OIMHS: An Optical Coherence Tomography Image Dataset Based on Macular Hole Manual Segmentation.

Macular holes, one of the most common macular diseases, require timely treatment. The morphological changes on optical coherence tomography (OCT) images provided an opportunity for direct observation of the disease, and accurate segmentation was needed to identify and quantify the lesions. Developments of such algorithms had been obstructed by a lack of high-quality datasets (the OCT images and the corresponding gold standard macular hole segmentation labels), especially for supervised learning-based segmentation algorithms. In such context, we established a large OCT image macular hole segmentation (OIMHS) dataset with 3859 B-scan images of 119 patients, and each image provided four segmentation labels: retina, macular hole, intraretinal cysts, and choroid. This dataset offered an excellent opportunity for investigating the accuracy and reliability of different segmentation algorithms for macular holes and a new research insight into the further development of clinical research for macular diseases, which included the retina, lesions, and choroid in quantitative analyses.

Lesion detection with fine-grained image categorization for myopic traction maculopathy (MTM) using optical coherence tomography.

BACKGROUND: Myopic traction maculopathy (MTM) are retinal disorder caused by traction force on the macula, which can lead to varying degrees of vision loss in eyes with high myopia. Optical coherence tomography (OCT) is an effective imaging technique for diagnosing, detecting and classifying retinopathy. MTM has been classified into different patterns by OCT, corresponding to different clinical strategies. PURPOSE: We aimed to engineer a deep learning model that can automatically identify MTM in highly myopic (HM) eyes using OCT images. METHODS: A five-class classification model was developed using 2837 OCT images from 958 HM patients. We adopted a ResNet-34 architecture to train the model to identify MTM: no MTM (class 0), extra-foveal maculoschisis (class 1), inner lamellar macular hole (class 2), outer foveoschisis (class 3), and discontinuity or detachment of foveal outer hyperreflective layers (class 4). An independent test set of 604 images from 173 HM patients was used to evaluate the model's performance. Classification performance was assessed according to the area under the curve (AUC), accuracy, sensitivity, specificity. RESULTS: Our model exhibited a high training performance for classification (F1-score of 0.953; AUCs of 0.961 to 0.998). In test set, it achieved sensitivities (91.67%-97.78 %) and specificities (98.33%-99.17%) as good as, or better than, those of experienced clinicians. Heatmaps were generated to provide visual explanations. CONCLUSIONS: We established a deep learning model for MTM classification using OCT images. This model performed equally well or better than retinal specialists and is suitable for large-scale screening and identifying MTM in HM eyes.

Artificial Intelligence-Based Quantification of Central Macular Fluid Volume and VA Prediction for Diabetic Macular Edema Using OCT Images.

INTRODUCTION: We studied the correlation of central macular fluid volume (CMFV) and central subfield thickness (CST) with best-corrected visual acuity (BCVA) in treatment-naïve eyes with diabetic macular edema (DME) 1 month after anti-vascular endothelial growth factor (VEGF) therapy. METHODS: This retrospective cohort study investigated eyes that received anti-VEGF therapy. All participants underwent comprehensive examinations and optical coherence tomography (OCT) volume scans at baseline (M0) and 1 month after the first treatment (M1). Two deep learning models were separately developed to automatically measure the CMFV and the CST. Correlations were analyzed between the CMFV and the logMAR BCVA at M0 and logMAR BCVA at M1. The area under the receiver operating characteristic curve (AUROC) of CMFV and CST for predicting eyes with BCVA [Formula: see text] 20/40 at M1 was analyzed. RESULTS: This study included 156 DME eyes from 89 patients. The median CMFV decreased from 0.272 (0.061-0.568) at M0 to 0.096 (0.018-0.307) mm3 at M1. The CST decreased from 414 (293-575) to 322 (252-430) µm. The logMAR BCVA decreased from 0.523 (0.301-0.817) to 0.398 (0.222-0.699). Multivariate analysis demonstrated that the CMFV was the only significant factor for logMAR BCVA at both M0 (ß = 0.199, p = 0.047) and M1 (ß = 0.279, p = 0.004). The AUROC of CMFV for predicting eyes with BCVA [Formula: see text] 20/40 at M1 was 0.72, and the AUROC of CST was 0.69. CONCLUSIONS: Anti-VEGF therapy is an effective treatment for DME. Automated measured CMFV is a more accurate prognostic factor than CST for the initial anti-VEGF treatment outcome of DME.

Analysis of Retinal Microstructure in Eyes with Dissociated Optic Nerve Fiber Layer (DONFL) Appearance following Idiopathic Macular Hole Surgery: An Optical Coherence Tomography Study.

(1) Purpose: This study aimed to evaluate morphological changes of the retina in eyes with dissociated optic nerve fiber layer (DONFL) appearance following internal limiting membrane (ILM) peeling for full-thickness idiopathic macular hole (IMH) on spectral-domain optical coherence tomography (SD-OCT). (2) Methods: We retrospectively analyzed 39 eyes of 39 patients with type 1 macular hole closure after a vitrectomy with ILM peeling procedure at a six-month minimum postoperative follow-up. The retinal thickness maps and cross-sectional OCT images were obtained from a clinical OCT device. The cross-sectional area of the retinal nerve fiber layer (RNFL) on cross-sectional OCT images was manually measured by ImageJ software. (3) Results: The inner retinal layers (IRLs) thickness thinned down much more in the temporal quadrant than in nasal quadrants at 2 and 6 months postoperatively (p < 0.001). However, the cross-sectional area of the RNFL did not change significantly at 2 and 6 months postoperatively (p > 0.05) when compared to preoperative data. In addition, the thinning of the IRL did not correlate with the best-corrected visual acuity (BCVA) at 6 months postoperatively. (4) Conclusions: The thickness of the IRL decreased in eyes with a DONFL appearance after ILM peeling for IMH. The thickness of the IRL decreased more in the temporal retina than in the nasal retina, but the change did not affect BCVA during the 6 months after surgery.

Quantitative evaluation of dissociated optic nerve fibre layer (DONFL) following idiopathic macular hole surgery.

OBJECTIVES: To quantitatively evaluate concentric macular dark spots (CMDS) on spectral-domain optical coherence tomography (SD-OCT) to determine the morphological characteristics of dissociated optic nerve fibre layer (DONFL) following the performance of internal limiting membrane (ILM) peeling in patients with full-thickness idiopathic macular hole (IMH) closure. METHODS: Retrospective study on patients who underwent a vitrectomy with ILM peeling procedure. BCVA, cross-sectional OCT scans, and three-dimensional reconstructions of en face OCT scans were analysed preoperatively, at 2, 6, 12 months post-operatively. A novel image analysis technique was used to automatically measure DONFL logical properties through the radius, area, the nerve fibre layer dissociation index (NFLDI), and depth of the CMDS. RESULTS: 53 eyes of 51 patients were included, and the mean follow-up was 11.53 ± 6.26 months. CMDS was found in 46 (86.79%) eyes within 2 months after ILM peeling and 50 (94.34%) eyes within 6 months after ILM peeling. CMDS concentrated on the temporal side of the macula in all 50 eyes (100%) at first detection. The area, NFLDI, and depth of CMDS in four quadrants developed significantly during the postoperative 6 months (p < 0.05), and then these changes slowed down and remained unchanged 12 months post-operatively. The morphological changes in the temporal quadrant were significantly greater than those in other quadrants at 2, 6, 12 months (all p < 0.05) post-operatively. CONCLUSIONS: CMDS mostly appeared and concentrated on the temporal side of the macula in IMHs within two months after ILM peeling and progressed within 6 months and remained unchanged after 12 months.

Association of sex with the global burden of vision impairment caused by neonatal preterm birth: An analysis from the global burden of disease study 2019.

Aims: To investigate the sex-specific global burden of neonatal preterm birth (NPB) vision impairment by year, age, and socioeconomic status using years lived with disability (YLDs). Methods: The global, regional, and national sex-specific YLD numbers, crude YLD rates, and age-standardized YLD rates of NPB-related moderate and severe vision loss and blindness were obtained from the Global Burden of Disease Study 2019. The Wilcoxon test and linear regression were used to investigate the relationship between sex difference in age-standardized YLD rates and the Human Development Index (HDI). Results: Between 1990 and 2019, the gender disparity in age-standardized YLD rates for NPB-related vision impairment remained stable, increasing from 10.2 [95% uncertainty interval (UI) 6.7-14.6] to 10.4 (95% UI 6.9-15.0) for men and 10.3 (95% UI 6.8-14.7) to 10.7 (95% UI 7.2-15.1) for women, with women consistently having higher age-standardized YLD rates. Between the ages of 25 and 75, women had higher YLD rates than males, with the biggest disparity in the 60-64 age group. In 2019, sex difference in age-standardized YLD rates across 195 nations was statistically significant. Women had higher age-standardized YLD rates than men in both low (Z = -3.53, p < 0.001) and very high HDI countries (Z = -4.75, p < 0.001). Additionally, age-standardized YLD rates were found to be adversely associated with HDI (male: Standardized ß = -0.435, female: Standardized ß = -0.440; p < 0.001). Conclusion: Despite advancements in worldwide NPB health care, sexual differences in NPB-related vision impairment burden showed little change. Female had higher burden than male, particularly in low and very high socioeconomic status countries.

Automatic Screening and Identifying Myopic Maculopathy on Optical Coherence Tomography Images Using Deep Learning.

Purpose: The purpose of this study was to engineer deep learning (DL) models that can identify myopic maculopathy in patients with high myopia based on optical coherence tomography (OCT) images. Methods: An artificial intelligence (AI) system was developed using 2342 qualified OCT macular images from 1041 patients with pathologic myopia admitted to the Affiliated Eye Hospital of Wenzhou Medical University (WMU). We adopted an ResNeSt101 architecture to train five independent models to identify the following five myopic maculopathies: macular choroidal thinning, macular Bruch membrane (BM) defects, subretinal hyper-reflective material (SHRM), myopic traction maculopathy (MTM), and dome-shaped macula (DSM). We tested the models with an independent test dataset that included 450 images obtained from 297 patients with high myopia. Focal loss was used to address class imbalance, and optimal operating thresholds were determined according to the Youden Index. The performance was quantified using the area under the receiver operating characteristic (AUC), sensitivity, specificity, and confusion matrix. Results: For the identification of myopic maculopathy, the AUCs of receiver operating characteristic (ROC) curves were 0.927 to 0.974 for 5 myopic maculopathies. Our AI system achieved sensitivities equal to or even better than those of junior retinal specialists (56.16-99.73%). The diagnosis of it is also interpretable that we provide visual explanations clearly via heatmaps. Conclusions: We developed a convolutional neural network (CNN)-based DL AI system for detection and classification of myopic maculopathy in patients with high myopia using OCT macular images. Our AI system achieved sensitivities equal to or even better than those of junior retinal specialists. Translational Relevance: This AI system can be widely applied in sophisticated situations in large-scale high myopia screening.

Winemaking Characteristics of Red-Fleshed Dragon Fruit from Three Locations in Guizhou Province, China.

The aim of this study was to identify the locations and harvest months in Guizhou province, China, producing the most suitable red dragon fruit (Hylocereus polyrhizus) for winemaking. Fruit from Guanling, Luodian and Zhenfeng counties was harvested separately from successive fruit cycles in August, September and October, respectively. The key traits measured were fruit weight, pulp yield, soluble solids content, and titratable acid. Wine characteristics measured were alcohol content, total carbohydrates, titratable acidity, volatile acidity, and betacyanin content. The overall suitability of fruit from each location for winemaking was evaluated using a multi-factor, unweighted, scorecard. On that basis, fruit from Guanling county harvested in August was the most suitable. Fruit from Luodian, and Zhenfeng was most suitable when harvested in August and September, and September, respectively. These results provide a preliminary guide for the sourcing of red dragon fruit from Guizhou for wine production.

Total glucosides of paeony (TGP) alleviates Sjogren's syndrome through inhibiting inflammatory responses in mice.

BACKGROUND: Sjogren's syndrome (SS) is an inflammatory autoimmune disease whose etiology is complicated. Total glucosides of paeony (TGP) has a variety of pharmacological effects. PURPOSE: To evaluate the therapeutic effects of TGP on SS in mice and anti-inflammatory mechanism. STUDY DESIGN: SS animal model was developed from C57BL/6J mice through immunological induction (SS mice) and NOD/ShiltJNju (NOD) mice. Inflammatory cytokines and other related indicators were measured. METHODS: TGP (720, 360, 180 mg/kg) was intragastrically administered for 6 or 16 weeks for SS mice and NOD mice, respectively. Average food and water intake, average body weight, saliva flow, submandibular gland (SMG) and spleen index, and SMG pathology were measured. ELISA was used to evaluate serum inflammatory cytokines in SS mice and autoantigens in NOD mice. Real-time PCR, Western blot and Luminex liquid suspension chip assay were applied to analyze SMG inflammatory cytokines mRNA and protein expression of NOD mice. RESULTS: Compared with SS mice, TGP treatment improved SMG pathological damage. TGP (720 mg/kg) treatment increased saliva flow, and reduced organ indexes and serum IL-6 and IFN-γ concentration. TGP (360 mg/kg) treatment decreased serum IFN-γ concentration. TGP (180 mg/kg) treatment for 6 weeks decreased average body weight. Compared with NOD mice, TGP treatment increased saliva flow from 9 to 15 weeks, decreased body weight, and alleviated pathological damage of SMG after 2 and 16 weeks. After 2 weeks of administration, TGP treatment inhibited serum concentration of SSB/La, SSA/Ro and α-fodrin, decreased TNF-α, IL-1ß and IFN-γ in SMG, and down-regulated protein expressions of BAFF and IL-17A and mRNA expressions of BAFF, TNF-α, IL-17A, CXCL9 and CXCL13 in SMG. After 8 weeks of administration, TGP treatment decreased the concentration of α-fodrin in serum, TNF-α and IL-6 in SMG, and down-regulated mRNA expressions of IL-17A, TNF-α, CXCL9, CXCL13 and BAFF and protein expressions of IL-17A and BAFF in SMG. After 16 weeks of administration, TGP treatment reduced serum SSA/Ro, SSB/La and α-fodrin concentration, and decreased BAFF protein expression and TNF-α, CXCL9, CXCL13, IL-17A, and BAFF mRNA expressions. CONCLUSION: TGP has a certain therapeutic effect on SS mice and NOD mice through inhibiting inflammatory responses.

Total glucosides of paeony attenuates animal psoriasis induced inflammatory response through inhibiting STAT1 and STAT3 phosphorylation.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is an immune system meditated disease, especially T cells. It disturbed many people around the world and hard to therapy. Paeonia lactiflora Pall has been used as a medicine in china for thousands of years. Recent studies found that the main component of Paeonia lactiflora Pall can alleviates the immune response in many diseases. In this study, we researched the effects and possible mechanisms of total glucosides of paeony (TGP) on animal psoriasis. AIM OF THE STUDY: To study the therapeutic effects and mechanisms of TGP in 5% propranolol cream-induced psoriasis in guinea pigs and Imiquimod (IMQ) cream-induced psoriasis in mice. MATERIALS AND METHODS: The effect of TGP was evaluated using a psoriasis-like model of guinea pigs and mice. Ear thickness was accessed, and pathology injury was observed by H&E staining. The levels of serum IL-1ß, IL-6, IL-12, IL-17, IL-23, TNF-α, and IFN-γ, skin IL-17A, IL-22 and orphan nuclear receptor (RORγt) mRNA expression, proliferating cell nuclear antigen (PCNA), total or phosphorylated signal transducers and activators of transcription (STAT1, STAT3) were determined by enzyme linked immunosorbent assays (ELISAs), real time PCR, immunohistochemical staining, and western blotting, respectively. RESULTS: Compared with model group, TGP treatment decreased the ear thickness, improved pathology of psoriasis, alleviated IMQ-induced keratinocyte proliferation, reduced the inflammatory cytokine, and downregulated IL-17A, IL-22, and RORγt mRNA in mice. Further study indicated that TGP inhibited STAT1 and STAT3 phosphorylation in lesion skins of psoriasis-like mice. CONCLUSIONS: TGP alleviates the symptoms of psoriasis-like guinea pigs and mice, and the possible mechanism may relate to inhibit T helper 17 (TH17) cell differentiation and keratinocytes proliferation by inhibiting STAT1 and STAT3 phosphorylation.

Propagermanium, a CCR2 inhibitor, attenuates cerebral ischemia/reperfusion injury through inhibiting inflammatory response induced by microglia.

CCR2 could recruit immune cells migrating into brain after ischemic stroke. It is unclear whether and why Propagermanium (PG, a CCR2 inhibitor) is able to protect against ischemic injury. Middle cerebral artery occlusion (MCAO) and reperfusion injury in C57BL/6 J male mice were performed in vivo to mimic ischemic stroke. Cultured BV2 microglia exposed to oxygen and glucose deprivation (OGD)/reoxygenation injury, LPS or IL-4 incubation were served in vitro. TTC staining, neurological score, brain water content, and MRI scan were performed to evaluate stroke outcome. Real time PCR, ELISA, and immunofluorescence were used to estimate inflammatory cytokines expression and releasing. Western blot was utilized to detect pSTAT1/STAT1 expression. Compared with MCAO mice, PG treatment significantly reduced infarction size and brain edema, improved neurological behavior at 72 h after MCAO. For inflammatory response, PG treatment inhibited inflammatory cytokines releasing, such as TNF-α, IFN-γ, IL-1ß, IL-6, IL-12, IL-17, and IL-23. Further studies indicated that PG treatment downregulated mRNA expression of pro-inflammatory iNOS and CD86, and inhibited CD16 expressed in microglia. In vitro, PG incubation inhibited BV2 polarized to pro-inflammatory phenotype through STAT1 downregulation, while had no obvious effect on anti-inflammatory phenotype. Our observations suggest that CCR2 inhibitor PG downregulated pro-inflammatory microglia polarization for decreasing pro-inflammatory microglia phenotype marker, and thereafter inhibited inflammatory responses after MCAO in a STAT1-dependent manner.

CCR2-dependent monocytes/macrophages exacerbate acute brain injury but promote functional recovery after ischemic stroke in mice.

Rationale: Peripheral blood monocytes are recruited into the ischemic brain and transform into macrophages after stroke. Nevertheless, the exact role of CCR2-dependent monocytes/macrophages in brain injury after stroke remains elusive. Methods: We used CCR2 knockout (KO) mice and the CCR2 pharmacological inhibitor, propagermanium (PG), to address the role of CCR2-dependent monocytes/macrophages in the acute stage and neurological functional recovery after middle cerebral artery (MCA) occlusion and reperfusion. Results: CCR2 KO resulted in smaller infarct size and lower mortality than in wild type (WT) mice, when measured 3 days after stroke. However, from 5 to 28 days after stroke, the KO mice had higher mortality and showed no obvious neurological functional recovery. In addition, WT mice treated with PG had similar stroke outcomes compared with CCR2 KO, as measured by T2 weighted MRI. Flow cytometry and real-time PCR analyses suggest that monocyte-derived macrophages (MoDMs) in the stroke brains mainly polarized to pro-inflammatory macrophages at the early stage, but gradually switched to anti-inflammatory macrophages at 7 days after stroke. In addition, adoptive transfer of anti-inflammatory macrophages into CCR2 KO mice at 4 and 6 days after stroke alleviated mortality and promoted neurological recovery. Conclusion: CCR2-dependent monocytes/macrophages are a double-edged sword; they worsen acute brain injury, but are essential for neurological recovery by promoting anti-inflammatory macrophage polarization.

XQ-1H protects against ischemic stroke by regulating microglia polarization through PPARγ pathway in mice.

Cerebral ischemic and reperfusion injury often accompany with inflammation, and lead to severe neuronal damage, which further result in neurological disorders and memory disorders. In this study, we researched XQ-1H, a novel derivative of ginkgolide B, protecting against ischemic stroke in mice through regulation of microglia polarization. Middle cerebral artery occlusion (MCAO)/reperfusion in mice is applied to mimic ischemic stroke in vivo. Immediately after MCAO, mice are intragastric administrated with different dose (31 or 62 mg/kg) of XQ-1H for one or continuative three days. The in vivo experiments indicated that post-treatment with XQ-1H decreased cerebral infarction size, lessened brain edema, improved behavior and memory recover, inhibited pro-inflammatory and promoted anti-inflammatory cytokines expression and releasing in MCAO mice. Oxygen-glucose deprivation/reoxygenation (OGD/R) injury in BV-2 (microglia) cells is served in vitro. The in vitro findings revealed that incubation with XQ-1H protected against BV2 from OGD/R injury, regulated BV2 polarized from pro-inflammatory into anti-inflammatory phenotype, and promoted PPARγ mobilizing from nuclear to cytoplasm. In conclusion, the present study demonstrates that XQ-1H alleviated ischemic stroke by regulating balance of pro-/anti-inflammatory microglia polarization through PPARγ pathway both in vivo and in vitro, offering an alternative medication for stroke associated with inflammation.

S-oxiracetam ameliorates ischemic stroke induced neuronal apoptosis through up-regulating α7 nAChR and PI3K / Akt / GSK3ß signal pathway in rats.

Ischemic stroke, the main reason for severe disabilities in the world, is associated with a high incidence of sensorimotor and cognitive dysfunction. In this study, we use the middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and oxygen glucose deprivation/reoxygenation (OGD/R) model in fetal rat primary cortical neurons to investigate whether and how S-oxiracetam (S-ORC) protect brain injury from ischemic stroke. The results revealed that S-ORC reduced brain infarct size and lessened neurological dysfunction after stroke. Further study demonstrated that S-ORC diminished TUNEL positive cells, increased cell viability, decreased LDH activity, and inhibited cell apoptotic rate. Furthermore, S-ORC inhibited neuronal apoptosis by activating the PI3K/Akt/GSK3ß signaling pathway via α7 nAChR, which was evidenced by α7 nAChR siRNA. In conclusion, our findings strongly suggest that S-ORC could be used as an effective neuroprotective agent for ischemic stroke due to its effect in preventing neuronal apoptosis.

S-oxiracetam protect against ischemic stroke via alleviating blood brain barrier dysfunction in rats.

The blood brain barrier (BBB) maintains the basic stability of the brain tissue under physiological conditions, while destroys and exaggerates brain edema and inflammatory response after ischemic stroke. In this study, we researched S-oxiracetam (S-ORC), a nootropic drug, alleviates BBB dysfunction and protects against ischemic stroke in rats. Middle cerebral artery occlusion(MCAO)/reperfusion in rats is applied to mimic ischemic stroke. One hour after reperfusion, rats are administered intravenously with different dose (0.12, 0.24, or 0.48g/kg) of S-ORC for continuative three days. Seventy-two hours after MCAO, TTC staining, hematoxylin and eosin (H&E) staining, brain water content, immunohistochemical staining, EB extravasation, western blot are provided to evaluate the protective effect and possible mechanism of S-ORC on BBB dysfunction. Furthermore, brain concentration of verapamil (P-glycoprotein substrate) and atenolol (paracellular transport marker) were assayed by UPLC-MS/MS co administration with or without S-ORC. The results show that post-treatment of S-ORC decreases cerebral infarct size, lessens brain edema, inhibits neutrophil infiltration and cytokines releasing. Furthermore, S-ORC treatment decreases EB leakage, downregulates MMP-9, upregulates occludin and claudin-5, and decreases brain concentration of verapamil and atenolol after MCAO surgery. In conclusion, the present study demonstrates that post-treatment of S-ORC alleviates BBB dysfunction by regulating tight junction proteins (TJPs), upregulating P-glycoprotein function, and protects against ischemic stroke as result.