Biologic therapies for psoriasis and eyes.

Psoriasis is a systemic inflammatory disorder, manifested mainly by skin lesions, but the inflammation also may affect the joints and eye. Many comorbidities have been described in association with psoriasis, including metabolic syndrome and coronary plaques. The pathomechanism of psoriasis is multifaceted. Both genetic and immunologic aspects play a role in stimulating inflammation. Genetic susceptibility is conditioned by presence of the human leukocyte antigen-C*06:02 risk allele and the inflammatory reaction secondary to cytokines, such as tumor necrosis factor α, interleukin 17 (IL-17), IL-20, IL-23, and interferon alfa. Besides the conventional therapy of topical steroids and immunosuppressants, biologic therapies are widely used in the treatment of psoriasis, psoriatic arthritis, and coexisting uveitis. In the majority of cases, biologic therapy has a beneficial effect on uveitis, but in some cases, some of these drugs can lead to serious side effects threatening vision.

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.

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.

Inflammatory Bowel Disease: Its Effects on Physical Activity, Sports Participation, and Athletes.

ABSTRACT: This article discusses the "bidirectional" relationship between inflammatory bowel disease (IBD) and physical activity. Intestinal symptoms and extraintestinal manifestations of IBD negatively impact a patient's ability to participate in sports. IBD also impacts athletic performance via its effects on muscle mass, muscle function, bone density, and fatigue. Surveys of IBD patients consistently show that IBD interferes with athletic participation. While IBD negatively affects physical activity, there is growing evidence that physical activity can be beneficial for IBD patients. Prospective studies have revealed that structured physical activities may positively influence inflammatory markers, disease activity, muscle strength, bone density, fatigue, stress, anxiety, and quality of life. This suggests that physical activity may be a simple and safe adjuvant therapy for IBD patients. Future studies assessing the optimal activity regimen are warranted. Finally, a cohort of professional athletes with IBD are described for the first time - football players in the National Football League.

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.

Systemic anti-inflammatory therapy aided by double-headed nanoparticles in a canine model of acute intraocular inflammation.

Novel approaches circumventing blood-ocular barriers in systemic drug delivery are lacking. We hypothesize receptor-mediated delivery of curcumin (CUR) across intestinal and ocular barriers leads to decreased inflammation in a model of lens-induced uveitis. CUR was encapsulated in double-headed polyester nanoparticles using gambogic acid (GA)-coupled polylactide-co-glycolide (PLGA). Orally administered PLGA-GA2-CUR led to notable aqueous humor CUR levels and was dosed (10 mg/kg twice daily) to adult male beagles (n = 8 eyes) with induced ocular inflammation. Eyes were evaluated using a semiquantitative preclinical ocular toxicology scoring (SPOTS) and compared to commercial anti-inflammatory treatment (oral carprofen 2.2 mg/kg twice daily) (n = 8) and untreated controls (n = 8). PLGA-GA2-CUR offered improved protection compared with untreated controls and similar protection compared with carprofen, with reduced aqueous flare, miosis, and chemosis in the acute phase (<4 hours). This study highlights the potential of PLGA-GA2 nanoparticles for systemic drug delivery across ocular barriers.

Parental Uveitis Influences Offspring With an Increased Susceptibility to the Experimental Autoimmune Uveitis.

Purpose: Previous studies have shown that parental abnormal physiological conditions such as inflammation, stress, and obesity can be transferred to offspring. The purpose of this study was to investigate the impact of parental uveitis on the development and susceptibility to experimental autoimmune uveitis (EAU) in offspring. Methods: Parental male and female B10RIII mice were immunized with interphotoreceptor retinoid binding protein (IRBP) 161-180 in complete Freund's adjuvant and were immediately allowed to mate. Gross examination of the offspring gestated with EAU was performed to determine the influence of parental uveitis on offspring development after birth. Gene expression profiles were analyzed in the affected eyes of offspring under EAU to identify differentially expressed genes (DEGs). Adult offspring were given 5, 25, and 50 µg IRBP161-180 to compare their susceptibility to EAU. Immunized mice were clinically and pathologically evaluated for the development of EAU. Ag-specific T-cell proliferation and IL-17 production from spleens and lymph nodes were evaluated on day 14 or 35 after immunization. Results: Hair loss, delay of eye opening, and swollen spleens in the offspring from parents with uveitis were observed from day 14 to 39 after birth. DEGs were involved in the immune system process, muscle system process, and cell development. The altered antigen processing and presentation, cell adhesion molecules, and phagosome in the eyes of the offspring from uveitis-affected parents were enriched. Offspring gestated with EAU showed a susceptibility to EAU and an earlier onset and higher severity of EAU compared to the control group mice. IRBP-specific lymphocyte proliferation and IL-17 production were observed in the EAU offspring with exposure to parental uveitis. Conclusions: The results suggest that mouse parents with uveitis can increase their offspring's susceptibility to EAU, probably through altering cell adhesion molecules and antigen processing and presentation related to the T-cell proliferation and Th17 response.

[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.

Advances in the treatment of uveitis in patients with spondyloarthritis - is it the time for biologic therapy?

Spondyloarthritis (SpA) is a heterogeneous group of diseases that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), inflammatory bowel disease-associated spondyloarthritis (IBD-SpA), and undifferentiated spondyloarthritis (unSpA). This group of diseases shares several clinical, imaging, and genetic features; the integration of these diseases in the group of SpA is needed for an early diagnosis and a prompt treatment. Uveitis is the most common extra-articular manifestation of SpA. HLA-B27-associated acute anterior uveitis (AAU) is the most frequent form of uveitis encountered in the SpA group. The general prevalence of HLA-B27-associated AAU in the group of SpA is about 30% and the general prevalence of SpA in patients with HLA-B27-associated AAU is over 50%. There are several differences in the clinical picture and evolution of HLA-B27-associated AAU in patients with SpA and knowing this is very important for the best therapeutic decision. Tumor necrosis factor α (TNFα) is a very important mediator not only in the pathogenic mechanisms of SpA, but also in the immune reactions that characterize HLA-B27-associated AAU in SpA. There is much evidence of the role of TNFα in SpA and HLA-B27-associated AAU, multiple studies showing efficacy of anti-TNFα drugs not only on rheumatic manifestations but also on ocular involvement. Conventional therapy of HLA-B27-associated AAU with local or systemic glucocorticoids and immunosuppressive drugs (sulfasalazine, methotrexate, azathioprine, etc.) in order to diminish the ocular inflammation is associated with many side effects, some of them being very severe and even life threatening. Therefore, new treatments, especially biologic therapy with anti-TNFα drugs, open a new opportunity for the treatment of these patients. It is very important to emphasize that antibody anti-TNFα agents (infliximab, adalimumab, golimumab) may be more efficient than soluble receptors of TNFα (etanercept) in decreasing the risk of HLA-B27-associated AAU in patients with SpA. The aim of this review made by a group of ophthalmologists and rheumatologists with recent and fruitful experience regarding the anti-TNF treatment of uveitis in patients with SpA is to make the community of ophthalmologists aware of this biologic therapy and that it is the right time to use it. Abbreviations: AU = anterior uveitis; AAU = acute anterior uveitis; AS = ankylosing spondylitis; ASAS = Assessment of SpondyloArthritis Society; DBP = vitamin D binding protein; ESSG = European Spondyloarthropathy Study Group; HLA-B27 = human leukocyte antigen B27; IBD = inflammatory bowel disease; PsA = psoriatic arthritis; ReA = reactive arthritis; SpA = spondyloarthritis; TLRs = Toll-like receptors; TNFα = tumor necrosis factor α; unSpA = undifferentiated spondyloarthritis.

The use of biologic therapies in uveitis.

PURPOSE: Non-infectious uveitis has been long controlled with the use of corticosteroids with many side effects and poor control in some cases. The purpose of this paper was to assess the different biologic agents (in this case infliximab and adalimumab) and to compare their efficacy in the treatment of uveitis. RESULTS: Adalimumab has been proven very successful in replacing or aiding corticosteroid therapy in different autoimmune mediated uveitis (Juvenile Idiopathic Arthritis, Rheumatoid arthritis, sarcoidosis) whereas infliximab has been used intravenously and recently intravitreally with very promising results in controlling Behcet's related uveitis. CONCLUSION: Biologic Response Modifiers represent the future of therapy in immune-mediated uveitis. Abbreviations AU = Anterior Uveitis, BCVA = Best Corrected Visual Acuity, BRM = Biologic Response Modifiers, CME = Cystoid Macular Oedema, CPR = C Protein Reactive, ESR = Erythrocyte Sediment Rate, HSV = Herpes Simplex Virus, ICAM = Intercellular Adhesion Molecules, IMT = Immunomodulatory Therapy, JIA = Juvenile Idiopathic Arthritis, MMP = Matrix Metalloproteinases, MTX = Methotrexate, RA = Rheumatoid Arthritis, TB = Tuberculosis, VCAM = Vascular Adhesion Molecules.

[Uveitis treated with biotherapy and/or DMARD: Analysis from the French Pharmacovigilance Study Base]. / Uvéites sous biothérapies et/ou DMARDs en rhumatologie : analyse de la base de données déclarative de la pharmacovigilance nationale française.

PURPOSE: To report the characteristics of uveitis cases occurring while on biologic therapy or disease-modifying antirheumatic drugs (DMARDs) reported to the French national pharmacovigilance database. METHODS: All the uveitis cases occurring in patients with chronic rheumatologic diseases, chronic inflammatory intestinal diseases or connective tissue diseases, while treated with DMARDs and/or biologic therapies between 2000 and 2015 and reported to the French National Pharmacovigilance Database were collected. RESULTS: During the study period, 32 cases of uveitis were reported (15 men, 17 women). Two patients were treated with one DMARD alone, 24 with biologic therapy alone, and six with both treatments. Anterior uveitis was diagnosed in 19 patients (8 cases were bilateral); intermediate uveitis was found (unilaterally) in one patient; posterior and diffuse uveitis occurred in 5 and 2 cases respectively. Five cases were inconclusive with regard to the anatomical type of uveitis. The uveitis was of infectious origin in 5 cases: 2 toxoplasmosis, 2 herpes virus and 1 tuberculosis. In the 27 other cases, it was not possible to state whether the uveitis was associated with the underlying disease (uncontrolled) or a side effect of the biologic/DMARD treatments. The occurrence of the uveitis led to 9 switches in biologic therapy and 13 discontinuations of treatment (8 complete discontinuations, 5 discontinuations only until uveitis remission was obtained). In 4 cases, the treatments were not modified. The database does not specify the ultimate course or rheumatologic disease activity at the time of the uveitis. CONCLUSIONS: The presence of uveitis while on biologic therapy must not be taken to indicate a therapeutic failure, especially if the ocular manifestation is isolated. In the case of uveitis occurring in patients treated with biologic therapies and/or DMARDs, infectious complications should be ruled out.

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.

Management of Uveitis in Spondyloarthropathy: Current Trends.

Spondyloarthritis is a chronic inflammatory disease predominantly affecting joints of the axial skeleton. However, as many as 50% of patients with this disease may have extra-articular manifestations, which include uveitis; psoriasis; inflammatory bowel disease such as Crohn disease or ulcerative colitis; cardiovascular manifestations in the form of conduction abnormalities, atherosclerosis, or valvular heart disease; pulmonary involvement; and rarely renal involvement. Uveitis occurs in 25% to 40% of patients with spondyloarthritis. Management of uveitis is crucial to prevent morbidity caused by vision loss and secondary complications. Treatment ranges from local therapies to systemic drugs and varies depending on the severity and response to treatment. Categories of medical treatment include nonsteroidal anti-inflammatory agents, corticosteroids, and steroid-sparing agents. Biologic therapies such as antitumor necrosis factor agents act early in the disease process and have revolutionized the field of rheumatology, including management of uveitis. This review will focus on the management of ophthalmic manifestations in spondyloarthropathies.

Pluripotent stem cell models of Blau syndrome reveal an IFN-γ-dependent inflammatory response in macrophages.

BACKGROUND: Blau syndrome, or early-onset sarcoidosis, is a juvenile-onset systemic granulomatosis associated with a mutation in nucleotide-binding oligomerization domain 2 (NOD2). The underlying mechanisms of Blau syndrome leading to autoinflammation are still unclear, and there is currently no effective specific treatment for Blau syndrome. OBJECTIVES: To elucidate the mechanisms of autoinflammation in patients with Blau syndrome, we sought to clarify the relation between disease-associated mutant NOD2 and the inflammatory response in human samples. METHODS: Blau syndrome-specific induced pluripotent stem cell (iPSC) lines were established. The disease-associated NOD2 mutation of iPSCs was corrected by using a CRISPR-Cas9 system to precisely evaluate the in vitro phenotype of iPSC-derived cells. We also introduced the same NOD2 mutation into a control iPSC line. These isogenic iPSCs were then differentiated into monocytic cell lineages, and the statuses of nuclear factor κB pathway and proinflammatory cytokine secretion were investigated. RESULTS: IFN-γ acted as a priming signal through upregulation of NOD2. In iPSC-derived macrophages with mutant NOD2, IFN-γ treatment induced ligand-independent nuclear factor κB activation and proinflammatory cytokine production. RNA sequencing analysis revealed distinct transcriptional profiles of mutant macrophages both before and after IFN-γ treatment. Patient-derived macrophages demonstrated a similar IFN-γ-dependent inflammatory response. CONCLUSIONS: Our data support the significance of ligand-independent autoinflammation in the pathophysiology of Blau syndrome. Our comprehensive isogenic disease-specific iPSC panel provides a useful platform for probing therapeutic and diagnostic clues for the treatment of patients with Blau syndrome.

Ruthenium-106 brachytherapy for choroidal melanoma without transpupillary thermotherapy: Similar efficacy with improved visual outcome.

PURPOSE: To evaluate efficacy and toxicity of two different protocols for eye-conserving treatment of patients with small to intermediate-sized choroidal melanomas; the current ruthenium-106 (Ru106) brachytherapy protocol and the preceding protocol of Ru106-brachytherapy with transpupillary thermotherapy (Ru106/TTT). METHODS AND MATERIALS: Long-term outcomes of 449 consecutive patients, of whom 196 (43.6%) treated using Ru106/TTT and 253 (56.3%) treated using Ru106, were compared in terms of local control, survival, eye preservation and visual outcome. RESULTS: Median follow-up was 82.8 months. Patients in the Ru106-group had smaller, less centrally located tumours and better pre-treatment visual acuity (VA). Five-year cumulative incidence of local failure was 11.2% for Ru106/TTT and 5.2% for Ru106, which was not statistically significant after correction for differences in baseline characteristics (hazard ratio for Ru106 = 0.57, p = 0.14). Cumulative incidence of distant metastases was 11.2 versus 6.2%, and cumulative incidence of cause-specific death was 22.4 versus 5.5% for Ru106/TTT and Ru106 respectively. Enucleation was performed in 9.2 versus 4.0% for Ru106/TTT versus Ru106; 5.1 versus 3.2% for local failure and 2.6 versus 0.8% for complications. At one year of follow-up, significantly more patients had lost useful vision (VA < 0.33) in the Ru106/TTT-group than in the Ru106-group (50.0 versus 24.5%). After two and three years, the differences decreased (54.6 versus 34.0% and 61.7 versus 45.8%, respectively) and lost statistical significance. CONCLUSIONS: Both the current Ru106 and the preceding Ru106/TTT-protocols provided excellent tumour control, cosmetic and functional eye preservation and vital prognosis. The Ru106-protocol yielded prolonged preservation of VA and should be regarded the current standard of treatment.

Juvenile idiopathic arthritis-associated uveitis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is autoimmune in nature with the predominant involvement of CD4(+) T cells. However, the underlying pathogenic mechanisms remain unclear, particularly regarding interplay between genetic and environmental factors. JIA-associated uveitis comes in several forms, but the most common presentation is of the chronic anterior uveitis type. This condition is usually asymptomatic and thus screening for JIA-associated uveitis in at-risk patients is paramount. Early detection and treatment aims to stop inflammation and prevent the development of complications leading to visual loss, which can occur due to both active disease and burden of disease treatment. Visually disabling complications of JIA-associated uveitis include cataracts, glaucoma, band keratopathy and macular oedema. There is a growing body of evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. This includes more traditional treatments, such as methotrexate, as well as newer biological therapies. This review highlights the epidemiology of JIA-associated uveitis, the underlying pathogenesis and how affected patients may present. The current guidelines and criteria for screening, diagnosis and monitoring are discussed along with approaches to management.

[Biologics in uveitis]. / Uvéites et biothérapies.

Biotherapies used in clinical practice for the treatment of uveitis include monoclonal antibodies and fusion proteins (anti-TNFα, anakinra, tocilizumab and rituximab), interferons (IFN) and intravenous immunoglobulins (IVIg). IFN is capable of inducing prolonged remission and continued after his discontinuation, in 20-40% of patients. Side effects (flu-like, psychological effects) limit its use in practice. Anti-TNFα (infliximab and adalimumab) represents an attractive alternative therapeutic in severe uveitis refractory to immunosuppressants, especially in Behçet's disease. They are generally (>90% of cases) and rapidly effective but their action is often suspensive. Anti-TNFα requires an extended prescription or takes over from another immunosuppressant once ocular inflammation has been controlled. IVIg are used for the treatment of Birdshot's disease. Tolerance of IVIg is good but their efficacy is transient. Rituximab showed an efficacy in few observations of various inflammatory eye diseases (uveitis, scleritis and idiopathic inflammatory pseudo-tumors or associated with granulomatosis with polyangiitis) and cicatricial pemphigoid. The risk of infection limits its use in refractory diseases to conventional therapy. Anakinra (a soluble antagonist of IL-1r) showed interesting results in terms of efficiency in one small open study in Behçet's disease. Its safety profile is good and with a quick action that could be interesting for the treatment of severe uveitis.

Amelioration of experimental autoimmune uveoretinitis by inhibition of glyceraldehyde-derived advanced glycation end-product formation.

AGEs are permanently modified macromolecule derivatives that form through nonenzymatic glycation of amino groups of proteins. Glycer-AGEs are highly toxic and play an important role in the pathogenesis of chronic inflammatory diseases. However, the contribution of glycer-AGEs to the pathogenesis of uveitis is unclear. In this study, we measured serum levels of glycer-AGEs in 100 patients with endogenous uveitis (22 with HLA-B27-associated uveitis, 20 with VKH disease, 14 with Behçet's disease, and 44 with sarcoidosis) and 33 healthy volunteers. We then examined the effect of the AGE inhibitor in a mouse model of human endogenous uveitis (EAU) by continuous oral administration of pyridoxamine at 200 or 400 mg/kg/day. Regardless of the etiology, serum glycer-AGE levels were significantly higher in patients with uveitis than in healthy subjects. Treatment with 400 mg/kg pyridoxamine significantly reduced the clinical and histological severity of EAU and was accompanied by a significant decrease in serum and retinal glycer-AGE levels and suppression of translocation of NF-κB p65 into the nucleus of retinal cells. Serum glycer-AGE levels may therefore serve as a biomarker of human uveitis, as well as systemic inflammation, and may contribute to the progression of uveitis, including diabetic iritis, via the activation of NF-κB.