Analysis of HLA Profiles in 390 Uveitis Cases: Insights into Clinical Presentations.

Objective: This study aimed to explain the associations between different types of uveitis and human leukocyte antigen (HLA)-B27, HLA-DR4, and HLA-DRw53. Methods: A retrospective analysis of 390 uveitis cases was conducted among inpatients and outpatients diagnosed at Weifang Eye Hospital from 2013 to 2016. All 390 patients underwent HLA-B27 examination, and an additional 40 patients underwent examination for HLA-DR4 and HLA-DRw53. Gender, age, corrected visual acuity (CVA), and recurrence frequency were statistically analyzed based on the onset site and etiology classification. Results: Among the 390 enrolled patients, 206 were male, and 183 were female, with ages ranging from 6 to 87 years (mean: 44.2). The disease onset was classified into anterior uveitis (AU), panuveitis (panU), posterior uveitis (PU), and intermediate uveitis in 180, 112, 88, and 10 cases, respectively. HLA-B27 was positive in 94 cases (53 males and 41 females), yielding a positive rate of 24.1%. In AU patients, 80 (44.4%) tested positive for HLA-B27, while 8 (7.1%) panU patients and 6 PU patients (6.8%) were HLA-B27 positive; none of the intermediate uveitis (IU) patients exhibited HLA-B27 positivity. HLA-B27, HLA-DR4, and HLA-DRw53 examinations were performed on 40 patients with binocular uveitis, resulting in 2 HLA-B27 positive cases, 15 HLA-DR4 positive cases, and 20 HLA-DRw53 positive cases, with positive rates of 5%, 37.5%, and 50%, respectively. Among 25 Vogt Koyanagi-Harada (VKH) cases, 1 tested positive for HLA-B27, 22 were positive for HLA-DR4, and 24 were positive for HLA-DRw53, with positive rates of 4%, 88%, and 96%, respectively. No positive HLA-B27, HLA-DR4, or HLA-DRw53 cases were found among the 10 cases of Behcet's disease (BD). Conclusions: Human leukocyte antigens (HLAs) play a significant role in the mechanism of uveitis. HLA-B27 exhibits high diagnostic value in acute AU, while HLA-DR4 and HLA-DRw53 are crucial for diagnosing binocular uveitis, particularly Vogt Koyanagi-Harada (VKH) syndrome. Further investigation is warranted to explore the relationship between HLA-DR4, HLA-DRw53, and uveitis.

Prompt and Sustained Suppression of Intraocular Inflammation with Adalimumab in Pediatric Patients with Non-Infectious Uveitis Resistant to Traditional Managements: A 6-Month Follow-Up Research.

PURPOSE: To assess the efficacy of adalimumab (ADA) on visual acuity (VA), ocular inflammation, vitreous haze and central macular thickness (CMT) in pediatric refractory non-infectious uveitis. METHODS: Thirty-one eyes of 16 pediatric patients with uveitis of various etiologies were treated with ADA. VA, intraocular active inflammatory cells, vitreous haze, and CMT were evaluated at the baseline and 2nd, 4th, 12th, and 24th weeks following ADA treatment. RESULTS: Twenty-three of 31 eyes had active and the remaining 8 eyes had inactive uveitis (with frequent relapse) before ADA therapy. VA (LogMAR) increased at 12th week following ADA treatment (p< .001). Intraocular inflammation degrees significantly improved within 4 weeks (p< .001). Vitreous haze decreased at fourth week and stabilized at 12th week (p= .038). CMT started to decrease within weeks and stabilized at 12th week (p= .006). CONCLUSIONS: ADA was found to be safe and effective to suppress intraocular inflammation in pediatric non-infectious uveitis, which prevented sight-threatening complications.

Mendelian Randomization Shows a Causal Effect of Low Vitamin D on Non-infectious Uveitis and Scleritis Risk.

PURPOSE: To investigate a causal relationship between Vitamin D levels and non-infectious uveitis and scleritis using Mendelian randomization (MR) techniques. DESIGN: Two-sample Mendelian randomization case-control study. METHODS: The study setting was a biobank of an academic, integrated health care system. The patient population comprised 375 case patients with a non-infectious uveitis and/or scleritis diagnosis and no diagnosis of infectious, trauma-related, or drug-induced uveitis/scleritis. In addition, there were 4167 controls with no uveitis or scleritis diagnosis. Causal effect estimates of low 25-hydroxy Vitamin D (25OHD) on uveitis/scleritis risk were calculated. RESULTS: We found an association of genetically decreased 25OHD with uveitis/scleritis risk (odds ratio [OR] = 2.16, 95% CI = 1.01-4.64, P = .049, per SD decrease in log25OHD). In a first sensitivity MR analysis excluding the genetic variants that are unlikely to have a role in biologically active 25OHD, effect estimates were consistent with those from the primary analysis (OR = 2.38, 95% CI =1.06-5.36, P = 0.035, per SD of log25OHD). Furthermore, in a second sensitivity analysis using only the 6 variants within the CYP2R1 locus (which encodes 25OHD hydroxylase, the liver enzyme responsible for converting Vitamin D to 25OHD), genetically decreased 25OHD was strongly associated with increased uveitis/scleritis risk (OR = 6.42, 95% CI = 3.19-12.89, P = 1.7 × 10-7, per SD of log25OHD). CONCLUSIONS: Our findings suggest a causal relationship between low Vitamin D levels and higher risk of non-infectious uveitis and scleritis. Vitamin D supplementation may be a low-cost, low-risk intervention to mitigate non-infectious uveitis and scleritis risk, and should be explored in a prospective trial.

The 2021 Portuguese Society of Ophthalmology joint guidelines with Paediatric Rheumatology on the screening, monitoring and medical treatment of juvenile idiopathic arthritis-associated uveitis.

AIM: To develop the first Ophthalmology joint guidelines with Paediatric Rheumatology with recommendations on the screening, monitoring and medical treatment of juvenile idiopathic arthritis-associated uveitis (JIA-U), endorsed by the Portuguese Society of Ophthalmology (SPO). METHODS: A systematic literature review was conducted to include publications up to July 14th 2020, with no language restrictions, in order to include all the international position papers/guidelines concerning the medical management of JIA-U and randomised clinical trials assessing the efficacy and safety of medical treatment in this field. We searched through MEDLINE (PubMed), Scopus, Web of Science and Cochrane Library. The Delphi modified technique to generate consensus was used. Preliminary evidence statements were subject to an anonymous agreement assessment and discussion process using an online survey, followed by further discussion and update at a national meeting. A draft of the manuscript with all recommendations was then circulated among all participants and suggestions were incorporated. The final version was again circulated before publication. RESULTS: Twenty-six recommendations were developed focusing on the following topics: general management (3), screening and follow-up of uveitis (4), treatment (17) and health education in JIA-U among patients and families (2). CONCLUSION: These guidelines were designed to support the shared medical management of patients with JIA-U and emphasize the need for a multidisciplinary approach between Ophthalmology and Paediatric Rheumatology regarding the comprehensive care of JIA-U. We acknowledge that updating these recommendations will be warranted in the future, as more evidence becomes available. KEY-WORDS: juvenile idiopathic arthritis, uveitis, biological treatment, conventional immunosuppressive treatment, multidisciplinary management, guidelines, consensus, review, Delphi Technique.

Juvenile idiopathic arthritis-associated uveitis in the era of biological therapy: how the disease changed in more than 20 years of observation in a tertiary referral center in Rome (Italy).

OBJECTIVES: To describe the ophthalmological characteristics in a Juvenile idiopathic arthritis (JIA) cohort and to evaluate how therapeutic advances have changed the course of the uveitis. METHODS: Analysis of a retrospective cohort study of consecutive JIA pediatric patients including JIA-associated uveitis (JIA-U) and comparison with a previous study in the same uveitis center assessed before the wide-spread of biological therapy. RESULTS: The total of 49 JIA patients were analyzed, of whom 18 JIA-U, compared with a JIA-U past cohort of 66 patients. Systemic corticosteroids were used significantly less in the current JIA-U group (p = 0.008) than in the past one. JIA-U present cohort was on therapy more frequently with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) than the past group (p = 0.039), mostly treated with methotrexate (93.3%). Furthermore, a larger use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) was described in the current JIA-U group (p = 0.005) also associated with csDMARDs (p = 0.003). Adalimumab was used more (72.7%) in the present JIA-U cohort compared to a larger treatment with infliximab (61.5%) in the past (p = 0.005). Higher number of uveitis recurrences was observed in the previous cohort compared to the current one (p = 0.005). Fewer complications were described in this study than in the previous: posterior synechiae (p = 0.007), cataract (p < 0.001), band keratopathy (p < 0.001), and elevated intraocular pressure (IOP) (p = 0.047). CONCLUSION: Current therapies reduced the uveitis recurrences and ocular complications including cataract due also to the lower use of corticosteroids. The new close collaboration with the pediatric rheumatologic center in the same University has contributed to the care improvement and decrease of uveitis complications.

Yoga-induced uveitis glaucoma hyphema syndrome.

A 74-year-old pseudophakic white woman with pseudoexfoliation syndrome presented with right eye pain and photophobia and was found to have pseudophacodenesis with recurrent episodes of anterior uveitis, microhyphema, and elevated intraocular pressure (IOP). All episodes occurred after yoga sessions with intensive facedown postures. Ultrasound biomicroscopy (UBM) performed in supine and prone positions demonstrated significant change in the lens-bag complex position, with lens-iris touch. The patient underwent intraocular lens (IOL) explantation, anterior vitrectomy, and flanged intrascleral haptic-fixated IOL placement via double-needle technique, with resolution of all symptoms.

Efficacy and safety of certolizumab pegol in pregnant women with uveitis. Recommendations on the management with immunosuppressive and biologic therapies in uveitis during pregnancy.

OBJECTIVES: Clinicians often face the challenge of providing effective and safe therapy for pregnant women with uveitis. Certolizumab pegol (CZP) differs from other anti-TNFα agents due to its limited placental transfer. In this study we assessed the efficacy of CZP in pregnant women with uveitis. We also provided information on outcomes of pregnant women and neonates exposed to CZP. METHODS: We carried out a multicentre study of women with uveitis who received CZP during pregnancy and their neonates. The main visual outcomes were visual acuity (VA), intraocular inflammation and corticosteroid-sparing effect. Pregnancy outcomes, maternal and neonatal infections and congenital malformations were also assessed. RESULTS: We studied 14 women (23 affected eyes); mean age of 34.3±5.5 years. The underlying diseases were spondyloarthritis (n=7), idiopathic (n=2), and Vogt-Koyanagi-Harada, rheumatoid arthritis, juvenile idiopathic arthritis, punctate inner choroidopathy and Behçet's disease (1 each). The patterns of ocular involvement were anterior (n=10), posterior (n=2), intermediate (n=1), panuveitis (n=1). Cystoid macular oedema was present in one patient (1 eye). Uveitis was bilateral in nine cases and chronic in seven patients. CZP was started before getting pregnant in ten patients and after conceiving in four. All patients achieved or maintained ocular remission throughout pregnancy. Fifteen healthy infants were born. Only one woman presented a mild infection during pregnancy. Neither infections nor malformations were observed in neonates after a follow-up of 6 months. Six infants were breastfed and all of them received scheduled vaccinations without complications. CONCLUSIONS: Certolizumab pegol is effective and safe in women with uveitis during pregnancy.

Biological therapy in refractory cases of uveitis and scleritis: An analysis of 18 cases from a tertiary eye care center from South India.

Purpose: To evaluate the effectiveness of biologic therapy in a cohort of patients with various types of refractory non-infectious uveitis and scleritis. Methods: A retrospective observational study on patients with non-infectious uveitis and scleritis who were not responding or had a high recurrence rate with the conventional treatment and had received biologic therapy. Results: We studied 18 patients (33 eyes) who received biological therapy between January 2017 and November 2019. The mean age was 30 ± 17 years and mean duration of uveitis was 36.8 months (range 1-120 months). Anterior uveitis (27.7%) was most commonly observed followed by scleritis, panuveitis, posterior, and intermediate uveitis. The most common etiology was Behçet's disease (4 patients, 22.2%) followed by juvenile idiopathic arthritis (3 patients, 16.6%), granulamotosis polyangitis, and idiopathic (2 patients each, 11.1%). Majority had trialled one or more immunosuppressive and were refractory in nature. Maximum patients had received adalimumab (61%) followed by infliximab (22%), rituximab (12%), and golimumab (6%). The median prednisolone dose was reduced from 30 mg (range 7.5-60 mg) to 5 mg (range 0-10 mg) after biological therapy (P = 0.002). Significant visual improvement was observed post biologic therapy (mean log mar VA 0.41 ± 0.62 improved to 0.23 ± 0.48 at the final visit, P = 0.008). Maximum number of patients (16 patients, 89%) responded well with biological therapy. Three patients developed recurrence and systemic complications were observed in two patients. Conclusion: Biologic therapy is effective in non-infectious refractory uveitis who were resistant to conventional therapy and may prolong disease recurrence.

Drug Retention Rate and Causes of Discontinuation of Adalimumab in Uveitis: Real-World Data from the Biotherapies in Uveitis (BioÚvea) Study Group.

PURPOSE: To study the drug retention rate (DRR), causes, and predictors of discontinuation of adalimumab (ADA) in a real-world uveitis setting. DESIGN: Multicentric, nationwide, registry-based, ambispective, observational study. PARTICIPANTS: Patients treated with ADA for noninfectious uveitis (NIU) in the Biotherapies for Uveitis (BioÚvea) Spanish registry from November 2016 to November 2017. METHODS: Demographics, clinical data, timing, and reasons for discontinuation, if occurred, were recorded. The DRR and drug retention time (DRT) were estimated using the Kaplan-Meier method. Median follow-up was analyzed by reverse Kaplan-Meier. Log-rank test was used for comparisons. Cox proportional-hazards model (PHM) and propensity score matching were used to identify predictors for discontinuation due to inefficacy and adverse events. MAIN OUTCOME MEASURES: Drug retention rate and DRT. RESULTS: A total of 392 patients were analyzed, including 218 women. Median age was 39 (interquartile range, 25) years. Nonanterior uveitis was recorded in 242 patients. Median follow-up was 49.07 (0.97-131.67) months, median DRT (survival) was 69.3 months, and 14 patients were lost to follow-up. The DRR at 6, 12, 24, and 60 months was 92.97%, 87.68%, 76.31%, and 54.28%, respectively. Adalimumab was discontinued in 151 patients. Discontinuation was due to lack or loss of efficacy in 74 patients, adverse event in 34 patients, and sustained quiescence in 25 patients. Recorded adverse events included infections in 10 patients and malignant neoplasms in 3 patients. Concurrent classic immunomodulatory therapy (IMT) was given to 251 patients. We did not find DRT differences regarding the use of concurrent IMT. Adalimumab was prescribed as a second or greater biotherapy line in 76 patients who showed shorter DRT (P = 0.038). Starting ADA in nonbiotherapy-naive patients was a predictor for "discontinuation due to inefficacy," whereas undifferentiated uveitis was a predictor for "discontinuation due to adverse event." Drug retention time was significantly shorter when spared or intensified, mainly due to discontinuation after sustained quiescence. CONCLUSIONS: Drug retention rate of ADA in uveitis at 60 months was 54.28%, with a good safety profile. The use of concurrent IMT did not show a significant influence on DRT. The use of ADA as a second or further biotherapy could be predictive for discontinuation due to inefficacy. Undifferentiated uveitis may be prone to premature discontinuation of ADA due to adverse events.

Patterns of Vitamin D Levels and Exposures in Active and Inactive Noninfectious Uveitis Patients.

PURPOSE: To compare serum vitamin D levels and patterns of ultraviolet light and dietary exposure among patients with active and inactive noninfectious uveitis and population controls. DESIGN: Prospective case-control study. All participants (n = 151) underwent serum 25-hydroxy vitamin D measurement and completed a questionnaire on vitamin D intake and ultraviolet light exposure. Serum 25-hydroxy vitamin D levels were compared between active and inactive uveitis groups and with local population estimates. PARTICIPANTS: Adult patients with active and inactive noninfectious uveitis were recruited from 2 Victorian tertiary hospitals and 1 private ophthalmic practice. METHODS: Serum 25-hydroxy vitamin D levels were compared between patients with active and inactive uveitis and population-based estimates of serum 25-hydroxy vitamin D levels, stratified by geographic region and season. Vitamin D intakes and exposures based on questionnaire results, including vitamin D supplementation and sunlight exposures on weekdays and weekends, were compared between active and inactive uveitis groups. MAIN OUTCOME MEASURES: Serum vitamin D levels, intake of vitamin D, and exposure to sources of vitamin D. RESULTS: The median level of serum vitamin D in those with active uveitis (n = 74) was 46 nmol/l (interquartile range [IQR], 29-70 nmol/l), significantly lower than in the inactive control group (n = 77) at 64 nmol/l (IQR, 52-79 nmol/l; P < 0.001). The active uveitis group also showed lower median serum vitamin D levels than the local population median of 62 nmol/l (IQR, 46-77 nmol/l). Vitamin D supplementation also was associated significantly with uveitis inactivity (P = 0.026, Kendall's τ test). In a subanalysis of vitamin D-deficient participants, sun exposure was associated significantly with uveitis inactivity (P = 0.014 for weekday and weekend analyses). CONCLUSIONS: Participants with active uveitis showed significantly lower serum 25-hydroxy vitamin D levels than inactive uveitis patients and local population-based estimates. Vitamin D supplementation was found to be associated with decreased uveitis activity, as was sun exposure in those with vitamin D deficiency. These results suggest that vitamin D supplementation should be studied as an option for the prevention of uveitis relapse in at-risk patients.

Ocular complications of Garcinia cambogia extract diet pills: Case report.

BACKGROUND: Garcinia cambogia contains hydroxycitric acid. Hydroxycitric acid is a potent competitive inhibitor of adenosine triphosphate citrate lyase which is a key enzyme in the synthesis of fatty acids. Hydroxycitric acid also regulates the level of serotonin. In these regards, hydroxycitric acid has been reported to exhibit weight loss activity. Adverse reactions of G. cambogia from numerous clinical studies demonstrated relatively mild reactions. However, there are some complications of G. cambogia reported in the past: acute liver injury, acute hepatitis, and hepatic failure. However, ocular complications of G. cambogia have not been reported yet. CASE PRESENTATION: A 35-year-old female visited our clinic with decreased vision in the left eye and ocular pain in both eyes for the last 6 days. She also complained of headache, dizziness, and nausea. She had taken G. cambogia extract more than the recommended dose. There was myopic shift with anterior chamber shallowing in both eyes, especially in the left eye. Moreover, swelling and retinal folds of peripapillary retinal nerve fiber layer and macula were observed in both eyes. These ocular complications of G. cambogia extract resolved after discontinuation of the extract and topical and oral steroid treatment. Herein, we report the first case of ocular complications of G. cambogia extract diet pill assessed with optical coherence tomography of optic disk and macula along with dual Scheimpflug analyzer. CONCLUSION: It is necessary that physicians dealing with obesity advice patients about possible visual disturbance of this extract when taken in overdose so that they can see an ophthalmologist immediately.

[Clinical features and therapy of uveitis in childhood]. / A gyermekkori uveitis klinikai jellemzoi és terápiája.

Introduction: Uveitis is characterized by inflammation of the middle layer of the eye. Its overall incidence is low. Autoimmune diseases and infections are the most common underlying diseases. Out of the autoimmune diseases, juvenile idiopathic arthritis is associated most frequently with uveitis. The topical ophthalmological treatment may fail in a significant proportion of the patients and immunomodulatory therapy may be required. Aim and method: In a retrospective study, data of 33 children diagnosed and treated with uveitis at the Department of Pediatrics and Ophthalmology, University of Pécs during the last 5 years were collected and analyzed. Results: The mean age of the patients was 9.3 (0.3-17.8) years. Boys and girls were equally affected with an exception of patients with juvenile idiopathic arthritis where female predominance was found. An underlying disease could be identified in 60% of the cases (20/33). Uveitis was associated in 12 patients with juvenile idiopathic arthritis, in 2 patients with Behcet's disease and in a single case with inflammatory bowel disease. Infections have been proven in 5 patients. The autoimmune diseases caused an eye inflammation typically in anterior localization, in contrast to the infections that resulted in posterior uveitis. The majority of the patients required systemic treatment. 3 of them received systemic corticosteroid and 18 patients methotrexate as disease-modifying antirheumatic drug. 13 children with severe disease activity required biological therapy (adalimumab injection). Remission could be achieved in 1.45 (0.75-2.5) months. Conclusion: Pediatric uveitis is of great importance. Early diagnosis, adequate therapy and follow-up require multidisciplinary cooperation. Orv Hetil. 2019; 160(34): 1335-1339.

Therapeutic advances in juvenile idiopathic arthritis - associated uveitis.

PURPOSE OF REVIEW: The aim of this review is to highlight recent changes in the treatment of juvenile idiopathic arthritis (JIA) - associated uveitis in the era of biologics. RECENT FINDINGS: Early introduction of steroid-sparing therapies is paramount for appropriate management. Biologic therapies have improved the therapeutic management of JIA-uveitis and adalimumab is currently approved for pediatric-onset noninfectious chronic anterior uveitis with an inadequate response to topical steroids and methotrexate. Recent studies suggest that ocular complications in JIA-uveitis are less frequent compared with previous publications. However, patients with JIA-uveitis seem to be particularly dependent on classical immunosuppressive drugs or biologics. Indications for primary lens implantation have expanded considerably with the evolution of materials and better control of inflammation with biologics. The rate of serious adverse events related to new therapeutic approaches seem acceptable, however longer term follow-up is necessary. SUMMARY: Improvement in the initial screening and improved inflammation control with biologics has considerably reduced the potentially sight-threatening prognosis of JIA-uveitis.

Familial Blau syndrome:First molecularly confirmed report from India.

Blau syndrome (BS) is a rare autoinflammatory disorder characterized by the clinical triad of arthritis, uveitis, and dermatitis due to heterozygous gain-of-function mutations in the NOD2 gene. BS can mimic juvenile idiopathic arthritis (JIA)-associated uveitis, rheumatoid arthritis, and ocular tuberculosis. We report a family comprising a mother and her two children, all presenting with uveitis and arthritis. A NOD2 mutation was confirmed in all the three patients - the first such molecularly proven case report of familial BS from India.

Effect of Uveitis on the Development of Keratopathy: A Population-Based Cohort Study.

Purpose: The purpose of this study was to evaluate the effect of uveitis on the development of various keratopathies via the use of the National Health Insurance Research Database (NHIRD) in Taiwan. Methods: Approximately 1 million patients were randomly sampled from the registry of the NHIRD. Patients diagnosed with uveitis by ophthalmologists were enrolled in the study group after exclusion. Each individual in the study group was age and sex matched to four non-uveitis individuals who serve as the control group. In addition to keratopathy, other possible risk factors and medications were included in the multivariate model, and the effects of different subtypes of uveitis for developing keratopathies were also analyzed. Results: A total of 4773 uveitis patients (2662 male and 2111 female) and 19,092 non-uveitis patients (10,648 male and 8444 female) were enrolled. There were 406 events of keratopathy in the study group, and another 764 events occurred in the control group. A higher incidence rate was found in the study group after adjustment (adjusted hazard ratio [aHR]: 1.772), with a greater cumulative probability (P < 0.0001). For the subgroup analysis, anterior uveitis (aHR = 1.765) and panuveitis (aHR = 3.386) increased the risk of developing keratopathies. Moreover, male sex was associated with a higher aHR than female sex for developing keratopathies in the study group. Conclusions: The presence of uveitis significantly elevates the risk for developing keratopathy.

Pediatric Uveitis.

Pediatric uveitis differs from adult-onset uveitis and is a topic of special interest because of its diagnostic and therapeutic challenges. Children with uveitis are often asymptomatic and the uveitis is often chronic, persistent, recurrent, and resistant to conventional treatment. Anterior uveitis is the most common type of uveitis in children; the prevalence of intermediate, posterior, and panuveitis varies geographically and among ethnic groups. Regarding etiology, most cases of pediatric uveitis are idiopathic but can be due to systemic inflammatory disorders, infections, or a manifestation of masquerade syndrome. Ocular complications include cataracts, hypotony or glaucoma, band keratopathy, synechiae formation, macular edema, optic disc edema, choroidal neovascular membranes, and retinal detachment. These complications are often severe, leading to irreversible structural damage and significant visual disability due to delayed presentation and diagnosis, persistent chronic inflammation from suboptimal treatment, topical and systemic corticosteroid dependence, and delayed initiation of systemic disease‒modifying agents. Treatment for noninfectious uveitis is a stepwise approach starting with corticosteroids. Immunomodulatory therapy should be initiated in cases where quiescence cannot be achieved without steroid dependence. Patients should be monitored regularly for complications of uveitis along with systemic and ocular adverse effects from treatments. The goals are to achieve steroid-free durable remission, to reduce the risk of sight-threatening complications from the uncontrolled ocular inflammation, and to avoid the impact of lifelong burden of visual loss on the child and their family. Multidisciplinary management will ensure holistic care of affected children and improve the support for their families.

Contribution of diagnostic tests for the etiological assessment of uveitis, data from the ULISSE study (Uveitis: Clinical and medicoeconomic evaluation of a standardized strategy of the etiological diagnosis).

PURPOSE: ULISSE is the only study that prospectively assessed the efficiency of a standardized strategy, compared to an open strategy for the etiologic diagnosis of uveitis. Our aim was to evaluate the diagnostic yield of the tests prescribed in the ULISSE study to clarify their relevance. METHODS: ULISSE is a non-inferiority, prospective, multicenter and cluster randomized study. The standardized strategy is a two-steps strategy: in the first step, common standard tests were performed, and in the second step, tests were guided by the clinical and anatomic type of uveitis. We reported the relevance of the diagnostic tests used in the standardized strategy, as well as the profitability of the tests that were prescribed to more than twenty patients in each group. Based on diagnostic criteria, either an ophthalmologist, or an internist, established the profitability of a test by considering whether the test lead to a diagnosis or not. RESULTS: Among the 676 patients included (standardized 303; open 373), a diagnosis was made for 152 (50.4%) in the standardized group and 203 (54.4%) in the open group. The most common entities were HLA-B27 associated uveitis (22%), spondyloarthritis (11%), sarcoidosis (18%), tuberculosis (10.7%) and herpes virus infections (8.5%). Among the first step's systematic tests, tuberculin skin test was the most contributive investigation (17.1%), followed by chest X-ray (8.4%), C reactive protein and ESR (6.6% and 5.1%), complete blood count (2.2%) and VDRL (2.0%). The second step's most often contributive tests were: HLA B27 (56.3%), chest-CT (30.3%) and angiotensin converting enzyme (ACE) (16.5%). HLA B27 and ACE were significantly more contributive in the standardized group than in the open group. Immunological tests were never contributive. Among the free investigations, or among the investigations guided by clinical or paraclinical findings, the most often contributive tests were: Quantiferon® (24%), electrophoresis of serum protein (7.8%) and sacroiliac imagery (46.4%). Intracellular serologies (1.7%), serum calcium (2.1%) and hepatic tests (3.3%) were exceptionally contributive. Among the third intention tests, labial salivary gland biopsies were contributive in 17.9% of cases, but the profitability of other invasive investigations (anterior chamber tap, vitrectomy, bronchoscopy and lumbar puncture) or specialized imagery (18F-FDG PET, Brain MRI) could not be determined since these test were rarely performed. CONCLUSION: Only a few diagnostic tests are useful for the etiological assessment of uveitis. They are often cheap, simple, more often guided by the clinical findings, and lead to an etiological diagnosis in most patients. On the other hand, some tests are never or exceptionally contributive, such as immunological tests or intracellular serologies. Further studies are required to evaluate the profitability of third intention imagery and invasive investigations.

Amelioration of Endotoxin-Induced Inflammatory Toxic Response by a Metal Chelator in Rat Eyes.

Purpose: Metal ions play a key role in exacerbating toxicity associated with oxidative stress and inflammation. This study examines the effects of a formulation containing the metal chelator ethylenediaminetetraacetic acid (EDTA) and permeability enhancer methyl sulfonyl methane (MSM) on the early course of inflammation in endotoxin-induced uveitis (EIU). The proprietary MSM/EDTA formulation of Livionex, Inc., which was used for this study, is covered by several patents and pending patent applications. Methods: EIU was induced by using subcutaneous injection of lipopolysaccharide (LPS) into the thighs of Lewis rats. Treatment consisted of topical application to the eyes of either PBS or eye drops designated as ME that contain EDTA and MSM. Clinical signs of uveitis were monitored at 6 and 24 hours postinjection. Oxidative and inflammatory markers were evaluated by ELISA or immunohistochemistry. Results: Rats treated with ME showed fewer clinical signs of uveitis including reduced miosis, fibrinous exudates, and dilated blood vessels. The aqueous humor of treated rats contained fewer leukocytes, lower protein levels, and less PGE2. Formation of protein adducts with the lipid peroxidation end-product, 4-hydroxynonenal, expression of NF-κB, TNF-α, and MMP-9 were all reduced in rats treated with ME. Conclusions: Our results indicate that ME eye drops downregulate the ocular inflammatory response in LPS treated rats, suggesting that induction of EIU involves metal ions and chelation therapy with ME is a potential treatment for uveitis.