AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induc...AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.展开更多
BACKGROUND Chronic idiopathic uveitis(CIU)and juvenile idiopathic arthritis-associated uveitis(U-JIA)are both vision-threatening conditions that share similar autoimmune mechanisms,but treatment approaches differ sign...BACKGROUND Chronic idiopathic uveitis(CIU)and juvenile idiopathic arthritis-associated uveitis(U-JIA)are both vision-threatening conditions that share similar autoimmune mechanisms,but treatment approaches differ significantly.In managing U-JIA,various treatment options are employed,including biological and non-biological disease-modifying anti-rheumatic drugs.These drugs are effective in clinical trials.Given the lack of established diagnostic and treatment guidelines as well as the limited number of therapeutic options available,patients with CIU frequently do not receive optimal and timely immunosuppression.This study highlighted the necessity for additional research to develop novel diag-nostic techniques,targeted therapies,and enhanced treatment outcomes for young individuals with CIU.AIM To compare the characteristics and outcomes of U-JIA and CIU.METHODS A retrospective cohort study analyzed data from 110 pediatric patients(under 18 years old)with U-JIA and 40 pediatric patients with CIU.Data was collected between 2012 and 2023.The study focused on demographic,clinical,treatment,and outcome variables.RESULTS The median onset age of arthritis was 6.4 years(2.7 years;9.3 years).In 28.2%of cases uveitis preceded the onset of arthritis.In 17.3%of cases it occurred simultan-eously.In 53.6%of cases it followed arthritis.Both groups had similar onset ages,antinuclear antibodies/human leukocyte antigen positivity rates,and ESR levels,with a slight predominance of females(60.9%vs 42.5%,P=0.062),and higher C-reactive protein levels in the U-JIA group.Anterior uveitis was more prevalent in patients with U-JIA(P=0.023),although the frequency of symptomatic,unilateral,and complicated forms did not differ significantly.The use of methotrexate(83.8%vs 96.4%)and biologics(64.7%vs 82.1%)was comparable,as was the rate of remission on methotrexate treatment(70.9%vs 56.5%)and biological therapy(77.8%vs 95%),but a immunosuppressive treatment delay in CIU observed.Patients with CIU were less likely to receive methotrexate[hazard ratio(HR)=0.48,P=0.005]or biological treatment(HR=0.42,P=0.004),but they were more likely to achieve remission with methotrexate(HR=3.70,P=0.001).CONCLUSION Treatment of uveitis is often limited to topical measures,which can delay systemic therapy and affect the outcome.Methotrexate and biological agents effectively manage eye inflammation.It is essential to develop standardized protocols for the diagnosis and management of uveitis,and collaboration between rheumatologists and ophthal-mologists is needed to achieve optimal outcomes in the treatment of CIU.展开更多
BACKGROUND Uveitis associated with juvenile idiopathic arthritis(U-JIA)is a vision-threatening condition.Estimates of prevalence of uveitis in patients with known juvenile idiopathic arthritis range from 11.6%to 30.0%...BACKGROUND Uveitis associated with juvenile idiopathic arthritis(U-JIA)is a vision-threatening condition.Estimates of prevalence of uveitis in patients with known juvenile idiopathic arthritis range from 11.6%to 30.0%.First-line treatment includes topical glucocorticoids;methotrexate(MTX)is used if topical corticosteroids are ineffective.In severe cases biological therapy like adalimumab may be prescribed.Complications,including vision loss,may be related to the disease and the ongoing treatment(topical corticosteroids).In severe cases surgical intervention is often necessary and is typically associated with poor vision outcomes.AIM To highlight the characteristics of operated U-JIA and to identify predictors of treatment failure.METHODS A retrospective cohort study analyzed data from 68 pediatric patients(under 18 years old)with U-JIA between 2007 and 2023.The study focused on demographic,clinical,treatment,and outcome variables.Survival analysis using Kaplan-Meier curves and the Cox proportional hazards model was performed to estimate the impact of surgical intervention on the course of uveitis and to identify predictors of treatment failure.RESULTS Eye surgery was performed on 17(25%)patients with U-JIA.It was associated with an earlier onset of uveitis(P=0.017),lower uveitis remission rate[odds ratio=5.29,95%confidence interval(CI):1.23-24.90,P=0.015],longer time to remission(P=0.036),reduced probability of achieving remission on MTX(P=0.033),and the necessity of the following treatment with biological diseasemodifying antirheumatic drugs(odds ratio=5.60;95%CI:1.11-55.19,P=0.021)with similar efficacy with biological treatments in operated and non-operated cases.Kaplan-Meier curves showed a borderline difference in time to surgical intervention based on the MTX initiation cutoff(P=0.065)although earlier MTX initiation might be associated with a higher likelihood of deferred surgery.CONCLUSION Operated patients exhibited an aggressive early-onset uveitis profile that needed early and more intensive treatment.Delayed and failed MTX treatment as well as delayed switching to biologics often required subsequent eye surgery.展开更多
Background:Noninfectious uveitis,a chronic ocular inflammatory disease,is char-acterized by the activation of immune cells in the eye,with most studies focusing on the role of the adaptive immune system in the disease...Background:Noninfectious uveitis,a chronic ocular inflammatory disease,is char-acterized by the activation of immune cells in the eye,with most studies focusing on the role of the adaptive immune system in the disease.However,limited data exist on the potential contribution of the innate immune system,specifically the nucleotide-binding oligomerization domain and leucine-rich repeat receptor-3(NLRP3)inflamma-some pathway.This pathway has previously been identified as a driver of inflammation in several low-grade,progressive inflammatory eye diseases such as diabetic retin-opathy.The aim of this study was to determine whether the NLRP3 inflammasome pathway plays a role in the pathogenesis and chronicity of experimental autoimmune uveitis(EAU).Methods:EAU was induced in C57BL/6J mice via intraperitoneal pertussis toxin and subcutaneous interphotoreceptor retinoid-binding protein injections.After 12 weeks,eyes were enucleated,and whole eye sections were assessed for inflammasome,macrophage,and microglial markers in the retina,ciliary body,and cornea using immunohistochemistry.Results:Our study confirmed higher NLRP3 inflammasome activation(increased ex-pression of NLRP3 and cleaved caspase 1 labeling)in EAU mouse retinas compared to controls.This correlated with increased astrogliosis and microglial activation through-out the eye.Migratory innate and adaptive peripheral immune cells(macrophages and leukocytes)were also found within the retina and ciliary body of EAU mice.Connexin43 proteins,which form hexameric hemichannels that can release adeno-sine triphosphate(ATP),an upstream inflammasome priming signal,were also found upregulated in the retina and cornea of EAU mice.Conclusion:Overall,our findings support the idea that in the EAU model there is active inflammation,even 12 weeks post induction,and that it can be correlated to inflammasome activation.This contributes to the pathogenesis and chronicity of non-infectious uveitis,and our results emphasize that targeting the inflammasome path-way could be efficacious for noninfectious uveitis treatment.展开更多
AIM: To characterize the clinical features, diagnosis, treatment and prognosis of uveitis associated with ankylosing spondylitis (AS) in Chinese patients. METHODS: Two hundred and three patients with uveitis associate...AIM: To characterize the clinical features, diagnosis, treatment and prognosis of uveitis associated with ankylosing spondylitis (AS) in Chinese patients. METHODS: Two hundred and three patients with uveitis associated with AS followed-up in the Third Military Medical University Daping Hospital between 2005 and 2010 were retrospectively evaluated in this study. Complete ophthalmological examinations were evaluated at baseline and during the follow-up period. The gender, age, follow-up time, mean frequency of uveitis onset, and accompanying eye examination findings, history, demographical parameters were reviewed. All the patients presented complete clinical and radiologic (sacroiliac, lumbar, dorsal and cervical spine, knee, ankle, shoulder, hip, elbow) evaluation. HLA-B27 typing was also searched. RESULTS: There were 203 patients diagnosed with AS associated welt's. All showed sacroiliac X-ray changes indicative of AS. There were 184 male and 19 female patients. The average age of patients was 35 +/- 12 (range 18-50). Mean follow-up period was 2.4 years (1-5 years). Acute anterior wets was the most common type of uveitis in both genders. 121 eyes presented unilateral involvement (55.2%), and 92 eyes presented bilateral involvement (45.3%) with onset alternately. 22 eyes occurred hypopyon, 16 eyes were found anterior vitreous cells, 7 eyes were noted reactive macular edema or exudation, 29 eyes presented posterior synechiae of iris, and 14 eyes presented cataract, 9 eyes presented secondary glaucoma, 2 eyes presented bend corneal degeneration and 1 eyes presented atrophy of eyeball. At the final visit, uveitis was well controlled in most patients. CONCLUSION: AS associated with uveitis in Chinese patients mainly manifests as acute anterior uveitis. A combination of corticosteroids with other mydriasis agents is effective for most AS associated with uveitis patients. In general, the prognosis is good in these cases.展开更多
Uveitis is an inflammatory disease affecting the uvea,which includes the iris,ciliary body and choroid(1).Noninfective uveitis is more prevalent in developed countries and primarily impacts individuals of working age,...Uveitis is an inflammatory disease affecting the uvea,which includes the iris,ciliary body and choroid(1).Noninfective uveitis is more prevalent in developed countries and primarily impacts individuals of working age,with a mean onset of around 40 years.It accounts for 5-10%of severe vision impairment globally(1,2).This form of uveitis is often associated with systemic diseases,such as ankylosing spondylosis,juvenile idiopathic arthritis,sarcoidosis and Behcet’s disease(2,3).展开更多
AIM:To characterize a Portuguese population of patients with juvenile idiopathic arthritis(JIA)and to evaluate possible associations between clinical factors and ocular involvement.METHODS:Patients diagnosed with JIA ...AIM:To characterize a Portuguese population of patients with juvenile idiopathic arthritis(JIA)and to evaluate possible associations between clinical factors and ocular involvement.METHODS:Patients diagnosed with JIA in the previous 20y in Hospital Garcia de Orta were included.Data were assessed from Reuma.pt database.Associations between demographic(age and sex),clinical(articular involvement,extra-articular manifestations,biological therapy),laboratory data[anti-nuclear antibodies,anti-cyclic citrullinated peptide(CCP)antibodies,rheumatoid factor,human leukocyte antigen B27(HLA-B27),C-reactive protein,erythrocyte sedimentation rate]and ocular involvement were assessed.Statistical analysis was performed using Chi-square for categorical variables and Mann-Whitney test for continuous variables.RESULTS:Totally 91 patients were included,11(12%)with previous episodes of uveitis.There was a statistically significant preponderance of early age at JIA diagnosis(mean 4.73 vs 9.58y,P=0.008),antinuclear antibodies positivity(P=0.01),and oligoarticular subtype(P=0.04)in the Juvenile idiopathic arthritis-associated uveitis(JIA-U)group.Ocular complications occurred in 36.4%of patients(n=4):cataracts(n=2),band keratopathy(n=1)and posterior synechiae(n=1).The occurrence of complications was corelated with a shorter period between JIA diagnosis and the first JIA-U episode(mean 0.67 vs 4.88y,P=0.012)but not with age at JIA diagnosis or articular involvement.There was erythrocyte sedimentation rate elevation in the 12mo preceding uveitis(mean 40.5 mm/h,range 13-83).CONCLUSION:The occurrence of JIA-U shortly after JIA diagnosis is shown to be a potential risk factor for ocular complications.展开更多
AIM:To use two-sample Mendelian randomization(MR)method to study uveitis causal association with wet age-related macular degeneration(wAMD)risk from the genetic level.METHODS:Two-sample MR analysis was used to assess ...AIM:To use two-sample Mendelian randomization(MR)method to study uveitis causal association with wet age-related macular degeneration(wAMD)risk from the genetic level.METHODS:Two-sample MR analysis was used to assess the causal role of uveitis on wAMD risk,using the 8 genetic variants associated strongly with uveitis as instrumental variables.Besides,eight MR methods[inverse variance weighted(IVW),weighted median,MR-Egger regression,weighted mode,simple mode,robust adjusted profile score(RAPS),contamination inverse-variance weighted method,and debiased inverse-variance weighted method]were used to get the whole causal estimate for multiple instrumental single nucleotide polymorphism(SNPs).The MR analysis was based on Europeans.RESULTS:Uveitis was related to a higher risk of wAMD[odds ratio(OR):1.08,95%confidence interval(CI)1.03–1.12;P=1.03×10^(-3)]with the IVW method.No heterogeneity and directional pleiotropy were detected.On the contrary,no significant results were detected in reverse MR analysis.CONCLUSION:Uveitis is related to an increased risk of wAMD.Due to the high blindness rate of wAMD,understanding and controlling the risk factors of AMD is of great significance for reducing its incidence and early diagnosis and treatment.展开更多
Non-infectious uveitis(NIU),although a highly blinding but preventable cause of blindness around the world,has few approved pharmaceuticals for its treatment.Lack of access to effective treatment is likely a major cau...Non-infectious uveitis(NIU),although a highly blinding but preventable cause of blindness around the world,has few approved pharmaceuticals for its treatment.Lack of access to effective treatment is likely a major cause of poor visual outcomes in NIU.However,despite a revolution in rheumatologic disease treatment with the advent of multiple biologic therapeutics selectively targeting the immune response,there remains a gap in the long-term management of NIU.Adalimumab remains the only systemic medication approved for the treatment of NIU by the Food and Drug Administration(FDA).All other systemic treatments,including older anti-metabolites such as methotrexate and mycophenolate,are used offlabel for NIU,posing significant treatment challenges.Given the nature and rarity of the disease,there are few well designed,large,clinical trials evaluating the efficacy of novel therapeutic agents within this field.We therefore read with great interest Srivastava et al.’s randomized clinical trial on the efficacy of filgotinib,a Janus kinase inhibitor(JAKi),in active NIU(1).The early termination of the trial due to business considerations highlights the industry difficulty in FDA medication approval for NIU.展开更多
Juvenile idiopathic arthritis(JIA)is the most common rheumatic disease of childhood,and juvenile idiopathic associated uveitis(JIA-U)is the most frequently noted extra-articular manifestation.JIA-U can present asympto...Juvenile idiopathic arthritis(JIA)is the most common rheumatic disease of childhood,and juvenile idiopathic associated uveitis(JIA-U)is the most frequently noted extra-articular manifestation.JIA-U can present asymptomatically and lead to ocular complications,so regular screening and monitoring are needed to prevent potentially sight-threatening sequelae.Topical glucocorticoids such as prednisolone acetate are usually the first line of treatment for anterior uveitis associated with JIA-U,but long-term use may be associated with cataract,ocular hypertension and glaucoma.Disease modifying anti-rheumatic drugs(DMARDs)such as methotrexate allow tapering of the corticosteroids to prevent long-term complications.Biologic therapies have been increasingly used as targeted therapies for JIA-U,particularly monoclonal antibodies targeting the proinflammatory cytokine TNF-αsuch as adalimumab and infliximab.One recent,multicenter,prospective,randomized clinical trial provided evidence of the efficacy of adalimumab with methotrexate for JIA-U compared to methotrexate alone.Another clinical trial studying the interleukin-6 inhibitor tocilizumab for JIA-U showed promise in tapering topical corticosteroids.Additionally,JAK inhibitors are emerging biologic therapies for JIA-U in patients refractory to TNF-αinhibitors,with a clinical trial assessing the efficacy of baricitinib for JIA-U underway.While clinical trials on these novel biologics are limited,further investigation of these agents may provide additional therapeutic options for JIA-U.展开更多
Autoimmune uveitis is one of the most common inflammatory eye diseases leading to blindness globally.Its etiology is primarily associated with autoimmune responses.Patients with this condition often exhibit complex an...Autoimmune uveitis is one of the most common inflammatory eye diseases leading to blindness globally.Its etiology is primarily associated with autoimmune responses.Patients with this condition often exhibit complex and chronic disease courses,with a high propensity for recurrence.Current treatments mainly involve corticosteroids and immunosuppressive agents,which,despite their effectiveness,entail significant side effects that severely impact patients'vision and quality of life.There are still unresolved questions regarding the etiology and immunopathogenesis of autoimmune uveitis,and traditional high-throughput sequencing techniques fall short of adequately elucidating its pathogenic mechanisms at the cellular level.With the continuous advancement of single-cell sequencing technology,an increasing number of studies are leveraging this approach to deeply investigate the pathogenesis of autoimmune uveitis,thereby offering new insights for identifying novel diagnostic and therapeutic targets.This paper reviews the latest applications of single-cell sequencing technology in exploring the pathogenesis of autoimmune uveitis.Through the utilization of this technology,researchers can gain a more comprehensive understanding of cellular-level changes in patients,providing robust support for the search for new therapeutic avenues.These studies offer new directions for the diagnosis and treatment of autoimmune uveitis and provide valuable information for the development of future therapeutic strategies and approaches.展开更多
AIMTo compare the safety and efficacy of phacoemulsification and small incision cataract surgery (SICS) in patients with uveitic cataract.METHODSIn a prospective, randomized multi-centric study, consecutive patients w...AIMTo compare the safety and efficacy of phacoemulsification and small incision cataract surgery (SICS) in patients with uveitic cataract.METHODSIn a prospective, randomized multi-centric study, consecutive patients with uveitic cataract were randomized to receive phacoemulsification or manual SICS by either of two surgeons well versed with both the techniques. A minimum inflammation free period of 3mo (defined as less than 5 cells per high power field in anterior chamber) was a pre-requisite for eligibility for surgery. Superior scleral tunnel incisions were used for both techniques. Improvement in visual acuity post-operatively was the primary outcome measure and the rate of post-operative complications and surgical time were secondary outcome measures, respectively. Means of groups were compared using t-tests. One way analysis of variance (ANOVA) was used when there were more than two groups. Chi-square tests were used for proportions. Kaplan Meyer survival analysis was done and means for survival time was estimated at 95% confidence interval (CI). A P value of <0.05 was considered statistically significant.RESULTSOne hundred and twenty-six of 139 patients (90.6%) completed the 6-month follow-up. Seven patients were lost in follow up and another six excluded due to either follow-up less than six months (n=1) or inability implant an intraocular lens (IOL) because of insufficient capsular support following posterior capsule rupture (n=5). There was significant improvement in vision after both the procedures (paired t-test; P<0.001). On first postoperative day, uncorrected distance visual acuity (UDVA) was 20/63 or better in 31 (47%) patients in Phaco group and 26 (43.3%) patients in SICS group (P=0.384). The mean surgically induced astigmatism (SIA) was 0.86±0.34 dioptres (D) in the phacoemulsification group and 1.16±0.28 D in SICS group. The difference between the groups was significant (t-test, P=0.002). At 6mo, corrected distance visual acuity (CDVA) was 20/60 or better in 60 (90.9%) patients in Phaco group and 53 (88.3%) in the manual SICS group (P=0.478). The mean surgical time was significantly shorter in the manual SICS group (10.8±2.9 versus 13.2±2.6min) (P<0.001). Oral prednisolone, 1 mg/kg body weight was given 7d prior to surgery, continued post-operatively and tapered according to the inflammatory response over 4-6wk in patients with previously documented macular edema, recurrent uveitis, chronic anterior uveitis and intermediate uveitis. Rate of complications like macular edema (Chi-square, P=0.459), persistent uveitis (Chi-square, P=0.289) and posterior capsule opacification (Chi-square, P=0.474) were comparable between both the groups.CONCLUSIONManual SICS and phacoemulsification do not differ significantly in complication rates and final CDVA outcomes. However, manual SICS is significantly faster. It may be the preferred technique in settings where surgical volume is high and access to phacoemulsification is limited, such as in eye camps. It may also be the appropriate technique for uveitic cataract under such circumstances.展开更多
Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveiti...Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosuppressive treatment for uveitis since first introduced in 1950 s,its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs,classified into alkylating agent,antimetabolites and T cell inhibitors,have been widely used as corticosteroid-sparing agents,each with characteristic safety/tolerance profiles on different uveitis entities. Recently,biologic agents,which target specific molecules in immunopathogenesis of uveitis,have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However,lack of large randomized controlled clinical trials,concerns about efficacy and safety of long-term usage,and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs(from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation,but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities(conventional immunosuppressive agents,biologics and local drug delivery systems) on hand,the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity,treatment availability,safety/tolerability,effectiveness,patient compliance,cost concerns and suggestions from related specialists such as rheumatologists and pediatricians. The focus of this review is to provide an overview of each treatment modality on safety/tolerability and effectiveness,which are believed to be the two most important factors affecting treatment decision making.展开更多
AIM： To assess the levels of the neutrophil to lymphocyte ratio（N/L） and the platelet to lymphocyte ratio（P/L） in patients with idiopathic acute anterior uveitis（AAU） and to compare with healthy controls.METHOD...AIM： To assess the levels of the neutrophil to lymphocyte ratio（N/L） and the platelet to lymphocyte ratio（P/L） in patients with idiopathic acute anterior uveitis（AAU） and to compare with healthy controls.METHODS： Thirty-six male patients with idiopathic AAU and 36 male healthy subjects were enrolled in this retrospective study.Complete ophthalmological examination and complete blood count measurements results of all subjects were evaluated.RESULTS： There was a significant difference in N/L and P/L between idiopathic AAU and control groups（P=0.006,P=0.022）.Also,correlation analysis revealed a significant correlation between C-reactive protein（CRP） and N/L（P= 0.002;r=0.461）.CONCLUSION： Our study for the first time provides evidence of N/L and P/L may be useful biomarkers in patients with idiopathic AAU.N/L is correlated with CRP,so it can be a useful biomarker to predict the prognosis in idiopathic AAU.展开更多
AIM：To test the therapeutic effects of delayed treatment of mesenchymal stem cells（MSCs） in recurrent experimental autoimmune uveitis（r EAU）.METHODS： The efficacy of different regimens of MSC administration in r...AIM：To test the therapeutic effects of delayed treatment of mesenchymal stem cells（MSCs） in recurrent experimental autoimmune uveitis（r EAU）.METHODS： The efficacy of different regimens of MSC administration in r EAU were tested by evaluation of clinical and pathological intraocular inflammation,as well as retinal structural and functional integrity using optical coherence tomography（OCT） and electroretinogram（ERG）.The retinal sections were also immunostained with antibodies to glial fibrillary acidic protein（GFAP）and rhodopsin（RHO）. RESULTS： Delayed treatment of MSCs effectively alleviated the severity of intraocular inflammation with relative intact of outer retinal structure and function.Moreover,double therapies with longer interval led to an even better clinical evaluation,as well as a trend of decrease in relapse and amelioration of retinal function.MSC therapies also effectively reduced GFAP expression and increased RHO expression in the retina.CONCLUSION： MSC administration can effectively treat developed diseases of rEAU,and multiple therapies can provide additional therapeutic benefits.展开更多
AIM: To conduct a systematic review and Meta-analysis to examine the association between uveitis and psoriatic disease, and to evaluate whether one condition predisposes individuals to the other. METHODS: We performed...AIM: To conduct a systematic review and Meta-analysis to examine the association between uveitis and psoriatic disease, and to evaluate whether one condition predisposes individuals to the other. METHODS: We performed a comprehensive search of Pub Med and EMBASE to identify cohort studies examining the association between uveitis and psoriatic disease [psoriasis and/or psoriatic arthritis(Ps A)]. We used a random-effects model to calculate the pooled relative risks(RRs) adjusted for confounders, along with the 95% confidence intervals(CIs). RESULTS: This Meta-analysis included a total of 6 studies and a maximum of 80 178 648 participants. Compared with non-psoriatic controls, uveitis risk was significantly elevated in patients with psoriasis(RR=1.49;95%CI: 1.08-2.07), and Ps A(RR=3.16;95%CI: 2.16-4.63). Furthermore, pre-existing uveitis was associated with a significantly increased risk of psoriasis(RR=1.62;95%CI: 1.44-1.83), and Ps A(RR=4.44;95%CI: 3.52-5.60).CONCLUSION: The results of this systematic review and Meta-analysis suggest an overall positive bidirectional association between uveitis and psoriatic disease(psoriasis and Ps A), warranting increased awareness among clinicians involved in the management of these two conditions.Therefore, there remains a need for more detailed studies of the possible common pathogenesis of psoriatic disease and uveitis.展开更多
AIM: To evaluate the therapeutic effect of pupilloplasty combined with phacomulsification and intraocular lens implantation(PPI) in uveitis-induced cataract.METHODS: Total 28 patients with uveitis-induced cataract wer...AIM: To evaluate the therapeutic effect of pupilloplasty combined with phacomulsification and intraocular lens implantation(PPI) in uveitis-induced cataract.METHODS: Total 28 patients with uveitis-induced cataract were enrolled. Within 3 mo before the PPI, 7 cases accompanied with glaucoma maintained carteolol hydrochloride for lowering intraocular pressure, and 1 case maintained glucocorticoid for anti-inflammation. The baseline characteristics, treatment processes, and outcomes of enrolled cases were retrospectively analyzed. Hematoxylin and eosin(HE) staining was performed to reveal the histopathological changes of iris tissues.RESULTS: Iris hemorrhage was the only intraoperative complication observed in 2 cases. After the surgery, normal intraocular pressure, right position of intraocular lens, and improved visual gain [best corrected visual acuity(BCVA)>0.5] were achieved. Postoperative keratic precipitates was observed in 2 cases, which was recovered within 1 wk. During the follow-up of 5-10 y, no recurrence of uveitis was found in 27 cases(96.43%). Uveitis only recurred in one case with the onset of ankylosing spondylitis. HE staining showed iris stroma(all samples), pigment cell hyperplasia in pigment epithelium(n=9) and stroma(n=19), inflammatory cell infiltration in iris(n=7), and neovascularization in iris surface(n=2).CONCLUSION: PPI improves the visual gain and prevents the long-term recurrence of uveitis in patients with uveitis-induced cataract, including those with preoperative intraocular pressure abnormality(glaucoma) and inflammation(active uveitis). Uveitis presents stroma atrophy, pigment cell hyperplasia, and inflammatory cell infiltration, even in a quiet state.展开更多
AIM:To report the clinical characteristics,treatment and outcomes of active syphilitic uveitis in human immunodeficiency virus(HIV)positive patients and compare them with the previously published data.METHODS:Retrospe...AIM:To report the clinical characteristics,treatment and outcomes of active syphilitic uveitis in human immunodeficiency virus(HIV)positive patients and compare them with the previously published data.METHODS:Retrospective analysis of the case series from an infectious disease center in southern China was conducted.Comprehensive review of previously published cases of HIV positive syphilitic uveitis was conducted using the PubMed and Web of Science databases and the references listed in the identified articles.RESULTS:Twelve HIV positive patients with active syphilitic uveitis were collected.All were male,with age of 36.3y(range 27 to 53y).Five(41.7%)had a history of syphilis,and three of them had received anti-syphilis treatment.Ocular manifestations included corneal epithelial defect(13%),complicated cataract(17.4%),vitreous opacity(82.6%),optic disc edema(26.1%),macular edema(30.4%),neuro-retinitis(43.5%),and retinal hemorrhage(26.1%).After standardized syphilitic treatment,intraocular inflammation was reduced and vision improved in all cases.The literature review summarizes 105 previously reported cases of HIV positive syphilitic uveitis.High serum rapid plasma regain(RPR)titers may be associated with severe uveitis and poor vision.Treatment with penicillin,ceftriaxone sodium,or penicillin plus benzylpenicillin instead of using benzylpenicillin alone can significantly improve bestcorrected visual acuity(BCVA)in HIV positive ocular syphilis patients.CONCLUSION:For HIV positive syphilitic uveitis patients,prompt diagnosis and appropriate treatment and follow-up are paramount.In our series,the clinical manifestations are diverse.Syphilis patients treated by penicillin G or long-acting penicillin before may still develop syphilitic uveitis.Patients who relapse after long-term penicillin treatment can still benefit from penicillin G.展开更多
AIM:To quantitatively evaluate the risk of anxiety and depression in patients with uveitis via performing a Metaanalysis.METHODS:Three electronic database(Pub Med,Embase,and Cochrane Library databases)were searched fo...AIM:To quantitatively evaluate the risk of anxiety and depression in patients with uveitis via performing a Metaanalysis.METHODS:Three electronic database(Pub Med,Embase,and Cochrane Library databases)were searched for studies recording data about uveitis and anxiety as well as depression simultaneously up to January 2021.The incidence rate and standard mean difference(SMD)with a 95%confidence interval(95%CI)were calculated to analyse the association using random-effects models based on heterogeneity tests.RESULTS:In total,12 observational studies containing 874 patients with uveitis were included.The results showed that there was a significant association between uveitis and anxiety(SMD=0.97,95%CI:0.39 to 1.54,P=0.0009)and depression(SMD=0.79,95%CI:0.51 to 1.07,P<0.00001).The overall morbidities of anxiety and depression in patients with uveitis were 39%and 17%,respectively.With subgroup analysis,the heterogeneity actually came from different kinds of uveitis.Specifically,the incidence rates of both anxiety and depression were relatively low in patients with anterior uveitis(33%and 15%),moderate in patients with infectious uveitis(46%and 22%),and high in patients with unspecified uveitis(59%and 35%).CONCLUSION:It is preliminarily indicated that patients with uveitis may have a high risk of anxiety and depression.Ophthalmologists and psychologists should pay more attention to the psychological state when dealing with patients with uveitis.Further high-quality studies with detailed direct data are needed to draw more precise conclusions.展开更多
AIM:To assess the correlation between disorganization of the retinal inner layers(DRIL)and best-corrected visual acuity(BCVA)in patients with uveitis and macular edema(UME)who underwent systemic treatment using optica...AIM:To assess the correlation between disorganization of the retinal inner layers(DRIL)and best-corrected visual acuity(BCVA)in patients with uveitis and macular edema(UME)who underwent systemic treatment using optical coherence tomography(OCT).METHODS:A retrospective clinical study of 23 patients(30 eyes)with DRIL and 23 patients(31 eyes)without DRIL secondary to UME were included.All patients underwent comprehensive ophthalmic examinations at baseline,3,6,and 12 mo after local and systemic treatment.The OCTbased parameters included foveal center point thickness(FCPT),mean thickness(MT),and diameters of DRIL in horizontal and vertical directions.BCVA and OCT-based parameters were compared between the two groups.The relationship between each OCT parameter and BCVA was evaluated using linear correlation and regression analysis.RESULTS:At the initial visit,the mean baseline FCPT was 441.03±128.68μm in the eyes with DRIL and 337.26±99.31μm in the eyes without DRIL(P=0.001).No significant differences were observed in MT(P=0.357).The mean size of transverse and vertical diameters of DRIL was 684.07±267.51 and 267.07±104.61μm at baseline,respectively.There was significant improvement in BCVA and OCT-based parameters at 3,6,and 12 mo in all cases(P<0.001 for each timepoint).In addition,significant differences were detected in BCVA and OCT parameters between eyes with and without DRIL at each time point(P<0.01 for each timepoint).A greater DRIL range at baseline was associated with a worse baseline BCVA(transverse diameter of DRIL:r=0.875,P<0.001;vertical diameter of DRIL:r=0.622,P<0.001).The transverse diameter of baseline DRIL was found to be significantly correlated with the final BCVA(P=0.003).CONCLUSION:The improvement in BCVA is associated with DRIL in patients with UME.DRIL is an easy-todetermine and robust imaging biomarker that could help predict BCVA prognosis in eyes with UME.展开更多
基金Supported by the National Natural Science Fundation of China(No.82101107No.81471575).
文摘AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.
文摘BACKGROUND Chronic idiopathic uveitis(CIU)and juvenile idiopathic arthritis-associated uveitis(U-JIA)are both vision-threatening conditions that share similar autoimmune mechanisms,but treatment approaches differ significantly.In managing U-JIA,various treatment options are employed,including biological and non-biological disease-modifying anti-rheumatic drugs.These drugs are effective in clinical trials.Given the lack of established diagnostic and treatment guidelines as well as the limited number of therapeutic options available,patients with CIU frequently do not receive optimal and timely immunosuppression.This study highlighted the necessity for additional research to develop novel diag-nostic techniques,targeted therapies,and enhanced treatment outcomes for young individuals with CIU.AIM To compare the characteristics and outcomes of U-JIA and CIU.METHODS A retrospective cohort study analyzed data from 110 pediatric patients(under 18 years old)with U-JIA and 40 pediatric patients with CIU.Data was collected between 2012 and 2023.The study focused on demographic,clinical,treatment,and outcome variables.RESULTS The median onset age of arthritis was 6.4 years(2.7 years;9.3 years).In 28.2%of cases uveitis preceded the onset of arthritis.In 17.3%of cases it occurred simultan-eously.In 53.6%of cases it followed arthritis.Both groups had similar onset ages,antinuclear antibodies/human leukocyte antigen positivity rates,and ESR levels,with a slight predominance of females(60.9%vs 42.5%,P=0.062),and higher C-reactive protein levels in the U-JIA group.Anterior uveitis was more prevalent in patients with U-JIA(P=0.023),although the frequency of symptomatic,unilateral,and complicated forms did not differ significantly.The use of methotrexate(83.8%vs 96.4%)and biologics(64.7%vs 82.1%)was comparable,as was the rate of remission on methotrexate treatment(70.9%vs 56.5%)and biological therapy(77.8%vs 95%),but a immunosuppressive treatment delay in CIU observed.Patients with CIU were less likely to receive methotrexate[hazard ratio(HR)=0.48,P=0.005]or biological treatment(HR=0.42,P=0.004),but they were more likely to achieve remission with methotrexate(HR=3.70,P=0.001).CONCLUSION Treatment of uveitis is often limited to topical measures,which can delay systemic therapy and affect the outcome.Methotrexate and biological agents effectively manage eye inflammation.It is essential to develop standardized protocols for the diagnosis and management of uveitis,and collaboration between rheumatologists and ophthal-mologists is needed to achieve optimal outcomes in the treatment of CIU.
文摘BACKGROUND Uveitis associated with juvenile idiopathic arthritis(U-JIA)is a vision-threatening condition.Estimates of prevalence of uveitis in patients with known juvenile idiopathic arthritis range from 11.6%to 30.0%.First-line treatment includes topical glucocorticoids;methotrexate(MTX)is used if topical corticosteroids are ineffective.In severe cases biological therapy like adalimumab may be prescribed.Complications,including vision loss,may be related to the disease and the ongoing treatment(topical corticosteroids).In severe cases surgical intervention is often necessary and is typically associated with poor vision outcomes.AIM To highlight the characteristics of operated U-JIA and to identify predictors of treatment failure.METHODS A retrospective cohort study analyzed data from 68 pediatric patients(under 18 years old)with U-JIA between 2007 and 2023.The study focused on demographic,clinical,treatment,and outcome variables.Survival analysis using Kaplan-Meier curves and the Cox proportional hazards model was performed to estimate the impact of surgical intervention on the course of uveitis and to identify predictors of treatment failure.RESULTS Eye surgery was performed on 17(25%)patients with U-JIA.It was associated with an earlier onset of uveitis(P=0.017),lower uveitis remission rate[odds ratio=5.29,95%confidence interval(CI):1.23-24.90,P=0.015],longer time to remission(P=0.036),reduced probability of achieving remission on MTX(P=0.033),and the necessity of the following treatment with biological diseasemodifying antirheumatic drugs(odds ratio=5.60;95%CI:1.11-55.19,P=0.021)with similar efficacy with biological treatments in operated and non-operated cases.Kaplan-Meier curves showed a borderline difference in time to surgical intervention based on the MTX initiation cutoff(P=0.065)although earlier MTX initiation might be associated with a higher likelihood of deferred surgery.CONCLUSION Operated patients exhibited an aggressive early-onset uveitis profile that needed early and more intensive treatment.Delayed and failed MTX treatment as well as delayed switching to biologics often required subsequent eye surgery.
基金funded by a Maurice and Phyllis Paykel Trust Grant(203134)supported by a Buchanan Ocular Therapeutics Unit Doctoral Scholarship.Odunayo O.Mugisho is supported by a Neurological Foundation First Postdoctoral Research Fellowship(2001 FFE)+2 种基金an Auckland Medical Research Foundation Grant(1121013)an Auckland Medical Research Foundation Postdoctoral Fellowship(1323001)supported by the Buchanan Charitable Foundation,with part of her salary also supported by the Health Research Council of New Zealand(20/317).
文摘Background:Noninfectious uveitis,a chronic ocular inflammatory disease,is char-acterized by the activation of immune cells in the eye,with most studies focusing on the role of the adaptive immune system in the disease.However,limited data exist on the potential contribution of the innate immune system,specifically the nucleotide-binding oligomerization domain and leucine-rich repeat receptor-3(NLRP3)inflamma-some pathway.This pathway has previously been identified as a driver of inflammation in several low-grade,progressive inflammatory eye diseases such as diabetic retin-opathy.The aim of this study was to determine whether the NLRP3 inflammasome pathway plays a role in the pathogenesis and chronicity of experimental autoimmune uveitis(EAU).Methods:EAU was induced in C57BL/6J mice via intraperitoneal pertussis toxin and subcutaneous interphotoreceptor retinoid-binding protein injections.After 12 weeks,eyes were enucleated,and whole eye sections were assessed for inflammasome,macrophage,and microglial markers in the retina,ciliary body,and cornea using immunohistochemistry.Results:Our study confirmed higher NLRP3 inflammasome activation(increased ex-pression of NLRP3 and cleaved caspase 1 labeling)in EAU mouse retinas compared to controls.This correlated with increased astrogliosis and microglial activation through-out the eye.Migratory innate and adaptive peripheral immune cells(macrophages and leukocytes)were also found within the retina and ciliary body of EAU mice.Connexin43 proteins,which form hexameric hemichannels that can release adeno-sine triphosphate(ATP),an upstream inflammasome priming signal,were also found upregulated in the retina and cornea of EAU mice.Conclusion:Overall,our findings support the idea that in the EAU model there is active inflammation,even 12 weeks post induction,and that it can be correlated to inflammasome activation.This contributes to the pathogenesis and chronicity of non-infectious uveitis,and our results emphasize that targeting the inflammasome path-way could be efficacious for noninfectious uveitis treatment.
基金Supported by National Natural Science Foundation of China (No. 30400487)International Cooperation Project of Guangdong Province, China (No. 2004B50301002)"1135" Talent Doctor Foundation of Daping Hospital, China(2008-2012)
文摘AIM: To characterize the clinical features, diagnosis, treatment and prognosis of uveitis associated with ankylosing spondylitis (AS) in Chinese patients. METHODS: Two hundred and three patients with uveitis associated with AS followed-up in the Third Military Medical University Daping Hospital between 2005 and 2010 were retrospectively evaluated in this study. Complete ophthalmological examinations were evaluated at baseline and during the follow-up period. The gender, age, follow-up time, mean frequency of uveitis onset, and accompanying eye examination findings, history, demographical parameters were reviewed. All the patients presented complete clinical and radiologic (sacroiliac, lumbar, dorsal and cervical spine, knee, ankle, shoulder, hip, elbow) evaluation. HLA-B27 typing was also searched. RESULTS: There were 203 patients diagnosed with AS associated welt's. All showed sacroiliac X-ray changes indicative of AS. There were 184 male and 19 female patients. The average age of patients was 35 +/- 12 (range 18-50). Mean follow-up period was 2.4 years (1-5 years). Acute anterior wets was the most common type of uveitis in both genders. 121 eyes presented unilateral involvement (55.2%), and 92 eyes presented bilateral involvement (45.3%) with onset alternately. 22 eyes occurred hypopyon, 16 eyes were found anterior vitreous cells, 7 eyes were noted reactive macular edema or exudation, 29 eyes presented posterior synechiae of iris, and 14 eyes presented cataract, 9 eyes presented secondary glaucoma, 2 eyes presented bend corneal degeneration and 1 eyes presented atrophy of eyeball. At the final visit, uveitis was well controlled in most patients. CONCLUSION: AS associated with uveitis in Chinese patients mainly manifests as acute anterior uveitis. A combination of corticosteroids with other mydriasis agents is effective for most AS associated with uveitis patients. In general, the prognosis is good in these cases.
文摘Uveitis is an inflammatory disease affecting the uvea,which includes the iris,ciliary body and choroid(1).Noninfective uveitis is more prevalent in developed countries and primarily impacts individuals of working age,with a mean onset of around 40 years.It accounts for 5-10%of severe vision impairment globally(1,2).This form of uveitis is often associated with systemic diseases,such as ankylosing spondylosis,juvenile idiopathic arthritis,sarcoidosis and Behcet’s disease(2,3).
文摘AIM:To characterize a Portuguese population of patients with juvenile idiopathic arthritis(JIA)and to evaluate possible associations between clinical factors and ocular involvement.METHODS:Patients diagnosed with JIA in the previous 20y in Hospital Garcia de Orta were included.Data were assessed from Reuma.pt database.Associations between demographic(age and sex),clinical(articular involvement,extra-articular manifestations,biological therapy),laboratory data[anti-nuclear antibodies,anti-cyclic citrullinated peptide(CCP)antibodies,rheumatoid factor,human leukocyte antigen B27(HLA-B27),C-reactive protein,erythrocyte sedimentation rate]and ocular involvement were assessed.Statistical analysis was performed using Chi-square for categorical variables and Mann-Whitney test for continuous variables.RESULTS:Totally 91 patients were included,11(12%)with previous episodes of uveitis.There was a statistically significant preponderance of early age at JIA diagnosis(mean 4.73 vs 9.58y,P=0.008),antinuclear antibodies positivity(P=0.01),and oligoarticular subtype(P=0.04)in the Juvenile idiopathic arthritis-associated uveitis(JIA-U)group.Ocular complications occurred in 36.4%of patients(n=4):cataracts(n=2),band keratopathy(n=1)and posterior synechiae(n=1).The occurrence of complications was corelated with a shorter period between JIA diagnosis and the first JIA-U episode(mean 0.67 vs 4.88y,P=0.012)but not with age at JIA diagnosis or articular involvement.There was erythrocyte sedimentation rate elevation in the 12mo preceding uveitis(mean 40.5 mm/h,range 13-83).CONCLUSION:The occurrence of JIA-U shortly after JIA diagnosis is shown to be a potential risk factor for ocular complications.
基金Supported by the National Natural Science Foundation of China(No.82201163)Natural Science Foundation Youth Foundation of Shaanxi Province(No.2023-JC-QN-0861)Shaanxi Province Key Research and Development Program(No.2021SF-332).
文摘AIM:To use two-sample Mendelian randomization(MR)method to study uveitis causal association with wet age-related macular degeneration(wAMD)risk from the genetic level.METHODS:Two-sample MR analysis was used to assess the causal role of uveitis on wAMD risk,using the 8 genetic variants associated strongly with uveitis as instrumental variables.Besides,eight MR methods[inverse variance weighted(IVW),weighted median,MR-Egger regression,weighted mode,simple mode,robust adjusted profile score(RAPS),contamination inverse-variance weighted method,and debiased inverse-variance weighted method]were used to get the whole causal estimate for multiple instrumental single nucleotide polymorphism(SNPs).The MR analysis was based on Europeans.RESULTS:Uveitis was related to a higher risk of wAMD[odds ratio(OR):1.08,95%confidence interval(CI)1.03–1.12;P=1.03×10^(-3)]with the IVW method.No heterogeneity and directional pleiotropy were detected.On the contrary,no significant results were detected in reverse MR analysis.CONCLUSION:Uveitis is related to an increased risk of wAMD.Due to the high blindness rate of wAMD,understanding and controlling the risk factors of AMD is of great significance for reducing its incidence and early diagnosis and treatment.
基金Unrestricted departmental grant from Research to Prevent Blindness.T.M.J.receives funding from the National Institutes of Health(K12TR005104).
文摘Non-infectious uveitis(NIU),although a highly blinding but preventable cause of blindness around the world,has few approved pharmaceuticals for its treatment.Lack of access to effective treatment is likely a major cause of poor visual outcomes in NIU.However,despite a revolution in rheumatologic disease treatment with the advent of multiple biologic therapeutics selectively targeting the immune response,there remains a gap in the long-term management of NIU.Adalimumab remains the only systemic medication approved for the treatment of NIU by the Food and Drug Administration(FDA).All other systemic treatments,including older anti-metabolites such as methotrexate and mycophenolate,are used offlabel for NIU,posing significant treatment challenges.Given the nature and rarity of the disease,there are few well designed,large,clinical trials evaluating the efficacy of novel therapeutic agents within this field.We therefore read with great interest Srivastava et al.’s randomized clinical trial on the efficacy of filgotinib,a Janus kinase inhibitor(JAKi),in active NIU(1).The early termination of the trial due to business considerations highlights the industry difficulty in FDA medication approval for NIU.
基金This project was supported by unrestricted departmental grant from Research to Prevent Blindness,Inc.to the Emory Eye Center,Emory University School of Medicine,National Eye Institute/National Institutes of Health core grant P30-EY06360(Department of Ophthalmology,Emory University School of Medicine)National Eye Institute of the National Institutes of Health under award number K23 EY030158(Shantha),R01EY030521(STAH),and R01 EY029594(SY)The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the views or policies of the Department of Health and Human Services,nor does mention of trade names,commercial products,or organizations imply endorsement by the U.S.Government.
文摘Juvenile idiopathic arthritis(JIA)is the most common rheumatic disease of childhood,and juvenile idiopathic associated uveitis(JIA-U)is the most frequently noted extra-articular manifestation.JIA-U can present asymptomatically and lead to ocular complications,so regular screening and monitoring are needed to prevent potentially sight-threatening sequelae.Topical glucocorticoids such as prednisolone acetate are usually the first line of treatment for anterior uveitis associated with JIA-U,but long-term use may be associated with cataract,ocular hypertension and glaucoma.Disease modifying anti-rheumatic drugs(DMARDs)such as methotrexate allow tapering of the corticosteroids to prevent long-term complications.Biologic therapies have been increasingly used as targeted therapies for JIA-U,particularly monoclonal antibodies targeting the proinflammatory cytokine TNF-αsuch as adalimumab and infliximab.One recent,multicenter,prospective,randomized clinical trial provided evidence of the efficacy of adalimumab with methotrexate for JIA-U compared to methotrexate alone.Another clinical trial studying the interleukin-6 inhibitor tocilizumab for JIA-U showed promise in tapering topical corticosteroids.Additionally,JAK inhibitors are emerging biologic therapies for JIA-U in patients refractory to TNF-αinhibitors,with a clinical trial assessing the efficacy of baricitinib for JIA-U underway.While clinical trials on these novel biologics are limited,further investigation of these agents may provide additional therapeutic options for JIA-U.
基金supported by the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-005)the State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University.
文摘Autoimmune uveitis is one of the most common inflammatory eye diseases leading to blindness globally.Its etiology is primarily associated with autoimmune responses.Patients with this condition often exhibit complex and chronic disease courses,with a high propensity for recurrence.Current treatments mainly involve corticosteroids and immunosuppressive agents,which,despite their effectiveness,entail significant side effects that severely impact patients'vision and quality of life.There are still unresolved questions regarding the etiology and immunopathogenesis of autoimmune uveitis,and traditional high-throughput sequencing techniques fall short of adequately elucidating its pathogenic mechanisms at the cellular level.With the continuous advancement of single-cell sequencing technology,an increasing number of studies are leveraging this approach to deeply investigate the pathogenesis of autoimmune uveitis,thereby offering new insights for identifying novel diagnostic and therapeutic targets.This paper reviews the latest applications of single-cell sequencing technology in exploring the pathogenesis of autoimmune uveitis.Through the utilization of this technology,researchers can gain a more comprehensive understanding of cellular-level changes in patients,providing robust support for the search for new therapeutic avenues.These studies offer new directions for the diagnosis and treatment of autoimmune uveitis and provide valuable information for the development of future therapeutic strategies and approaches.
文摘AIMTo compare the safety and efficacy of phacoemulsification and small incision cataract surgery (SICS) in patients with uveitic cataract.METHODSIn a prospective, randomized multi-centric study, consecutive patients with uveitic cataract were randomized to receive phacoemulsification or manual SICS by either of two surgeons well versed with both the techniques. A minimum inflammation free period of 3mo (defined as less than 5 cells per high power field in anterior chamber) was a pre-requisite for eligibility for surgery. Superior scleral tunnel incisions were used for both techniques. Improvement in visual acuity post-operatively was the primary outcome measure and the rate of post-operative complications and surgical time were secondary outcome measures, respectively. Means of groups were compared using t-tests. One way analysis of variance (ANOVA) was used when there were more than two groups. Chi-square tests were used for proportions. Kaplan Meyer survival analysis was done and means for survival time was estimated at 95% confidence interval (CI). A P value of <0.05 was considered statistically significant.RESULTSOne hundred and twenty-six of 139 patients (90.6%) completed the 6-month follow-up. Seven patients were lost in follow up and another six excluded due to either follow-up less than six months (n=1) or inability implant an intraocular lens (IOL) because of insufficient capsular support following posterior capsule rupture (n=5). There was significant improvement in vision after both the procedures (paired t-test; P<0.001). On first postoperative day, uncorrected distance visual acuity (UDVA) was 20/63 or better in 31 (47%) patients in Phaco group and 26 (43.3%) patients in SICS group (P=0.384). The mean surgically induced astigmatism (SIA) was 0.86±0.34 dioptres (D) in the phacoemulsification group and 1.16±0.28 D in SICS group. The difference between the groups was significant (t-test, P=0.002). At 6mo, corrected distance visual acuity (CDVA) was 20/60 or better in 60 (90.9%) patients in Phaco group and 53 (88.3%) in the manual SICS group (P=0.478). The mean surgical time was significantly shorter in the manual SICS group (10.8±2.9 versus 13.2±2.6min) (P<0.001). Oral prednisolone, 1 mg/kg body weight was given 7d prior to surgery, continued post-operatively and tapered according to the inflammatory response over 4-6wk in patients with previously documented macular edema, recurrent uveitis, chronic anterior uveitis and intermediate uveitis. Rate of complications like macular edema (Chi-square, P=0.459), persistent uveitis (Chi-square, P=0.289) and posterior capsule opacification (Chi-square, P=0.474) were comparable between both the groups.CONCLUSIONManual SICS and phacoemulsification do not differ significantly in complication rates and final CDVA outcomes. However, manual SICS is significantly faster. It may be the preferred technique in settings where surgical volume is high and access to phacoemulsification is limited, such as in eye camps. It may also be the appropriate technique for uveitic cataract under such circumstances.
文摘Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosuppressive treatment for uveitis since first introduced in 1950 s,its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs,classified into alkylating agent,antimetabolites and T cell inhibitors,have been widely used as corticosteroid-sparing agents,each with characteristic safety/tolerance profiles on different uveitis entities. Recently,biologic agents,which target specific molecules in immunopathogenesis of uveitis,have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However,lack of large randomized controlled clinical trials,concerns about efficacy and safety of long-term usage,and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs(from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation,but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities(conventional immunosuppressive agents,biologics and local drug delivery systems) on hand,the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity,treatment availability,safety/tolerability,effectiveness,patient compliance,cost concerns and suggestions from related specialists such as rheumatologists and pediatricians. The focus of this review is to provide an overview of each treatment modality on safety/tolerability and effectiveness,which are believed to be the two most important factors affecting treatment decision making.
文摘AIM： To assess the levels of the neutrophil to lymphocyte ratio（N/L） and the platelet to lymphocyte ratio（P/L） in patients with idiopathic acute anterior uveitis（AAU） and to compare with healthy controls.METHODS： Thirty-six male patients with idiopathic AAU and 36 male healthy subjects were enrolled in this retrospective study.Complete ophthalmological examination and complete blood count measurements results of all subjects were evaluated.RESULTS： There was a significant difference in N/L and P/L between idiopathic AAU and control groups（P=0.006,P=0.022）.Also,correlation analysis revealed a significant correlation between C-reactive protein（CRP） and N/L（P= 0.002;r=0.461）.CONCLUSION： Our study for the first time provides evidence of N/L and P/L may be useful biomarkers in patients with idiopathic AAU.N/L is correlated with CRP,so it can be a useful biomarker to predict the prognosis in idiopathic AAU.
基金Supported by the National Natural Science Foundation of China(No.81371005No.81428012)Tianjin Municipal Science and Technology Commission(No.15JCZDJC35600)
文摘AIM：To test the therapeutic effects of delayed treatment of mesenchymal stem cells（MSCs） in recurrent experimental autoimmune uveitis（r EAU）.METHODS： The efficacy of different regimens of MSC administration in r EAU were tested by evaluation of clinical and pathological intraocular inflammation,as well as retinal structural and functional integrity using optical coherence tomography（OCT） and electroretinogram（ERG）.The retinal sections were also immunostained with antibodies to glial fibrillary acidic protein（GFAP）and rhodopsin（RHO）. RESULTS： Delayed treatment of MSCs effectively alleviated the severity of intraocular inflammation with relative intact of outer retinal structure and function.Moreover,double therapies with longer interval led to an even better clinical evaluation,as well as a trend of decrease in relapse and amelioration of retinal function.MSC therapies also effectively reduced GFAP expression and increased RHO expression in the retina.CONCLUSION： MSC administration can effectively treat developed diseases of rEAU,and multiple therapies can provide additional therapeutic benefits.
基金Supported by the National Natural Science Foundation of China(No.81570847)the Natural Science Foundation of Hunan Province(No.2016JJ4095)the Programs of Science-Technology Commission of Hunan Province(No.2015JC3036)。
文摘AIM: To conduct a systematic review and Meta-analysis to examine the association between uveitis and psoriatic disease, and to evaluate whether one condition predisposes individuals to the other. METHODS: We performed a comprehensive search of Pub Med and EMBASE to identify cohort studies examining the association between uveitis and psoriatic disease [psoriasis and/or psoriatic arthritis(Ps A)]. We used a random-effects model to calculate the pooled relative risks(RRs) adjusted for confounders, along with the 95% confidence intervals(CIs). RESULTS: This Meta-analysis included a total of 6 studies and a maximum of 80 178 648 participants. Compared with non-psoriatic controls, uveitis risk was significantly elevated in patients with psoriasis(RR=1.49;95%CI: 1.08-2.07), and Ps A(RR=3.16;95%CI: 2.16-4.63). Furthermore, pre-existing uveitis was associated with a significantly increased risk of psoriasis(RR=1.62;95%CI: 1.44-1.83), and Ps A(RR=4.44;95%CI: 3.52-5.60).CONCLUSION: The results of this systematic review and Meta-analysis suggest an overall positive bidirectional association between uveitis and psoriatic disease(psoriasis and Ps A), warranting increased awareness among clinicians involved in the management of these two conditions.Therefore, there remains a need for more detailed studies of the possible common pathogenesis of psoriatic disease and uveitis.
文摘AIM: To evaluate the therapeutic effect of pupilloplasty combined with phacomulsification and intraocular lens implantation(PPI) in uveitis-induced cataract.METHODS: Total 28 patients with uveitis-induced cataract were enrolled. Within 3 mo before the PPI, 7 cases accompanied with glaucoma maintained carteolol hydrochloride for lowering intraocular pressure, and 1 case maintained glucocorticoid for anti-inflammation. The baseline characteristics, treatment processes, and outcomes of enrolled cases were retrospectively analyzed. Hematoxylin and eosin(HE) staining was performed to reveal the histopathological changes of iris tissues.RESULTS: Iris hemorrhage was the only intraoperative complication observed in 2 cases. After the surgery, normal intraocular pressure, right position of intraocular lens, and improved visual gain [best corrected visual acuity(BCVA)>0.5] were achieved. Postoperative keratic precipitates was observed in 2 cases, which was recovered within 1 wk. During the follow-up of 5-10 y, no recurrence of uveitis was found in 27 cases(96.43%). Uveitis only recurred in one case with the onset of ankylosing spondylitis. HE staining showed iris stroma(all samples), pigment cell hyperplasia in pigment epithelium(n=9) and stroma(n=19), inflammatory cell infiltration in iris(n=7), and neovascularization in iris surface(n=2).CONCLUSION: PPI improves the visual gain and prevents the long-term recurrence of uveitis in patients with uveitis-induced cataract, including those with preoperative intraocular pressure abnormality(glaucoma) and inflammation(active uveitis). Uveitis presents stroma atrophy, pigment cell hyperplasia, and inflammatory cell infiltration, even in a quiet state.
基金Supported by the“Zhujiang Talent Program”High Talent Project of Guangdong Province(No.2019QN01Y162)the Natural Science Foundation of Guangdong Province(No.2020A1515010072,No.2023A1515010167)。
文摘AIM:To report the clinical characteristics,treatment and outcomes of active syphilitic uveitis in human immunodeficiency virus(HIV)positive patients and compare them with the previously published data.METHODS:Retrospective analysis of the case series from an infectious disease center in southern China was conducted.Comprehensive review of previously published cases of HIV positive syphilitic uveitis was conducted using the PubMed and Web of Science databases and the references listed in the identified articles.RESULTS:Twelve HIV positive patients with active syphilitic uveitis were collected.All were male,with age of 36.3y(range 27 to 53y).Five(41.7%)had a history of syphilis,and three of them had received anti-syphilis treatment.Ocular manifestations included corneal epithelial defect(13%),complicated cataract(17.4%),vitreous opacity(82.6%),optic disc edema(26.1%),macular edema(30.4%),neuro-retinitis(43.5%),and retinal hemorrhage(26.1%).After standardized syphilitic treatment,intraocular inflammation was reduced and vision improved in all cases.The literature review summarizes 105 previously reported cases of HIV positive syphilitic uveitis.High serum rapid plasma regain(RPR)titers may be associated with severe uveitis and poor vision.Treatment with penicillin,ceftriaxone sodium,or penicillin plus benzylpenicillin instead of using benzylpenicillin alone can significantly improve bestcorrected visual acuity(BCVA)in HIV positive ocular syphilis patients.CONCLUSION:For HIV positive syphilitic uveitis patients,prompt diagnosis and appropriate treatment and follow-up are paramount.In our series,the clinical manifestations are diverse.Syphilis patients treated by penicillin G or long-acting penicillin before may still develop syphilitic uveitis.Patients who relapse after long-term penicillin treatment can still benefit from penicillin G.
文摘AIM:To quantitatively evaluate the risk of anxiety and depression in patients with uveitis via performing a Metaanalysis.METHODS:Three electronic database(Pub Med,Embase,and Cochrane Library databases)were searched for studies recording data about uveitis and anxiety as well as depression simultaneously up to January 2021.The incidence rate and standard mean difference(SMD)with a 95%confidence interval(95%CI)were calculated to analyse the association using random-effects models based on heterogeneity tests.RESULTS:In total,12 observational studies containing 874 patients with uveitis were included.The results showed that there was a significant association between uveitis and anxiety(SMD=0.97,95%CI:0.39 to 1.54,P=0.0009)and depression(SMD=0.79,95%CI:0.51 to 1.07,P<0.00001).The overall morbidities of anxiety and depression in patients with uveitis were 39%and 17%,respectively.With subgroup analysis,the heterogeneity actually came from different kinds of uveitis.Specifically,the incidence rates of both anxiety and depression were relatively low in patients with anterior uveitis(33%and 15%),moderate in patients with infectious uveitis(46%and 22%),and high in patients with unspecified uveitis(59%and 35%).CONCLUSION:It is preliminarily indicated that patients with uveitis may have a high risk of anxiety and depression.Ophthalmologists and psychologists should pay more attention to the psychological state when dealing with patients with uveitis.Further high-quality studies with detailed direct data are needed to draw more precise conclusions.
文摘AIM:To assess the correlation between disorganization of the retinal inner layers(DRIL)and best-corrected visual acuity(BCVA)in patients with uveitis and macular edema(UME)who underwent systemic treatment using optical coherence tomography(OCT).METHODS:A retrospective clinical study of 23 patients(30 eyes)with DRIL and 23 patients(31 eyes)without DRIL secondary to UME were included.All patients underwent comprehensive ophthalmic examinations at baseline,3,6,and 12 mo after local and systemic treatment.The OCTbased parameters included foveal center point thickness(FCPT),mean thickness(MT),and diameters of DRIL in horizontal and vertical directions.BCVA and OCT-based parameters were compared between the two groups.The relationship between each OCT parameter and BCVA was evaluated using linear correlation and regression analysis.RESULTS:At the initial visit,the mean baseline FCPT was 441.03±128.68μm in the eyes with DRIL and 337.26±99.31μm in the eyes without DRIL(P=0.001).No significant differences were observed in MT(P=0.357).The mean size of transverse and vertical diameters of DRIL was 684.07±267.51 and 267.07±104.61μm at baseline,respectively.There was significant improvement in BCVA and OCT-based parameters at 3,6,and 12 mo in all cases(P<0.001 for each timepoint).In addition,significant differences were detected in BCVA and OCT parameters between eyes with and without DRIL at each time point(P<0.01 for each timepoint).A greater DRIL range at baseline was associated with a worse baseline BCVA(transverse diameter of DRIL:r=0.875,P<0.001;vertical diameter of DRIL:r=0.622,P<0.001).The transverse diameter of baseline DRIL was found to be significantly correlated with the final BCVA(P=0.003).CONCLUSION:The improvement in BCVA is associated with DRIL in patients with UME.DRIL is an easy-todetermine and robust imaging biomarker that could help predict BCVA prognosis in eyes with UME.
