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The aim of this work is to investigate the differences in the measurement of foveal retinal thickness in myopic patients between two display modes (1:1 pixel and 1:1 micron) on optical coherence tomography (OCT).Horizontal OCT line scan through the central fovea was used for manual measurement of foveal retinal thickness under the two display modes, and the values were compared using Wilcoxon signed-rank test. Correlations between the OCT image tilting angle (OCT ITA) and differences in OCT measurement were analyzed by Spearman's test.127 participants with a median age of 28 years, a median spherical equivalent (SE) of - 8.5 D, and a median axial length (AL) of 27.04 mm. There were significant differences between the two display modes, with a median absolute difference (median relative difference) of 13.33 μm (2.75%) for the central foveal thickness (CFT), 5.33 μm (1.28%) for the Henle fiber and outer nuclear layer thickness (HFL + ONL), 3 μm (6.47%) for the external limiting membrane to ellipsoid zone distance (ELM-EZ), and 4 μm (8.77%) for the ellipsoid zone to retinal pigment epithelium distance (EZ-RPE) (all p 0.05). The differences in foveal retinal thickness between the two display modes were significantly correlated with the OCT ITA (r = 0.732 for CFT, 0.561 for HFL + ONL, 0.642 for ELM-EZ, and 0.471 for EZ-RPE, all p 0.05).Disparities between the two display modes were found in the manual measurement of foveal retinal thickness and correlated to the OCT ITA.

Aims To develop and validate a nomogram using retinal vasculature features and clinical variables to predict coronary artery disease (CAD) in patients with suspected angina. Methods The prediction model consisting of 795 participants was developed in a training set of 508 participants with suspected angina due to CAD, and data were collected from January 2018 to June 2019. The held-out validation was conducted with 287 consecutive patients from July 2019 to November 2019. All patients with suspected CAD received optical coherence tomography angiography (OCTA) examination before undergoing coronary CT angiography. LASSO regression model was used for data reduction and feature selection. Multivariable logistic regression analysis was used to develop the retinal vasculature model for predicting the probability of the presence of CAD. Results Three potential OCTA parameters including vessel density of the nasal and temporal perifovea in the superficial capillary plexus and vessel density of the inferior parafovea in the deep capillary plexus were further selected as independent retinal vasculature predictors. Model clinical electrocardiogram (ECG) OCTA (clinical variables＋ECG＋OCTA) was presented as the individual prediction nomogram, with good discrimination (AUC of 0.942 [95% CI, 0.923-0.961] and 0.897 [95% CI, 0.861-0.933] in the training and held-out validation sets, respectively) and good calibration. Decision curve analysis indicated the clinical applicability of this retinal vasculature nomogram. Conclusions The presented retinal vasculature nomogram based on individual probability can accurately identify the presence of CAD, which could improve patient selection and diagnostic yield of aggressive testing before determining a diagnosis.

An image-based deep learning model was developed to detect different morphological patterns of diabetic macular edema based on optical coherence tomography images with high accuracy and transparency. This model could help ophthalmologists to make personalized therapeutic strategies for patients with diabetic macular edema., Purpose: To develop a deep learning (DL) model to detect morphologic patterns of diabetic macular edema (DME) based on optical coherence tomography (OCT) images. Methods: In the training set, 12,365 OCT images were extracted from a public data set and an ophthalmic center. A total of 656 OCT images were extracted from another ophthalmic center for external validation. The presence or absence of three OCT patterns of DME, including diffused retinal thickening, cystoid macular edema, and serous retinal detachment, was labeled with 1 or 0, respectively. A DL model was trained to detect three OCT patterns of DME. The occlusion test was applied for the visualization of the DL model. Results: Applying 5-fold cross-validation method in internal validation, the area under the receiver operating characteristic curve for the detection of three OCT patterns (i.e., diffused retinal thickening, cystoid macular edema, and serous retinal detachment) was 0.971, 0.974, and 0.994, respectively, with an accuracy of 93.0%, 95.1%, and 98.8%, respectively, a sensitivity of 93.5%, 94.5%, and 96.7%, respectively, and a specificity of 92.3%, 95.6%, and 99.3%, respectively. In external validation, the area under the receiver operating characteristic curve was 0.970, 0.997, and 0.997, respectively, with an accuracy of 90.2%, 95.4%, and 95.9%, respectively, a sensitivity of 80.1%, 93.4%, and 94.9%, respectively, and a specificity of 97.6%, 97.2%, and 96.5%, respectively. The occlusion test showed that the DL model could successfully identify the pathologic regions most critical for detection. Conclusion: Our DL model demonstrated high accuracy and transparency in the detection of OCT patterns of DME. These results emphasized the potential of artificial intelligence in assisting clinical decision-making processes in patients with DME.

Inflammation is known to be involved in the progression of diabetic retinopathy. Follicular helper T cells (Tfh) play critical roles in the differentiation of long-live plasma cells and production of antibodies, whereas circulating CD4+CXCR5+ T cells may act as a counterpart to measure Tfh cell disorders. In this study, we investigated whether Tfh could be involved in the development of diabetic retinopathy (DR) by assessing circulating Tfh cells in peripheral blood. Data showed that serum levels of total IgG and IgA were both significantly increased in type 2 diabetes mellitus (T2DM) patients with proliferative diabetic retinopathy (PDR) than with non-PDR. Also, B cell activation and differentiation were both enhanced in T2DM patients with PDR. Little changes were detected in levels of Th1, Th2, and Th17 cells. As indicated by elevated serum levels and supernatant from cultured PBMC of IL-21, we found increased circulating Tfh cells in PDR patients with dysregulated subsets. This study suggests the involvement of circulating Tfh cells in DR and, in particular, the pathogenesis of PDR.

Importance A high prevalence of retinal abnormalities have been reported in congenital heart disease (CHD), but quantitative analysis of retinal vasculature is scarce. Optical coherence tomography angiography (OCTA) is a noninvasive method to quantitatively assess the retinal microvasculature. Background To investigate the retinal microvasculature changes in CHD patients by using OCTA. Design Cross‐sectional study. Participants A total of 158 participants including 57 cyanotic CHD (CCHD) patients, 60 acyanotic CHD (ACHD) patients and 41 control subjects were included. Methods All participants underwent a comprehensive ophthalmologic examination, including refraction measurement, intraocular pressure measurement and OCTA. Main Outcome Measures Vessel density (VD) was measured within the radial peripapillary capillary (RPC), superficial capillary plexus (SCP) and deep capillary plexus (DCP) of the macula. Results CCHD patients had significantly lower VD in the RPC, SCP and DCP (all P

IntroductionSeizures are a common complication that leads to neurological deficits and affects outcomes after aneurysmal subarachnoid haemorrhage (aSAH). However, whether to use prophylactic anticonvulsants in patients with aSAH remains controversial. Our study aims to determine whether short-term (7 days) sodium valproate could prevent seizure occurrence and improve neurological function in patients with SAH caused by anterior circulation aneurysm rupture and treated with clipping.Methods and analysisIn this multicentre randomised evaluator-blind placebo-controlled trial, 182 eligible patients with good-grade aSAH planned for surgical clipping will be enrolled from four neurosurgical centres in China. In addition to standard care, patients will be randomly assigned to receive sodium valproate 20 mg/kg daily or matching placebo. After aneurysmal clipping, patients will be followed up at discharge, 90 days and 180 days. The primary outcomes are the incidence of early and late seizures. The secondary outcomes include aSAH-related complications, sodium valproate-related adverse effects, modified Rankin Scale (mRS) (on discharge, at 90 days, 180 days), rate of good outcome (defined as mRS 0–2), all-cause death (at 90 days, 180 days) and Montreal Cognitive Assessment score (at 180 days). All analyses are by intention-to-treat.Ethics and disseminationThis study will be conducted according to the principles of Declaration of Helsinki and good clinical practice guidelines. This trial involves human participants and has been approved by the ethics committee of West China Hospital. Informed consent will be achieved from each included patient and/or their legally authorised representative. Preliminary and final results from this study will be disseminated through manuscript publishing and international congresses presentations. Any protocol amendments will be approved by the ethics committee of West China Hospital and subsequently updated on ChiCTR.Trial registration numberChiCTR.org identifier: ChiCTR2100050161.

Mycophenolic acid (MPA) is an occurring antibiotic produced through Penicillium brevicompactum. Its production was achieved by systematic process optimization under submerged fermentation. In shake flask, single-factor test experiments, Box-Behnken design (BBD) experiments, and fermentation strategy were determined, and the MPA yield was reached at 3002 ± 47, 3610 ± 51, and 4748 ± 59 µg/mL, respectively. For fermentation strategy, MPA production was 58.1% higher than that initial fermentation condition without optimization. Then, the optimized medium was further carried out in 5-L stirred fermenter for 180 h; MPA titer was increased from 3712 ± 65 µg/mL to 5786 ± 76 µg/mL, 55.9% higher than that of single-factor optimized medium. The results of this investigation will provide a vital step toward industrial-scale production of MPA.

Background. Intracranial vertebrobasilar trunk large (≥10 mm) aneurysms (IVBTLAs) are rare and challenging to manage. In this study, we describe the natural prognosis and evaluate the safety and efficacy of endovascular treatment of IVBTLAs compared with conservative therapy. Methods. This prospective multicenter cohort study included patients with IVBTLAs, who chose either endovascular treatment (endovascular group) or conservative therapy (conservative group) after discussion with their doctors. The primary endpoint was the incidence of serious adverse events (SAEs) related to the target vessel, while secondary endpoints included target vessel-related mortality, major stroke, other serious adverse events, and aneurysm occlusion rate. Results. In total, 258 patients were referred to our two centers for the management of vertebrobasilar aneurysms, and 69 patients had IVBTLAs. Among them, 51 patients underwent endovascular treatment, and 18 patients received conservative therapy. The incidence of target vessel-related SAEs was 15.7% (8/51) in the endovascular group and 44.4% (8/18) in the conservative group ( P = 0.031 ). The target vessel-related mortality was 2.0% (1/51) in the endovascular group and 38.9% (7/18) in the conservative group ( P < 0.001 ). The cumulative survival rates in the endovascular group and conservative group within 1-year, 3-year, and 5-year were 98.0% vs. 83.3%, P = 0.020 ; 98.0% vs. 66.7%, P = 0.001 ; and 98.0% vs. 35.6%, P < 0.001 , respectively. Multivariate analysis revealed conservative therapy, giant aneurysm, and ischemic onset as risks factor for SAEs. Conclusions. Compared with conservative treatment, endovascular treatment of the IVBTLAs may be associated with a lower incidence of SAEs, with higher 1-year, 3-year, and 5-year survival rates. Conservative therapy, giant aneurysm, and ischemic onset were associated with a high risk of SAEs.

ObjectiveTo analyze the complications and long-term results of endovascular management of vertebrobasilar trunk large (≥10 mm) aneurysms (VBTLAs) and identify predictors of outcomes.MethodsBetween 2014 and 2020, 6,987 patients with intracranial aneurysms were referred to our center for aneurysm management and 2,224 patients have undergone the endovascular procedures. We retrospectively reviewed the database and identify all the patients with VBTLAs.ResultsA total of 62 VBTLAs were identified. The median aneurysm size was 13.4 mm [interquartile range (IQR) 11.5–18.7]. Among them, 24 aneurysms were treated with overlapping stent techniques, 18 aneurysms were treated with flow diversion, 14 aneurysms were treated with single stent-assisted coiling, and 6 aneurysms were treated with coiling alone. Ten patients were treated with parent artery occlusion or unilateral vertebral artery occlusion. Periprocedural complications were occurred in 7 (11.3%) patients. Clinical follow-up was obtained at the median of 27.5 months (IQR 15.3–58.5). The overall complication rate was 16.1% (10/62), including nine ischemic events and one hemorrhagic event. The combined disability and neurological mortality rate was 12.9% (8/62), with 4 (6.5%) deaths. The favorable outcome rate at follow-up was 87.1% (54/62). The complication-free cumulative survival rates at 1 and 5 years were 86.8 and 82.0%, respectively. The overall cumulative survival rates at 1 and 5 year were 96.5 and 89.8%, respectively. In the multivariate Cox regression analysis, longer procedure time (>115 min) (P = 0.037) and ischemic onset (P = 0.005) predict complications. Angiography follow-up was available for 36 patients at the median of 6.0 months (IQR 6–12), with a complete occlusion rate of 77.8% (28/36). Two (5.6%) aneurysms were recanalized and subsequently received the retreatment. Subgroup analysis did not find any differences in the complete occlusion rate between endovascular strategies.ConclusionEndovascular management of VBTLAs has a reasonable safety profile with favorable 5-year cumulative survival rates and imaging outcomes at follow-up. Prolonged procedure and ischemic onset are associated with a high risk of overall complications.

To compare circular (circRNA) expression levels in the vitreous humour between PDR (proliferative diabetic retinopathy) and the control groups. The present study collected vitreous humour samples of both the PDR group and the control group (composed of rhegmatogenous retinal detachment, idiopathic macular hole and idiopathic macular epiretinal membrane). All the samples were subjected to circRNA and mRNA sequencing as well as bioinformatic analysis. The vitreous humour of the PDR and control groups was collected during PPV surgery. Compared to the control group, 122 upregulated and 9 downregulated circRNAs, and 818 upregulated mRNAs and 864 downregulated mRNAs were identified. We further selected 12 circRNAs to validate the RNA expression level by qPCR; results showed that with the exception of 2 downregulated circRNAs the remaining were significantly upregulated in the PDR group, which was consistent with RNA sequencing results. Bioinformatic analysis was conducted to predict possible miRNAs absorbed by circRNAs. Each circRNA could interact with at least five miRNAs. We randomly chose three miRNAs to test the expression level in the vitreous humour by qPCR and found these miRNAs were significantly downregulated in the PDR group. The changed profiling of circRNAs in the vitreous humour was reliable and may become a promising biomarker of DR and the circRNA–miRNA–mRNA network. It may also play an important role in the progression of DR.

Purpose: Retinal vein occlusion is associated with an increased risk of cardiovascular diseases. Anti-vascular endothelial growth factor has been widely used as a treatment option. However, the sys...

To evaluate the edema reduction after intravitreal injection of ranibizumab (IVR) in two diabetic macular edema (DME) components in the same eye using optical coherence tomography (OCT).Totally 113 eyes with mixed OCT pattern of DME were included. All the eyes underwent best-corrected visual acuity (BCVA) examination and OCT scanning at baseline and follow-up visits (1, 3, and 6 months after 3 monthly consecutive IVR). The mixed OCT pattern of DME was classified into 2 OCT components: serous retinal detachment (SRD) component and non-SRD component. Foveal thickness of the SRD component (SRDFT) and the non-SRD component (NSRDFT) was compared between baseline and follow-up visits. Reduction and reduction ratio of the SRDFT and the NSRDFT at each follow-up were compared. When calculating the NSRDFT reduction ratio, we innovatively optimized a commonly used formula by subtracting the normal foveal thickness from the baseline NSRDFT.SRDFT was 265.6 ± 175.4 μm at baseline and was significantly decreased to 126.7 ± 114.4 μm at 1 month, to 110.5 ± 103.4 μm at 3 months, and to 110.4 ± 89.6 μm at 6 months (all P 0.001). NSRDFT was 409.5 ± 173.1 μm at baseline and was significantly decreased to 274.1 ± 140.4 μm at 1 month, to 249.1 ± 95.9 μm at 3 months, and to 254.1 ± 90.4 μm at 6 months (all P 0.001). There was no significant difference in reduction or reduction ratio between NSRDFT and SRDFT during follow-up (all P 0.05). The correlation between BCVA and SRDFT was most significant at baseline (r = 0.366, P 0.001) and the correlation between BCVA and NSRDFT was most significant at 6 months (r = 0.426, P 0.001). BCVA improvement was more significantly correlated with reduction or reduction ratio of SRDFT at each follow-up timepoint (r = 0.271-0.426, all P 0.01).IVR was effective in reducing both the SRD and non-SRD components of DME according to our optimized formula. The association between BCVA improvement and edema reduction was more significant in the SRD component.

Intracranial vertebrobasilar dissecting aneurysms (VBDAs) are associated with a greater tendency to rupture and a greater risk of worse outcomes than anterior circulation aneurysms. Spontaneous healing of a VBDA is very rare, and there have been very few case reports of spontaneous healing of an aneurysm. We describe a case of intracranial vertebral artery dissecting aneurysm that healed spontaneously and disappeared completely on follow-up images.A 40-years-old woman was referred to the neurology department because of a persistent headache, especially in the left occiput.Magnetic resonance angiography and computed tomography angiography showed a left vertebral artery dissection-like aneurysm (4.5 × 2.0 × 2.5 mm in size) with proximal parent artery mild stenosis (40%).Flunarizine hydrochloride was administered for symptomatic treatment and follow-up angiography was performed.Digital subtraction angiography and magnetic resonance angiography showed that the aneurysm had completely disappeared at 3 months follow-up. High-resolution magnetic resonance vessel wall imaging revealed intimal thickening and mild stenosis in the left intracranial vertebral artery without an aneurysm signal. In addition, enhancement scanning revealed that the aneurysm area was moderately enhanced. MR-vessel wall imaging at 7 months follow-up showed that the enhancement was slightly reduced compared with the previous time.This case illustrates the relatively plastic nature of a vertebral dissecting aneurysm, indicating that spontaneous healing remains possible.

PURPOSE To investigate the safety and effect of the Pipeline Embolization Device (PED) Flex device in the treatment of large unruptured posterior circulation aneurysms in a single center. MATERIALS AND METHODS Patients with large unruptured posterior circulation aneurysms which were treated with the PED Flex device were enrolled. The clinical, endovascular and follow-up data were analyzed, and the O'Kelly-Marotta (OKM) grading system was used to assess the aneurysm occlusion status. RESULTS Fourteen patients with 14 large posterior circulation aneurysms who were treated with the PED Flex device were enrolled. The maximal diameter of aneurysm was 17.0 ± 3.9 mm. Fourteen PED Flex devices were deployed in 14 patients, with a technical success rate of 100%. All stents covered the aneurysm neck with good wall adherence and patent parent artery. Ten (71.4%) aneurysms were treated with a single PED Flex device each, and four (28.6%) patients experienced additional coiling. No neurological complications occurred in the periprocedural period. The mRS was 0 in eleven (78.6%) patients, 1 in two (14.3%), and 2 in one (7.1%) at discharge. All patients were followed up at 6-28 months (median 18), with an mRS score of 0 in all patients. Twelve (85.7%) patients experienced digital subtraction angiography 6-28 (median 18) months after the embolization procedure, and the OKM grade was D in nine (75%), C in two (16.7%), and B in one (8.3%). CONCLUSION The Pipeline Flex Embolization Device can be safely applied to treat large unruptured posterior circulation aneurysms with a high complete aneurysm occlusion rate at follow-up.

Background To develop a machine learning (ML) model for the prediction of the idiopathic macular hole (IMH) status at 1 month after vitrectomy and internal limiting membrane peeling (VILMP) surgery. Methods A total of 288 IMH eyes from four ophthalmic centers were enrolled. All eyes underwent optical coherence tomography (OCT) examinations upon admission and one month after VILMP. First, 1,792 preoperative macular OCT parameters and 768 clinical variables of 256 eyes from two ophthalmic centers were used to train and internally validate ML models. Second, 224 preoperative macular OCT parameters and 96 clinical variables of 32 eyes from the other two centers were utilized for external validation. To fulfill the purpose of predicting postoperative IMH status (i.e., closed or open), five ML algorithms were trained and internally validated by the ten-fold cross-validation method, while the best-performing algorithm was further tested by an external validation set. Results In the internal validation, the mean area under the receiver operating characteristic curves (AUCs) of the five ML algorithms were 0.882-0.951. The AUC, accuracy, sensitivity, and specificity of the best-performing algorithm (i.e., random forest, RF) were 0.951, 0.892, 0.973, and 0.904, respectively. In the external validation, the AUC of RF was 0.940, with an accuracy of 0.875, a specificity of 0.875, and a sensitivity of 0.958. Conclusions Based on the preoperative OCT parameters and clinical variables, our ML model achieved remarkable accuracy in predicting IMH status after VILMP. Therefore, ML models may help optimize surgical planning for IMH patients in the future.

Retinopathy of prematurity (ROP) is the leading cause of childhood blindness worldwide. Prediction of ROP before onset holds great promise for reducing the risk of blindness.To develop and validate a deep learning (DL) system to predict the occurrence and severity of ROP before 45 weeks' postmenstrual age.This retrospective prognostic study included 7033 retinal photographs of 725 infants in the training set and 763 retinal photographs of 90 infants in the external validation set, along with 46 characteristics for each infant. All images of both eyes from the same infant taken at the first screening were labeled according to the final diagnosis made between the first screening and 45 weeks' postmenstrual age. The DL system was developed using retinal photographs from the first ROP screening and clinical characteristics before or at the first screening in infants born between June 3, 2017, and August 28, 2019.Two models were specifically designed for predictions of the occurrence (occurrence network [OC-Net]) and severity (severity network [SE-Net]) of ROP. Five-fold cross-validation was applied for internal validation.Area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity to evaluate the performance in ROP prediction.This study included 815 infants (450 [55.2%] boys) with mean birth weight of 1.91 kg (95% CI, 1.87-1.95 kg) and mean gestational age of 33.1 weeks (95% CI, 32.9-33.3 weeks). In internal validation, mean AUC, accuracy, sensitivity, and specificity were 0.90 (95% CI, 0.88-0.92), 52.8% (95% CI, 49.2%-56.4%), 100% (95% CI, 97.4%-100%), and 37.8% (95% CI, 33.7%-42.1%), respectively, for OC-Net to predict ROP occurrence and 0.87 (95% CI, 0.82-0.91), 68.0% (95% CI, 61.2%-74.8%), 100% (95% CI, 93.2%-100%), and 46.6% (95% CI, 37.3%-56.0%), respectively, for SE-Net to predict severe ROP. In external validation, the AUC, accuracy, sensitivity, and specificity were 0.94, 33.3%, 100%, and 7.5%, respectively, for OC-Net, and 0.88, 56.0%, 100%, and 35.3%, respectively, for SE-Net.In this study, the DL system achieved promising accuracy in ROP prediction. This DL system is potentially useful in identifying infants with high risk of developing ROP.

AimsTo develop a deep learning (DL) model for automatic classification of macular hole (MH) aetiology (idiopathic or secondary), and a multimodal deep fusion network (MDFN) model for reliable prediction of MH status (closed or open) at 1 month after vitrectomy and internal limiting membrane peeling (VILMP).MethodsIn this multicentre retrospective cohort study, a total of 330 MH eyes with 1082 optical coherence tomography (OCT) images and 3300 clinical data enrolled from four ophthalmic centres were used to train, validate and externally test the DL and MDFN models. 266 eyes from three centres were randomly split by eye-level into a training set (80%) and a validation set (20%). In the external testing dataset, 64 eyes were included from the remaining centre. All eyes underwent macular OCT scanning at baseline and 1 month after VILMP. The area under the receiver operated characteristic curve (AUC), accuracy, specificity and sensitivity were used to evaluate the performance of the models.ResultsIn the external testing set, the AUC, accuracy, specificity and sensitivity of the MH aetiology classification model were 0.965, 0.950, 0.870 and 0.938, respectively; the AUC, accuracy, specificity and sensitivity of the postoperative MH status prediction model were 0.904, 0.825, 0.977 and 0.766, respectively; the AUC, accuracy, specificity and sensitivity of the postoperative idiopathic MH status prediction model were 0.947, 0.875, 0.815 and 0.979, respectively.ConclusionOur DL-based models can accurately classify the MH aetiology and predict the MH status after VILMP. These models would help ophthalmologists in diagnosis and surgical planning of MH.

Background To develop a deep learning (DL) model for prediction of idiopathic macular hole (MH) status after vitrectomy and internal limiting membrane peeling (VILMP) based on optical coherence tomography (OCT) images from four ophthalmic centers. Methods Eyes followed up at 1 month after VILMP for full-thickness MH were included. In the internal training set, 920 preoperative macular OCT images (as the input) and post-operative status of MH (closed or open, as the output) of 256 eyes from two ophthalmic centers were used to train the DL model using VGG16 algorithm. In the external validation set, 72 preoperative macular OCT images of 36 MH eyes treated by VILMP from another two ophthalmic centers were used to validate the prediction accuracy of the DL model. Results In internal training, the mean of overall accuracy for prediction of MH status after VILMP was 84.6% with a mean area under the receiver operating characteristic (ROC) curve (AUC) of 91.04% (sensitivity 85.37% and specificity 81.99%). In external validation, the overall accuracy of predicting MH status after VILMP was 84.7% with an AUC of 89.32% (sensitivity 83.33% and specificity 87.50%). The heatmaps showed that the area critical for prediction was at the central macula, mainly at the MH and its adjacent retina. Conclusions The DL model trained by preoperative macular OCT images can be used to predict postoperative MH status after VILMP. The prediction accuracy of our DL model has been validated by multiple ophthalmic centers.

Background: Stent retriever thrombectomy is the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO) in anterior circulation. The aim of the trial is to evaluate whether the new thrombectomy device-Skyflow can achieve the same safety and efficacy as Solitaire FR in the treatment.Method: This study is a prospective, multicenter, stratified randomized, single blind, paralleled, positive controlled, non-inferiority clinical trial. The safety and efficacy of vascular recanalization in AIS patients who are treated with either a new thrombectomy device-Skyflow or with Solitaire FR and within 8 h of symptom onset will be compared. A total of 192 patients will be enrolled, each group with 96 patients. The primary endpoint is successful recanalization rate after the operation. The secondary efficacy endpoints are the time from artery puncture to successful recanalization (mTICI 2b-3), NIHSS scores of 24 h (18–36 h), and 7 ± 2 days after the operation, mRS scores, and the rate of patients with mRS 0–2 scores 90 ± 14 days after the operation, and the success rate of instrument operation. The safety endpoints are the rate of symptomatic intracranial hemorrhage (sICH) and subarachnoid hemorrhage at 24 h (18–36 h) post-operation, incidence of adverse events (AE) and serious adverse events (SAE), all-cause mortality, and incidence of device defects.Discussion: This trial will provide information on the safety and efficacy of Sky-flow stent retriever in the treatment of AIS patients with anterior circulation LVO. The success of this trial will be the basis for the product to be finally officially listed and applied in China.Trial registration: Registered on 11 March 2018 with Chinese clinical trial registry. Registration number is ChiCTR1800015166.

Background As a new endovascular reconstruction technique, flow diverter (FD) shows excellent efficacy and safety for treatment of intracranial aneurysms. In a previous multicenter, randomized, controlled, pre-market study, Tubridge FD showed remarkably higher complete occlusion rate compared with traditional stent-assisted coiling. However, a nonsignificant higher complication rate in the Tubridge group was noted. Considering the learning curve, the safety, and long-term outcomes of Tubridge FD should be verified in new prospective, real world, multicenter, post-market trials. Methods This study is a prospective, multicenter, single-arm, post-market clinical trial that evaluates the safety and efficacy of Tubridge in the treatment of patients with intracranial aneurysms by reconstructing parent artery. We expect 200 participants who meet the inclusion and exclusion criteria to be included. Clinical information and angiographic results (Raymond–Roy grading scale, RRGS) will be recorded objectively. The primary endpoint will be the complete occlusion rate of the target aneurysm (RRGS 1) at 12-month follow-up. Secondary endpoints will include the adequate occlusion rate (RRGS 1 & 2) and the rate of major in-stent stenosis (>50%) at 12-month follow-up, technique success rate, changes of modified Rankin Scale before and after the procedure, the rate of aneurysm related disability, neurological mortality, and all-cause mortality within follow-up period. Discussion This post-market, prospective trial may offer more information on the safety and long-term outcomes of Tubridge FD. When the study is complete, the results may provide us a new strategy for the treatment of intracranial aneurysms. Trial registration: WHO-Chinese Clinical Trial Registry: ChiCTR2000032282.

Inflammation is known to be involved in the progression of diabetic retinopathy. Follicular helper T cells (Tfh) play critical roles in the differentiation of long-live plasma cells and production of antibodies, whereas circulating CD4

BackgroundFlow diverter (FD) is widely used in the treatment of intracranial aneurysms. However, thromboembolic events (TEs) continue to be the major complications during the periprocedural phase. To evaluate the safety and efficacy of the prophylactic use of tirofiban, combined with the conventional dual antiplatelet therapy (DAT), as a new antiplatelet protocol in patients with intracranial aneurysms treated with FDs.MethodsAt least 3–5 days before the procedure, daily DAT were administrated to the patients. Tirofiban was administered as an intravenous bolus (5 µg/kg) over a 3 min period during or immediately after FD deployment, followed by a 0.05 µg/kg/min maintenance infusion for 24–48 hours. Periprocedural TEs and hemorrhagic events (HEs) were recorded.ResultsA total of 331 patients were included, including 229 (69.2%) who received tirofiban administration (tirofiban group) and 102 (30.8%) who received only DAT (non-tirofiban group). Periprocedural TEs occurred in 12 (3.6%) patients, including eight (7.8%) in the non-tirofiban group and four (1.7%) in the tirofiban group. In multivariate analysis, patients receiving tirofiban administration had significantly lower TEs as compared with those who received only DAT (P=0.004). Balloon angioplasty and longer procedure time (>137 min) were also risk factors for TEs. Also, no increase was observed in the rate of HEs related to tirofiban administration.ConclusionsThe current study suggested that prophylactic administration of tirofiban combined with conventional oral DAT seems safe and efficient for preventing TEs during FD treatment of unruptured intracranial aneurysms. Balloon angioplasty and prolonged procedure are associated with a high risk of TEs.

Purpose To investigate retinal neurovascular structural changes in patients with essential hypertension. Methods This observational cross-sectional study consisted of 199 right eyes from 169 nondiabetic essential hypertensive patients, divided into groups as follows: group A, 113 patients with hypertensive retinopathy (HTNR); group B, 56 patients without HTNR; and a control group of 30 healthy subjects. Peripapillary retinal nerve fiber layer (RNFL), radial peripapillary segmented (RPC), ganglion cell-inner plexiform layer (GC-IPL), and superficial (SVP) and deep (DVP) vascular plexus density at the macula (6 × 6 mm2) were measured by optical coherence tomography angiography (OCTA). Results DVP density was significantly reduced in groups A and B compared to the control group (group A DVP, P = 0.001; group B DVP P = 0.002). GC-IPL, RNFL thickness, and RPC and SVP density in group A were significantly decreased compared to the control group or group B (all P < 0.05). In hypertensive patients, GC-IPL and RNFL thickness were negatively correlated with severity of HTNR (GC-IPL, r = -0.331, P < 0.001; RNFL, r = -0.583, P < 0.001) and level of home blood pressure monitoring (HBPM) (GC-IPL, r = -0.160, P = 0.050; RNFL, r = -0.282, P = 0.001) and were positively correlated with SVP (GC-IPL, r = 0.267, P = 0.002; RNFL, r = 0.361, P < 0.001) and RPC density (GC-IPL, r = 0.298, P < 0.001; RNFL, r = 0.663, P < 0.001). Among subjects with grade 2 or 3 retinopathy, the superior RNFL was significantly thinner in patients with high HBPM level than in those with normal HBPM level (grade 2, P = 0.016; grade 3, P = 0.006). Conclusions Reduction of retinal vessel density and RNFL thickness is observed in patients with HTNR and is inversely associated with level of HBPM.

Purpose. To evaluate the impact of restoration of foveal bulge (FB) in optical coherence tomography (OCT) images on visual acuity after resolution of diabetic macular edema with coexisting serous retinal detachment (SRD-DME). Methods. A total of 52 eyes with resolved SRD-DME and an intact ellipsoid zone at the central fovea were included. All eyes underwent best-corrected visual acuity (BCVA) examination and OCT scanning at baseline and follow-up visits (1, 3, and 6 months). The eyes were divided into two groups according to the presence of FB at 6 months. BCVA, central foveal thickness (CFT), height of SRD (SRDH), outer nuclear layer (ONL) thickness, photoreceptor inner segment (PIS), and outer segment (POS) length were compared between the two groups. Results. A FB was found in 25 of 52 (48%) eyes at 6 months. The FB (+) group had lower SRDH at baseline, and better BCVA, longer POS length at 6 months (all P<0.05). There was no significant difference in the CFT, ONL thickness, and PIS length at 6 months between the two groups (all P>0.05). More eyes in the FB (+) group had complete SRD resolution at 1 month (P=0.009) and 3 months (P=0.012). Eyes with complete SRD resolution at 1 month (P=0.009) or 3 months (P=0.012) were more likely to have a FB at 6 months. Conclusions. The Presence of the FB is associated with better BCVA after resolution of SRD-DME. Eyes with lower baseline SRDH or faster SRD resolution are more likely to have a FB at 6 months.

AimsTo investigate the function and the corresponding neurovascular structures in patients with diabetes without clinically detectable retinopathy.Methods Sixty-six patients with type 2 diabetes without retinopathy (NDR) and 62 healthy controls were recruited. The 16 and 32 Tds flicker electroretinography (ERG) was performed using a mydriasis-free, full-field flicker ERG recording device (RETeval). The vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP), FD300 and ganglion cell complex (GCC) thickness in the macula were quantified using optical coherence tomography angiography (OCTA). The retinal nerve fibre layer (RNFL) thickness and the radial peripapillary capillary (RPC) density in the peripapillary area were also measured with OCTA.ResultsParafoveal and perifoveal VD in both SCP and DCP decreased in NDR group in comparison to control group (all pConclusionFunctional and structural impairments have already started in diabetic retina even in the absence of visible retinal lesions. Subtle microvascular abnormalities rather than ganglion cell loss might be associated with early functional changes in NDR patients. Poor control of blood glucose was associated with delayed implicit time of flicker ERG in preclinical diabetic retinopathy.

Object: Follow-up evaluation of intracranial aneurysms treated by flow-diverting stents using MRI is challenging due to the presence of imaging artifacts. This study evaluated 3D T1-SPACE in combination with 3D-TOF sequence for follow-up evaluation of intracranial aneurysms treated with Pipeline embolization devices.Methods: Forty patients with 53 intracranial aneurysms who were treated with Pipeline Embolization Devices from October 2018 to July 2019 were enrolled in this study. All patients were evaluated for aneurysm occlusion and stent patency 4 to 7 months post-treatment using 3D T1-SPACE sequence, 3D-TOF MRA, and DSA examinations.Results: With regards to aneurysm occlusion, the intermodality (DSA and 3D-TOF MRA) agreement was good (κ = 0.755). The specificity of 3D-TOF MRA was 94.4% (34/36), the sensitivity was 76.5% (13/17), the total coincidence rate was 88.7% (47/53). With regards to the patency of the stented arteries after PED treatment, 3D T1-SPACE sequence was more accurate compared to 3D-TOF MRA (Z = −6.283, P < 0.001), with a no-artifact rate of 95.7% (44/46).Conclusions: 3D T1-SPACE sequence provides better image quality and higher accuracy for evaluating stented parent arteries compared to TOF-MRA. 3D-TOF MRA may be valuable in the evaluation of aneurysm occlusion. The combination of these two modalities may be used for long-term follow-up of intracranial aneurysms treated with Pipeline Embolization Devices.

Purpose: To compare vessel density in macular and peripapillary area between control subjects and patients with non-proliferative diabetic retinopathy (NPDR) using optical coherence tomography angiography (OCTA) and to evaluate the association between RNFL thickness and different stage of diabetic retinopathy. Methods: A total of 170 eyes (normal control, 43; mild NPDR, 43; moderate NPDR, 42; severe NPDR, 42) underwent OCTA imaging. Optical coherence tomography angiographic parameters were vessel densities of superficial capillary plexus (SCP), deep capillary plexus (DCP) in macular area and peripapillary area. Results: Vessel density of SCP and DCP in macular area, peripapillary area as well as RNFL thickness were 53.13%±3.03%, 52.07%±2.28%, 53.78%±3.66% and 128.86μm±11.32μm, respectively, in control subjects; 50.24%±3.81%, 47.40%±45.02%, 46.50%±6.03% and 124μm±13.97μm, respectively, in mild NPDR; 46.80%±5.23%; 44.39%±3.99%; 44.64%±4.23%; 121.02μm±20.86μm, respectively, in moderate NPDR; 42.82%±5.46%, 42.34%±5.14%, 43.16%±4.47%, 118.60μm±21.91μm in severe NPDR. The reduction of vessel density of SCP and DCP in macular area, peripapillary area as well as RNFL thickness were correlated with increasing severity of DR. Vessel density of SCP and DCP in macular area, peripapillary area and foveal density 300 (FD 300) in normal control were significantly higher than that of mild, moderate and severe NPDR groups. (all P

Objective: In-stent restenosis (ISR) after stenting for intracranial stenosis is a significant issue. This study aimed to evaluate the usefulness of the 3D T1-SPACE technique in the follow-up of patients after stent implantation. Methods: Fifteen patients with intracranial arterial stenosis were prospectively enrolled 6–8 months after stenting. Digital subtraction angiography (DSA) and 3D T1-SPACE imaging were performed to evaluate the degree of stenosis and the enhancement of the vessel wall. Bland–Altman plots were used to assess the agreement between the two imaging methods, and the Pearson correlation coefficient was calculated as a measure of the linear correlation. Results: Eight Enterprise stents and seven Wingspan stents were used in 15 patients. The follow-up DSA after 6–8 months showed that the degree of stenosis was 40% (range, 30–72%), and ISR occurred in 4 of 15 (26.7%) lesions. The degree of stenosis assessed using the 3D T1-SPACE imaging technique was 35% (range, 30–75%). All four patients with ISR demonstrated significant enhancement. The Pearson correlation coefficient between the two methods was 0.959 (p < 0.05), and the Bland–Altman plot showed that all data points were within the consistency limits ([Formula: see text] ± 1.96 s). Conclusion: As a non-invasive imaging modality, 3D T1-SPACE showed great consistency with DSA in measuring the degree of stenosis after intracranial stenting. It may be used as an optional method for detecting ISR. Advances in knowledge: This study evaluated the usefulness of 3D T1-SPACE technique in the follow-up of patients after stent implantation, which could be used as an optional and non-invasive method in detection of in-stent restenosis.

BACKGROUND: This study aimed to predict the treatment outcomes in patients with diabetic macular edema (DME) after 3 monthly anti-vascular endothelial growth factor (VEGF) injections using machine learning (ML) based on pretreatment optical coherence tomography (OCT) images and clinical variables. METHODS: An ensemble ML system consisting of four deep learning (DL) models and five classical machine learning (CML) models was developed to predict the posttreatment central foveal thickness (CFT) and the best-corrected visual acuity (BCVA). A total of 363 OCT images and 7,587 clinical data records from 363 eyes were included in the training set (304 eyes) and external validation set (59 eyes). The DL models were trained using the OCT images, and the CML models were trained using the OCT images features and clinical variables. The predictive posttreatment CFT and BCVA values were compared with true outcomes obtained from the medical records. RESULTS: For CFT prediction, the mean absolute error (MAE), root mean square error (RMSE), and R(2) of the best-performing model in the training set was 66.59, 93.73, and 0.71, respectively, with an area under receiver operating characteristic curve (AUC) of 0.90 for distinguishing the eyes with good anatomical response. The MAE, RMSE, and R(2) was 68.08, 97.63, and 0.74, respectively, with an AUC of 0.94 in the external validation set. For BCVA prediction, the MAE, RMSE, and R(2) of the best-performing model in the training set was 0.19, 0.29, and 0.60, respectively, with an AUC of 0.80 for distinguishing eyes with a good functional response. The external validation achieved a MAE, RMSE, and R(2) of 0.13, 0.20, and 0.68, respectively, with an AUC of 0.81. CONCLUSIONS: Our ensemble ML system accurately predicted posttreatment CFT and BCVA after anti-VEGF injections in DME patients, and can be used to prospectively assess the efficacy of anti-VEGF therapy in DME patients.