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Müller cells play a critical role in the closure of macular holes, and their proliferation and migration are facilitated by the internal limiting membrane (ILM). Despite the importance of this process, the underlying molecular mechanism remains underexplored. This study investigated the effects of ILM components on the microRNA (miRNA) profile of Müller cells. Rat Müller cells (rMC-1) were cultured with a culture insert and varying concentrations of ILM component coatings, namely, collagen IV, laminin, and fibronectin, and cell migration was assessed by measuring cell-free areas in successive photographs following insert removal. MiRNAs were then extracted from these cells and analyzed. Mimics and inhibitors of miRNA candidates were transfected into Müller cells, and a cell migration assay and additional cell viability assays were performed. The results revealed that the ILM components promoted Müller cell migration (p < 0.01). Among the miRNA candidates, miR-194-3p was upregulated, whereas miR-125b-1-3p, miR-132-3p, miR-146b-5p, miR-152-3p, miR-196a-5p, miR-542-5p, miR-871-3p, miR-1839-5p, and miR-3573-3p were significantly downregulated (p < 0.05; fold change > 1.5). Moreover, miR-152-3p and miR-196a-5p reduced cell migration (p < 0.05) and proliferation (p < 0.001), and their suppressive effects were reversed by their respective inhibitors. In conclusion, miRNAs were regulated in ILM component-activated Müller cells, with miR-152-3p and miR-196a-5p regulating Müller cell migration and proliferation. These results serve as a basis for understanding the molecular healing process of macular holes and identifying potential new target genes in future research. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) may be associated with ABCA4 variants and is characterized by the accumulation of visual cycle-byproduct lipofuscin. Reducing retinol-binding protein 4 (RBP4), a retinol transporter protein, may reduce lipofuscin production. This study aims to assess the associations between plasma RBP4, the ABCA4 variation, and AMD severity. Sixty-seven participants were grouped into healthy/mild AMD (n = 32) and severe AMD (n = 35) groups. The latter group was older than the former group and had higher levels of RBP4 (36.8 ± 8.3 vs. 30.4 ± 7.0 μg/mL, p = 0.0012). The ten participants with six ABCA4 linked-variants had higher RBP4 than those without (37.8 ± 7.7 vs. 32.4 ± 7.9 μg/mL; p = 0.026), and eight of them had severe AMD. Univariate analyses showed that severe AMD was related to older age (OR, 1.26; 95% CI, 1.13–1.40; p < 0.0001) and to higher RBP4 levels (OR, 1.12; 95% CI, 1.04–1.20; p = 0.003), whereas the linked ABCA4 variants had no associations. After adjustment, however, only age remained significantly associated with severe AMD. This pilot study shows a trend of higher plasma RBP4 levels in severe AMD or the ABCA4-linked variants, and further age-matched studies are warranted. [ABSTRACT FROM AUTHOR]

This study aims to investigate the outcomes and risk factors associated with poor vision (vision less than counting fingers, 2.0 logMAR, Snellen vision 20/2000) in patients with posterior or combined persistent fetal vasculature (PFV), with or without surgery. We retrospectively reviewed the medical records of patients who were diagnosed with PFV from January 2008 to April 2021. We included 51 eyes of 44 patients who presented with PFV, of which 38 eyes underwent surgical correction (pars plicata/plana vitrectomy, with or without lensectomy, and intraocular lens implantation) at the median age of 6.0 months (range: 0.7 to 82.0). The mean follow-up was 68.8 months ± 38.0 months. The axial length change in the eyes undergoing surgery was significantly higher than the eyes without surgery (p = 0.025). Initial anterior chamber collapse and retinal detachment were associated with poor vision (p = 0.006 and p = 0.002, respectively). In addition, 37% of eyes with posterior or combined PFV had vision better than counting fingers. Surgery for eyes with PFV could result in better eye growth. Visual outcomes remained poor and were associated with the level of macular abnormality. Initial anterior chamber collapse and retinal detachment at presentation were the risk factors for poor visual outcomes. Vitrectomy for selected PFV eyes is valuable and associated with a better cosmetic outcome (better eye growth). [ABSTRACT FROM AUTHOR]

This retrospective cohort study aimed to assess the systemic effects of three commonly available anti-vascular endothelial growth factor intravitreal injections in patients with diabetes, using data taken from a multi-institutional database in Taiwan. Patient data were sourced from the multi-institutional Chang Gung Research Database. Participants were divided into groups based on treatment with bevacizumab, ranibizumab, or aflibercept. Baseline characteristics were matched among the groups by the inverse probability of treatment weighting. The incidence rate of outcome events was calculated as the number of events divided by 100 person-years of follow-up. The cumulative incidence function was used to estimate the incidence rate of the outcome events among groups. The incidence of ischemic stroke was higher in the ranibizumab group than the bevacizumab and aflibercept groups (1.65, 0.92, and 0.61 per 100 person-years, respectively). The incidence of major adverse lower-limb events was higher in the bevacizumab group (2.95), followed by ranibizumab (2.00) and aflibercept (0.74). Major bleeding was relatively higher in bevacizumab (12.1) compared to ranibizumab (4.3) and aflibercept (3.8). All-cause death was higher for both bevacizumab (3.26) and aflibercept (2.61) when compared to ranibizumab (0.55), and all-cause admission was found to be highest with bevacizumab (58.6), followed by aflibercept (30.2), and ranibizumab (27.6). The bevacizumab group demonstrated a greater decrease in glycated hemoglobin compared to the baseline level (−0.33%). However, a few differences in the clinical condition between the groups were still observed after matching. In conclusion, this study suggests that different anti-vascular endothelial growth factor agents may be associated with various and differing systemic adverse events. The differences might also be attributed to differences in patient characteristics and clinical status. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP), a vasoproliferative vitreoretinal disorder, is the leading cause of childhood blindness worldwide. Although angiogenic pathways have been the main focus, cytokine-mediated inflammation is also involved in ROP etiology. Herein, we illustrate the characteristics and actions of all cytokines involved in ROP pathogenesis. The two-phase (vaso-obliteration followed by vasoproliferation) theory outlines the evaluation of cytokines in a time-dependent manner. Levels of cytokines may even differ between the blood and the vitreous. Data from animal models of oxygen-induced retinopathy are also valuable. Although conventional cryotherapy and laser photocoagulation are well established and anti-vascular endothelial growth factor agents are available, less destructive novel therapeutics that can precisely target the signaling pathways are required. Linking the cytokines involved in ROP to other maternal and neonatal diseases and conditions provides insights into the management of ROP. Suppressing disordered retinal angiogenesis via the modulation of hypoxia-inducible factor, supplementation of insulin-like growth factor (IGF)-1/IGF-binding protein 3 complex, erythropoietin, and its derivatives, polyunsaturated fatty acids, and inhibition of secretogranin III have attracted the attention of researchers. Recently, gut microbiota modulation, non-coding RNAs, and gene therapies have shown promise in regulating ROP. These emerging therapeutics can be used to treat preterm infants with ROP. [ABSTRACT FROM AUTHOR]

Congenital stationary night blindness (CSNB) is an inherited retinal disease (IRD) that causes night blindness in childhood with heterogeneous genetic, electrophysical, and clinical characteristics. The development of sequencing technologies and gene therapy have increased the ease and urgency of diagnosing IRDs. This study describes seven Taiwanese patients from six unrelated families examined at a tertiary referral center, diagnosed with CSNB, and confirmed by genetic testing. Complete ophthalmic exams included best corrected visual acuity, retinal imaging, and an electroretinogram. The effects of identified novel variants were predicted using clinical details, protein prediction tools, and conservation scores. One patient had an autosomal dominant CSNB with a RHO variant; five patients had complete CSNB with variants in GRM6, TRPM1, and NYX; and one patient had incomplete CSNB with variants in CACNA1F. The patients had Riggs and Schubert–Bornschein types of CSNB with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. This is the first report of CSNB patients in Taiwan with confirmed genetic testing, providing novel perspectives on molecular etiology and genotype–phenotype correlation of CSNB. Particularly, variants in TRPM1, NYX, and CACNA1F in our patient cohort have not previously been described, although their clinical significance needs further study. Additional study is needed for the genotype–phenotype correlation of different mutations causing CSNB. In addition to genetic etiology, the future of gene therapy for CSNB patients is reviewed and discussed. [ABSTRACT FROM AUTHOR]

Tissue inhibitors of metalloproteinases (TIMPs) play a crucial role in endogenous angiogenesis besides the regulation of matrix metalloproteinase (MMP) activity. Associations between TIMP-2 gene polymorphisms and the risk of retinopathy of prematurity (ROP) were examined. Premature infants born between 2009 and 2018 were included. Five single-nucleotide polymorphisms (SNPs) of TIMP-2 were analyzed with real-time polymerase chain reaction (PCR). Multivariate logistic regression was applied to model associations between TIMP-2 polymorphisms and ROP susceptibility and severity. The GA+AA genotype in individuals with the TIMP-2 polymorphism of rs12600817 was associated with a higher risk of ROP (odds ratio [OR]: 1.518, 95% confidence interval [CI]: 1.028–2.242) compared with their wild-type genotypes. The AA genotype (OR: 1.962, 95% CI: 1.023–3.762) and the AA+GA genotype (OR: 1.686, 95% CI: 1.030–2.762) in individuals with the rs12600817 polymorphism had higher risks of severe, treatment-requiring ROP relative to their wild-type counterparts. In patients with treatment-requiring ROP, the AG+GG genotypes in the TIMP-2 polymorphism of rs2889529 were correlated with the treatment response (p = 0.035). The TIMP-2 polymorphism of rs12600817 help in predicting ROP risks in preterm infants, while the polymorphism of rs2889529 can serve as a genetic marker in evaluating the ROP treatment response. [ABSTRACT FROM AUTHOR]

The adsorption of tear film compositions such as proteins and lipids on the orthokeratology lenses often lead to infection or corneal damage. In order to investigate whether polysaccharides could prevent tear compositions from being adsorbed on the lens, alginic acid and lambda-carrageenan were added into artificial tear solution. By measuring daily adsorption of cholesterol, lysozyme, and albumin, our results showed that polysaccharides could weakly prevent cholesterol adsorption. In addition, polysaccharides could also reduce albumin deposition over time. Although the effect of polysaccharides on lysozyme adsorption was distinct depending on the concentrations of polysaccharides, the overall results demonstrated that polysaccharides could decrease protein deposition over time. Our results provided an in vitro evidence that polysaccharides may be applied as coating materials on the lens or as the composition of artificial tear solutions or eyedrops, in order to prevent adsorption of tear film compositions that may lead to a reduced incidence of infection or corneal damage for orthokeratology lens wearers. [ABSTRACT FROM AUTHOR]

Staphylococcus lugdunensis endophthalmitis is an uncommon intraocular infection with potentially visually devastating consequences. S. lugdunensis endophthalmitis have been reported following cataract surgery, trauma, intravitreal injections of anti-vascular endothelial growth factor agents and dexamethasone implant. We report four cases of postoperative S. lugdunensis endophthalmitis after cataract extraction (three patients) and combined pars plana vitrectomy and cataract extraction (one patient). The onset of presentation of endophthalmitis was acute (within 2 weeks) in two patients, subacute (2 to 6 weeks) in one patient, and chronic (more than 6 weeks) in one patient. All patients had presenting visual acuity (VA) of hand motions or worse and were treated with pars plana vitrectomy with intravitreal antibiotics. The final VA was 20/50 in two patients, 4/200 in one patient with pre-existing myopic maculopathy, and no light perception in one patient with retinal detachment. In antibiotic susceptibility testing, S. lugdunensis isolates were resistant to penicillin (3/4, 75%), but all were susceptible to vancomycin, oxacillin, teicoplanin, tigecycline, and sulfamethoxazole-trimethoprim. S. lugdunensis may be associated with acute or chronic endophthalmitis. Favorable visual outcomes can be achieved with prompt diagnosis and management. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia (S. maltophilia) is a Gram-negative, opportunistic pathogen that can lead to ocular infections, such as keratitis and endophthalmitis. The purpose of this study was to determine the antibiotic susceptibility and minimum inhibitory concentrations (MICs) of S. maltophilia isolates from ocular infections and to evaluate the differences in antibiotic MICs between keratitis and endophthalmitis isolates. The disc diffusion method revealed that S. maltophilia isolates exhibited 91% susceptibility to levofloxacin and moxifloxacin and 61% susceptibility to trimethoprim–sulfamethoxazole (TMP–SMX). The E-test indicated that S. maltophilia isolates exhibited 40%, 100%, 72%, 91%, 91%, and 93% susceptibility to ceftazidime, tigecycline, TMP–SMX, levofloxacin, gatifloxacin, and moxifloxacin, respectively. The MIC90 values of amikacin, ceftazidime, cefuroxime, tigecycline, TMP–SMX, levofloxacin, gatifloxacin, and moxifloxacin were >256, >256, >256, 3, >32, 1, 2, and 0.75 µg/mL, respectively. The geometric mean MICs of ceftazidime, TMP–SMX, levofloxacin, gatifloxacin, and moxifloxacin were significantly lower for the keratitis isolates than for the endophthalmitis isolates (p = 0.0047, 0.003, 0.0029, 0.0003, and 0.0004, respectively). Fluoroquinolones showed higher susceptibility and lower MICs for the S. maltophilia isolates when compared with other antibiotics. Fluoroquinolones can be recommended for treating S. maltophilia ocular infections. Tigecycline and TMP–SMX could be alternative antibiotics for S. maltophilia ocular infections. [ABSTRACT FROM AUTHOR]

Gilbert's syndrome is mainly diagnosed through genetic analysis and is primarily detected through a mutation in the promoter region of the UGT1A1 gene. However, most of the research has been conducted on Caucasian populations. In this study, we studied the Han population in Taiwan to investigate the possibility of other mutations that could cause Gilbert's syndrome. This study comprised a test group of 45 Taiwanese individuals with Gilbert's syndrome and 180 healthy Taiwanese individuals as a control group. We extracted DNA from the blood samples and then used Axiom Genome-Wide TWB 2.0 array plates for genotyping. Out of 302,771 single nucleotide polymorphisms (SNPs) from 225 subjects, we detected 57 SNPs with the most significant shift in allele frequency; 27 SNPs among them were located in the UGT1A region. Most of the detected SNPs highly correlated with each other and are located near the first exon of UGT1A1, UGT1A3, UGT1A6, and UGT1A7. We used these SNPs as an input for the machine learning algorithms and developed prediction models. Our study reveals a good association between the 27 SNPs detected and Gilbert's syndrome. Hence, this study provides a reference for diagnosing Gilbert's syndrome in the Taiwanese population in the future. [ABSTRACT FROM AUTHOR]

This prospective study aimed to explore the effect of medical intraocular pressure (IOP) reduction on structural and capillary vessel density (VD) change by optical coherence tomography (OCT) angiography in early glaucoma. Patients with newly diagnosed glaucoma and a follow-up of ≥6 months were enrolled. An ocular examination that included slit-lamp bio-microscopy, pneumatic tonometry, gonioscopy, standard automated perimetry, and OCT angiography was performed. Quantitative OCT angiography parameters were assessed using a linear mixed model that was adjusted for inter-eye correlation. The correlations between IOP changes and OCT angiography parameter changes were analyzed using Spearman's correlation test. In total, 52 eyes of 36 participants, including 33 glaucoma eyes of 17 participants and 19 healthy eyes of 19 participants served as the case and control groups, respectively. The IOP of the case group decreased from a baseline mean of 20.4 ± 0.8 mmHg to 15.7 ± 0.5 mmHg at 3 months (p < 0.001) and to 16.1 ± 0.5 mmHg at 6 months (p < 0.001). For the subgroup with an IOP reduction of >20%, the deep macula VD was negatively correlated with baseline IOP and significantly decreased at 3 months follow-up. Additionally, change in retinal nerve fiber layer (RNFL) was positively correlated with a change in IOP at 6 months. In conclusion, the deep-layer macula VD was correlated with baseline IOP and influenced by the reduction in IOP in the short term. The changes in VD revealed the vulnerability of the deep vascular complex. The OCTA parameters provide in vivo monitoring information during medical treatment for early glaucoma. [ABSTRACT FROM AUTHOR]

Endogenous endophthalmitis is an uncommon intraocular infection with potentially devastating consequences on vision. Klebsiella pneumoniae is highly prevalent in East Asian countries, with an increasing incidence recently worldwide. This retrospective study investigates infection sources and antibiotic susceptibilities of K. pneumoniae in patients with endogenous K. pneumoniae endophthalmitis (EKE) in Northern Taiwan. One hundred and fifty-seven patients with EKE were reviewed between January 1996 and April 2019. Pyogenic liver abscess (120/157, 76.4%) was the most common infection source, followed by pneumonia (13, 8.3%), urinary tract infection (7, 4.5%), and intravenous drug use (4, 2.5%). Bilateral involvement was identified in 12.1% (19/157) of patients, especially in patients with pyogenic liver abscess (16/120, 13.3%), pneumonia (2/13, 15.4%), and urinary tract infection (1/7, 14.3%). The antibiotic susceptibility rates were 98.1%, 92.5%, 97.5%, 96.8%, 100%, 99.3%, and 100% for amikacin, cefuroxime, ceftazidime, ceftriaxone, carbapenems, ciprofloxacin, and levofloxacin, respectively. Four extended-spectrum β-lactamase-producing multidrug-resistant (MDR) K. pneumoniae isolates were identified. In conclusion, pyogenic liver abscess was the major infection source in EKE. In addition, K. pneumoniae was still highly susceptible to ceftazidime and amikacin, and the MDR K. pneumoniae isolates were not common in EKE. [ABSTRACT FROM AUTHOR]

Background: Immune response assessed by the quantification of neutralizing antibodies (nAbs) and predictors associated with immunogenicity after the prime-boost ChAdOx1 (Oxford–AstraZeneca) COVID-19 vaccine in hemodialysis (HD) patients remains unclear. Methods: This prospective study enrolled 174 HD patients and 67 healthy subjects to evaluate antibodies against the spike protein 1 and receptor-binding domain of severe acute respiratory syndrome coronavirus type 2 after prime-booster vaccination, by using enzyme-linked immunosorbent assay and applied spline-based generalized additive model regression analysis to predict 50% neutralization titer (NT50). The correlation between HD parameters and NT50 was analyzed. Results: NT50 was lower in HD patients compared with healthy controls after the prime-boost dose (p < 0.001). The geometric mean titer ratios were higher in first-dose seronegative than in the seropositive subgroup in HD patients and healthy controls (6.96 vs. 2.36, p = 0.002, and 9.28 vs. 1.26, p = 0.011, respectively). After two doses of ChAdOx1, one-way ANOVA showed that Ca × P was positively associated with NT50 (p trend = 0.043) and multiple linear regression showed the similar results (p = 0.021). Kt/V (a quantification of dialysis adequacy) (OR = 20.295, p = 0.005) could independently predict seroconversion (NT50 ≥ 35.13 IU/mL). Conclusion: Adequacy of hemodialysis could independently predict seroconversion in HD subjects vaccinated with prime-boost doses of ChAdOx1. [ABSTRACT FROM AUTHOR]

Endogenous fungal endophthalmitis (EFE) is a vision-threatening intraocular infection and a rare complication of fungemia. Early diagnosis and prompt aggressive treatment are crucial to avoid vision loss. We retrospectively reviewed the data of 37 patients (49 eyes) with EFE who were treated at a tertiary referral hospital from January 2000 to April 2019. The most common risk factor was diabetes (24 patients; 65%), followed by recent hospitalization, urinary tract disease, liver disease, and immunosuppressive therapy. Two or more risk factors were detected in 24 patients (65%), and yeasts (29 patients; 78%) were more commonly detected than mold (8 patients; 22%). The most common fungal isolates were Candida spp. (78%), especially Candida albicans (70%). Moreover, 24 eyes in 21 patients underwent vitrectomy, and 2 eyes underwent evisceration. Retinal detachment (RD) occurred in 17 eyes (35%) in 14 patients, and eyes without RD exhibited significantly superior visual outcomes (p = 0.001). A comparison of the initial VA between the better (20/200 or better) and worse groups (worse than 20/200) revealed that better initial VA was related to a superior visual outcome (p = 0.003). Therefore, to achieve superior visual outcomes, early diagnosis and prompt treatment are necessary for patients with EFE. [ABSTRACT FROM AUTHOR]

This study aimed to compare the clinical performance between a smartphone-based fundus photography device and a contact imaging device for retinopathy of prematurity (ROP) screening. All patients were first examined with binocular indirect ophthalmoscopy (BIO), which served as the reference standard. The patients were then assessed by two devices. Imaging quality, ability to judge the zone and stage of ROP, agreement with the BIO results, vital signs, and pain scores were compared between these two devices. In total, 142 eyes of 71 infants were included. For the smartphone-based fundus photography, image quality was graded excellent or acceptable in 91.4% of examinations, although it was still significantly inferior to that of the contact imaging device (p < 0.001). The smartphone-based fundus photography images had moderate agreement with the BIO results regarding the presence or absence of plus disease (Cohen's κ = 0.619), but evaluating the zone (p < 0.001) and stage (p < 0.001) of ROP was difficult. Systemic parameters, except for heart rate, were similar between the two imaging devices (all p > 0.05). In conclusion, although the smartphone-based fundus photography showed moderate agreement for determining the presence or absence of plus disease, it failed to identify the zone and stage of ROP. [ABSTRACT FROM AUTHOR]

The association between myopia control efficacy in children treated with orthokeratology and corneal epithelial thickness is still unknown. The aim of this study was to explore the corneal epithelial thickness and its association with axial length changes in children treated with orthokeratology. This retrospective cohort study enrolled children aged from 9 to 15 years who had received orthokeratology for myopia control and had been followed up for at least 1 year. Anterior segment optical coherence tomography was performed to generate wide epithelial thickness maps of the patients. Annual axial length changes were calculated from the axial length at 6 months after the initiation of orthokeratology lens wear and at final measurements. Corneal epithelial thickness data were obtained from 24 sectors and a central 2 mm zone of the wide epithelial thickness map. Associations between annual axial length changes and corneal epithelial thickness for each sector/zone of the wide epithelial thickness map, and orthokeratology treatment data were determined by generalized estimating equations. Finally, a total of 83 eyes of 43 patients (mean age 11.2 years) were included in the analysis. The mean annual axial length change was 0.169 mm; when regressing demographic and ortho-k parameters to mean annual axial length changes, age and target power were both negatively associated with them (β = −14.43, p = 0.008; β = −0.26, p = 0.008, respectively). After adjusting for age and target power, the annual axial length changes were positively associated with the corneal epithelium thickness of IT1, I1, SN2, and S2 sectors of the wide epithelial thickness map, and negatively with that of the I3 sector. In conclusion, we identified associations between annual axial length changes and the corneal epithelium thickness of certain sectors in children treated with orthokeratology. This may facilitate the design of orthokeratology lenses with enhanced efficacy for myopia control. [ABSTRACT FROM AUTHOR]

Background: Data are lacking regarding predictors of quantification of neutralizing antibodies (nAbs) based on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 50% neutralization titer (NT50) after a single dose of COVID-19 vaccine in hemodialysis (HD) patients. Methods: This prospective single-center study enrolled 200 HD patients and 82 healthy subjects to estimate antibodies against the SARS-CoV-2 viral spike protein 1 and receptor-binding domain after a first dose of a COVID-19 vaccine (ChAdOx1 or mRNA-1273), measured by enzyme-linked immunosorbent assay and applied spline-based generalized additive model regression analysis to predict NT50 converted to international units. Results: After the first dose of ChAdOx1, multiple linear regression showed that age (p = 0.011) and cardiothoracic ratio (p = 0.002) were negatively associated with NT50. Older age (OR = 0.958, p = 0.052) and higher cardiothoracic ratio (OR < 0.001, p = 0.037) could predict negative humoral response (NT50 < 35.13 IU/mL). NT50 was lower in HD patients compared with healthy controls receiving ChAdOx1 (10.68 vs. 43.01 IU/m, p < 0.001) or mRNA-1273 (36.39 vs. 262.2 IU/mL, p < 0.001). ChAdOx1 elicited lower GMTs than mRNA-1273 in the HD cohort (10.68 vs. 36.39 IU/mL, p < 0.001) and in healthy controls (43.01 vs. 262.22 IU/mL, p < 0.001). Conclusion: High cardiothoracic ratio and old age could independently predict a decline in nAb titers in an HD cohort vaccinated with a single dose of ChAdOx1. [ABSTRACT FROM AUTHOR]

An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients. [ABSTRACT FROM AUTHOR]

We aim to evaluate magnitudes of higher order aberrations (HOAs) from 3rd–6th order after scleral buckling (SB) for rhegmatogenous retinal detachment (RRD). A retrospective cross-sectional study of 19 patients with RRD who received SB (six receiving encircling SB, thirteen receiving segmental SB) was conducted. A wavefront analysis for surveying HOAs and other ophthalmic parameters were collected. Data between operated and fellow eyes, and a subgroup analysis of operated eyes, were analyzed by the Mann–Whitney U test, while a generalized linear model was applied to evaluate the correlation of HOAs to best-corrected visual acuity (BCVA) and optical symptoms. BCVA in the operated eyes was significantly worse (LogMAR: 0.18 ± 0.23 versus 0.05 ± 0.07, p = 0.001). Tilt (0.32 ± 0.14 versus 0.13 ± 0.08, p = 0.004), defocus (1.78 ± 0.47 versus 1.05 ± 0.17, p = 0.019) and coma (0.43 ± 0.11 versus 0.27 ± 0.09, p = 0.016) were significantly increased after SB. All root mean square (RMS), including RMS-3, RMS-4 and total RMS, were higher in operated eyes (all p < 0.05). Regarding Zernike terms, a significant elevation of vertical coma in the operated eyes was found (p = 0.038). In addition, tilt (0.41 ± 0.10 versus 0.17 ± 0.12, p = 0.007), defocus (2.27 ± 0.58 versus 0.82 ± 0.39, p = 0.001) and coma (0.59 ± 0.17 versus 0.11 ± 0.10, p = 0.015) were higher in the segmental subgroup, whereas spherical aberration (SA) was higher in the encircling subgroup (0.22 ± 0.04 versus 0.40 ± 0.15, p = 0.024) and RMS-4 and total RMS were increased in the segmental subgroup (both p < 0.05). Besides, tilt was correlated to worse BCVA (p = 0.036), whereas all four HOAs were correlated to the presence of optical symptoms (all p < 0.05). In conclusion, SB may increase HOAs, which could be associated with unfavorable postoperative visual outcomes and subject symptoms. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a global pandemic public health burden affecting one in five of the general population in their lifetime. For high-risk individuals, early detection and prediction of HF progression reduces hospitalizations, reduces mortality, improves the individual's quality of life, and reduces associated medical costs. In using an artificial intelligence (AI)-assisted genome-wide association study of a single nucleotide polymorphism (SNP) database from 117 asymptomatic high-risk individuals, we identified a SNP signature composed of 13 SNPs. These were annotated and mapped into six protein-coding genes (GAD2, APP, RASGEF1C, MACROD2, DMD, and DOCK1), a pseudogene (PGAM1P5), and various non-coding RNA genes (LINC01968, LINC00687, LOC105372209, LOC101928047, LOC105372208, and LOC105371356). The SNP signature was found to have a good performance when predicting HF progression, namely with an accuracy rate of 0.857 and an area under the curve of 0.912. Intriguingly, analysis of the protein connectivity map revealed that DMD, RASGEF1C, MACROD2, DOCK1, and PGAM1P5 appear to form a protein interaction network in the heart. This suggests that, together, they may contribute to the pathogenesis of HF. Our findings demonstrate that a combination of AI-assisted identifications of SNP signatures and clinical parameters are able to effectively identify asymptomatic high-risk subjects that are predisposed to HF. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia has been reported in various ocular infections, including keratitis, conjunctivitis, preseptal cellulitis, and endophthalmitis, all of which may lead to vision loss. However, the S. maltophilia strain is resistant to a wide variety of antibiotics, including penicillins, third-generation cephalosporins, aminoglycosides, and imipenem. In this study, we retrospectively reviewed the clinical characteristics, antibiotic susceptibility, antimicrobial minimum inhibitory concentrations (MICs), and visual outcomes for S. maltophilia endophthalmitis. The data of 9 patients with positive S. maltophilia cultures in a tertiary referral center from 2010 to 2019 were reviewed. Cataract surgery (n  =  8, 89%) was the most common etiology, followed by intravitreal injection (n  =  1, 11%). S. maltophilia's susceptibility to levofloxacin and moxifloxacin was observed in 6 cases (67%). Seven isolates were resistant to sulfamethoxazole-trimethoprim (78%). The MIC90 for S. maltophilia was 256, 256, 256, 8, 12, 12, 12, and 8 μg/mL for amikacin, cefuroxime, ceftazidime, tigecycline, sulfamethoxazole-trimethoprim, levofloxacin, galtifloxacin, and moxifloxacin, respectively. Final visual acuity was 20/200 or better in 5 patients (56%). Fluoroquinolones and tigecycline exhibited low antibiotic MIC90. Therefore, the results suggest that fluoroquinolones can be used as first-line antibiotics for S. maltophilia endophthalmitis. [ABSTRACT FROM AUTHOR]

Background: Dialyzed patients are vulnerable to coronavirus infection disease 2019 (COVID-19). The incidence and outcome of COVID-19 in hemodialysis (HD) patients in Taiwan remain unclear. A series of preventive measures were executed to combat COVID-19 transmission among HD patients. Methods: We carried out a series of forward-looking and practical preventive strategies of COVID-19 control in our HD center. Incidences of COVID-19 of our HD unit were compared with those of national and local estimates from a community outbreak from 15 May to 30 June 2021. Prognostic factors associated with mortality were analyzed. Results: The national incidence of COVID-19 was 0.062%; being highest in Taipei City (0.173%), followed by New Taipei City (0.161%) and Keelung (0.083%). The overall incidence in Keelung HD patients was 0.666%. One patient of our HD center contracted COVID-19 from the household; however, we have contained secondary transmission in our HD center by implementing strict preventive measures. The mortality rate of HD patients in Keelung was 66.6%. The median Ct value of HD patients was 17.53 (11.75–27.90) upon diagnosis. The deceased patients had a higher cardiac/thoracic ratio than alive (0.61 vs. 0.55, p = 0.036). Conclusions: Taking aggressive and proactive infection preventive measures impedes the secondary transmission of COVID-19 in HD facilities. COVID-19-associated mortality was high in HD patients, being the high cardiac-thoracic ratio, an important prognostic factor for clinical outcome of infected HD patients. [ABSTRACT FROM AUTHOR]

Feeling comfortable is the greatest concern for contact lens wearers, and it has been suggested that in vivo comfort could be corresponded to the in vitro friction coefficient of contact lenses. How tear albumin could affect the friction coefficient of silicone hydrogel and hydrogel contact lenses was analyzed by sliding a lens against a quartz glass in normal and extremely high concentration of albumin solution. Albumin deposition testing and surface roughness analysis were also conducted. The results showed that the friction coefficient of tested contact lenses did not correspond to both the albumin deposition amount and surface roughness, but we proposed a model of how albumin might act as a lubricant on the surface of some hydrogel and silicone hydrogel contact lenses. In conclusion, albumin provided lubrication for silicone hydrogel contact lenses regardless of albumin concentrations, while albumin only acted as a lubricant for hydrogel contact under normal concentration. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the association of add-on dipeptidyl peptidase-4 inhibitor (DPP4i) therapy and the progression of diabetic retinopathy (DR). In this retrospective population-based cohort study, we examined Taiwanese patients with type 2 diabetes, preexisting DR, and aged ≥40 years from 2009 to 2013. Prescription of DPP4i was defined as a medication possession ratio of ≥80% during the first 6 months. The outcomes included vitreous hemorrhage (VH), tractional retinal detachment, macular edema, and interventions including retinal laser therapy, intravitreal injection (IVI), and vitrectomy. Of 1,767,640 patients, 62,824 were eligible for analysis. After matching, the DPP4i and non-DPP4i groups each contained 20,444 patients. The risks of VH (p = 0.013) and macular edema (p = 0.035) were higher in the DPP4i group. The DPP4i group also had higher risks of receiving surgical interventions (retinal laser therapy (p < 0.001), IVI (p = 0.049), vitrectomy (p < 0.001), and any surgical intervention (p < 0.001)). More patients in the DPP4i group received retinal laser therapy (p < 0.001) and IVI (p = 0.001) than in the non-DPP4i group. No between-group differences in cardiovascular outcomes were noted. In the real-world database study, add-on DPP4i therapy may be associated with the progression of DR in patients with type 2 diabetes. No additional cardiovascular risks were found. The early progression of DR in rapid glycemic control was inconclusive in our study. The possible effect of add-on DPP4i therapy in the progression of DR in patients with type 2 diabetes requires further research. [ABSTRACT FROM AUTHOR]

Nasal methicillin-resistant Staphylococcus aureus (MRSA) colonies are an essential reservoir of infection, especially for patients with diabetes. However, data on MRSA colonization in patients with type 1 diabetes are limited. We investigated the epidemiology of MRSA colonization in patients with type 1 diabetes. This prospective cross-sectional study was conducted in a medical center (Chang Gung Memorial Hospital) in Taiwan from 1 July to 31 December 2020. Nasal sampling and MRSA detection were performed. The molecular characteristics of MRSA isolates were tested, and factors associated with MRSA colonization were analyzed. We included 245 patients with type 1 diabetes; nasal MRSA colonization was identified in 13 (5.3%) patients. All isolates belonged to community-associated MRSA genetic strains; the most frequent strain was clonal complex 45 (53.8%), followed by ST59 (30.8%) (a local community strain). MRSA colonization was positively associated with age ≤ 10 years, body mass index < 18 kg/m2, and diabetes duration < 10 years; moreover, it was negatively associated with serum low-density lipoprotein cholesterol ≥ 100 mg/dL. No independent factor was reported. The nasal MRSA colonization rate in type 1 diabetes is approximately 5% in Taiwan. Most of these colonizing strains are community strains, namely clonal complex 45 and ST59. [ABSTRACT FROM AUTHOR]

Enterococcus faecalis is known to cause severe acute endophthalmitis and often leads to poor visual outcomes in most ophthalmic infections. This retrospective study is to report the clinical settings, antimicrobial susceptibility patterns, and visual outcome of E. faecalis endophthalmitis at a tertiary referral institution in Taoyuan, Taiwan. E. faecalis endophthalmitis was diagnosed in 37 eyes of 37 patients. Post-cataract surgery was the most common cause (n = 27, 73%), followed by bleb-associated (n = 3, 8%), endogenous (n = 2, 5%), corneal ulcer-related (n = 2, 5%), post-vitrectomy (n = 1, 3%), post-pterygium excision (n = 1, 3%), and trauma (n = 1, 3%). Visual acuities upon presentation ranged from counting fingers to no light perception. Pars plana vitrectomy with intravitreal antibiotics were performed in 23 eyes (76%) as primary or secondary treatment. All isolates (37/37, 100%) were sensitive to vancomycin, penicillin, ampicillin, and teicoplanin. Six of 22 eyes (27%) were resistant to high-level gentamicin (minimum inhibitory concentration > 500 mg/L). Final visual acuities were better than 20/400 in 11 eyes (30%), 5/200 to hand motions in 4 eyes (11%), and light perception to no light perception in 22 eyes (59%). Three eyes were treated with evisceration. Compared with non-cataract subgroups, the post-cataract subgroup showed a significant difference of better visual prognosis (p = 0.016). [ABSTRACT FROM AUTHOR]

Feeling comfortable is an important issue for contact lens wearers as contact lenses are worn for an extensive period of time. It has been shown that the in vitro friction coefficient of contact lenses is correlated to the degree of in vivo comfort, thus many studies focus on establishing friction testing methods for investigating the friction coefficient of contact lenses or contact lens care solution. We have previously demonstrated the lubricating property of poly-gamma-glutamic acid (γ-PGA)-containing care solution, and it could reduce the high friction coefficient caused by lysozyme. However, the mechanism of how γ-PGA-containing care solution reduces the lysozyme-induced friction coefficient of contact lenses is unclear. We investigated the bio-tribological effect of γ-PGA on ionic contact lenses in the presence of lysozyme by testing load and velocity variations. The ability to remove lysozyme deposition by γ-PGA and viscosity analysis of γ-PGA-containing care solutions were also investigated to understand the potential mechanism. Our results showed that the friction coefficient of γ-PGA-containing care solution with lysozyme was the lowest in both load and velocity variations, and γ-PGA functions distinctly in the lysozyme-ionic contact lens system. We proposed a model of how γ-PGA could reduce the friction coefficient in these two conditions. [ABSTRACT FROM AUTHOR]

Orthokeratology lenses are commonly used for myopia control, especially in children. Tear lipids and proteins are immediately adsorbed when the lens is put on the cornea, and protein deposition may cause discomfort or infection. Therefore, we established an in vitro protein deposition analysis by mimicking the current cleaning methods for orthokeratology lens wearers for both short-term and long-term period. The results showed that the amounts of tear proteins accumulated daily and achieved a balance after 14 days when the lens was rubbed to clean or not. Protein deposition also affected the optical characteristics of the lens regardless of cleaning methods. Our results provided an in vitro analysis for protein deposition on the lens, and they may provide a potential effective method for developing care solutions or methods that can more effectively remove tear components from orthokeratology lenses.