2Memristor-1Capacitor Integrated Temporal Kernel for High-Dimensional Data Mapping.

Compact but precise feature-extracting ability is core to processing complex computational tasks in neuromorphic hardware. Physical reservoir computing (RC) offers a robust framework to map temporal data into a high-dimensional space using the time dynamics of a material system, such as a volatile memristor. However, conventional physical RC systems have limited dynamics for the given material properties, restricting the methods to increase their dimensionality. This study proposes an integrated temporal kernel composed of a 2-memristor and 1-capacitor (2M1C) using a W/HfO2 /TiN memristor and TiN/ZrO2 /Al2 O3 /ZrO2 /TiN capacitor to achieve higher dimensionality and tunable dynamics. The kernel elements are carefully designed and fabricated into an integrated array, of which performances are evaluated under diverse conditions. By optimizing the time dynamics of the 2M1C kernel, each memristor simultaneously extracts complementary information from input signals. The MNIST benchmark digit classification task achieves a high accuracy of 94.3% with a (196×10) single-layer network. Analog input mapping ability is tested with a Mackey-Glass time series prediction, and the system records a normalized root mean square error of 0.04 with a 20×1 readout network, the smallest readout network ever used for Mackey-Glass prediction in RC. These performances demonstrate its high potential for efficient temporal data analysis.

Visual field prediction using a deep bidirectional gated recurrent unit network model.

Although deep learning architecture has been used to process sequential data, only a few studies have explored the usefulness of deep learning algorithms to detect glaucoma progression. Here, we proposed a bidirectional gated recurrent unit (Bi-GRU) algorithm to predict visual field loss. In total, 5413 eyes from 3321 patients were included in the training set, whereas 1272 eyes from 1272 patients were included in the test set. Data from five consecutive visual field examinations were used as input; the sixth visual field examinations were compared with predictions by the Bi-GRU. The performance of Bi-GRU was compared with the performances of conventional linear regression (LR) and long short-term memory (LSTM) algorithms. Overall prediction error was significantly lower for Bi-GRU than for LR and LSTM algorithms. In pointwise prediction, Bi-GRU showed the lowest prediction error among the three models in most test locations. Furthermore, Bi-GRU was the least affected model in terms of worsening reliability indices and glaucoma severity. Accurate prediction of visual field loss using the Bi-GRU algorithm may facilitate decision-making regarding the treatment of patients with glaucoma.

Data Preprocessing and Augmentation Improved Visual Field Prediction of Recurrent Neural Network with Multi-Central Datasets.

INTRODUCTION: The purpose of this study was to determine whether data preprocessing and augmentation could improve visual field (VF) prediction of recurrent neural network (RNN) with multi-central datasets. METHODS: This retrospective study collected data from five glaucoma services between June 2004 and January 2021. From an initial dataset of 331,691 VFs, we considered reliable VF tests with fixed intervals. Since the VF monitoring interval is very variable, we applied data augmentation using multiple sets of data for patients with more than eight VFs. We obtained 5,430 VFs from 463 patients and 13,747 VFs from 1,076 patients by setting the fixed test interval to 365 ± 60 days (D = 365) and 180 ± 60 days (D = 180), respectively. Five consecutive VFs were provided to the constructed RNN as input and the 6th VF was compared with the output of the RNN. The performance of the periodic RNN (D = 365) was compared to that of an aperiodic RNN. The performance of the RNN with 6 long- and short-term memory (LSTM) cells (D = 180) was compared with that of the RNN with 5-LSTM cells. To compare the prediction performance, the root mean square error (RMSE) and mean absolute error (MAE) of the total deviation value (TDV) were calculated as accuracy metrics. RESULTS: The performance of the periodic model (D = 365) improved significantly over aperiodic model. Overall prediction error (MAE) was 2.56 ± 0.46 dB versus 3.26 ± 0.41 dB (periodic vs. aperiodic) (p < 0.001). A higher perimetric frequency was better for predicting future VF. The overall prediction error (RMSE) was 3.15 ± 2.29 dB versus 3.42 ± 2.25 dB (D = 180 vs. D = 365). Increasing the number of input VFs improved the performance of VF prediction in D = 180 periodic model (3.15 ± 2.29 dB vs. 3.18 ± 2.34 dB, p < 0.001). The 6-LSTM in the D = 180 periodic model was more robust to worsening of VF reliability and disease severity. The prediction accuracy worsened as the false-negative rate increased and the mean deviation decreased. CONCLUSION: Data preprocessing with augmentation improved the VF prediction of the RNN model using multi-center datasets. The periodic RNN model predicted the future VF significantly better than the aperiodic RNN model.

Comparisons of efficacy and safety between preserved and preservative-free brimonidine tartrate in glaucoma and ocular hypertension: a parallel-grouped, randomized trial.

This multicenter (four institutions), randomized, investigator-masked, parallel-group clinical trial evaluated and compared the efficacy and safety of preservative-free and preserved brimonidine tartrate 0.15% in open-angle glaucoma and ocular hypertension. Sixty eyes of 60 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomized to preserved (n = 31) and preservative-free (n = 29) brimonidine groups. The enrolled eyes received brimonidine monotherapy three times daily. Main outcome measures were corneal/conjunctival staining score, ocular surface disease index, patient satisfaction score, drug tolerance, and drug adherence rate 12 weeks post first administration. Secondary outcome measurements included visual acuity, IOP, drug tolerance, tear-film break-up time, hemodynamic changes including blood pressure and heart rates, and ocular adverse events. After 12 weeks, both preserved and preservative-free groups showed similar IOP reduction, corneal and conjunctival staining scores, drug tolerance, and adherence rates. The preservative-free group showed significantly better tear-film break-up time and higher patient satisfaction regarding drug use and management. Systolic and diastolic blood pressure reductions during the 12 weeks were significantly lower in the preserved group than in the preservative-free group. Preservative-free brimonidine tartrate showed comparable efficacy and safety, better corneal tear film stability, and patient satisfaction than preserved brimonidine.

The choroidal microvasculature of the parapapillary area as a biomarker of glaucoma development in the fellow eye of patients with unilateral glaucoma.

PURPOSE: To investigate the factors associated with the development of glaucoma in the healthy eyes of unilateral glaucoma patients. MATERIALS AND METHODS: This was a retrospective observational case series study. All participants had unilateral primary open-angle glaucoma at the initial visit and were divided into two groups: one in which the fellow eyes developed glaucoma during the follow-up period and one in which the fellow eyes remained healthy. A complete ophthalmic examination, including best-corrected visual acuity testing, slit-lamp examination, intraocular pressure measurement, retinal nerve fiber layer and optic disk photographs, a 30-2 visual field test, and optical coherence tomography with angiography, was performed over a follow-up period of at least 3 years. RESULTS: A total of fifty-six patients were enrolled, and over the course of the study period, 11 patients developed glaucoma in the fellow eyes, while the fellow eyes of 45 patients remained healthy. At the baseline, the glaucomatous eye had a larger area of beta parapapillary atrophy, lower parapapillary choroidal vascular density (pCVD) within the area, and a lower prevalence of microvascular dropout than normal fellow eyes (P < 0.001, 0.013, 0.001, respectively). In the multivariate analysis, a reduced pCVD in the gamma parapapillary atrophy (γPPA) region was significantly associated with the development of glaucoma in normal eyes (odds ratio, 0.566; 95% CI, 0.342, 0.935; P = 0.026). CONCLUSIONS: The pCVD within the γPPA region at baseline is the risk factor for the development of glaucoma in the normal fellow eye of patients with unilateral glaucoma.

The Efficacy of Atelocollagen to Inhibit Fibrotic Proliferation in Tenon Tissue: in vitro study.

INTRODUCTION: To evaluate the safety and efficacy of atelocollagen in preventing the fibrotic change of human tenon tissue induced by transforming growth factor ß1 (TGFß1) Methods: Primary cultured human Tenon's fibroblasts (HTFs) were incubated with TGFß1 alone, and with a various concentrations of atelocollagen respectively. Cell viability was measured by cell counting kit-8 (CCK8). The mRNA levels of α-smooth muscle actin (α-SMA), vimentin, fibronectin, zonular occludens scaffolding protein (ZO-1), cellular communication network factor 2 (CCN2) and interleukin-6 (IL-6) were measured by quantitative reverse transcription polymerase chain reaction (RT-PCR), western blot and immunofluorescence analysis. Wound healing assay and collagen contraction assay were additionally evaluated for identifying the inhibitory effect of atelocollagen in HTFs. To elucidate the mechanism by which atelocollagen affects HTFs proliferation, the phospho-extracellular-signal-regulated kinases (pERK)/total-extracellular-signal-regulated kinases (tERK), phospho-focal adhesion kinase (pFAK)/total-focal adhesion kinase (tFAK), and pSmad3/tSmad3 protein expression ratios were measured by Western blot. RESULTS: The safety of atelocollagen in HTF was identified by CCK8 analysis. The expression of α-SMA and vimentin in HTFs treated with 0.023% and 0.046% atelocollagen significantly decreased at both mRNA and protein levels, while that of ZO-1 in 0.046% atelocollagen increased compared with TGFß1-treated cells. The protein expression of fibronectin, CCN2, and IL-6 in HTFs treated with 0.023% and 0.046% atelocollagen significantly decreased. Immunofluorescence microscopy of α-SMA and ZO-1 showed results similar to those of the western blot. In the wound scratch assays, cell migration was significantly attenuated in HTFs treated with 0.005% atelocollagen. Atelocollagen at 0.005, 0.011, and 0.023% significantly inhibited the gel contraction induced by TGFß1 at both 24 h and 48 h. The increase in pERK/tERK and pSmad3/tSmad3 protein expression ratios in TGFß1-treated HTFs significantly decreased after treatment with 0.023 and 0.046% atelocollagen. CONCLUSION: Since atelocollagen gel effectively suppresses the proliferation of HTFs in TGFß1 - induced transdifferentiation, it may be a potential therapeutic agent in glaucoma surgery.

A Phase 3, Multicenter, Randomized, Controlled Trial to Evaluate Immune Equivalence and Safety of Multidose and Single-dose Formulations of Vi-DT Typhoid Conjugate Vaccine in Healthy Filipino Individuals 6 Months to 45 Years of Age.

Trial Design: Phase 3, randomized, controlled, multicenter, equivalence trial. Methods: Recruitment of participants occurred between 04Februray2020 and 15July2020 at four centers in the Philippines: University of the East - Ramon Magsaysay Memorial Medical Center Inc., Quezon City; University of Philippines Manila - National Institute of Health, Ermita Manila; Asian Hospital and Medical Center, Metro Manila, Philippines Study; and Medical Research Unit, Tropical Disease Foundation, Makati City, Metro Manila, Philippines. Participants: 1800 adults and children 6-months to 45-years of age. Interventions: Participants received a single injection of multidose (MD) or single dose (SD) Vi-DT as test vaccines or meningococcal conjugate vaccine as a comparator. Objective: To evaluate immune equivalence of SD and MD formulations of Vi-DT, and to assess the safety of both formulations compared with comparator vaccine. Outcome Measurement: Blood draw for immunogenicity was performed at baseline prior to vaccine receipt and at four weeks after vaccination for a subset of participants to determine anti-Vi IgG geometric mean titers (GMT) and seroconversion rates. The primary outcome was comparison of anti Vi-IgG seroconversion and GMT between the two formulations of Vi-DT at 4 weeks following vaccine administration. Immune equivalence of MD and SD formulations was confirmed when the two-tailed 95% confidence interval (CI) of the GMT ratio is within [0.67, 1.5] at a two-sided significance level of 0.05. All participants were followed for safety events for six months after vaccine administration. Randomization: Participants were randomized to receive SD Vi-DT, MD Vi-DT, or meningococcal conjugate vaccines in 2.5:2.5:1 allocation ratio. Blinding: Study participants and observers were blinded to treatment assignment. Findings: Immune equivalence of SD (n=252) and MD (n=247) formulations was confirmed by anti-Vi IgG GMT ratio of 1.14 (95%CI: 0.91, 1.43) with respective GMTs in the MD and SD groups of 640.62 IU/mL (95%CI: 546.39, 751.11) and 562.57 IU/mL (95%CI: 478.80, 661.00) (p=0.259). Similarly, anti-Vi IgG seroconversion rate difference between the two formulations of ‒0.43% (95%CI: -4.42, 3.56) confirmed immune equivalence with corresponding seroconversion rates of 98.38% (95%CI: 95.91, 99.37) and 98.81% (95%CI: 96.56, 99.59) in MD and SD Vi-DT formulations, respectively (p=0.722). Both formulations of Vi-DT had a satisfactory safety profile - all five serious adverse events reported during the study were unrelated to the investigational product. Interpretation: The MD and SD formulations of Vi-DT elicited robust and equivalent immune responses following one dose vaccination, and both formulations demonstrated a favorable safety profile. Trial Registration: ClinicalTrials.gov: NCT04204096. Funding: This study was funded by the Bill & Melinda Gates Foundation (OPP 1115556).

Cytotoxicities and wound healing effects of contact lens multipurpose solution on human corneal epithelial cell.

CLINICAL RELEVANCE: Contact lens multipurpose solutions (MPSs) contain several components that have the potential to cause corneal epithelial cell toxicity. Evaluating the components and the toxic effect of MPS should be considered for effective eye care. BACKGROUND: The cytotoxic and wound healing effects of five commercially available MPSs on human corneal epithelial cells (HCECs) are is investigated. METHODS: The following commercially available MPSs were used: Queen's PLURISOL®, Frenz®, Boston SIMPLUS®, DL+PLUS EYE® (DL), and NEW YORK DEFINE® (NY). The proliferation of HCECs exposed to each MPS for 1, 6, and 24 h and the cytotoxicity of these solutions were analyzed using methyl thiazolyl tetrazolium-based colorimetric and lactate dehydrogenase leakage assays, respectively. The cellular morphology was evaluated by inverted phase-contrast and electron microscopy. A scratch-wound assay was performed to measure wound widths 24 h after confluent HCEC monolayers were scratch-wounded. RESULTS: The tested MPS had a time-dependent inhibitory effect on HCEC proliferation and cytotoxicity, significantly at 24 h after exposure (p< 0.05 in all MPSs). HCECs exposed to MPS detached from the bottom of the culture dishes, showed degenerative changes such as loss of microvilli, cytoplasmic vacuole formation and nuclear condensation, and decreased wound healing, compared to the controls (p< 0.001 in Boston, DL and NY). Among the tested MPS, DL and NY were more cytotoxic and showed less wound healing. CONCLUSION: MPS has a toxic effect on HCECs, which is dependent on the concentration of the disinfecting component. Since the components that constitute the MPS are absorbed and retained in the lens, cautious scrutiny of the concentration and attention to lens cleaning are warranted to mitigate the related cytotoxicity.

Comparison of ocular surface assessment and adherence between preserved and preservative-free latanoprost in glaucoma: a parallel-grouped randomized trial.

Given that nonadherence is related to subject characteristics and drug tolerance and preserved eye drops tend to be more intolerable than preservative-free ones, we conducted a phase 4, parallel-grouped, investigator-blind, active-control, randomized, multicenter study. A total of 51 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomly assigned to the preserved latanoprost group (n = 26) and the preservative-free latanoprost group (n = 25). The efficacy variables were corneal/conjunctival staining grade, Ocular Surface Disease Index (OSDI), adherence at 12 weeks after the first administration; corneal/conjunctival staining grade at 4 weeks; and IOP, tear break-up time (TBUT), and hyperemia score at 4 and 12 weeks. The safety variables included visual acuity and drug tolerance questionnaire results. There was no statistically significant difference in corneal/conjunctival staining grade, OSDI, or TBUT between the groups at 4 and 12 weeks. However, the adherence rate was higher and the hyperemia score was lower in the preservative-free group than in the preserved group. The severity and duration of stinging/burning sensation were lower in the preservative-free group than in the preserved group. Overall, preservative-free latanoprost showed better ocular tolerance assessed by hyperemia scores and stinging/burning symptoms following higher adherence than preserved latanoprost.

Visual Field Inference From Optical Coherence Tomography Using Deep Learning Algorithms: A Comparison Between Devices.

Purpose: To develop a deep learning model to estimate the visual field (VF) from spectral-domain optical coherence tomography (SD-OCT) and swept-source OCT (SS-OCT) and to compare the performance between them. Methods: Two deep learning models based on Inception-ResNet-v2 were trained to estimate 24-2 VF from SS-OCT and SD-OCT images. The estimation performance of the two models was evaluated by using the root mean square error between the actual and estimated VF. The performance was also compared among different glaucoma severities, Garway-Heath sectorizations, and central/peripheral regions. Results: The training dataset comprised images of 4391 eyes from 2350 subjects, and the test dataset was obtained from another 243 subjects (243 eyes). In all subjects, the global estimation errors were 5.29 ± 2.68 dB (SD-OCT) and 4.51 ± 2.54 dB (SS-OCT), and the estimation error of SS-OCT was significantly lower than that of SD-OCT (P < 0.001). In the analysis of sectors, SS-OCT showed better performance in all sectors except for the inferonasal sector in normal vision and early glaucoma. In advanced glaucoma, the estimation error of the central region was worsened in both OCTs, but SS-OCT was still significantly better in the peripheral region. Conclusions: Our deep learning model estimated the VF 24-2 better with a wide field image of SS-OCT than did with retinal nerve fiber layer and ganglion cell-inner plexiform layer images of SD-OCT. Translational Relevance: This deep learning method can help clinicians to determine the VF from OCT images. OCT manufacturers can equip this system to provide additional VF data.

Relationship between peripapillary vessel density and visual function based on Garway-Heath sectorization in open-angle glaucoma.

Purpose: To investigate the relationship between peripapillary vessel density (pVD) and visual field sensitivity (VFS) and between peripapillary retinal nerve fiber layer thickness (pRNFLT) and VFS, based on Garway-Heath sectorization in open-angle glaucoma patients. Methods: Sixty-six eyes of healthy subjects and 84 eyes of glaucoma subjects were included. All subjects underwent several eye examinations, including standard automated perimetry and optical coherence tomography angiography. Sectoral structure-function relationships based on the Garway-Heath sectorization were compared among normal subjects, the 'mild glaucoma,' and 'moderate-to-severe glaucoma' group. Multivariate analyses were performed for each sector to determine the factors related to VFS. The diagnostic abilities of vessel density parameters and RNFLT were evaluated by calculating the area under the receiver operating characteristic curves (AUROC). Results: The correlation between pVD-VFS and pRNFLT-VFS was statistically significant in the glaucoma group independent of the VFS sector. In the glaucoma group, VFS in the temportal sector was statistically related in a multivariate model to pVD, pRNFLT and age (R2 = 0.721; P = 0.007, < 0.001, .15, respectively). We found pRNFLT and age were significantly associated with VFS in glaucoma. The AUROC values of pVD in the inferotemporal sector of the total, mild, and moderate-to-severe glaucoma (0.843, 0.714, and 0.972, respectively) were comparable to pRNFLT in this sector (0.833, 0.718, 0.948, respectively). Conclusion: Since the relationship between pVD and VFS in the papillomacular area was significant, measuring pVD and RNFLT in the corresponding area will be valuable in expanding our pathophysiologic knowledge of the paracentral field defects in glaucoma.

A randomised, prospective study of the effects of 3% diquafosol on ocular surface following cataract surgery.

There is still no established therapeutic solution for postoperative Dry Eye Syndrome (DES) after cataract surgery, in spite of progress in surgical techniques. Diquafosol tetrasodium (DQS), a recently developed ophthalmic solution, has been reported to be effective in DES, but no study evaluated post-cataract surgery lipid layer thickness (LLT) changes in healthy patients who used DQS postoperatively. We randomly divided participants into two groups; the DQS group was treated six times daily with DQS after cataract surgery, and the sodium hyaluronate (HA) group was treated with HA in the same way. Throughout study period, the DQS group showed significantly higher tear break up time (TBUT) and LLT than HA group. In multivariate analysis, better preoperative TBUT, Schirmer's I test score, ocular surface disease index (OSDI) score, and LLT were significantly associated with improved postoperative outcomes in each parameter. Also, the postoperative use of DQS served as an independent parameter of better TBUT, OSDI score, and LLT in postoperative 15 weeks. Treatment with 3% DQS following cataract surgery showed more improvement in TBUT and LLT, compared with 0.1% HA. Improving TBUT and LLT preoperatively and using 3% DQS postoperatively, could be a reliable choice for managing DES after cataract surgery.Trial Registration: ISRCTN registry with ISRCTN 18755487.

Efficacy of 0.05% cyclosporine A on the lipid layer and meibomian glands after cataract surgery: A randomized, double-masked study.

PURPOSE: To quantitatively evaluate the effects of 0.05% cyclosporine A (CsA) on lipid layer thickness (LLT) and meibomian glands after cataract surgery using the LipiView® ocular surface interferometer. METHODS: This study was a prospective randomized double-masked clinical trial conducted by Pusan National University Yangsan Hospital between April 04, 2019, and November 31, 2019. Sixty-two participants were recruited, and 12 of them were not enrolled because they had undergone previous treatments for ocular surface diseases. The participants were adult patients with cataract, exhibiting normal lid position; they did not present any other ocular disease and did not meet the exclusion criteria of the clinical trial. Fifty subjects were enrolled in the study. The randomized subjects received treatment with 0.05% CsA (group A) or 0.5% carboxymethyl cellulose (CMC) (group B) over the 3 months following the cataract surgery. Subjective and objective assessments were performed at preoperative and postoperative visits. Ocular Surface Disease Index (OSDI), tear breakup time (TBUT), and Schirmer's I test were performed by the same surgeon, and LLT and meiboscore were determined using the LipiView® interferometer. RESULTS: Fifty subjects subjects enrolled consisted of men (50%) and women (50%), with a mean (SD) age of 65.94 (10.35) years. Four subjects in group A and five in group B were excluded from the analysis as they were lost to follow-up within 1 month after cataract surgery. Thus, the study comprised 41 eyes of 41 subjects; 21 subjects were treated with CsA and 20 subjects with CMC. Comparing the clinical measurements between groups A and B taken at the last visit, while controlling the effects of the preoperative values, TBUT and LLT showed significant differences (p = 0.035 and p = 0.047, respectively, by ANCOVA). The TBUT between the subjects using CsA and those using CMC after cataract surgery showed a significant difference during follow up (p = 0.003 by repeated measures ANOVA). In the multivariate analysis, preoperative LLT and the use of CsA were found to be independent parameters for postoperative LLT (R2 = 0.303; p = 0.008 and p = 0.045, respectively), whereas the follow-up duration exhibited a positive correlation with the difference between the preoperative and postoperative values of LLT in the group treated with CsA (R2 = 0.738 and p < 0.001). CONCLUSION: Treatment with 0.05% CsA following cataract surgery is effective in improving TBUT and LLT in comparison with 0.5% CMC. A higher preoperative value of LLT and the postoperative use of CsA could be significant determinants of a higher postoperative LLT value. TRIAL REGISTRATION: ISRCTN registry with ISRCTN 10173448.

IgG4-related disease presenting as recurrent scleritis combined with optic neuropathy.

BACKGROUND: We report a case of atypical presentation of IgG4-related disease (IgG4-RD) with recurrent scleritis and optic nerve involvement. CASE PRESENTATION: A 61-year-old male presented with ocular pain and injection in his left eye for 2 months. Ocular examination together with ancillary testing led to the diagnosis of scleritis, which relapsed in spite of several courses of steroid treatment. After cessation of steroid, the patient complained of severe retro-orbital pain and blurred vision. His best corrected vision was count finger, the pupil was mid-dilated and a relative afferent pupillary defect was found. Funduscopic examination demonstrated disc swelling. Magnetic resonance imaging (MRI) showed enhancing soft tissue encasing the left globe, medial rectus muscle and optic nerve. Systemic work-up revealed multiple nodules in right lower lung and a biopsy showed histopathological characteristics of IgG4-RD. Long-term treatment with corticosteroids and a steroid-sparing agent (methotrexate) led to significant improvement in signs and symptoms with no recurrence for 2 years. CONCLUSIONS: This case highlights the significance of IgG4-RD in the differential diagnosis of recurrent scleritis. IgG4-RD may cause optic neuropathy resulting in visual loss. Early diagnosis and proper treatment can prevent irreversible organ damage and devastating visual morbidity.

Association between metabolic risk factors and optic disc cupping identified by deep learning method.

PURPOSE: This study aims to investigate correlation between metabolic risk factors and optic disc cupping and the development of glaucoma. METHODS: This study is a retrospective, cross-sectional study with over 20-year-old patients that underwent health screening examinations. Intraocular pressure (IOP), fundus photographs, Body Mass Index (BMI), waist circumference (WC), serum triglycerides, serum HDL cholesterol (HDL-C), serum LDL cholesterol (LDL-C), systolic blood pressure (BP), diastolic BP, and serum HbA1c were obtained to analyse correlation between metabolic risk factors and glaucoma. Eye with glaucomatous optic neuropathy(GON) was defined as having an optic disc with either vertical cup-to-disc ratio(VCDR) ≥ 0.7 or a VCDR difference ≥ 0.2 between the right and left eyes by measuring VCDR with deep learning approach. RESULTS: The study comprised 15,585 subjects and 877 subjects were diagnosed as GON. In univariate analyses, age, BMI, systolic BP, diastolic BP, WC, triglyceride, LDL-C, HbA1c, and IOP were significantly and positively correlated with VCDR in the optic nerve head. In linear regression analysis as independent variables, stepwise multiple regression analyses revealed that age, BMI, systolic BP, HbA1c, and IOP showed positive correlation with VCDR. In multivariate logistic analyses of risk factors and GON, higher age (odds ratio [OR], 1.054; 95% confidence interval [CI], 1.046-1.063), male gender (OR, 0.730; 95% CI, 0.609-0.876), more obese (OR, 1.267; 95% CI, 1.065-1.507), and diabetes (OR, 1.575; 95% CI, 1.214-2.043) remained statistically significant correlation with GON. CONCLUSIONS: Among the metabolic risk factors, obesity and diabetes as well as older age and male gender are risk factors of developing GON. The glaucoma screening examinations should be considered in the populations with these indicated risk factors.

Prediction of visual field from swept-source optical coherence tomography using deep learning algorithms.

PURPOSE: To develop a deep learning method to predict visual field (VF) from wide-angle swept-source optical coherence tomography (SS-OCT) and compare the performance of three Google Inception architectures. METHODS: Three deep learning models (with Inception-ResNet-v2, Inception-v3, and Inception-v4) were trained to predict 24-2 VF from the macular ganglion cell-inner plexiform layer and the peripapillary retinal nerve fibre layer map obtained by SS-OCT. The prediction performance of the three models was evaluated by using the root mean square error (RMSE) between the actual and predicted VF. The performance was also compared among different glaucoma severities and Garway-Heath sectorizations. RESULTS: The training dataset comprised images of 2220 eyes from 1120 subjects, and the test dataset was obtained from another 305 subjects (305 eyes). In all subjects, the global prediction errors (RMSEs) were 4.44 ± 2.09 dB, 4.78 ± 2.38 dB, and 4.85 ± 2.66 dB for the Inception-ResNet-v2, Inception-v3, and Inception-v4 architectures, respectively, and the prediction error of Inception-ResNet-v2 was significantly lower than the other two (P < 0.001). As glaucoma progressed, the prediction error of all three architectures significantly worsened to 6.59 dB, 7.33 dB, and 7.79 dB, respectively. In the analysis of sectors, the nasal sector had the lowest prediction error, followed by the superotemporal sector. CONCLUSIONS: Inception-ResNet-v2 achieved the best performance, and the global prediction error (RMSE) was 4.44 dB. As glaucoma progressed, the prediction error became larger. This method may help clinicians determine VF, particularly for patients who are unable to undergo a physical VF test.

Immunogenicity and safety of a 12-valent pneumococcal conjugate vaccine in infants aged 6-10 weeks: a randomized double-blind active-controlled trial.

BACKGROUND: Pneumococcal diseases among children aged <5 years worldwide are associated with high annual mortality rates. PURPOSE: This study aimed to evaluate the immunogenicity and safety of GBP411, a 12-valent pneumococcal conjugant vaccine, with a dosing schedule of 2 primary doses plus 1 booster dose (2p+1) in healthy infants. METHODS: This randomized active-controlled (Prevnar 13) double-blind phase 2 trial enrolled healthy subjects aged 6-10 weeks. Three serum concentrations of pneumococcal serotype-specific immunoglobulin G (IgG) were evaluated using the pneumococcal serotype-specific pneumonia polysaccharide enzyme-linked immunosorbent assay at 1 month after the primary doses and before and 1 month after the booster dose. The pneumococcal serotype-specific IgG titer was evaluated using a multiplex opsonophagocytic assay in a subset of 15 subjects per group. RESULTS: After administration of the primary doses, the proportion of subjects who achieved pneumococcal serotype-specific IgG concentrations of >0.35 µg/mL was lower for some serotypes in the GBP411 group than in the comparator group (6B: 20.83% vs. 39.22%, P=0.047 and 19A: 58.33% vs. 90.20%, P<0.001). However, after administration of the booster dose, >97% of the subjects in each group achieved IgG concentrations of ≥0.35 µg/mL for all 12 serotypes. Increased immunogenicity was observed for some serotypes that showed significant intergroup differences after administration of the primary doses but not after the booster dose. We also found no significant intergroup difference in the overall incidence of solicited local adverse events. Furthermore, the overall incidence of solicited systemic adverse events was significantly lower in the GBP411 group than in the comparator vaccine group (79.59% vs. 98.04%; P=0.003). CONCLUSION: The GBP411 vaccine with a dosing schedule of 2p+1 may be immunogenic and safe for healthy infants.

Design, synthesis, and discovery of novel oxindoles bearing 3-heterocycles as species-specific and combinatorial agents in eradicating Staphylococcus species.

A series of new functionalized 3-indolylindolin-2-ones, 3-(1-methylpyrrol-2-yl)indolin-2-ones, and 3-(thiophen-2-yl)indolin-2-ones were synthesized by using novel indium (III)-catalysed reaction of various 3-diazoindolin-2-ones with indoles, 1-methylpyrrole, or thiophene via one-pot procedure. The newly synthesized compounds were characterized and screened for their in vitro antibacterial activity against various Staphylococcus species, including methicillin-resistant Staphylococcus aureus. results revealed that five compounds KS15, KS16, KS17, KS19, and KS20 exhibited potent and specific antibacterial activity against Staphylococcus species albeit inactive against Gram-negative bacteria. Especially, compounds exhibited superior antibacterial potency against Staphylococcus epidermidis compared to the reference drug streptomycin. The most potential compound KS16 also increased the susceptibility of Staphylococcus aureus to ciprofloxacin, gentamicin, kanamycin, and streptomycin. Among them, KS16 was found to be a synergistic compound with gentamicin and kanamycin. Furthermore, the cellular level of autolysin protein was increased from the KS16-treated Staphylococcus aureus cells. Finally, in vitro CCK-8 assays showed that KS16 exhibited no cytotoxicity at the minimum inhibitory concentrations used for killing Staphylococcus species. From all our results, novel oxindole compounds directly have lethal action or boost existing antibiotic power with the reduction of doses and toxicity in the treatment of multidrug-resistant Staphylococcus species.

Diagnostic Ability of Macular Vessel Density in the Ganglion Cell-Inner Plexiform Layer on Optical Coherence Tomographic Angiography for Glaucoma.

PURPOSE: The purpose of this study was to analyze the macular vessel density layer-by-layer and compare the diagnostic value of each in diagnosing glaucoma. METHODS: This was a prospective comparative cross-sectional study, and the setting was glaucoma referral practice. The study participants were patients with primary open-angle glaucoma undergoing treatment with drugs, and age-matched normal controls who visited our clinic for regular eye examinations for refractive errors. All participants were investigated using macular optical coherence tomographic angiography, fundus photography, and 24-2 visual field (VF) testing. Average vessel densities in the retinal nerve fiber-ganglion cell-inner plexiform layer (IPL), retinal nerve fiber-ganglion cell layer (GCL), retinal nerve fiber layer (RNFL), ganglion cell-IPL, GCL, and IPL segments on optical coherence tomographic angiography. RESULTS: Fifty-eight glaucomatous eyes of 58 participants and 52 healthy eyes of 52 normal subjects were included in the study. The average vessel densities of all segments, except the RNFL in the glaucoma group, were significantly lower than that in normal subjects. The average vessel density in the ganglion cell-IPL showed the highest correlation with the mean deviation and VF index of the VF (r = 0.515 and 0.538, respectively) and the best area under receiver operating characteristic curve to discriminate between patients with glaucoma and patients with normal eyes (0.750). CONCLUSIONS: The present study demonstrated that macular vessel density in the ganglion cell-IPL has a higher diagnostic ability and better correlation with functional damage in glaucoma than that in the superficial vascular plexus. TRANSLATIONAL RELEVANCE: These findings suggest that the macular vessel density in the ganglion cell-inner plexiform layer is better than that in the conventional superficial vascular plexus for detecting glaucoma.

Effect of topical glaucoma medication on tear lipid layer thickness in patients with unilateral glaucoma.

Purpose: To compare the lipid layer thickness (LLT) using the LipiView® ocular surface interferometer (TearScience® Inc, Morrisville, NC) between the eye treated with glaucoma medication and untreated normal eye in the unilateral glaucoma patients, and evaluate the effect of topical glaucoma medication on the LLT parameters in glaucoma eyes. Methods: The participants in this cross-sectional comparative study were unilateral glaucoma patients treated with topical glaucoma medications for more than 12 months. Three LLT parameters (average, minimum, and maximum) obtained by the LipiView® were compared between the glaucomatous eye and normal eye. The factors associated with LLT parameters in the eyes treated with glaucoma medication were investigated with multiple regression analysis. Results: Thirty patients with unilateral normal tension glaucoma were enrolled in the present study. Lipid layer average, minimum, and maximum were 64.83 ± 16.50, 51.63 ± 16.73, and 82.53 ± 20.62 in glaucomatous eyes, 77.26 ± 17.81, 62.83 ± 20.99, and 86.13 ± 15.42 in normal eyes. Lipid layer average and minimum were significantly thinner than those in normal eyes (P < 0.001, P < 0.001, respectively). Longer duration of glaucoma eye drops and a greater number of glaucoma medications were associated with the lower LLT average (ß = -0.456, P < 0.001, ß = -8.517, P = 0.003, respectively), and increasing glaucoma medications have a significant correlation with lower LLT minimum in glaucoma eyes (ß = -8.814, P = 0.026). Conclusion: The present study highlights that patients with long-term glaucoma medications need to be assessed for LLT parameters objectively evaluate their ocular surface health.