Safety and effectiveness of intravitreal dexamethasone implant in patients with ocular toxocariasis.

AIMS: To evaluate the safety and effectiveness of intravitreal dexamethasone (DEX) implant in patients with active uveitis due to ocular toxocariasis (OT). METHODS: Seventy-eight patients with OT were recruited in this retrospective study, including 51 patients in DEX group treated with intravitreal DEX implant and 27 patients in control group without intervention. The reduction of vitreous haze scores (VHS), the best-corrected visual acuity (BCVA) changes, intraocular pressure (IOP) and cataract progression and formation were recorded at baseline (V0), 1 (V1), 3 (V3) and 6 months (V6) after treatment in DEX group, and V0 and V6 in control group. RESULTS: There was no change in VHS and BCVA in control group between V0 and V6. Better VHS (p=0.001) and BCVA (p=0.022) was achieved in DEX group; the rate of VHS=0 was 0%, 67.4%, 42.9% and 44.9% at V0, V1, V3 and V6, respectively (p＜0.001), and the mean BCVA was improved from logMAR 1.5±0.9 to 1.2±0.9 at V1, 1.4±1.0 at V3 and 1.4±1.2 at V6. A favourable BCVA at V1 was associated with older age (p=0.038) and uninvolved macula (p=0.000) in DEX group. No significant difference in IOP elevation ≥10 mm Hg, cataract progression and formation between groups. More eyes needed retinal surgery in control group (p<0.001). CONCLUSIONS: This was the first study to investigate use of intravitreal DEX implant in OT patients, which can efficiently reduce ocular inflammation and improve BCVA in macular uninvolved patients.

Development of ε-poly(L-lysine) carbon dots-modified magnetic nanoparticles and their applications as novel antibacterial agents.

Magnetic nanoparticles (MNPs) are widely applied in antibacterial therapy owing to their distinct nanoscale structure, intrinsic peroxidase-like activities, and magnetic behavior. However, some deficiencies, such as the tendency to aggregate in water, unsatisfactory biocompatibility, and limited antibacterial effect, hindered their further clinical applications. Surface modification of MNPs is one of the main strategies to improve their (bio)physicochemical properties and enhance biological functions. Herein, antibacterial ε-poly (L-lysine) carbon dots (PL-CDs) modified MNPs (CMNPs) were synthesized to investigate their performance in eliminating pathogenic bacteria. It was found that the PL-CDs were successfully loaded on the surface of MNPs by detecting their morphology, surface charges, functional groups, and other physicochemical properties. The positively charged CMNPs show superparamagnetic properties and are well dispersed in water. Furthermore, bacterial experiments indicate that the CMNPs exhibited highly effective antimicrobial properties against Staphylococcus aureus. Notably, the in vitro cellular assays show that CMNPs have favorable cytocompatibility. Thus, CMNPs acting as novel smart nanomaterials could offer great potential for the clinical treatment of bacterial infections.

Root-shaped antibacterial alginate sponges with enhanced hemostasis and osteogenesis for the prevention of dry socket.

Tooth extraction commonly causes uncontrolled bleeding, loss of blood clots, and bacterial infection, leading to the dry socket and bone resorption. Thus, it is highly attractive to design a bio-multifunctional scaffold with outstanding antimicrobial, hemostatic, and osteogenic performances for avoiding dry sockets in clinical applications. Herein, alginate (AG)/quaternized chitosan (Qch)/diatomite (Di) sponges were fabricated via electrostatic interaction, Ca2+ cross-linking, as well as lyophilization methods. The composite sponges are facilely made into the shape of the tooth root, which could be well integrated into the alveolar fossa. The sponge shows a highly interconnected and hierarchical porous structure at the macro/micro/nano levels. The prepared sponges also possess enhanced hemostatic and antibacterial abilities. Moreover, in vitro cellular assessment indicates that the developed sponges have favorable cytocompatibility and significantly facilitate osteogenesis by upregulating the formation of alkaline phosphatase and calcium nodules. The designed bio-multifunctional sponges display great potential for trauma treatment after tooth extraction.

Familial Exudative Vitreoretinopathy and Systemic Abnormalities in Patients With CTNNB1 Mutations.

Purpose: Familial exudative vitreoretinopathy (FEVR) is an inherited vitreoretinopathy. This study aimed to analyze the ocular phenotypes and systemic features of patients with CTNNB1 mutations. Methods: Whole exome sequencing was performed in the probands, and Sanger sequencing was used to verify the mutations and perform segregation analysis in the available family members. A luciferase assay was used to assess the effect of the mutant ß-catenin on transcription. Comprehensive ocular examinations were performed on the probands and family members. Systemic features were evaluated and followed up. Results: A total of 763 FEVR families were enrolled. Seven different CTNNB1 mutations, including 5 novels and 2 known mutations, were detected in 8 families, accounting for 1.05% of all FEVR families. Compared to wild-type CTNNB1, the CTNNB1 mutants failed to induce luciferase reporter activity in SuperTopFlash (STF) cells. Among the 16 eyes of the 8 probands, 2 (12.5%) eyes were classified as stage 2 FEVR, 8 (50.0%) as stage 4, and 6 (37.5%) as stage 5. All the patients had varying degrees of systemic abnormalities and presented with motor, speech, and developmental delays over time. Among the eight families with CTNNB1 mutations, seven were de novo mutations, and one proband inherited the mutation from his asymptomatic mother. Conclusions: This study provides detailed descriptions of the ocular phenotypes of patients with CTNNB1 mutations that presented as severe FEVR, and accompanied with other systemic abnormalities. Five novel mutations identified in this study, expanded the mutation spectrum of CTNNB1-associated FEVR.

Skills assessment after a grape-based microsurgical course for ophthalmology residents: randomised controlled trial.

AIMS: To introduce and assess a course using grapes as training models for ophthalmology residents to acquire basic microsurgical skills. METHODS: Ophthalmology residents who were novices at microsurgery were included. Participants were randomised into a 1:1 ratio to a 4-hour training programme based on fruit models (group A) or virtual reality (VR) modulator and silicone suture pads (group B), respectively. Before and after training, questionnaires were designed to measure their self-confidence with ophthalmic operations and with their coming role as surgical assistants. After training, each participant provided their interest in further studying microsurgery and was assessed for their general competence of ophthalmic microsurgery on porcine eyes. RESULTS: Eighty-three participants were included, with 42 ones in group A and 41 ones in group B. After training, participants in group A performed better in the uniformities of the suture span (p<0.05), suture thickness (p<0.05) and tissue protection (p<0.05) during the corneal suturing assessment. The overall scores of corneal suturing and circular capsulorhexis in the porcine eye in group A were comparable to those in group B (p=0.26 and 0.87, respectively). Group A showed a more positive attitude to withstand the training for more than 4 hours (p<0.001), as well as a higher willingness to receive more times of the training in the future (p<0.001). CONCLUSIONS: Training models based on grapes are equal to VR simulators and silicon suture pads to provide solid training tasks for ophthalmology residents to master basic microsurgical skills, and might have advantages in lower economic cost, and easy availability. TRIAL REGISTRATION NUMBER: ChiCTR2000040439.

The Development of Electroretinographic Oscillatory Potentials in Healthy Young Children.

PURPOSE: This study aimed to summarize the electroretinographic oscillatory potential (OP) responses in healthy young children recorded by RETeval. METHODS: By using the RETeval system, we recorded the implicit times and amplitudes of the OPs (OP1-5), in 132 healthy children aged from 0 to 11 years old. The age, gender, and data of implicit time and amplitude of each child were recorded and analyzed. Correlation analysis was performed between age and implicit time/amplitude. RESULTS: No correlation was shown between the implicit times and amplitudes with gender. The implicit times and amplitudes of OP1-5 matured over 10 years of age, with exponential time constants of 1.9, 2.2, 1.8, 1.7, and 1.6 years and 2.1, 2.9, 2.8, 3.0, and 3.2 years, respectively. The majority of the trend occurred within the first 4.6 years. CONCLUSIONS: In order to diagnose and evaluate vision-related disorders, the OP response is commonly used. The percentiles and age dependence of OP responses calculated and shown in this study could be regarded as reference data in age-matched pediatric patients.

Ocular manifestations of Chinese patients with copy number variants in the NDP gene.

Purpose: Familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND) are genetic disorders that can be caused by mutations in the NDP gene and affect retinal vasculature growth and development. This study aimed to describe the copy number variations (CNVs) in the NDP gene in Chinese FEVR families and the associated phenotypes. Methods: This study recruited 651 FEVR families. SeqCNV was used to analyze the CNVs in the families without mutations in known FEVR-associated genes. Multiplex ligation-dependent probe amplification and semiquantitative multiplex PCR were performed to verify the NDP CNVs. The probands and family members underwent complete ocular examinations. Results: NDP CNVs were identified in four patients from three unrelated families, accounting for 15% of the patients with NDP mutations and 0.46% of the entire FEVR cohort. Exon 2 deletions were detected in two families, and whole gene deletion was identified in one family. The affected individuals were born blind with total retinal detachment. Conclusions: The findings confirm that CNVs are a common NDP mutation type. The CNV-associated phenotype is congenital blindness with total retinal detachment. Antenatal genetic analyses and fetal ultrasound can facilitate early diagnosis and interventions in patients with NDP mutations.

CTNND1 variants cause familial exudative vitreoretinopathy through the Wnt/cadherin axis.

Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder that can cause vision loss. CTNND1 encodes a cellular adhesion protein p120-catenin (p120), which is essential for vascularization with unclear function in postnatal physiological angiogenesis. Here, we applied whole-exome sequencing to 140 probands of FEVR families and identified 3 candidate variants in the human CTNND1 gene. We performed inducible deletion of Ctnnd1 in the postnatal mouse endothelial cells (ECs) and observed typical phenotypes of FEVR with reactive gliosis. Using unbiased proteomics analysis combined with experimental approaches, we conclude that p120 is critical for the integrity of adherens junctions (AJs) and that p120 activates Wnt signaling activity by protecting ß-catenin from glycogen synthase kinase 3 beta-ubiqutin-guided (Gsk3ß-ubiquitin-guided) degradation. Treatment of CTNND1-depleted human retinal microvascular ECs with Gsk3ß inhibitors LiCl or CHIR-99021 enhanced cell proliferation. Moreover, LiCl treatment increased vessel density in Ctnnd1-deficient mouse retinas. Variants in CTNND1 caused FEVR by compromising the expression of AJs and Wnt signaling activity. Genetic interactions between p120 and ß-catenin or α-catenin revealed by double-heterozygous deletion in mice showed that p120 regulates vascular development through the Wnt/cadherin axis. In conclusion, variants in CTNND1 can cause FEVR through the Wnt/cadherin axis.

FZD4 in a Large Chinese Population With Familial Exudative Vitreoretinopathy: Molecular Characteristics and Clinical Manifestations.

Purpose: The purpose of this study was to establish a genotype-phenotype correlation of familial exudative vitreoretinopathy (FEVR) caused by FZD4 gene mutations. Methods: Six hundred fifty-one probands and their family members were recruited based on a clinical diagnosis of FEVR between 2015 and 2021 at Zhongshan Ophthalmic Center. Ocular examinations were performed in all participants. Targeted gene panel sequencing and whole-exome sequencing were performed in the probands, and Sanger sequencing was used to verify the mutations and segregation analysis was performed in the family members. Results: Fifty-one FZD4 mutations (24 novels and 27 known) were detected in 84 families. Of these 168 eyes with FEVR, the eyes at stages 1, 2, 3, 4, and 5 were 29 (17.3%), 15 (8.9%), 19 (11.3%), 55 (32.7%), and 12 (7.1%), respectively. Exact stage of 38 (22.6%) eyes could not be determined. The FEVR phenotypes were more severe in the probands than the phenotypes in the family members (P < 0.001). The families were divided into two groups, probands that inherited the variant from the mother, and probands that inherited the variant from the father. In addition, the FEVR stage differences between these two groups were different (P < 0.05). Despite the mutations being located in different domains of FZD4, no significant differences were identified among the domains in terms of FEVR staging, retinal folds, retinal detachment, temporal midperipheral vitreoretinal interface abnormality, and foveal hypoplasia. Conclusions: The FZD4 probands had severer phenotype than the family members, and the FEVR stage difference was greater between the probands and mothers than that between the probands and fathers.

Choroidal Neovascularization in Pediatric Patients: Analysis of Etiologic Factors, Clinical Characteristics and Treatment Outcomes.

Background and Objectives: Choroidal neovascularization (CNV) is a common pathologic lesion that occurs in various chorioretinopathy, but very limited published data have reported in pediatric patients. This study aimed to investigate the etiologic factors, clinical features, and treatment outcomes of choroidal neovascularization (CNV) in children. Methods: In this study, 33 eyes in 30 patients aged 18 years or younger with CNV were included. Comprehensive ophthalmic examination was performed in all the patients. The demographic profiles, laterality, visual acuity, optical coherence tomographic findings, fundus fluorescein angiographic findings, and the underlying pathology were analyzed. The types, locations, treatment outcomes, and recurrences of CNV were noted. Results: The average age was 11.2 ± 4.6 (range, 1-18) years. Most CNVs affecting children were classic and type 2. The most common etiologic factors of CNV in pediatric patients were congenital/developing abnormalities (9/30, 30.0%) and inflammatory retinochoroidopathy (9/30, 30.0%), followed by idiopathic CNV (8/30, 26.7%). Subtype analysis showed that the etiologic factor was inflammatory retinochoroidopathy in children 12 years or older, whereas congenital/developing abnormalities were present in children younger than 12 years. Eyes with active CNVs required a mean of 1.40 ± 0.58 injections. No recurrence was observed during follow-up. Conclusions: The etiologic factors of CNV in young Chinese patients were diverse, with congenital/developing abnormalities, inflammatory retinochoroidopathy and idiopathic CNV being the 3 most common ones. Eyes with active CNVs had good responses to antivascular endothelial growth factor treatment with low recurrence.

Application of the dual-factor model of mental health among Chinese new generation of migrant workers.

BACKGROUND: Traditional models of mental health focus on psychopathological symptoms. In contrast, the dual-factor model of mental health integrates positive mental health and psychopathology into a mental health continuum, which is an adaptation and complement to the traditional mental health research paradigm. The new generation of migrant workers is an important part of current Chinese society. Their identity has created a sense of loneliness, rootlessness, and alienation. This paper validates the applicability of the dual-factor model of mental health among new generation migrant workers in China. METHODS: In this study, 600 new generation migrant workers were recruited and tested on the symptom checklist 90, satisfaction with life scale, perceived stress scale, employee engagement inventory. Descriptive statistics and ANOVA were performed, the differences between the unidimensional model and dual-factor model were also tested. RESULTS: The results showed that the dual-factor model of the mental health approach had better construct validity than the unidimensional model. And four subgroups could be significantly discriminated by the dual-factor model: mentally healthy (58.45%), vulnerable (30.87%), symptomatic but content (3.11%), and troubled (7.57%). Compared to the other three groups, workers who were mentally healthy showed higher perceived work values and lower perceived work stress. CONCLUSIONS: The study suggests that a dual-factor model of mental health can be applied to new generation migrant workers in China, with positive mental health and psychopathology being important predictors of mental health.

Generation of induced pluripotent stem cell (iPSC) line ZOCi003-A derived from peripheral blood mononuclear cells of X-linked juvenile retinoschisis harboring a hemizygous mutation in RS1 gene.

X-linked juvenile retinoschisis (XLRS) is an inherited disease characterized by splitting within inner retinal layers and impaired vision, which begins in childhood and occurs mostly in males. Peripheral blood mononuclear cells (PBMCs) were isolated from a seven-year-old boy carrying a hemizygous mutation in RS1 gene, and were reprogrammed into human induced pluripotent stem cells (iPSCs) using non-integrative episomal vectors. The cell line, ZOCi003-A, had normal karyotype, expressed pluripotency markers, and could differentiate into three germ layers in vivo. This IPSC line may be used for studying the molecular basis of XLRS and selecting potential therapeutic targets and drugs.

Mydriasis-Free Flicker Electroretinograms in 204 Healthy Children Aged 0-18 Years: Reference Data From Two Cohorts.

Purpose: The purpose of this study was to summarize the flicker electroretinogram responses (ERGs) in healthy children using RETeval, a small handheld mydriasis-free full-field flicker ERG system. Methods: Flicker ERGs were recorded with the use of the RETeval system in 204 healthy children (aged 18 years and below) from 2 countries, China and the United States. The effects on ERG measurements of the subject's demographics and location were analyzed. Results: The implicit times have no correlation with the population (China cohort and US cohort), sex, and refractive error. In contrast, the amplitudes were dependent on demographics. The amplitude differences were small compared to the 95% reference interval; therefore, a single (age-corrected) reference interval can be used in both locations and both sexes. The implicit times and amplitudes mature over the first decade of life with exponential time constants of 2.5 years and 4.1 years, respectively, whereas most of the trend is within the first 6 years (implicit times) and 9 years (amplitudes). Conclusions: The age dependence and percentiles obtained in this study could serve as reference data against which the ERG responses from pediatric patients can be compared. Translational Relevance: The flicker ERG is one of the standard methods for the assessment and diagnosis of vision-related disorders. This study provides reference data in pediatric subjects, which can then be used to aid in the interpretation of flicker ERG results.

Whole-Gene Deletions of FZD4 Cause Familial Exudative Vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is an inherited disorder characterized by abnormalities in the retinal vasculature. The FZD4 gene is associated with FEVR, but the prevalence and impact of FZD4 copy number variation (CNV) on FEVR patients are unknown. The aim of this study was to better understand the genetic features and clinical manifestations of patients with FZD4 CNVs. A total of 651 FEVR families were recruited. Families negative for mutations in FEVR-associated genes were selected for CNV analysis using SeqCNV. Semiquantitative multiplex polymerase chain reaction and multiplex ligation-dependent probe amplification were conducted to verify the CNVs. Four probands were found to carry whole-gene deletions of FZD4, accounting for 5% (4/80) of probands with FZD4 mutations and 0.6% (4/651) of all FEVR probands. The four probands exhibited similar phenotypes of unilateral retinal folds. FEVR in probands with CNVs was not more severe than in probands with FZD4 missense mutations (p = 1.000). Although this is the first report of FZD4 CNVs and the associated phenotypes, the interpretation of FZD4 CNVs should be emphasized when analyzing the next-generation sequencing data of FEVR patients because of their high prevalence.

The Research on the Outpatient Cost Adjustment Framework of the Urban Workers in a Southern China City During 2013 to 2015.

Based on a large amount of data, the study aimed to analyze all expenses of outpatients in a southern China city from 2013 to 2015. It draws a conclusion that the total cost of outpatient has increased in the past 3 years, and various cost indexes either increased or decreased in different ways. Drug costs and treatment fees are the main influencing factors for the change in total outpatient cost. The structural change from 2013 to 2015 was 70.15%. Drug costs, laboratory fees, and inspection fees are the main indexes that account for the increasing total outpatient costs. This study puts emphasis on the cost of human resources, which eliminates the phenomenon of "Yi Yao Yang Yi" (support medical cost with medicine) and "Yi Xie Yang Yi" (support medical cost with medical device). This study also focuses on the balance of outpatient cost, as well as the compensation function of medical insurance, which encourages multiple participation and coordinated adjustment.