Kurarinone regulates Th17/Treg balance and ameliorates autoimmune uveitis via Rac1 inhibition.

INTRODUCTION: Autoimmune uveitis (AU) is a severe intraocular autoimmune disorder with a chronic disease course and a high rate of blindness. Kurarinone (KU), a major component of the traditional Chinese medicine Sophorae Flavescentis Radix, possesses a wide spectrum of activities and has been used to treat several inflammation-related diseases. OBJECTIVE: We aimed to investigate the effects of KU on AU and its modulatory mechanisms. METHODS: We used an experimental autoimmune uveitis (EAU) animal model and characterized the comprehensive immune landscape of KU-treated EAU mice using single-cell RNA sequencing (scRNA-seq). The retina and lymph nodes were analyzed. The siRNAs and selective inhibitors were used to study the signaling pathway. The effect of KU on peripheral blood mononuclear cells (PBMCs) from uveitis patients was also examined. RESULTS: We found that KU relieved chorioretinal lesions and immune cell infiltration in EAU model mice. Subsequent single-cell analysis revealed that KU downregulated the EAU-upregulated expression of inflammatory and autoimmune-related genes and suppressed pathways associated with immune cell differentiation, activation, and migration in a cell-specific manner. KU was implicated in restoring T helper 17 (Th17)/regulatory T (Treg) cell balance by alleviating inflammatory injury and elevating the expression of modulatory mediators in Tregs, while simultaneously ameliorating excessive inflammation by Th17 cells. Furthermore, Rac1 and the Id2/Pim1 axis potentiated the pathogenicity of Th17 cells during EAU, which was inhibited by KU treatment, contributing to the amelioration of EAU-induced inflammation and treatment of AU. In addition, KU suppressed inflammatory cytokine production in activated human PBMCs by inhibiting Rac1. Integration of the glucocorticoid-treated transcriptome suggests that KU has immunomodulatory effects on lymphocytes. CONCLUSION: Our study constructed a high-resolution atlas of the immunoregulatory effects of KU treatment on EAU and identified its potential therapeutic mechanisms, which hold great promise in treating autoimmune disorders.

An aging-related immune landscape in the hematopoietic immune system.

BACKGROUND: Aging is a holistic change that has a major impact on the immune system, and immunosenescence contributes to the overall progression of aging. The bone marrow is the most important hematopoietic immune organ, while the spleen, as the most important extramedullary hematopoietic immune organ, maintains homeostasis of the human hematopoietic immune system (HIS) in cooperation with the bone marrow. However, the overall changes in the HIS during aging have not been described. Here, we describe a hematopoietic immune map of the spleen and bone marrow of young and old mice using single-cell sequencing and flow cytometry techniques. RESULTS: We observed extensive, complex changes in the HIS during aging. Compared with young mice, the immune cells of aged mice showed a marked tendency toward myeloid differentiation, with the neutrophil population accounting for a significant proportion of this response. In this change, hypoxia-inducible factor 1-alpha (Hif1α) was significantly overexpressed, and this enhanced the immune efficacy and inflammatory response of neutrophils. Our research revealed that during the aging process, hematopoietic stem cells undergo significant changes in function and composition, and their polymorphism and differentiation abilities are downregulated. Moreover, we found that the highly responsive CD62L + HSCs were obviously downregulated in aging, suggesting that they may play an important role in the aging process. CONCLUSIONS: Overall, aging extensively alters the cellular composition and function of the HIS. These findings could potentially give high-dimensional insights and enable more accurate functional and developmental analyses as well as immune monitoring in HIS aging.

Persistence of severe global inequalities in the burden of blindness and vision loss from 1990 to 2019: findings from the Global Burden of Disease Study 2019.

AIMS: To assess the global burden and economic inequalities in the distribution of blindness and vision loss between 1990 and 2019. METHODS: A secondary analysis of the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. Data for disability-adjusted life-years (DALYs) due to blindness and vision loss were extracted from the GBD 2019. Data for gross domestic product per capita were extracted from the World Bank database. Slope index of inequality (SII) and concentration index were computed to assess absolute and relative cross-national health inequality, respectively. RESULTS: Countries with high, high-middle, middle, low-middle and low Socio-demographic Index (SDI) had decline of age-standardised DALY rate of 4.3%, 5.2%, 16.0%, 21.4% and 11.30% from 1990 to 2019, respectively. The poorest 50% of world citizens bore 59.0% and 66.2% of the burden of blindness and vision loss in 1990 and 2019, respectively. The absolute cross-national inequality (SII) fell from -303.5 (95% CI -370.8 to -236.2) in 1990 to -256.0 (95% CI -288.1 to -223.8) in 2019. The relative inequality (concentration index) for global blindness and vision loss remained essentially constant between 1991 (-0.197, 95% CI -0.234 to -0.160) and 2019 (-0.193, 95% CI -0.216 to -0.169). CONCLUSION: Though countries with middle and low-middle SDI were the most successful in decreasing burden of blindness and vision loss, a high level of cross-national health inequality persisted over the past three decades. More attention must be paid to the elimination of avoidable blindness and vision loss in low-income and middle-income countries.

Assessment of Peripapillary Retinal Nerve Fiber Layer Optical Density Ratios in Healthy Eyes Using Optical Coherence Tomography with Different Analytical Radii.

PURPOSE: To explore the characteristics and determinants of peripapillary retinal nerve fiber layer (RNFL) optical density (OD) by optical coherence tomography (OCT) in healthy eyes with varied analytical radii. METHODS: Peripapillary OCT scans centered at the optic disc of 150 eyes from 150 healthy subjects (64 males and 86 females) were included. Under 5 analytical circles with different radii (1.45 mm, 1.7 mm, 1.95 mm, 2.2 mm and 2.45 mm), the circumpapillary circular cross-sectional images were exported for further analysis using Image J. Peripapillary RNFL and retinal pigment epithelium (RPE) OD in different quadrants and clock-hours were obtained. RNFL optical density ratio (ODR) was then calculated as RNFL OD divided by RPE OD. A linear mixed-effects model analysis was performed to assess the relationship between RNFL ODR and analytical radius, accounting for axial length, age, spherical equivalent, thickness and image score. RESULTS: The RNFL ODRs had a double-hump pattern with peaks in the superior and inferior quadrants and troughs in the temporal and nasal areas. In the linear mixed-effects model analysis, a trend of decreasing mean RNFL ODR with increasing analytical radius was found (0.9227 ± 0.0689, 0.9063 ± 0.0620, 0.8916 ± 0.0552, 0.8729 ± 0.0553 and 0.8575 ± 0.0564 respectively, p = 0.034). RNFL ODR values was negatively correlated with age (p < 0.001), positively correlated with corresponding RNFL thickness (p < 0.001). No significant correlation was found between RFNL ODR and image score, axial length and spherical equivalent. CONCLUSIONS: RNFL ODR profile showed a comparable double-hump configuration with RNFL thickness. RNFL ODR values tended to decrease with larger analytical circles and older age, and increase with corresponding RNFL thickness. These factors should be considered when interpreting RNFL ODR in glaucoma assessment.

Intravitreal dexamethasone implants facilitate the management of refractory Behçet's uveitis with vasculitis.

To investigate the efficacy and safety of dexamethasone (DEX) implant, Ozurdex ®, as an adjunctive treatment for refractory Behçet's uveitis (BU), a total of 61 patients (80 eyes) were included in this cross-sectional study and divided into the non-DEX and DEX groups. After >12 months of treatment, the improvement in the fluorescein angiography score and vitritis score was significantly higher in the DEX group than in the non-DEX group. Although the posterior capsule opacification score was exacerbated, the rate of low-dose systemic glucocorticoid was higher and the relapse times were fewer in the DEX group. Therefore, Ozurdex® is an effective and safe option for patients with BU that are refractory to systemic immunosuppressant treatments by controlling vasculitis, stabilizing vitreous inflammation, preventing recurrence, and reducing daily glucocorticoid doses.

Sleep loss potentiates Th17-cell pathogenicity and promotes autoimmune uveitis.

BACKGROUND: Sleep loss (SL) is a health issue associated with the higher risk of autoimmune and inflammatory disorders. However, the connection between SL, the immune system, and autoimmune diseases remains unknown. METHODS: We conducted mass cytometry, single-cell RNA sequencing, and flow cytometry to analyze how SL influences immune system and autoimmune disease development. Peripheral blood mononuclear cells from six healthy subjects before and after SL were collected and analyzed by mass cytometry experiments and subsequent bioinformatic analysis to identify the effects of SL on human immune system. Sleep deprivation and experimental autoimmune uveitis (EAU) mice model were constructed, and scRNA-seq data from mice cervical draining lymph nodes were generated to explore how SL influences EAU development and related autoimmune responses. RESULTS: We found compositional and functional changes in human and mouse immune cells after SL, especially in effector CD4+ T and myeloid cells. SL upregulated serum GM-CSF levels in healthy individuals and in patients with SL-induced recurrent uveitis. Experiments in mice undergoing SL or EAU demonstrated that SL could aggravate autoimmune disorders by inducing pathological immune cell activation, upregulating inflammatory pathways, and promoting intercellular communication. Furthermore, we found that SL promoted Th17 differentiation, pathogenicity, and myeloid cells activation through the IL-23Th17GM-CSF feedback mechanism, thus promoting EAU development. Lastly, an anti-GM-CSF treatment rescued SL-induced EAU aggravation and pathological immune response. CONCLUSIONS: SL promoted Th17 cells pathogenicity and autoimmune uveitis development, especially through the interaction between Th17 and myeloid cells involving GM-CSF signaling, providing possible therapeutic targets for the SL-related pathological disorders.

Single-cell analysis of immune cells on gingiva-derived mesenchymal stem cells in experimental autoimmune uveitis.

Gingiva-derived mesenchymal stem cells (GMSCs) have shown astonishing efficacy in the treatment of various autoimmune diseases. However, the mechanisms underlying these immunosuppressive properties remain poorly understood. Here, we generated a lymph node single-cell transcriptomic atlas of GMSC-treated experimental autoimmune uveitis mice. GMSC exerted profound rescue effects on T cells, B cells, dendritic cells, and monocytes. GMSCs rescued the proportion of T helper 17 (Th17) cells and increased the proportion of regulatory T cells. In addition to globally altered transcriptional factors (Fosb and Jund), we observed cell type-dependent gene regulation (e.g., Il17a and Rac1 in Th17 cells), highlighting the GMSCs' cell type-dependent immunomodulatory capacity. GMSCs strongly influenced the phenotypes of Th17 cells, suppressing the formation of the highly inflammatory CCR6-CCR2+ phenotype and enhancing the production of interleukin (IL) -10 in the CCR6+CCR2+ phenotype. Integration of the glucocorticoid-treated transcriptome suggests a more specific immunosuppressive effect of GMSCs on lymphocytes.

Global, regional, and national burden of multiple sclerosis from 1990 to 2019: Findings of global burden of disease study 2019.

Background: The global rising prevalence and incidence of multiple sclerosis (MS) has been reported during the past decades. However, details regarding the evolution of MS burden have not been fully studied. This study aimed to investigate the global, regional, and national burden and temporal trends in MS incidence, deaths, and disability-adjusted life years (DALYs) from 1990 to 2019 using the age-period-cohort analysis. Methods: We performed a secondary comprehensive analysis of incidence, deaths, and DALYs of MS by calculating the estimated annual percentage change from 1990 to 2019 obtained from the Global Burden of Disease (GBD) 2019 study. The independent age, period, and birth cohort effects were evaluated by an age-period-cohort model. Results: In 2019, there were 59,345 incident MS cases and 22,439 MS deaths worldwide. The global number of incidences, deaths, and DALYs of MS followed an upward trend, whereas the age-standardized rates (ASR) slightly declined from 1990 to 2019. High socio-demographic index (SDI) regions had the highest ASR of incidences, deaths, and DALYs in 2019, while the rate of deaths and DALYs in medium SDI regions are the lowest. Six regions which include high-income North America, Western Europe, Australasia, Central Europe, and Eastern Europe had higher ASR of incidences, deaths, and DALYs than other regions in 2019. The age effect showed that the relative risks (RRs) of incidence and DALYs reached the peak at ages 30-39 and 50-59, respectively. The period effect showed that the RRs of deaths and DALYs increased with the period. The cohort effect showed that the later cohort has lower RRs of deaths and DALYs than the early cohort. Conclusion: The global cases of incidence, deaths, and DALYs of MS have all increased, whereas ASR has declined, with different trends in different regions. High SDI regions such as European countries have a substantial burden of MS. There are significant age effects for incidence, deaths, and DALYs of MS globally, and period effects and cohort effects for deaths and DALYs.

Adalimumab plus Conventional Therapy versus Conventional Therapy in Refractory Non-Infectious Scleritis.

Long-term systemic glucocorticoids and non-specific immunosuppressants remain the mainstay of treatment for refractory scleritis, and result in serious side-effects and repeated inflammation flares. To assess the efficacy and safety of additional adalimumab, patients diagnosed with refractory non-infectious scleritis were enrolled. They were assigned to the conventional-therapy (CT, using systemic glucocorticoids and other immunosuppressants) group or the adalimumab-plus-conventional-therapy (ACT) group according to the treatments they received. The primary outcome was time to achieve sustained remission, assessed by a reduction in modified McCluskey's scleritis scores. Other outcomes included changes in McCluskey's scores, scleritis flares, best-corrected visual acuity, and spared glucocorticoid dosage. Patients in the ACT group achieved faster remission than those in the CT group, as the median periods before remission were 4 months vs. 2.5 months (p = 0.016). Scleritis flares occurred in 11/11 eyes in the CT group and 5/12 eyes in the ACT group (p = 0.005). Successful glucocorticoid sparing was realized in both groups, but the ACT group made it faster. No severe adverse events were observed. Data suggest that adalimumab plus conventional therapy could shorten the time to remission, reduce disease flares, and accelerate glucocorticoid withdrawal compared with conventional therapy alone.

Integration of Massive Open Online Course (MOOC) in Ophthalmic Skills Training for Medical Students: Outcomes and Perspectives.

PURPOSE: To integrate a massive open online course (MOOC) into conventional clinical ophthalmology teaching and investigate its impact on the skills of medical students. METHODS: This was a nonrandomized, prospective, and comparative study. Seventy-six medical students were assigned to 2 groups before their clinical teaching. Some were asked to follow a MOOC for slitlamp microscope examination but used textbook for preview of visual acuity test (SLMM group, n=39), while others were required to take a MOOC for visual acuity test and previewed slitlamp microscopy using textbook (VATM group, n=37). All the students then underwent conventional clinical ophthalmology teaching on slitlamp microscopy and visual acuity test. Their performance was evaluated using Direct Observation of Procedural Skills (DOPS). Students were also asked to complete a 5-item questionnaire about their learning experience and comment on the MOOC. RESULTS: Students in the SLMM group obtained overall higher scores in the slitlamp practical skills (47.64±4.01 vs 44.68±5.99, P=0.013), while those in the VATM group performed better in the visual acuity test (46.45±4.90 vs 43.78±4.94, P=0.004). MOOC was deemed to increase learning interests (4.13 of 5 points) and motivation (4.01 of 5 points) but was more preferred as an additional tool to traditional teaching methods (4.34 of 5 points) rather than to replace them (2.92 of 5 points). CONCLUSIONS: MOOC offers an added benefit in improving clinical skills and is worth advocating as an additional tool for clinical ophthalmic education.

Multicellular immune dynamics implicate PIM1 as a potential therapeutic target for uveitis.

Uveitis is a severe autoimmune disease, and a common cause of blindness; however, its individual cellular dynamics and pathogenic mechanism remain poorly understood. Herein, by performing single-cell RNA sequencing (scRNA-seq) on experimental autoimmune uveitis (EAU), we identify disease-associated alterations in cell composition and transcriptional regulation as the disease progressed, as well as a disease-related molecule, PIM1. Inhibiting PIM1 reduces the Th17 cell proportion and increases the Treg cell proportion, likely due to regulation of PIM1 to the protein kinase B (AKT)/Forkhead box O1 (FOXO1) pathway. Moreover, inhibiting PIM1 reduces Th17 cell pathogenicity and reduces plasma cell differentiation. Importantly, the upregulation of PIM1 in CD4+ T cells and plasma cells is conserved in a human uveitis, Vogt-Koyanagi-Harada disease (VKH), and inhibition of PIM1 reduces CD4+ T and B cell expansion. Collectively, a dynamic immune cellular atlas during uveitis is developed and implicate that PIM1 may be a potential therapeutic target for VKH.

Potential productivity loss from uncorrected and under-corrected presbyopia in low- and middle-income countries: A life table modeling study.

Objective: To estimate the burden of potential productivity losses due to uncorrected and under-corrected presbyopia in LMICs among the working-age population in both the cross-sectional and longitudinal manner. Methods: We extracted data for the prevalence of presbyopia from the Global Burden of Diseases (GBD), Injuries, and Risk Factors Study 2019. Data for the gross domestic product (GDP) per capita were extracted from the World Bank database and Central Intelligence Agency's World Factbook. We introduced life table models to construct age cohorts (in 5-year age groups) of the working-age population (aged from 40 to 64 years old) in LMICs, with simulated follow-up until 65 years old in people with and without uncorrected presbyopia. The differences in productivity-adjusted life years (PALYs) lived and productivity between these two cohorts were calculated. The potential productivity loss was estimated based on GDP per capita. The WHO standard 3% annual discount rate was applied to all years of life and PALYs lived. Results: In 2019, there were 238.40 million (95% confidence interval [CI]: 150.92-346.78 million) uncorrected and under-corrected presbyopia cases in LMICs, resulting in 54.13 billion (current US dollars) (95% confidence interval [CI]: 34.34-79.02 billion) potential productivity losses. With simulated follow-up until retirement, those with uncorrected and under-corrected presbyopia were predicted to experience an additional loss of 155 million PALYs (an average loss of 0.7 PALYs per case), which was equivalent to a total loss of US$ 315 billion (an average loss of US$ 1453.72 per person). Conclusions: Our findings highlight the considerable productivity losses due to uncorrected and under-corrected presbyopia in LMICs, especially in a longitudinal manner. There is a great need for the development of enabling eye care policies and programs to create access to eye care services, and more healthcare investment in the correction of presbyopia in the working-age population in LMICs. This study could provide evidences for some potential health-related strategies for socio-economic development.

Comparison of Vault Measurements Using a Swept-Source OCT-Based Optical Biometer and Anterior Segment OCT.

Background: To newly describe the vault measurement by using a widely used swept-source OCT-based optical biometer (IOLMaster700) and accessd the accuracy of vault measurement. Methods: This was a retrospective, cross-sectional study. All patients underwent implantable Collamer lens (ICL) implantation surgery without complications. IOLMaster700 and AS-OCT analyses were conducted for each eye on the same day in the same condition. Measurements of anterior chamber depth (ACD), corneal-ICL (C-ICL), and vault values were made and recorded. The repeatability of the IOL Master700 measurements was quantified based upon intraclass correlation coefficient (ICC) values. Correlations between IOL Master700 and AS-OCT measurements made with these different analytical approaches were assessed. The agreement of instruments was evaluated using Bland-Altman plots. Results: The IOLMaster700 instrument yielded highly reliable measurements of vault, C-ICL, and ACD (ICC = 0.996, 0.995, 0.995, respectively). Vault, C-ICL and ACD values as measured using the IOLMaster700, was slightly smaller than that measured via AS-OCT, but these differences were not significant (p = 0.652, p = 0.121 and p = 0.091, respectively). The vault, C-ICL, and ACD measurements by these two instruments were strongly correlated (r = 0.971, r = 0.944, and r = 0.963, respectively; all p < 0.001). The 95% limits of agreement for vault, C-ICL, and ACD measurements between the two devices were-0.08 to 0.08 mm,-0.14 to 0.11 mm, and-0.13 to 0.10 mm, respectively. Conclusions: The IOLMasrer700 can measure implanted ICL vault with a high degree of accuracy and repeatability. Good correlations and agreement were observed between IOLMaster700 and AS-OCT in measuring vault, C-ICL, and ACD measurements.

Single-cell RNA sequencing depicts the local cell landscape in thyroid-associated ophthalmopathy.

There is a specific reactivity and characteristic remodeling of the periocular tissue in thyroid-associated ophthalmopathy (TAO). However, local cell changes responsible for these pathological processes have not been sufficiently identified. Here, single-cell RNA sequencing is performed to characterize the transcriptional changes of cellular components in the orbital connective tissue in individuals with TAO. Our study shows that lipofibroblasts with RASD1 expression are highly involved in inflammation and adipogenesis during TAO. ACKR1+ endothelial cells and adipose tissue macrophages may engage in TAO pathogenesis. We find CD8+CD57+ cytotoxic T lymphocytes with the terminal differentiation phenotype to be another source of interferon-γ, a molecule actively engaging in TAO pathogenesis. Cell-cell communication analysis reveals increased activity of CXCL8/ACKR1 and TNFSF4/TNFRSF4 interactions in TAO. This study provides a comprehensive local cell landscape of TAO and may be valuable for future therapy investigation.

Systemic glucocorticoid-free therapy with adalimumab plus immunosuppressants versus conventional therapy in treatment-naïve Vogt-Koyanagi-Harada disease patients.

Background: High dose systemic glucocorticoid is the main therapy of treatment-naïve Vogt-Koyanagi-Harada (VKH) disease. However, series side effects induced by high dose systemic glucocorticoid frequently occur, which makes alternative therapy necessary for certain patients. This study sought to compare the efficacy and safety of systemic glucocorticoid-free (SGF) therapy with conventional therapy (CT) as an initial treatment for VKH patients. Methods: VKH patients who had not been systemically treated were enrolled. Patients were allocated into 2 therapeutic groups depending on their treatments. In CT group, patients received systemic glucocorticoid plus immunosuppressants (IS), and in SGF group, patients received adalimumab (ADA) plus IS. Patients received approximately 12 months treatment and visit monthly. The outcome parameters included the changes of best-corrected visual acuity (BCVA), intraocular inflammation (including anterior chamber cell grade and vitritis grade) and central macular thickness (CMT) (the change values define as the final-visit values subtracted from baseline counterparts). Other outcomes included the relapses times of ocular inflammation, adverse events (AEs), changes of optic nerve inflammation (ONI) and intraocular/extraocular manifestations. Results: A total of 30 patients (60 eyes) were included. with 19 patients (38 eyes) in CT group and 11 patients (22 eyes) in SGF group. After approximately 1 year of treatment, the improvements of BCVA were slight better in the SGF group (0.57±0.23) than in the CT group (0.40±0.26), (P=0.014). In both groups, the ocular inflammatory improvements in both groups were similar, with an improvement of AC cell grade of -1.5 (-2, -0.5) in CT group versus -1 (-2, -1) in SGF group (P=0.367); improvement of vitritis grade was 0 (-1.25, 0) in CT group and -1 (-1, -1) in SGF group (P=0.050). The improvement in CMT was similar in both groups, with -523.47±412.09 µm in CT group and -362.73±375.73 µm in SGF group (P=0.572). The mean number of relapses was 1 (0, 2) in the CT group and 0 (0, 2) in the SGF group (P=0.372). No severe AEs were observed in this study. Conclusions: SGF therapy is effective, safe, and well-tolerated in treatment-naïve VKH patients. SGF therapy seems to be a feasible option in patients with existing systemic diseases intolerant to glucocorticoid.

Prevalence of Visual Impairment in Preschool Children in Southern China.

Purpose: The goal of this study is to assess the prevalence and distribution of visual impairment in preschool children in southern China. Methods: Preschool children aged 36-83 months were enrolled in a vision screening program in Shantou City. Visual acuity test and non-cycloplegic refraction were conducted. According to the American Academy of Ophthalmology (AAO) guidelines, visual impairment was defined as uncorrected visual acuity (UCVA) in either eye <20/50, 20/40, and 20/32 in children aged 36-47, 48-59, and 60-83 months, respectively, as well as an interocular difference (IOD) of ≥ two lines of UCVA. Results: The UCVA test was successfully performed on 7,880 children (94.6% of the enrolled population). A total of 938 (11.9%; 95% CI 11.2-12.6) children were found to have reduced UCVA in the worse eye, and 393 (5%; 95% CI 4.5-5.5) of the children had an IOD of two or more lines. Combining the reduced UCVA with the IOD criteria identified 1,032 (13.1%; 95% CI 12.4-13.8) children with visual impairment. UCVA in preschool children improves with age naturally and boys have slightly better age-adjusted UCVA than girls. Causes of reduced visual acuity included uncorrected refractive error, amblyopia, congenital cataract, and others. The cylindrical diopter in the right eye of children with reduced vison was higher than that of children with normal vision (1.19 ± 1.05 vs. 0.52 ± 0.49, P < 0.001). A total of 146 (1.9%, 95% CI 1.6-2.2) of the preschool children wore spectacles. The proportion of wearing spectacles increased with age (χ2 = 35.714, P < 0.001), but with IOD increasing by.1 logMAR, the odds of wearing spectacles decreased by 44.8%. Conclusion: This study provided data on the prevalence of visual impairment in preschool children in China by large-scale school-based vision screening. Further studies should be conducted to verify the benefit from vision screening.

First observation of intraocular extranodal natural killer/T-cell lymphoma secondary to a retroperitoneal tumour: a case report and comparative review.

BACKGROUND: Vitreoretinal lymphomas are difficult to diagnose due to their insidious onset and inaccessible focal points. Natural killer/T-cell derived malignancies are rare as intraocular lymphomas and usually have a rapid progression and a poor prognosis. Therefore, it is essential to make a definite diagnosis, especially differentially with B-cell-derived lymphomas, which account for most cases of vitreoretinal lymphomas. CASE PRESENTATION: This case report describes a 55-year-old female reporting a 10-month history of painless decline in her vision of the right eye. Optical coherence tomography of the patient revealed hyperreflective nodules and irregular humps in the retinal pigment epithelium layer. The right vitreous was aspirated for diagnostic assessment, revealing an interleukin-10 level of 39.4 pg/mL and an interleukin-10/interleukin-6 ratio of 1.05. The right vitreous humor was positive for Epstein-Barr virus DNA. Upon a systemic examination, a high metabolic nodule was found in the retroperitoneal area and proven to be positive for Epstein-Barr virus-encoded mRNA, CD2, CD3ε, TIA-1, and Ki-67. Considering the homology of the two lesions, the patient was diagnosed with metastatic vitreoretinal lymphoma secondary to retroperitoneal extranodal natural killer/T-cell derived lymphoma. The patient received systemic chemotherapy and regular intravitreal injections of methotrexate. Her visual acuity of the right eye had improved from 20/125 to 20/32 at the latest follow-up. No new lesions were found. CONCLUSIONS: A definitive diagnosis of vitreoretinal lymphoma is challenging. On some occasions in which pathological evidence is missing, the available examination results and clinical observations must be comprehensively considered. This study herein summarized pertinent pieces of literature and reports and reviewed available practicable methods to make a definitive diagnosis of intraocular extranodal natural killer/T-cell lymphoma, which was particularly distinct from the common diffuse large B-cell lymphomas.

Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice.

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.

Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity.

Purpose: The purpose of this study was to elucidate the effects of interleukin (IL)-38 on experimental autoimmune uveitis (EAU) and its underlying mechanisms. Methods: Mice with EAU were treated with IL-38, and the retinas and cervical draining lymph nodes (CDLNs) were analyzed by flow cytometry. Single-cell RNA sequencing (scRNA-seq) was conducted to analyze the immune cell profiles of CDLNs from normal, EAU, and IL-38-treated mice. Results: Administration of IL-38 attenuated EAU symptoms and reduced the proportion of T helper 17 (Th17) and T helper 1 (Th1) cells in the retinas and CDLNs. In scRNA-seq analysis, IL-38 downregulated the IL-17 signaling pathway and reduced the expression of Th17 cell pathogenicity-related genes (Csf2 and Il23r), findings which were also confirmed by flow cytometry. In vitro, IL-38 reduced the granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation function of IL-23 and inhibited IL-23R expression in Th17 cells. Moreover, when co-cultured with Th17 cells, IL-38 prevented IL-23 production in antigen-presenting cells (APCs). Conclusions: Our data demonstrate the therapeutic effect of IL-38 on EAU, and suggest that the effect of IL-38 may be caused by dampening of the GM-CSF/IL-23R/IL-23 feedback loop between Th17 cells and APCs.