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Purpose: The index review aims to provide an update on the role of corticosteroids and steroid-sparing immunomodulatory therapy (IMT) in managing patients with infectious uveitis., Method: Narrative literature review., Results: Corticosteroids and immunomodulatory therapy (IMT) focus on the host defense system instead of the pathogen, adjusting exaggerated inflammatory reactions to reduce potential harm to ocular tissues. Systemic or local corticosteroids are primarily selected as adjunctive medication for infectious uveitis. Concomitant corticosteroids have also been used in cases of paradoxical worsening in ocular tuberculosis and immune recovery uveitis in cytomegalovirus (CMV) retinitis. While there is no well-established evidence to support the use of IMT in infectious uveitis, it is occasionally used in clinical settings to treat persistent inflammation following resolution of infection such as cases of ocular tuberculosis and ocular syphilis where an insufficient response is observed with corticosteroids., Conclusion: There is no consensus on the position of immunomodulatory therapy in the management of infectious uveitis with different etiologies. The index review provides an overview of available adjunctive corticosteroids and IMT options to assist clinicians in managing such disease entities more efficiently.

Aims: To investigate the correlation between widefield fundus fluorescein angiography (WF-FA) and anterior chamber laser flare photometry (LFP-flare) in Behçet uveitis (BU)., Methods: Patients with BU who underwent Heidelberg WF-FA between March 2016 and March 2018 were included. Demographics, ocular findings, LFP-flare, central macular thickness were retrospectively analyzed., Results: Eighty-six patients (162 eyes) were included. There was a high correlation between WF-FA leakage score and LFP-flare (rho: 0.691, p < .001). For a flare value of 5.75 ph/ms or higher, the sensitivity for predicting angiographic leakage was 70% and the specificity was 94% (AUC: 0.897, p < .001). Flare values that were equal or above 7.6 ph/ms were found to be 100% specific for leakage in the WF-FA., Conclusion: A strong correlation was found between WF-FA leakage and LFP-flare in patients with BU. High LFP-flare levels indicate subclinical posterior segment inflammation in clinically inactive BU.

Purpose: To report demographic and clinical profiles of children with uveitis in theTurkishpopulation., Methods: The data of the pediatric uveitis cases in the nation wide uveitis database were analyzed., Results: The study included 697 eyes of 442 patients with a meanage of 10.8 ± 3.8 years. There were 333 patients (75.3%) with non-infectious uveitis and 69 patients (15.6%) with infectious uveitis. Pars planitis (20.1%) was leading clinical form followed by idiopathic cases with uveitis other than pars planitis (18.8%), juvenile idiopathic arthritis(JIA) related uveitis (12.4%), Behçet uveitis (9.3%) and toxoplasma retinochoroiditis (7.9%). Ocular involvement was unilateral in 187 patients (42.3%) and bilateral in 255 patients (57.7%). The most common anatomiclocation of uveitis was anterior uveitis (39.1%), followed by intermediate uveitis (29.4%), panuveitis (16.1%) and posterior uveitis (15.4%)., Conclusion: The most common systemic association was JIA in the younger children and Behçet disease in the older children.

The 'MHC-I (major histocompatibility complex class I)-opathy' concept describes a family of inflammatory conditions with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. Classical MHC-I-opathies such as spondyloarthritis, Behçet's disease, psoriasis and birdshot uveitis are widely recognised for their strong association with certain MHC-I alleles and gene variants of the antigen processing aminopeptidases ERAP1 and ERAP2 that implicates altered MHC-I peptide presentation to CD8+T cells in the pathogenesis. Progress in understanding the cause and treatment of these disorders is hampered by patient phenotypic heterogeneity and lack of systematic investigation of the MHC-I pathway.Here, we discuss new insights into the biology of MHC-I-opathies that strongly advocate for disease-overarching and integrated molecular and clinical investigation to decipher underlying disease mechanisms. Because this requires transformative multidisciplinary collaboration, we introduce the EULAR study group on MHC-I-opathies to unite clinical expertise in rheumatology, dermatology and ophthalmology, with fundamental and translational researchers from multiple disciplines such as immunology, genomics and proteomics, alongside patient partners. We prioritise standardisation of disease phenotypes and scientific nomenclature and propose interdisciplinary genetic and translational studies to exploit emerging therapeutic strategies to understand MHC-I-mediated disease mechanisms. These collaborative efforts are required to address outstanding questions in the etiopathogenesis of MHC-I-opathies towards improving patient treatment and prognostication., Competing Interests: Competing interests: JCP: Grants or contracts from any entity German Research Foundation grants PR 241/5-2Consulting fees Boehringer IngelheimPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events paid activities as a speaker for Almirall, Boehringer Ingelheim, Janssen-Cilag, Novartis and Pfizer PK Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid All unpaid: Human Immunology (Elsevier) Editorial Board, Frontiers in Immunology Guest associate, Editor and review editor. Editorial board of International Journal of Immunogenetics SS: all support for the present manuscript (eg, funding, provision of study materials, medical writing, article processing charges, etc. Deutsche Forschungsgemeinschaft (DFG) to Jacobs University Bremen DM Grants or contracts from any entity Government of MaltaPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Sanofi, UriageSupport for attending meetings and/or travel Avene, Bioderma, UriageLeadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid Maltese Association of Dermatologists and VenereologistsIvan IP Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Novartis, Eli Lilly, Pfizer, Abbvie, Honoraria for lectures, payments directly to me RS Support for attending meetings and/or travel Abbvie and PfizerIna IK Consulting fees Amgen, Boehringer,GSK, SobiPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Abbvie, Amgen. Boehringer, GSK, Janssen, Lilly, MSD, Novartis, Pfizer, Sobi MvdS Grants or contracts from any entity Novartis, UCB, EliLillyPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events UCBSupport for attending meetings and/or travel UCBParticipation on a Data Safety Monitoring Board or Advisory Board Novartis, UCB, Abbvie GB Grants or contracts from any entity GSK, PfizerPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events GSK, AstraZeneca, Pfizer, Abbvie, Aenorasis, Novartis, Lilly IL Consulting fees Novartis, Alimera lT-T Consulting fees AbbVie, Turkey, NovartisPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events AbbVie, Turkey FC Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events LillySupport for attending meetings and/or travel UCB, NovartisParticipation on a data safety monitoring board or Advisory Board UCB, Novartis DMZ Grants or contracts from any entity European Society of OphthalmologyPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Zentiva, Alkaloid d.o.o., Inspharma d.o.o. MB Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Pfizer, Viatris, Lilly, MSD TJK All support for the present manuscript (eg, funding, provision of study materials, medical writing, article processing charges, etc). National Health & Medical Research Council GNT2011115Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid President, Australian Society for Medical Research MB Grants or contracts from any entity PFIZERConsulting fees PFIZERPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events FRENESIUS KABI, LILLYSupport for attending meetings and/or travel BIOGEN, PFIZER, JANSSEN RJUL Consulting fees UCB, Novartis, Abbvie, Eli-LillyPayment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events UCB, Novartis, Abbvie, Eli-Lilly, Amgen JN All research funding support for the present manuscript: NEI-NIH R01EY033495—research funds and R01EY031383—research fundsHonoraria for lectures: Harvard University, Northwestern University, Massachusetts General Hospital.Support for attending meetings and/or travel: NYU Department of Medicine, NIH-NEIParticipation Medical Advisory Board: ABDA (American Behçet’s Disease Association) DGMcG Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events Janssen, Abbvie, Novartis, UCB, BMS, Lilly., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: An effective therapy to reduce the number and severity of HLA-B27-related acute anterior uveitis (AAU) recurrences represents a clinical need. Curcumin is a promising therapeutic option in various inflammatory eye diseases. To enhance its absorption and eye tissue selectivity, a phospholipidic-curcumin complex (PHBC) has been formulated (Iphytoone®, Eye Pharma S.p.A.)., Aims: This study investigates if PHBC is effective and safe to decrease the number and intensity of HLA-B27-related AAU relapses., Methods: HLA-B27-related AAU patients were randomly divided to receive PHBC or placebo for 12 months (NCT03584724)., Results: Compared with the previous year, the number of relapses decreased in both groups. The proportion of responders was significantly higher in the PBHC group. The severity of attacks was comparable. The study drug was well tolerated., Conclusions: A beneficial effect of PHBC treatment is suggested because the proportion of responders was significantly higher in this group of patients.

Purpose of Review: Uveitis is a major manifestation of Behçet disease (BD) and potentially has a high morbidity. This article reviews recently published data on BD uveitis., Recent Findings: A set of classification criteria and a diagnostic algorithm have been developed for BD uveitis. Recent reports have confirmed male predominance and posterior segment inflammation in the majority of BD uveitis patients. A high uveitis attack severity score, fluorescein angiographic leakage at the posterior pole, and disruption of outer retinal layers on optical coherence tomography (OCT) predict poor visual outcome. OCT-angiography studies have suggested subclinical changes of retinal capillaries in patients with or without ocular involvement. In a randomized controlled trial, interferon-α was superior to cyclosporine. Favorable outcomes were reported with earlier initiation, optimization, and withdrawal of infliximab after remission. Adalimumab as first-line was superior to conventional therapy., Summary: Classification criteria will be used to select a homogeneous group of patients for research and the diagnostic algorithm may help ophthalmologists predict the probability of BD uveitis based on ocular findings. Fluorescein angiography and OCT are the routine imaging modalities. Clinical relevance of OCT-angiography is unclear. Interferon-α, infliximab, and adalimumab have proven superior efficacy compared to conventional therapy., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To establish expert recommendations for the management of ocular sarcoidosis (OS)., Methods: A question-based survey on the management of OS was circulated to international uveitis experts (members of the International Uveitis Study Group and the International Ocular Inflammation Society) electronically. Subsequently, a consensus workshop was conducted at the 7th International Workshop on Ocular Sarcoidosis (IWOS) in June 2019 in Sapporo, Japan as part of the Global Ocular Inflammation Workshops. Statements on the management of OS that were supported by a two-thirds majority of 10 international panel members of the workshop, after discussion and voting, were taken as consensus agreement., Results: A total of 98 participants from 29 countries responded to the questionnaire survey. The subsequent consensus workshop established recommendations for the management of OS in five sections. The first section concerned evaluation and monitoring of inflammation. The second, third and fourth sections described ocular manifestations that were indications for treatment, and the management of anterior uveitis, intermediate uveitis and posterior uveitis. In the fifth section, the use of systemic corticosteroids and systemic immunosuppressive drugs were detailed., Conclusions: Recommendations for management of OS were formulated through an IWOS consensus workshop., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Immunomodulatory agents are often used in the systemic treatment of non-infectious uveitis. These drugs consist of corticosteroids, conventional immunosuppressives, and biological agents. As it is known that they suppress the immune system, the most important concern associated with immunomodulatory therapy (IMT) is the increased risk of infection. The World Health Organization declared COVID-19 a pandemic on 11 March 2020. Although severe acute respiratory distress syndrome secondary to SARS-CoV-2 infection may develop in all people, patients who receive IMT may be at higher risk in terms of both the transmission of the infection and more severe disease course. Therefore, guidelines on the management of patients receiving IMT due to uveitis during the pandemic are needed. In this review, we examined the immunomodulatory drugs used in the treatment of uveitis in terms of infectious complications and the data of patients who received IMT during the COVID-19 pandemic and discussed recommendations for the use of these drugs. According to the latest information, patients who receive IMT may continue their treatment as long as there are no disruptions in regular complete blood count (especially white blood cell count >4,000/µL) and liver and kidney function tests. Patients diagnosed with COVID-19 should be managed with a multidisciplinary approach.

Objectives: To analyze and compare sociodemographic features between Behçet uveitis and other non-infectious uveitis., Materials and Methods: The data of adults with non-infectious uveitis in the nationwide uveitis database were analyzed and the sociodemographic features of patients with and without Behçet disease were compared., Results: This study included data of 4,978 eyes of 3,363 patients from 33 centers. The mean age at presentation was 38.7±13.3 (17-87) years. The mean age was 34.3±10.5 years in the Behçet uveitis group and 41.1±14.0 years in the other non-infectious uveitis group (p<0.001). Male predominance was seen in the Behçet uveitis group (67.7% vs. 32.3%) while female patients were more common in the other non-infectious uveitis group (54.4% vs. 45.6%, p<0.001). Regarding education level, the proportion of patients with low education was higher in the Behçet uveitis group than the other non-infectious uveitis group (49.6% vs. 43.4% in males, p=0.004; 61.5% vs. 59.2% in females, p=0.021). Having a low-income job or being currently unemployed, indicators of poor income, were more frequent in the Behçet uveitis group than in the other non-infectious uveitis group (32.0% vs. 22.8%, p<0.001). In the comparison of places of residence, the proportion of patients who lived in cities with low gross national product was 37.0% in the Behçet uveitis group and 31.1% in the other non-infectious uveitis group (p<0.001)., Conclusion: Patients with Behçet disease had lower education level and socioeconomic status than patients with other non-infectious uveitis entities.

Purpose : To develop an algorithm for the diagnosis of Behçet's disease (BD) uveitis based on ocular findings. Methods : Following an initial survey among uveitis experts, we collected multi-center retrospective data on 211 patients with BD uveitis and 207 patients with other uveitides, and identified ocular findings with a high diagnostic odds ratio (DOR). Subsequently, we collected multi-center prospective data on 127 patients with BD uveitis and 322 controls and developed a diagnostic algorithm using Classification and Regression Tree (CART) analysis and expert opinion. Results : We identified 10 items with DOR >5. The items that provided the highest accuracy in CART analysis included superficial retinal infiltrate, signs of occlusive retinal vasculitis, and diffuse retinal capillary leakage as well as the absence of granulomatous anterior uveitis or choroiditis in patients with vitritis. Conclusion : This study provides a diagnostic tree for BD uveitis that needs to be validated in future studies.

The aim of this review was to identify the imaging methods at our disposal to optimally manage posterior uveitis at the present time. The focus was put on methods that have become available since the 1990s, some 30 years after fluorescein angiography had revolutionised imaging of posterior uveitis in particular imaging of the retinal vascular structures in the 1960s. We have focussed our review on precise imaging methods that have been standardised and validated and can be used universally thanks to commercially produced and available instruments for the diagnosis and follow-up of posterior uveitis. The second part of this imaging review will deal with invasive imaging methods and in particular ocular angiography.

The aim of this review was to identify the imaging methods at our disposal to optimally manage posterior uveitis at the present time. The focus was put on methods that have become available since the 1990s, some 30 years after fluorescein angiography had revolutionized imaging of posterior uveitis in particular imaging of the retinal vascular structures in the 1960s. We have focussed our review on precise imaging methods that have been standardized and validated and can be used universally thanks to commercially produced and available instruments for the diagnosis and follow-up of posterior uveitis. The first part of this imaging review will deal with noninvasive imaging methods, focusing on fundus autofluorescence and optical coherence tomography as well as recent developments in imaging of the posterior segment.

Introduction : Behçet's disease uveitis (BDU) is a potentially blinding disorder. Systemic treatment with disease-modifying anti-rheumatic drugs (DMARDs) is mandatory in patients with intraocular inflammation involving the posterior segment of the eye. Areas covered : This article discusses existing systemic treatment with corticosteroids and conventional and biologic DMARDs as well as adjunctive local therapy in BDU. An overview is provided for a wide range of biologic DMARDs that have shown promise or investigated in clinical trials. Most recently introduced biologic DMARDs and targeted synthetic DMARDs are also reviewed for their potential in the treatment of BDU. Expert opinion : The prognosis of patients with BDU has remarkably improved after the introduction of biologic DMARDs. An expanding therapeutic armamentarium will allow treatment of most refractory cases. The ultimate goal is to provide drug-free remission with preservation of 20/20 vision.

Purpose: To provide an overview of the role of multimodality approach to the diagnosis and assessment of uveitic macular edema (UME). Methods: Review of literature. Results: Optical coherence tomography (OCT) has become the gold standard in the detection, quantification, monitoring of treatment, and determination of prognosis in UME. Fluorescein angiography provides essential information on blood-retinal barrier disruption as a result of intraocular inflammation and allows detection of associated retinal ischemia and neovascularization. Dye-less OCT angiography can reveal the presence of various qualitative and quantitative retinal microvascular changes mostly involving the deep capillary plexus. Reading acuity and retinal sensitivity assessed by microperimetry represent sensitive measures for visual dysfunction in UME and may supplement distance visual acuity in the follow-up of patients with UME. Conclusion: Conventional and new imaging modalities and ancillary tests complement each other in the diagnosis, assessment, and monitoring of patients with UME.

Uveitis is a complex disorder including both infectious and non-infectious etiologies. Clinical diagnosis is a challenge because many diseases share common clinical signs. Laboratory support is crucial for confirming the clinical diagnosis. Laboratory diagnosis includes direct tests and indirect tests. For example smear, culture, and molecular diagnostics demonstrate the pathogens, hence they are direct tests. Immunologic tests employ an antigen to detect presence of antibodies to a pathogen, or an antibody to detect the presence of an antigen, of the pathogen in the specimens. The immunological tests used in laboratories are made by producing artificial antibodies that exactly "match" the pathogen in question. When these antibodies come into contact with a sample they bind to the matching pathogen if found in the sample. Hence they are grouped under indirect evidence. There are several investigations in uveitis to reach the confirmed diagnosis including microbiological, immunological, imaging and molecular diagnostic testing. In this section we will discuss immunological investigations of infectious and non-infectious uveitis., Competing Interests: None

Purpose: To investigate the effect of interferon alfa-2a on T regulatory (Treg) cells, T helper 17 (Th17) cells, and expression of Toll-like receptors (TLRs) in Behçet disease (BD) patients with uveitis., Methods: Twenty-seven patients who received interferon alfa-2a for active BD uveitis despite conventional immunomodulatory therapies and healthy controls were enrolled. Peripheral blood Treg and Th17 cell frequencies were determined by flow cytometry as gated cells for CD3+CD4+Foxp3+ and CD3+CD4+IL17A+, respectively. Th17 RAR-related orphan receptor (ROR)γt mRNA expression was verified by real-time PCR (RT-PCR). Treg and Th17 cell cytokines were detected by ELISA in the supernatant of short-term cell cultures. RT-PCR was used to assess expression of TLR-2, TLR-3, TLR-4, TLR-8, and TLR-9 using cDNA prepared from CD4+ T cells and monocytes., Results: Treg and Th17 cell frequencies and Th17 RORγt expression were significantly elevated, and IL-10 concentration in Treg cell supernatants was significantly lower in BD patients than in controls. Th17 IL-17, IL-6, IL-21, IL-22, IL-23, IFN-γ, and TNF-α concentrations were significantly higher and all TLR expressions were significantly elevated in patients. Interferon alfa-2a led to a significant reversal in Treg and Th17 cell frequencies, Th17 RORγt expression, Treg and Th17 cell cytokine production, and TLR expression by CD4+ T cells and monocytes., Conclusions: Despite a relative increase in Treg cells, impaired IL-10 production suggests that Treg dysfunction may play a role in induction of BD uveitis. Favorable effects of interferon alfa-2a may be associated with recovery of Treg cell function, suppression of Th17 cells, and reduced expression of TLRs on CD4+ T cells and monocytes.

Purpose : To analyze the role of polymerase chain reaction (PCR) of ocular fluids in management of tubercular (TB) anterior, intermediate, posterior, and panuveitis. Methods: In Collaborative Ocular Tuberculosis Study (COTS)-1 (25 centers, n  = 962), patients with TB-related uveitis were included. 59 patients undergoing PCR of intraocular fluids (18 females; 53 Asian Indians) were included. Results: 59 (6.13%) of COTS-1 underwent PCR analysis. PCR was positive for Mycobacterium TB in 33 patients (23 males; all Asian Indians). 26 patients were PCR negative (18 males). Eight patients with negative PCR had systemic TB. Anti-TB therapy was given in 18 negative and 31 PCR cases. At 1-year follow-up, five patients with positive PCR (15.15%) and three with negative PCR (11.54%) had persistence/worsening of inflammation. Conclusions : Data from COTS-1 suggest that PCR is not commonly done for diagnosing intraocular TB and positive/negative results may not influence management or treatment outcomes in the real world scenario.

Purpose: Relapsing ocular inflammation occurs in about 70% of patients with Behçet's disease (BD) and can lead to permanent loss of vision. Neovascularization of the optic disc (NVD) or elsewhere in the retina (NVE) is a relatively uncommon but severe complication that lacks standardized treatment., Methods: We report on the therapeutic use of anti-TNF monoclonal antibodies for BD-associated NVD and NVE in one pediatric patient (subcutaneous adalimumab) and one young man (intravenous infliximab). Also, we review the previously published experience on biologic therapeutic options, namely anti-TNF agents and interferon-alpha in a total of three and eight patients, respectively., Results: A fast-onset therapeutic effect was observed in both patients leading to complete regression of neovascularizations., Conclusions: Both options may lead to regression of neovascularization, thus preventing loss of vision, but comparative studies need to determine the optimal treatment for this sight-threatening complication of BD.

Purpose: To screen for psychological disorders in patients with active uveitis., Methods: Patients were screened for depression (BDI-II), state anxiety (STAI-I), VR-QOL (NEI-VFQ-25), and HR-QOL (SF-36). Association of depression and anxiety with sociodemographic and clinical parameters and with VR-QOL and HR-QOL were analyzed. Multivariate linear regression models were constructed for NEI-VFQ-25 and SF-36 subscales., Results: Of 99 patients, 37.3% screened positive for depression and 52.5% for anxiety. Depressed patients had lower visual acuity in the better seeing eye (p = 0.013) and more frequently panuveitis (p = 0.018). Anxious patients were younger (p = 0.009), had earlier onset of uveitis (p = 0.015), and had more frequently panuveitis (p = 0.016). Bivariate comparisons showed significant associations between psychological disorders and VR-QOL and HR-QOL. Significant bivariate associations were mostly lost in multivariate analyses for anxiety, but were preserved for depression., Conclusions: A positive screening test for depression and anxiety is common in patients with uveitis. Low vision and panuveitis are associated with depression. Depression is associated with impairment of VR-QOL and HR-QOL.

Purpose: To describe the demographic and clinical profiles of uveitis patients seen at secondary and tertiary care centers in Turkey., Methods: A nationwide web-based registry of patients with uveitis was initiated in November 2008. We analyzed data from a single baseline registry-enrollment visit., Results: In 33 centers, 6967 eyes of 4863 consecutive patients were registered. The mean age at presentation was 36.6 ± 15.7 (1-92) years; 51.3% were male. Behçet disease was the leading diagnosis (24.9%), followed by ankylosing spondylitis and/or HLA-B27-associated anterior uveitis (9.7%), toxoplasmosis (7.1%), Fuchs uveitis (6.3%), and presumed herpetic anterior uveitis (6.0%). Visual acuity was 0.1 or worse in 22% of eyes. The most common ocular complications were posterior synechiae (16.2%) and cataract formation (16.2%)., Conclusions: Behçet disease is still the most common non-infectious etiology in Turkish uveitis patients, while ocular toxoplasmosis and herpetic anterior uveitis are the most common infectious uveitic entities.

Aim: To outline recommendations from an expert committee on the assessment and investigation of patients with severe inflammatory eye disease commencing immunosuppressive and/or biologic therapy., Method: The approach to assessment is based on the clinical experience of an expert committee and a review of the literature with regard to corticosteroids, immunosuppressive drug and biologic therapy and other adjunct therapy in the management of patients with severe sight-threatening inflammatory eye disease., Conclusion: We recommend a careful assessment and consultative approach by ophthalmologists or physicians experienced in the use of immunosuppressive agents for all patients commencing immunosuppressive and/or biologic therapy for sight threatening inflammatory eye disease with the aim of preventing infection, cardiovascular, metabolic and bone disease and reducing iatrogenic side effects., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the safety and efficacy of gevokizumab for the treatment of Behçet's disease uveitis in a prospective, open-label, randomized phase 2 trial., Methods: Behçet's disease patients with new acute ocular exacerbation or at risk of exacerbation received 30 or 60 mg gevokizumab every 4 weeks intravenously or subcutaneously, on top of a stable regimen of immunosuppressives and corticosteroids (≤20 mg/day equivalent prednisolone). Patients withdrew in cases of ocular exacerbation., Results: A total of 21 patients were included (17 acute and 4 at-risk; mean duration of uveitis 45.6 ± 37.4 months). There were no serious adverse events related to gevokizumab. Recorded adverse events were mostly associated with exacerbation of uveitis or its complications. Response was evaluated for 14 acute patients and all showed rapid control of acute ocular exacerbation, mostly within 1 week, without any increase in corticosteroid dosage., Conclusions: Gevokizumab was well tolerated and rapidly controlled acute ocular exacerbations of Behçet's disease uveitis without the need for high-dose corticosteroid.

Behçet disease is a chronic relapsing multisystem inflammatory disorder. Ocular involvement is characterized by a bilateral recurrent non-granulomatous panuveitis and retinal vasculitis. Posterior segment findings vary during the course of the disease, in parallel with the relapsing and remitting intraocular inflammation. Structural alterations occur with increased disease duration. Fluorescein angiography is the gold standard in revealing the extent and severity as well as the leaky and/or occlusive nature of retinal vasculitis. Multimodal imaging using color fundus photography, fluorescein angiography, and optical coherence tomography is essential in visualizing diagnostic features, detecting structural changes, and monitoring disease activity and response to treatment in patients with Behçet uveitis.

Objectives: Behçet's disease (BD) is a systemic inflammatory disorder of unknown etiology, characterised by recurring relapses and remissions. BD manifestations have been thought to be associated with the immunological abnormalities triggered by environmental factors in genetically susceptible individuals. Natural killer (NK) cells are important members of innate immunity with their cytotoxic activity and also cytokine secretions. They have the capacity to induce or dampen immune responses. Different study groups have reported conflicting results about NK cell activity in the BD pathogenesis, however, contribution of NK cells to BD is still unclear., Methods: NK cells from BD patients with uveitis (n=11) as well as age- and gender-matched healthy controls (n=9) were purified and intracytoplasmic cytokine levels of TNF-α, IFN-γ, IL-2, IL-4, IL-10, IL-12 and IL-13 were determined., Results: Increased TNF-α, IFN-γ and IL-2 in relapse period and increased IL-4 as well as a slight increase of IL-10 in remission period were observed., Conclusions: Our results show that NK cells are the contributors of BD pathogenesis with their NK1 profile in relapse periods, and also with their NK2 profile in remission periods, in BD patients with uveitis. An increase in IL-10 observed in remission periods may be linked to the regulatory potential of NK cells in the recurrent nature of BD manifestations.

Uveitis is occasionally encountered in multiple sclerosis (MS) patients. The objective of this report is to investigate whether uveitis has a prognostic impact on the clinical course of MS. Several clinical and demographic features were compared between 41 MS patients with uveitis and 100 randomly selected MS patients without uveitis. While there were no significant differences by means of gender, age of MS onset, oligoclonal band positivity and disease duration, EDSS and progression index (PI) scores of MS patients with uveitis were significantly lower than those without uveitis (p = 0.004 and <0.001, respectively). Our results suggest that uveitis might be used as a good prognostic factor., (© The Author(s), 2015.)

Optical coherence tomography (OCT) is a non-contact noninvasive technique that allows in vivo imaging of the retina, choroid, optic nerve head, retinal nerve fiber layer, and the anterior structures of the eye. It was introduced into clinical practice two decades ago. Advances in OCT technology have been achieved by searching ultra-high-resolution OCT, adaptive optics OCT, eye-tracking OCT, and changes in signal detection technique from time-domain (TD) to spectral-domain (SD) detection. Today, SD OCT has become a part of routine uveitis practice. Apart from its diagnostic value in uveitis, OCT has enabled objective assessment of treatment response and provided predictive value for visual recovery and prognosis of uveitic entities. It is the standard diagnostic technique in the detection, monitoring of treatment, and determination of prognosis in uveitic macular edema as well as other inflammatory macular pathologies, including epiretinal membrane formation, vitreomacular traction, foveal atrophy, and lamellar/full-thickness macular holes. OCT has also shed light on the pathophysiology of several posterior uveitic entities. SD OCT has enabled visualization of four lines in the sensory retina which represent the external limiting membrane, the photoreceptor inner and outer segment junction, the photoreceptor outer segment and the retina pigment epithelium junction, and the retina pigment epithelium-choriocapillaris complex. Thus, we have gained substantial information about the pathologic and structural changes in uveitic conditions with primary or secondary outer retinal involvement. SD OCT has also provided invaluable information on the inner retinal and the vitreoretinal interface changes in uveitic conditions. With the introduction of enhanced depth imaging, visualization of the choroid and choriocapillaries has become possible. Therefore, OCT has become an indispensible ancillary test in the diagnosis and management of inflammatory diseases involving the retina and/or the choroid. As OCT technology continues to develop further it will provide new insights into the retinal and choroidal structure and the pathogenesis of posterior uveitic entities.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease and the most common systemic association of uveitis in children. JIA is subdivided into seven clinically more homogeneous subtypes, using the International League of Associations for Rheumatology (ILAR) classification system: systemic arthritis, oligoarthritis, rheumatoid factor (RF)-negative polyarthritis, RF-positive polyarthritis, psoriatic arthritis, enthesitis-related arthritis, and undifferentiated arthritis. Uveitis is very rare in patients with systemic onset JIA and in patients with juvenile-onset rheumatoid arthritis. Patients with early-onset antinuclear antibody (ANA)-positive oligoarticular JIA have the highest risk of developing chronic iridocyclitis. Ocular involvement in enthesitis-related arthritis is characterized by recurrent acute symptomatic iridocyclitis. The diagnosis and differential diagnosis of JIA are based on history, physical examination, and laboratory investigations, including complete blood count, acute-phase reactants, ANA, RF, HLA-B27, and musculoskeletal imaging studies. Recent studies have revealed distinct gene expression profiles that may be useful in the diagnosis, classification, and follow-up of JIA patients.

Ocular involvement in Behçet disease (BD) is characterized by recurrent inflammatory attacks and spontaneous resolution of acute inflammatory signs. Both frequency and severity of uveitis attacks determine the magnitude of irreversible damage to intraocular structures and long-term visual prognosis. Recurrent attacks of occlusive retinal vasculitis lead to vision-threatening complications such as cystoid macular edema, retinal neovascularization, optic atrophy and retinal atrophy. This manuscript updates about the role of various drugs in the management of BD, discussing corticosteroids, disease modifying immunosuppressive drugs, and finally biologicals (anti-TNF-blocking agents and alpha interferon) which seem to be superior compared to all other available drugs in preventing loss of vision. Also recent findings from new biologicals will be summarized, and especially the role of these drugs in children will be discussed in detail. The authors suggest that at least moderate to severe retinal involvement should become treated with biologicals whenever available.

Abstract Juvenile idiopathic arthritis-associated uveitis (JIAU) accounts for a sizable proportion of uveitis cases in children and is an important cause of ocular morbidity in uveitis patients in this age group. The authors present the results of a survey conducted to obtain a better understanding of the current views and practices of ophthalmologists involved in the care of children with JIAU. A detailed questionnaire consisting of 54 questions addressing epidemiology, diagnosis, and therapy of JIAU was distributed to 67 uveitis specialists. The responses from 37 completed questionnaires were tabulated for this report. While the experts often agreed on aspects of the epidemiologic and clinical features of JIAU and its complications, considerable diversity of responses was noted-particularly with regard to practice patterns. Regarding diagnostics and disease monitoring, all experts favored ANA testing, whereas two-thirds also suggested HLA-B27 typing. Laser flare photometry was available to and routinely used by almost one-third of the experts. Optical coherence tomography (OCT) was used by more than half. The survey revealed an overall consensus on therapeutic strategies, including the use of both conventional immunosuppressive and biologic agents. Methotrexate was the initial choice for immunosuppression by most respondents. Most would add an anti-TNF-alpha agent following failure of traditional immunosuppressive therapy, and adalimumab was favored by almost half of the experts. Questions addressing the management of individual situations, such as the treatment of macular edema and perioperative management, revealed considerable differences in therapeutic approaches. The results of this survey support the development of international guidelines for the management of JIAU.

Purpose: To determine the efficacy and safety of different doses of secukinumab, a fully human monoclonal antibody for targeted interleukin-17A blockade, in patients with noninfectious uveitis., Design: Three multicenter, randomized, double-masked, placebo-controlled, dose-ranging phase III studies: SHIELD, INSURE, and ENDURE., Participants: A total of 118 patients with Behçet's uveitis (SHIELD study); 31 patients with active, noninfectious, non-Behçet's uveitis (INSURE study); and 125 patients with quiescent, noninfectious, non-Behçet's uveitis (ENDURE study) were enrolled., Methods: After an initial subcutaneous (s.c.) loading phase in each treatment arm, patients received s.c. maintenance therapy with secukinumab 300 mg every 2 weeks (q2w), secukinumab 300 mg monthly (q4w), or placebo in the SHIELD study; secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the INSURE study; or secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the ENDURE study., Main Outcome Measures: Reduction of uveitis recurrence or vitreous haze score during withdrawal of concomitant immunosuppressive medication (ISM). Other end points included best-corrected visual acuity, ISM use (expressed as a standardized ISM score), and safety outcomes., Results: After completion or early termination of each trial, there were no statistically significant differences in uveitis recurrence between the secukinumab treatment groups and placebo groups in any study. Secukinumab was associated with a significant reduction in mean total post-baseline ISM score (P = 0.019; 300 mg q4w vs. placebo) in the SHIELD study. Likewise, secukinumab was associated with a greater median reduction in ISM score versus placebo in the INSURE study, although no statistical analysis of the difference was conducted because of the small sample size. Overall, there was no loss in visual acuity reported in any treatment group during follow-up in all 3 studies. According to descriptive safety statistics, the frequencies of ocular and nonocular adverse events seemed to be slightly higher among secukinumab groups versus placebo across the 3 studies., Conclusions: The primary efficacy end points of the 3 studies were not met. The secondary efficacy data from these studies suggest a beneficial effect of secukinumab in reducing the use of concomitant ISM., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare Behçet uveitis patients who presented in the 1990s and 2000s., Methods: Records of 170 patients seen in 1990-1994 and 258 patients seen in 2000-2004 were reviewed. Presenting features were analyzed in the whole cohort. Uveitis attacks, vision, complications, and immunomodulatory treatment (IMT) were compared in patients with 3-year follow-up., Results: Posterior segment involvement was less common, visual acuity was better, and more patients received IMT before referral in the 2000s. Follow-up revealed no significant difference in number of uveitis attacks in the first 3 years. Less eyes lost useful vision, no patient became legally blind, and fewer severe ocular complications occurred in the 2000s. IMT was started within 3 months in more patients and interferon alfa-2a was used only in the latter study period., Conclusions: The findings suggest a milder disease at referral, lower rate of severe complications, and a better 3-year visual outcome in patients who presented in the early 2000s.

Any patient with a diagnosis of central serous chorioretinopathy (CSCR) should be questioned to determine any recent corticosteroid use, as the poor visual outcome may be due to unrecognized corticosteroid use. Atypical forms of CSCR may be misdiagnosed as an inflammatory serous retinal detachment, mainly Vogt-Koyanagi-Harada disease. CSCR that develops in association with preexisting uveitis could be a challenging diagnosis as it might be misinterpreted as a worsening of the primary inflammatory condition. Failure to differentiate CSCR from retinal or choroidal inflammatory diseases may result in inappropriate use of corticosteroids, leading to exacerbation of the condition and permanent visual loss. Discontinuation of corticosteroids should be the first step in the treatment of CSCR associated with corticosteroid therapy, and the use of immunosuppressive or immunomodulatory drugs may be required to control systemic or ocular inflammatory disease. The prognosis is usually favorable, but persistent visual loss may occur.

Aqueous flare and cells are the two inflammatory parameters of anterior chamber inflammation resulting from disruption of the blood-ocular barriers. When examined with the slit lamp, measurement of intraocular inflammation remains subjective with considerable intra- and interobserver variations. Laser flare cell photometry is an objective quantitative method that enables accurate measurement of these parameters with very high reproducibility. Laser flare photometry allows detection of subclinical alterations in the blood-ocular barriers, identifying subtle pathological changes that could not have been recorded otherwise. With the use of this method, it has been possible to compare the effect of different surgical techniques, surgical adjuncts, and anti-inflammatory medications on intraocular inflammation. Clinical studies of uveitis patients have shown that flare measurements by laser flare photometry allowed precise monitoring of well-defined uveitic entities and prediction of disease relapse. Relationships of laser flare photometry values with complications of uveitis and visual loss further indicate that flare measurement by laser flare photometry should be included in the routine follow-up of patients with uveitis.

Tumor necrosis factor-alpha (TNF-alpha) antagonists have been successfully used in refractory cases of pediatric uveitis.(1-7) We report our experience with the monoclonal anti-TNF-alpha antibody infliximab in the treatment of uveitis in 20 children. Twenty children with noninfectious uveitis were treated with infliximab as an initial line of immunomodulatory therapy (4 children) or for uncontrolled intraocular inflammation despite aggressive immunosuppressive therapy (16 children). Intraocular inflammation was controlled in the short term in all children; resistance developed in 4 children after long-term therapy.

Purpose: To analyze the referral patterns and clinical features of uveitis in tertiary eye care centers in Turkey., Methods: Uveitis services of eight university clinics collected data on uveitis patients who presented during 2004. Data were collected on a form including a questionnaire on socio-demographic and clinical features which were documented at presentation., Results: A total of 761 patients (1187 eyes) with a mean age of 35.5 years were included in the study. Male to female ratio was 1.04:1. The majority of patients (89.6%) were from an urban population, 53% were referrals and 43% had had uveitis for more than one year. The most common type of uveitis was anterior uveitis (52.5%) followed by panuveitis (28.1%), posterior uveitis (12.7%) and intermediate uveitis (6.7%). In 56.8% of patients an etiological classification was established. The most common etiology was Behcet's disease (32.1%), followed by Fuchs' heterochromic iridocyclitis (5.1%) and ocular toxoplasmosis (4.7%). Among 48 pediatric patients uveitis associated with juvenile idiopathic arthritis and ocular toxoplasmosis both having equal frequencies (12.5%) were the most common diagnosis. These were followed by Behcet's disease with juvenile-onset (10.4%). At the time of presentation, 6.25% of the patients were legally blind (having visual acuity less than 0.1 in the better seeing eye)., Conclusion: Compared to the uveitis series reported from other countries, Behcet uveitis was the leading cause of uveitis in this series. Uveitis associated with juvenile idiopathic arthritis and ocular toxoplasmosis were the most common cause of uveitis in childhood. On the other hand, entities like acquired immunodeficiency syndrome-related uveitis, presumed ocular histoplasmosis and Birdshot retinochoroidopathy were rare.

The purpose of this study was to investigate the referral patterns, demographic and clinical features, and visual prognosis of patients with sarcoid uveitis seen at 2 tertiary eye care centers in Turkey. A retrospective study was made of 44 patients with uveitis associated with biopsy-confirmed or presumed sarcoidosis. Thirty-four patients (77%) were female and 10 (23%) were male. The mean age at onset of uveitis was 39.8 years. Twenty-seven patients (61%) were referred without a diagnosis of sarcoidosis and 17 (39%) patients were referred with a diagnosis of systemic sarcoidosis. The duration of uveitis prior to referral was 2-15 years in 52% of the patients in the former group. At presentation, 37 patients (84%) had bilateral and 7 patients (16%) had unilateral uveitis, and 17 patients (39%) had only anterior uveitis. The most common ocular findings were granulomatous keratic precipitates, persistent posterior synechiae, and snowball vitreous opacities. Kaplan-Meier survival analysis estimated the risk of recurrence as 30% at 6 months and 61% at 5 years. New complications developed in 18 patients. Potential visual acuity was better than 0.4 in 80% of eyes. The estimated risk of losing potential visual acuity by at least 2 lines was 7% at 6 months and 43% at 5 years. None of the eyes lost useful vision (> 0.1) under the authors' care. The referral patterns suggest underrecognition of sarcoidosis as a cause of uveitis in Turkey. The demographic and clinical features of these patients were mostly similar to those reported from other countries, suggesting that the diagnosis may not be difficult in Turkish patients but requires an increased awareness of the disease in this population.

Objective: To investigate the effect of infliximab on the frequency of uveitis attacks and the visual prognosis in male patients with Behçet's disease in whom uveitis was resistant to combination therapy with corticosteroids, azathioprine, and cyclosporine., Methods: The study group comprised patients who were receiving combination therapy but experienced at least 2 attacks of posterior uveitis/panuveitis or retinal vasculitis during the 6-month period prior to enrollment. Infliximab infusions (5 mg/kg) were administered at weeks 0, 2, 6, and 14. Weeks 0-22 were defined as the infusion period, and weeks 23-54 were defined as the observation period. Patients continued to receive azathioprine and corticosteroids, but cyclosporine was discontinued after the screening visit. The primary outcome measures were the absence of uveitis attacks during the infusion period (remission), and the absence of uveitis attacks throughout the study period (sustained remission)., Results: Thirteen patients were enrolled in the study. Thirty-two uveitis attacks involving the posterior segment occurred during the previous-treatment period. During the infusion period, 4 patients (30.8%) remained attack-free, and 9 patients had a total of 13 uveitis attacks. Ten of these attacks (76.9%) occurred at either week 14 or week 22. One of 13 patients fulfilled the definition of sustained remission, and the remaining 12 patients had a total of 36 uveitis attacks during the observation period. The mean number of uveitis attacks and daily corticosteroid doses were significantly lower during the infusion period than during the previous-treatment period or the observation period. Although potential visual acuity was regained following infliximab infusion, this beneficial effect was not preserved until week 54. None of the patients experienced a serious adverse event., Conclusion: The results of this trial suggest that infliximab is effective in suppressing the occurrence of uveitis attacks, has a corticosteroid-sparing effect, and has favorable implications for the visual prognosis of patients with resistant Behçet's uveitis.

Purpose: We aimed to describe the demographic and clinical features, ocular manifestations, complications, visual prognosis, and treatment in a large population of Turkish patients with Behçet uveitis. We also aimed to compare visual prognosis between male and female sex and between patients who presented before and after 1990., Design: Observational case series., Methods: A retrospective study of 880 consecutive patients (1,567 eyes) with Behçet uveitis seen at the Uveitis Service, Department of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, from 1980 to 1998. All patients met the classification criteria of the International Study Group for Behçet's Disease. Information on the patient's sex, age at onset of uveitis, ocular features, ocular complications, visual acuity, and systemic treatment was collected., Results: Five hundred ninety-nine patients (68%) were male and 281 (32%) were female. The mean age at onset of uveitis was 28.5 years in male and 30 years in female patients. Ocular involvement was bilateral in 78.1% and unilateral in 21.9% of the patients. Panuveitis was the most common form in both sexes. Fundus lesions as well as sight-threatening complications were more common in males. At the beginning of the follow-up, potential visual acuity was 0.1 or less in 30.9% of eyes in males and 24.2% of eyes in females. Kaplan-Meier survival analysis estimated the risks of losing useful vision (>0.1) at 5 and 10 years for males and females as 21% vs 10% and 30% vs 17%, respectively. Male patients who presented in the 1990s had a significantly lower risk of losing vision compared with male patients who presented in the 1980s., Conclusion: Behçet uveitis starts frequently around the end of the third decade and has a male predominance. The disease is more severe and the risk of losing useful vision is higher in males than in females. However, this risk has been significantly reduced in the 1990s.

Purpose: To describe the demographic and clinical features, complications, treatment, and visual results in patients with childhood-onset Behçet uveitis., Design: Observational case series., Methods: A retrospective study was made of 36 consecutive patients with Behçet disease seen at the Uveitis Service, Department of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, between January 1975 and January 2002. Inclusion criteria were fulfillment of the classification criteria of the International Study Group for Behçet Disease and onset of uveitis at 16 years of age or younger. The medical records of 36 patients with childhood-onset Behçet uveitis were reviewed. The main outcome measures were sex, age at onset of uveitis, the initial symptom of Behçet disease, clinical ocular features, ocular complications, systemic treatment, complications of treatment, and final visual acuity., Results: Twenty-five patients were male, 11 were female. Mean age at onset of uveitis was 13.6 years. The initial symptom was oral ulcer in 63.8% of the patients. The majority of patients (83.3%) had bilateral involvement. Panuveitis was the most common form (86.2%). Retinal vasculitis and retinitis were the most common ocular findings seen in 83.3% and 68.2% of the involved eyes, respectively. Cataract, maculopathy, and optic atrophy were the most common complications seen in 46.9%, 45.4%, and 39.4% of the involved eyes, respectively. Immunosuppressive therapy was administered to 75% of the patients. Response to treatment was variable. The most common complications of systemic treatment were associated with corticosteroid therapy. Final visual acuity was worse than 0.1 in 22.7% of the involved eyes., Conclusions: Childhood-onset Behçet uveitis was more common among males. Bilateral panuveitis with retinal vasculitis and retinitis was the most common form of ocular involvement, similar to the adult patient. The treatment is challenging, as the use oral corticosteroids is associated with significant complications and the response to conventional immunosuppressive therapy is variable.