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Abstract Retinitis pigmentosa (RP) is characterized by progressive photoreceptor cells death accelerated by the proliferation and activation of microglia pathologically. No consensus exists on the treatment. Minocycline is recognized as a microglia inhibitor with great anti-inflammatory and neuro-protective functions. However, efficacy of minocycline in RP patients is lacking. We conducted a prospective, open-label, and single-arm trial, in which daily oral minocycline of 100 mg was administered for 12 months in RP patients with light-adapted 30 Hz flicker electroretinography (ERG) amplitude >0 µV in at least one eye (NCT04068207). The primary outcome was the proportion of participants with improvement in the ERG amplitude at month 12. The secondary outcomes included improvements of the following items: other ERGs amplitudes, visual field, best-corrected visual acuity, contrast sensitivity, color vision, and NEI-VFQ-25. 35 of 288 patients met inclusive criteria were enrolled (median [IQR] age, 36 [31–45] years; 17 female [48.6%]). 32 participants completed all examinations, while 3 participants completed the 12-month online visit via conducting NEI-VFQ-25. The primary outcome showed improvement was 34.3% (12 of 35 [95% CI 19.1–52.2]). Similarly, all secondary outcomes showed improvements. Adverse events were reported in 22 participants (62.9%) and were all resolved without extra medication during the study period. No severe adverse events were recorded. Our findings identified daily oral minocycline of 100 mg for 12 months was beneficial in improving the visual function of RP patients with good safety. This study indicates minocycline may be a promising therapy for RP, but a randomized controlled trial is still needed of further exploration.

This article presents a triple extraction technique for a power transformer fault information process based on a residual dilate gated convolution and self-attention mechanism. An optimized word input sequence is designed to improve the effectiveness of triple extraction. A residual dilate gated convolution is used to capture the middle-long distance information in the literature. A self-attention mechanism is applied to learn the internal information and capture the internal structure of input sequences. An improved binary tagging method with position information is presented to mark the start and the end of an entity, which improves the extraction accuracy. An object entity is obtained by a specific relationship r for a given subject. The nearest start-end pair matching the principle and probability estimation is applied to acquire the optimal solution of the set of triples. Testing results showed that the F1 score of the presented method is 91.98%, and the triple extraction accuracy is much better than the methods of BERT and Bi-LSTM-CRF.

Abstract Background Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. Methods The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. Discussion This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. Trial registration ClinicalTrials.gov : NCT04257656. Registered on 6 February 2020.

Abstract Background To develop a deep neural network able to differentiate glaucoma from non-glaucoma visual fields based on visual filed (VF) test results, we collected VF tests from 3 different ophthalmic centers in mainland China. Methods Visual fields obtained by both Humphrey 30–2 and 24–2 tests were collected. Reliability criteria were established as fixation losses less than 2/13, false positive and false negative rates of less than 15%. Results We split a total of 4012 PD images from 1352 patients into two sets, 3712 for training and another 300 for validation. There is no significant difference between left to right ratio (P = 0.6211), while age (P = 0.0022), VFI (P = 0.0001), MD (P = 0.0039) and PSD (P = 0.0001) exhibited obvious statistical differences. On the validation set of 300 VFs, CNN achieves the accuracy of 0.876, while the specificity and sensitivity are 0.826 and 0.932, respectively. For ophthalmologists, the average accuracies are 0.607, 0.585 and 0.626 for resident ophthalmologists, attending ophthalmologists and glaucoma experts, respectively. AGIS and GSS2 achieved accuracy of 0.459 and 0.523 respectively. Three traditional machine learning algorithms, namely support vector machine (SVM), random forest (RF), and k-nearest neighbor (k-NN) were also implemented and evaluated in the experiments, which achieved accuracy of 0.670, 0.644, and 0.591 respectively. Conclusions Our algorithm based on CNN has achieved higher accuracy compared to human ophthalmologists and traditional rules (AGIS and GSS2) in differentiation of glaucoma and non-glaucoma VFs.

This study examines the usefulness of both geometric and volumetric measurements of orbital soft tissues on CT scans to provide quantitative diagnostic guidance in image reading of thyroid eye disease (TED). Computed tomography (CT) images were obtained from 92 orbits and were classified as impaired motility (TED-IM) and normal motility (TED-NM). The TED-IM group was further divided into dysthyroid optic neuropathy (DON) and non-DON groups. There were 5 volumetric, 2 angular, and 3 ratio parameter measurements acquired from CT images to examine their feasibility in TED classification. We found that the mean volumes of extraocular muscle and retroorbital fat and their ratio to the orbital volume were significantly different between the two motility groups. The mean ratio of extraocular muscle volume in orbital apex and orbital apex volume (EMV-OA/OAV) was significantly larger in DON than non-DON patients (p < 0.05). The population distribution among TED-NM, non-DON, and DON groups significantly varied for different angles between the optic nerve and medial rectus and lateral rectus. In conclusion, geometric and volumetric measurements using CT scans help to quantitatively classify TED.

Background: Retinal degenerative disorders (RDs) are the main cause of blindness without curable treatment. Our previous studies have demonstrated that human-induced pluripotent stem cells can differentiate into retinal organoids with all subtypes of retina, which provides huge promise for treating these diseases. Before these methods can be realized, RD animal models are required to evaluate the safety and efficacy of stem cell therapy and to develop the surgical tools and procedures for cell transplantation in patients. This study involved the development of a monkey model of RD with controllable lesion sites, which can be rapidly prepared for the study of preclinical stem cell therapy among other applications. Methods: Sodium nitroprusside (SNP) in three doses was delivered into the monkey eye by subretinal injection (SI), and normal saline was applied as control. Structural and functional changes of the retinas were evaluated via multimodal imaging techniques and multifocal electroretinography (mfERG) before and after the treatment. Histological examination was performed to identify the target layer of the affected retina. The health status of monkeys was monitored during the experiment. Results: Well-defined lesions with various degrees of retinal degeneration were induced at the posterior pole of retina as early as 7 days after SNP SI. The damage of SNP was dose dependent. In general, 0.05 mM SNP caused mild structural changes in the retina; 0.1 mM SNP led to the loss of outer retinal layers, including the outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE); while 0.2 mM SNP impacted the entire layer of the retina and choroid. MfERG showed reduced amplitude in the damaged region. The structural and functional damages were not recovered at 7-month follow-up. Conclusion: A rapidly induced lesion site-controllable retinal degeneration monkey model was established by the subretinal administration of SNP, of which the optimal dose is 0.1 mM. This monkey model mimics the histological changes of advanced RDs and provides a valuable platform for preclinical assessment of stem cell therapy for RDs.

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Abstract Purpose  To identify the subtype frequency and clinical features of neovascular age-related macular degeneration (AMD) in Chinese patients. Methods  From January 2003 to August 2006, we investigated prospectively 155 newly diagnosed patients with presumed neovascular AMD. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed in both eyes of all patients. Subtype frequency and clinical features were recorded according to their angiograms. Results  Three subtypes of lesion were noted, which were polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP) and mixed lesions. Of the 155 patients, 105 (67.7%) had choroidal neovascularization (CNV) of the typical type seen in AMD, 38 (24.5%) had PCV and seven (4.5%) had RAP. In five (3.2%) additional cases, mixed lesions were noted. In 38 cases (47 eyes) with PCV, the rates of subfoveal, juxtafoveal and extrafoveal lesion were respectively 29.8% (14 eyes), 8.5% (four eyes), and 61.7% (29 eyes), compared with 75.6%, 14.6% and 9.8% for CNV lesion (P P  Conclusions  In this hospital-based study, PCV accounts for 24.5% of neovascular AMD and is the most common subtype, RAP is less frequent (4.5%), and mixed lesions are much less common in Chinese patients. PCV is least likely to involve the fovea in neovascular AMD. [ABSTRACT FROM AUTHOR]

Abstract To compare cone and rod system function in patients with early age- related macular degeneration (ARMD) and control group using multifocal electroretinogram (MERG) and perimetry, to investigate whether there is rod system dysfunction in the central retina in ARMD. Cone-mediated MERG, photopic sensitivity, rod-mediated MERG, and scotopic sensitivity in 16 eyes of control subjects and 24 eyes of early dry-form ARMD were measured with VERIS Science TM 4.0 and Octopus 101 perimetry. The latencies and average response densities of the summed responses and five ring retinal regions, average sensitivity of all locus and eight ring retinal regions in control eyes were compared with those in ARMD. Mean scotopic and photopic sensitivity of ARMD patients were significantly lower than that of normal controls. Sotopic sensitivity reduced more than photopic sensitivity and the greatest deficit was 2.55.0. The amplitudes of N1 and P1 wave in one ring (5.0) of rod MERG were significantly lower of ARMD patients than that of normal subjects. Our results suggest that rod function decreased and the parafoveal rod cells were predominantly damaged in ARMD. The rod function testing in macula may be a useful tool to diagnose and measure the fundus dysfunction of ARMD. [ABSTRACT FROM AUTHOR]

To measure and compare the multifocal electroretinography in normal control and X-linked juvenile retinoschisis, 13 cases (13 right eyes) of normal control and nine cases (17 eyes) of X-linked juvenile retinoschisis were measured with VERIS Science 4.0. Four cases (eight eyes) out of the nine retinoschisis cases were tested with Ganzfeld ERG at the same day. The results showed statistically significant difference of average response densities and latencies in six ring retinal regions between the normal control and retinoschisis. The trace array and 3-D topography of multifocal ERG showed multi-area amplitude decrease with absence or reduction of central peak amplitude in patients with retinoschisis. The P1/N1 ratio of multifocal ERG average response densities in six ring retinal regions was different from the b/a ratio of Ganzfeld ERG. The multifocal ERG and Ganzfeld ERG each had its advantage in the diagnosis of retinoschisis. [ABSTRACT FROM AUTHOR]

Purpose: To compare multifocal electroretinograms (ERGs) in control subjects and patients with central serous chorioretinopathy (CSC). Method: Eighteen eyes of control subjects and 15 eyes affected by CSC were tested with a VERIS Sciences 4.0 system. The average response densities and latencies of six annular retinal regions in control subjects were compared with those with CSC. Results: The N[SUB1], P[SUB1] average response densities of the first and second annuli were decreased and the N[SUB1], P[SUB1] latencies of first to third rings were delayed in CSC. Conclusion: The multifocal ERG can be used to evaluate retinal dysfunction in CSC. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and cytokine storm. Exploring the immuneinflammatory characteristics of COVID-19 patients is essential to reveal pathogenesis and predict progression. In this study, COVID-19 patients showed decreased CD3+, CD4+, and CD8+ T cells but increased neutrophils in circulation, exhibiting upregulated neutrophil-to-lymphocyte and neutrophil-to-CD8+ T cell ratio. IL-6, TNF-α, IL-1β, IL-18, IL-12/IL-23p40, IL-10, Tim-3, IL-8, neutrophil extracellular trap-related proteinase 3, and S100A8/A9 were elevated, whereas IFN-γ and C-type lectin domain family 9 member A (clec9A) were decreased in COVID-19 patients compared with healthy controls. When compared with influenza patients, the expressions of TNF-α, IL-18, IL-12/IL-23p40, IL-8, S100A8/A9 and Tim-3 were significantly increased in critical COVID-19 patients, and carcinoembryonic Ag, IL-8, and S100A8/A9 could serve as clinically available hematologic indexes for identifying COVID-19 from influenza. Moreover, IL-6, IL-8, IL-1β, TNF-α, proteinase 3, and S100A8/A9 were increased in bronchoalveolar lavage fluid of severe/critical patients compared with moderate patients, despite decreased CD4+ T cells, CD8+ T cells, B cells, and NK cells. Interestingly, bronchoalveolar IL-6, carcinoembryonic Ag, IL-8, S100A8/A9, and proteinase 3 were found to be predictive of COVID-19 severity and may serve as potential biomarkers for predicting COVID-19 progression and potential targets in therapeutic intervention of COVID-19. [ABSTRACT FROM AUTHOR]