence approach to classify pathogenic fungal genera of fungal keratitis using corneal confocal microscopy images.

PURPOSE: Fungal keratitis is a common cause of blindness worldwide. Timely identification of the causative fungal genera is essential for clinical management. In vivo confocal microscopy (IVCM) provides useful information on pathogenic genera. This study attempted to apply deep learning (DL) to establish an automated method to identify pathogenic fungal genera using IVCM images. METHODS: Deep learning networks were trained, validated, and tested using a data set of 3364 IVCM images that collected from 100 eyes of 100 patients with culture-proven filamentous fungal keratitis. Two transfer learning approaches were investigated: one was a combined framework that extracted features by a DL network and adopted decision tree (DT) as a classifier; another was a complete supervised DL model which used DL-based fully connected layers to implement the classification. RESULTS: The DL classifier model revealed better performance compared with the DT classifier model in an independent testing set. The DL classifier model showed an area under the receiver operating characteristic curves (AUC) of 0.887 with an accuracy of 0.817, sensitivity of 0.791, specificity of 0.831, G-mean of 0.811, and F1 score of 0.749 in identifying Fusarium, and achieved an AUC of 0.827 with an accuracy of 0.757, sensitivity of 0.756, specificity of 0.759, G-mean of 0.757, and F1 score of 0.716 in identifying Aspergillus. CONCLUSION: The DL model can classify Fusarium and Aspergillus by learning effective features in IVCM images automatically. The automated IVCM image analysis suggests a noninvasive identification of Fusarium and Aspergillus with clear potential application in early diagnosis and management of fungal keratitis.

LECT2 Ameliorates Blood-Retinal Barrier Impairment Secondary to Diabetes Via Activation of the Tie2/Akt/mTOR Signaling Pathway.

Purpose: Current treatments for diabetic retinopathy (DR) have considerable limitations, emphasizing the need for new therapeutic options. The effect of leukocyte cell-derived chemotaxin 2 (LECT2) on diabetes-induced blood-retinal barrier impairment and the possible underlying mechanism were investigated both in vivo and in vitro. Methods: Twenty diabetic and 22 nondiabetic eyes were included in this study. Additionally, we established a streptozotocin-induced diabetic mouse model and observed vascular leakage in mice treated with or without recombinant LECT2 (rLECT2) intravitreal injection (40 µg/mL, 1 µL). The levels of LECT2 and interendothelial junction proteins (ZO1, VE-cadherin, and occludin) were analyzed by western blot and/or immunofluorescence. Endothelial junctions in mouse retinas were observed by transmission electron microscopy (TEM). Moreover, confluent human retinal microvascular endothelial cells (HRMECs) and human umbilical vein endothelial cells (HUVECs) were treated (0-72 hours) with glucose (0 or 30 mM) in the presence or absence of rLECT2 (40-360 ng/mL). After treatment, intact cell monolayers were monitored for permeability to 40-kD FITC-dextran. Interendothelial junction targets and Tie2/Akt/mTOR signaling pathway components were investigated by western blot. Results: In diabetic human and mouse retinas and high-glucose (30 mM)-treated HRMECs and HUVECs, the levels of LECT2 and interendothelial junction proteins were decreased. rLECT2 treatment (80 ng/mL) significantly attenuated the hyperglycemia-induced reduction in endothelial cell barrier function and inhibited the migration and tube formation of HRMECs and HUVECs. In addition, rLECT2 increased the levels of interendothelial junction proteins via activation of the Tie2/Akt/mTOR signaling pathway. Furthermore, intravitreal rLECT2 injections increased the levels of interendothelial junction proteins and reversed diabetes-induced junction disruption. Conclusions: rLECT2 can increase the levels of interendothelial tight junction proteins through activation of the Tie2/Akt/mTOR signaling pathway and can ameliorate inner blood-retinal barrier impairment secondary to diabetes. LECT2 might be a potential target to prevent the progression of DR.

Investigation of SARS-CoV-2 on Ocular Surface of Coronavirus Disease 2019 Patients Using One-Step Reverse-Transcription Droplet Digital PCR.

PURPOSE: This study detects SARS-CoV-2 in the ocular surface through one-step reverse-transcription droplet digital PCR (one-step RT-ddPCR) and evaluates the possibility of the ocular surface as a possible transmission route. METHODS: A single-center prospective observational study was designed to investigate the viral loads in ocular surface. Specimens including the conjunctival swabs, nasopharyngeal swabs and blood were synchronously collected at a single time point for all COVID-19 patients. SARS-CoV-2 loads in nasopharyngeal swabs were tested by real-time polymerase chain reaction (PCR); the blood samples and conjunctival swabs were tested by real-time PCR and one-step RT-ddPCR. RESULTS: Sixty-eight COVID-19 patients confirmed by nasopharyngeal real-time PCR were recruited. In the single time point test, 40 cases showed positive SARS-CoV-2 detection in either the blood, tears, or nasopharynx, of which four cases were triple-positive, 10 were dual-positive, and 26 were single-positive. The positive rate of nasopharyngeal swab real-time PCR test was 22.1% (15/68). The positive rate of blood and conjunctival swabs by one-step RT-ddPCR was 38.2% (26/68) and 25% (17/68), respectively, whereas real-time PCR was all negative. Positive conjunctival swabs were significantly correlated with positive nasopharyngeal swabs (P = 0.028). The sampling lags from illness onset to sampling day in 3 out of 4 triple-positive patients and in 9 out of 10 dual-positive patients were respectively less than 9 days and less than 20 days. CONCLUSION: Our results indicate that the positive rate of SARS-CoV-2 on the ocular surface is much higher than expected. Transmission possibility through the ocular surface may be greatly underestimated.

Markers of the sympathetic, parasympathetic and sensory nervous system are altered in the human diabetic choroid.

BACKGROUND: We sought to evaluate alterations in markers of the autonomic nervous system in human diabetic choroid. METHODS: Eighteen eyeballs from subjects with diabetes and 22 eyeballs from subjects without diabetes were evaluated in this study. Synaptophysin, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DßH), neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), vesicular monoamine transporter II (VMAT-2), vesicular acetylcholine transporter (VAChT), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) levels were detected by western blot analysis and immunofluorescence was performed in some cases. Furthermore, differences in adrenergic (α1- and ß2-subtypes) and cholinergic (M1 and M3) receptor levels between diabetic subjects and controls were noted. RESULTS: Decreased synaptophysin levels were found in diabetic choroids by western blot analysis and a reduction of synaptophysin-immunoreactive nerves was also found by immunofluorescence. Furthermore, a decrease of the levels of the key enzyme (TH) and transporter (VMAT2) of norepinephrine was evident both by western blot analysis and immunofluorescence. Additionally, increased NPY, VAChT, nNOS, and CGRP levels were observed in diabetic choroids. The levels of adrenergic (ß2 subtype) and acetylcholine (M1 subtype) receptors decreased in diabetic choroids, as shown by western blotting and although the differences in α1 and M3 were not significant, there was a downward trend. CONCLUSIONS: In the diabetic choroid, the levels of neurotransmitters, enzymes, and receptors associated with choroidal blood flow regulation are altered. These changes may affect the regulation of choroidal blood flow and may be associated with impaired retinal function and retinal pathology.

Restoring VTA DA neurons excitability accelerates emergence from sevoflurane general anesthesia of anxiety state.

Preoperative anxiety is common and often comes with a higher probability of worse recovery. However, the neurological mechanism of the effect of preoperative anxiety on general anesthesia and subsequent awakening remains unknown. In this study, we report an anxious state results in delayed awakening in anxiety model mice from sevoflurane general anesthesia. More profound inhibition of DA neurons in the VTA contributes to delayed awakening. Optogenetic stimulation of VTA DA neurons can reverse the delay. The results indicate that VTA DA neurons may be involved in the delay in awakening from general anesthesia caused by anxiety.

Higher choroidal thickness and lower choriocapillaris blood flow signal density based on optical coherence tomography angiography in diabetics.

Diabetes mellitus (DM) is one of the fastest growing chronic diseases in the world and one of the main causes of vision loss. Whether or not diabetic choroidopathy (DC) is involved in the initiation and progression of diabetic ocular complications needs to be explored. We included 54 diabetic eyes from 36 diabetic patients, and 54 healthy eyes from 32 control subjects after propensity scores matching. All of the subjects were given pupil light and dark adaptation examination and optical coherence tomography angiography (OCTA). Scotopic pupil diameter (SPD), pupil contraction amplitude, and velocity of pupil contraction of the diabetic group were significantly lower than that of the healthy control group (P < 0.05).Choroidal thickness at temporal quadrant (at 750 µm) and superior quadrant (at 1500 µm and 2250 µm) increased in diabetic group compared to control group(P < 0.05).In the diabetic group, choriocapillaris blood flow signal density (CCBFSD) in the macular area (diameter = 2000 µm) were significantly decreased compared with the healthy control group (P < 0.05). Apparent changes in pupil and choroidal blood flow were observed in the diabetic patients.

Ocular manifestations and clinical characteristics of 535 cases of COVID-19 in Wuhan, China: a cross-sectional study.

PURPOSE: To investigate the ocular manifestations and clinical characteristics of COVID-19 patients caused by SARS-CoV-2 in Wuhan, China. METHODS: A total of 535 COVID-19 patients were recruited at Mobile Cabin Hospital and Tongji Hospital. Information on demographic characteristics, exposure history, ocular symptoms, eye drop medication, eye protections, chronic eye diseases, systemic concomitant symptoms, radiologic findings and SARS-CoV-2 detection in nasopharyngeal swabs by real-time PCR was collected from questionnaires and electronic medical records. RESULTS: Of 535 patients, 27 patients (5.0%) presented with conjunctival congestion and 4 patients had conjunctival congestion as the initial symptom. The average duration of conjunctival congestion was 5.9 ± 4.5 days (mean [SD]). The other ocular symptoms, including increased conjunctival secretion, ocular pain, photophobia, dry eye and tearing, were also found in patients with conjunctival congestion. Notably, hand-eye contact was independently correlated with conjunctival congestion in COVID-19 patients. We also found that some COVID-19 patients had chronic eye diseases, including conjunctivitis (33, 6.2%), xerophthalmia (24, 4.5%) and keratitis (14, 2.6%). Similar to the published studies, the most common clinical symptoms were fever, cough and fatigue. A total of 343 patients (64.1%) had positive SARS-CoV-2 detection in nasopharyngeal swabs. CONCLUSIONS: Conjunctival congestion is one of the COVID-19-related ocular symptoms, which could occur as the initial symptoms. Frequent hand-eye contact may be the risk factor for conjunctival congestion in COVID-19 patients. Screening of patients with conjunctival congestion by ophthalmologists is advocated during the outbreak of COVID-19. It is essential to provide eye-care equipment and strengthen education on eye protection.

Tissue Distribution of trans-Resveratrol and Its Metabolites after Oral Administration in Human Eyes.

Purpose. This study was performed to measure the concentration of trans-resveratrol and its three metabolites in human eyes. Methods. The patients who underwent pars plana vitrectomy for rhegmatogenous retinal detachment were included. The participants were orally given trans-resveratrol-based supplement (Longevinex®). A suitable amount of conjunctiva, aqueous humor, and vitreous humor were obtained during the operation. High-performance liquid chromatography (HPLC) with mass spectrometry (LC/MS/MS) was used to detect the concentration of trans-resveratrol and its three metabolites in the various samples. Results. The average concentration of resveratrol in the conjunctiva was 17.19 ± 15.32 nmol/g (mean ± SD). The concentration of resveratrol in the aqueous humor was close to the limit of detection, but its metabolites could be quantified. The concentrations of resveratrol metabolites in the aqueous humor can be detected. In the vitreous humor, the average concentration of resveratrol-3-O-sulfate was 62.95 ± 41.97 nmol/L. The sulfate conjugations of resveratrol were recovered in the conjunctiva, aqueous humor, and vitreous humor. Conclusions. Resveratrol and its three metabolites can be detected in the ocular tissues after oral administration. Although the concentration of parent resveratrol was low in the eyes, its metabolites could be detected and may have a role in the treatment of ocular diseases.