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Background: Posner Schlossman syndrome is a well-defined uveitis entity that is characterised by relapsing remitting unilateral anterior uveitis with markedly raised intraocular pressure. The aim of this study was to determine the risk factors for progression in patients with Posner Schlossman syndrome., Methods: Ninety-eight patients were enrolled in a retrospective case series. Progression was defined as a composite endpoint of any of development of permanent glaucoma (in patients with no evidence of glaucomatous loss on presentation), corneal failure, or chronic inflammation. Relapse was defined as a resolving episode of inflammation not meeting the criteria for progression., Results: Seventy seven percent of patients relapsed on average each 2.2 years. Forty percent of patients progressed. On univariate analysis, increased age at enrolment, immunocompromise at enrolment, the presence of glaucomatous optic neuropathy at enrolment, the performance of an anterior chamber tap and a positive anterior chamber tap were all associated with increased risk of progression. On multivariate analysis, age at enrolment, immunocompromise at enrolment, the performance of an anterior chamber tap, and the presence of glaucomatous optic neuropathy at enrolment were independently associated with increased risk of disease progression., Conclusions: Posner Schlossman syndrome is not a benign uveitis entity and risk of both relapse and progression are high. Older patients, immunocompromised patients, patients with glaucomatous optic neuropathy at enrolment and those with a positive anterior chamber tap are all at increased risk of progression., (© 2023 Royal Australian and New Zealand College of Ophthalmologists.)

The uveitides are a collection of over 30 diseases characterised by intraocular inflammation. Previous work demonstrated that the agreement among uveitis experts on diagnosis was modest at best with some pairs of experts having chance alone agreement on selected diseases. The Standardisation of Uveitis Nomenclature (SUN) is a17‐year collaboration among experts in uveitis, ocular image grading, informatics, and machine learning to improve clinical and translational uveitis research. The SUN "Developing Classification Criteria for the Uveitides" project used a rigorous, multi‐phase approach to develop classification criteria for 25 of the most common uveitic diseases. The project's phases were: (1) informatics; (2) case collection; (3) case selection; (4) machine learning; and (5) consensus review and publication. The results were classification criteria with a high degree of accuracy (93.3%–99.3% depending on anatomic class of the uveitis), the goal of which is to form the basis for future uveitis research. [ABSTRACT FROM AUTHOR]

New tumor therapies like immune checkpoint inhibitors and small molecule inhibitors of MEK and BRAF have increased the patient's survival rate but can be burdened with severe side-effects including uveitis. Here, we show the spectrum, treatment, and outcome of uveitis types induced by tumor treatment. In this retrospective study, we have included 54 patients from different centers who were developing uveitis under tumor therapy. A 16-item questionnaire was analyzed for type, treatment, and outcome of uveitis and type of tumor treatment, which we have correlated here. Irrespective of the tumor treatment, most patients developed anterior uveitis. All patients received corticosteroids and some additional immunosuppressive treatments. Cessation of tumor therapy was necessary only in a minority of cases. Ocular autoimmunity should be differentiated from toxic effects of cancer treatment and timely recognized since it can be generally well controlled by anti-inflammatory treatment, preserving the patient's vision without cessation of the tumor treatment. [ABSTRACT FROM AUTHOR]

Background: Inflammatory adverse events following COVID-19 vaccination are being reported amidst the growing concerns regarding vaccine's immunogenicity and safety, especially in patients with pre-existing inflammatory conditions. Methods: Multinational case series of patients diagnosed with an ocular inflammatory event within 14 days following COVID-19 vaccination collected from 40 centres over a 3 month period in 2021. Results: Seventy patients presented with ocular inflammatory events within 14 days following COVID-19 vaccination. The mean age was 51 years (range, 19–84 years). The most common events were anterior uveitis (n = 41, 58.6%), followed by posterior uveitis (n = 9, 12.9%) and scleritis (n = 7, 10.0%). The mean time to event was 5 days and 6 days (range, 1–14 days) after the first and second dose of vaccine, respectively. Among all patients, 36 (54.1%) had a previous history of ocular inflammatory event. Most patients (n = 48, 68.6%) were managed with topical corticosteroids. Final vision was not affected in 65 (92.9%), whereas 2 (2.9%) and 3 (4.3%) had reduction in visual acuity reduced by ≤3 lines and > 3 lines, respectively. Reported complications included nummular corneal lesions (n = 1, 1.4%), cystoid macular oedema (n = 2, 2.9%) and macular scarring (n = 2, 2.9%). Conclusion: Ocular inflammatory events may occur after COVID-19 vaccination. The findings are based on a temporal association that does not prove causality. Even in the possibility of a causal association, most of the events were mild and had a good visual outcome. [ABSTRACT FROM AUTHOR]

There has been steady progress in understanding the pathogenesis, clinical features, and effective treatment of acute anterior uveitis (AU) over the past 5 years. Large gene wide association studies have confirmed that AU is a polygenic disease, with overlaps with the seronegative arthropathies and inflammatory bowel diseases, associations that have been repeatedly confirmed in clinical studies. The role of the microbiome in AU has received increased research attention, with recent evidence indicating that human leukocyte antigen B27 (HLA B27) may influence the composition of the gut microbiome in experimental animals. Extensive clinical investigations have confirmed the typical features of acute AU (AAU) and its response to topical, regional and systemic immunosuppressive treatment. Increased understanding of the role of cytokines has resulted in studies confirming the value of anti-cytokine therapy [anti–tumor necrosis factor (anti-TNF) and interleukin 6 (IL-6) therapy] in severe and recurrent cases of AAU, particularly in subjects with an associated spondyloarthopathy (SpA) and in juvenile idiopathic arthritis (JIA)–associated AAU. [ABSTRACT FROM AUTHOR]

Importance Australian‐ and New Zealand‐based, uveitis‐specialized ophthalmologists have produced recommendations for the management of juvenile idiopathic arthritis (JIA)‐type chronic anterior uveitis. Background: Historically, the visual prognosis of JIA‐type chronic anterior uveitis has been poor. New medical advances are likely to improve outcomes, but recently published guidelines are tailored for ophthalmic care in Europe and the United States. Design This work involved a consensus survey and a panel meeting. Participants: The Australian and New Zealand JIA‐Uveitis Working Group (29 ophthalmologists) participated in the work. Methods: The Delphi technique was used to achieve consensus. Main Outcome Measures: This work yielded consensus statements. Results: The Working Group achieved consensus around 18 statements related to clinical evaluation, use of topical and regional corticosteroids, use of systemic corticosteroid and non‐corticosteroid immunomodulatory drugs, and management of secondary cataract and glaucoma in childhood JIA‐type uveitis. Conclusions and Relevance: Recommendations of the Australian and New Zealand JIA‐Uveitis Working Group provide current and regionally applicable advice for managing chronic anterior uveitis in children with JIA. [ABSTRACT FROM AUTHOR]

Purpose: To examine disease profile of tubercular uveitis (TBU) in Paediatric population. Methods: Among 945 patients of the retrospective multinational study by the Collaborative Ocular Tuberculosis Study (COTS)-1, 29 Paediatric patients diagnosed with TBU were analyzed. Results: Mean age of disease presentation was 12.8 (range 4–18 years), with predominance of males (n = 14/20; 70.0%) and Asian ethnicity (n = 25/29; 86.2%). Posterior uveitis (n = 14/28; 50%) was the most frequent uveitis phenotype, with choroidal involvement occurring in 64.7% (n = 11/17). Incidence of optic disc edema and macular edema was higher in children (n = 8/18; 44.4% and n = 5/18; 27.8%, respectively) than in adults (n = 160/942; 16.9% and n = 135/942; 14.3%, respectively). Comparison of optic disc edema between subgroups showed a significant difference (P =.006). All patients received oral corticosteroids, most of them with antitubercular therapy. Treatment failure developed in 4.8% (n = 1/21). Conclusions: Children have a more severe inflammatory response to the disease, and an intensive anti-inflammatory therapeutic regimen is required to achieve a positive treatment outcome. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a major infection that can affect the eye as first and sole presentation without features of systemic disease. Controversy exists regarding diagnosis and management of tubercular uveitis (TBU), further compounded by regional variations in disease expression. Purpose: Collaborative Ocular Tuberculosis Study (COTS)-1 aims to address knowledge deficits through collaboration amongst uveitis specialists across the globe by sharing the data of patients with TBU presented at participating centers from January 2004 to December 2014. Methods: Data collection was facilitated by a novel method of real-time encrypted web-based data entry allowing regular updates as new data and recommendations become available. Results: Information on clinical features, investigation findings, management, and treatment outcomes were reviewed to get an idea about real world scenario. Conclusion: The current review aims to focus on methodology and briefing of published reports from COTS group in COTS-1 study to highlight key messages from this large data. [ABSTRACT FROM AUTHOR]

Importance: Inflammatory‐mediated cystoid macular oedema (CMO) is the most common inflammatory‐mediated threat to vision in non‐infectious uveitis (NIU). Corticosteroid therapy is the cornerstone to the management of CMO in NIU. Sustained‐release dexamethasone (DEX) implant devices provide localized therapy. Background: The authors present a series documenting the efficacy of DEX implants for NIU in an Australian cohort. Design: A single centre, retrospective case series patients receiving DEX implants for NIU from 2012 to 2018 in a New South Wales tertiary eye hospital. Participants: Twenty eyes of 17 patients receiving DEX implants for confirmed cases of NIU of varying aetiologies. Methods: Cases from March 2012 and March 2018 were retrospectively selected with follow‐up assessment data recorded and analysed. All patients were seen at 1, 2 and 4 weeks post implant, then monthly. Minimum duration of follow‐up was 32 weeks. Main Outcome Measures: The primary outcome was change in central retinal thickness (CRT) of >20% at two consecutive visits. Secondary outcomes included change in best‐corrected visual acuity (BCVA), intraocular pressure and medication regimens. Results: Ninety‐five percent of patients achieved significant CRT reduction at 4, 8 and 16 weeks (P <.01). Sixty‐one percent demonstrated improved BCVA at week 8 (P <.05). Ninety percent of patients taking systemic corticosteroid therapy at commencement reduced their dose to below 7.5 mg/day. Adverse event frequency was low. Conclusions and Relevance: In keeping with larger studies, the authors suggest that DEX implants may effectively control uveitis refractory to other therapy, while improving BCVA and CRT. In addition, DEX usage has demonstrably reduced systemic steroid burden within the observed cohort. [ABSTRACT FROM AUTHOR]

The total number of patients diagnosed with uveitis during the study period was 1165, consisting of 735 with anterior uveitis (63%), 234 with posterior uveitis (20%), 109 with panuveitis (9%), and 87 with intermediate uveitis (8%). Patients with uveitis most commonly had a systemic association (679 patients; 58%), followed by no identifiable association (389 patients; 33%) and an ocular syndrome (97 patients; 8%). Our study was consistent with other studies in that after anterior uveitis, the next most common type of uveitis was posterior uveitis followed by panuveitis and least frequent, intermediate uveitis. By describing and analyzing the prevalence of SpA in patients with anterior uveitis, investigators found that among the 798 patients with anterior uveitis, 50% of patients were diagnosed with axial and 18% with peripheral SpA.[15]. [Extracted from the article]

Importance: Paediatric uveitis is a severe sight‐threatening uveitis due to disease progression and treatment failure. Biological agents are a promising new treatment. This study provides real‐world data on their use from Sydney, Australia. Background: Traditionally corticosteroids and non‐biological immunosuppressive agents were used to treat paediatric uveitis, often with poor outcomes. Design: Retrospective, chart review over an 8‐year period at a tertiary referral eye hospital. Participants: A total of 27 paediatric uveitis patients treated with biological agents. Methods: Chart review of demographic data and treatment outcomes. Main Outcome Measures: Treatment efficacy (corticosteroid‐sparing effect, topical steroid cessation/reduction, reduction in systemic‐steroid sparing agents, change in intraocular inflammation, visual acuity and central macular thickness); treatment failure; and adverse events. Data were collected at biological initiation, 6 weeks, 6 months and 12 months. Results: Biological therapy over 1 year was effective with prednisolone dose reduced to <5 mg/day in five of six patients (83%), number of systemic steroid‐sparing agents was reduced to ≤1 in two of four patients (50%) and cessation of topical steroid achieved in 12/41 of eyes (29%). Improvement of anterior chamber cells by two grades occurred in 20/25 eyes (80%), improvement of logMAR to ≤0.3 occurred in 12/18 eyes (67%) and macular oedema decreased in 4/5 eyes (80%). Treatment failure occurred in six eyes (13.01%) and five patients (18.5%) developed an adverse reaction. Conclusions and Relevance: Biological therapy was effective in paediatric patients with uveitis. Intraocular inflammation improved with maintained visual acuity, systemic corticosteroid dose decreased and there was a low frequency of adverse events. [ABSTRACT FROM AUTHOR]

Acute anterior uveitis (AAU) is the commonest type of uveitis and HLA-B27 AAU is the most frequently recognized type of acute anterior uveitis and anterior uveitis overall. Recent evidence indicates that acute anterior uveitis is a heterogenous disease, is polygenic and is frequently associated with the spondyloarthropathies (SpA). Studies of patients with AAU and animal models of disease indicate a role for innate immunity, the IL-23 cytokine pathway and exogenous factors, in the pathogenesis of both SpA and acute anterior uveitis. Recently described genetic associations cluster around immunologic pathways, including the IL-17 and IL-23 pathways, antigen processing and presentation, and lymphocyte development and activation. Patients with ankylosing spondylitis (AS) and AAU share other genetic markers, such as ERAP-1, which show strong evidence of gene–gene interaction and point to new mechanisms of disease pathogenesis. These observations have major implications for understanding the pathogenesis of HLA-B27 diseases, such as AAU, and may lead to the development of more specific therapy for AAU. Received 6 January 2016; revised 6 February 2016; accepted 18 February 2016; published online 31 May 2016 [ABSTRACT FROM PUBLISHER]

Purpose: To evaluate the patterns of acute and recurrent acute anterior uveitis (AAU) in a metropolitan tertiary referral center. Methods: A retrospective medical record review of a total of 241 patients with AAU presenting to Sydney Eye Hospital between June 2009 and June 2011 was performed. Patients who underwent typing for the HLA-B27 antigen were included in this study. Ninety-five patients were HLA-B27-positive and 146 were HLA-B27-negative. Results: Seronegative spondyloarthropathy ( n = 26, 11%) was the most common systemic disease association in the HLA-B27 positive patients. Posterior synechiae was the most common complication. Complications of cataract, ocular hypertension, secondary glaucoma, and cystoid macular edema were more common in HLA-B27-negative patients with a recurrent disease course. The most common newly diagnosed systemic disease was sarcoid ( n = 7), followed by ankylosing spondylitis ( n = 4), tuberculosis ( n = 2), and syphilis ( n = 2). Conclusions: This case series emphasizes the key role of the ophthalmologist in identifying previously undiagnosed systemic diseases. It also highlights the importance of differentiating latent from active infection, particularly tuberculosis and syphilis, through directed investigations to assess the risk to the patient of reactivation with systemic treatment. This study adds further evidence to our understanding that HLA-B27-negative patients have a poor visual prognosis. [ABSTRACT FROM AUTHOR]

A bstract Uveitis involves acute, recurrent or chronic inflammation of the uvea, and occurs when the normal state of ocular immune privilege has broken down. Accumulating evidence implicates the role of microbial triggers in the development of various forms of immune-mediated uveitis in addition to its causative role in infectious uveitis. Toll-like receptors (TLRs) are the most important pattern-recognition receptors of the innate immune system that recognize pathogen-associated molecular patterns of microbes. Activation of TLRs by pathogen-associated molecular patterns leads to the induction of an inflammatory cascade and activation of both innate and adaptive arms of the immune response. TLRs have been implicated in the pathogenesis of various inflammatory diseases, including uveitis. This review provides an update on recent progress in TLR research and uveitis, specifically summarizing new evidence for the role of TLRs in anterior uveitis. There have been important observations from studies involving human ocular tissue, clinical uveitis and from experimental animal models of uveitis, such as endotoxin-induced uveitis. The 'Toll rush' has certainly gained momentum, and future advances in this field have the potential for selectively targeting the TLR pathway and ultimately translating into better therapies for patients with sight-threatening uveitis. [ABSTRACT FROM AUTHOR]

The pathogenesis of human leukocyte antigen (HLA)-B27-associated diseases such as acute anterior uveitis (AAU) and ankylosing spondylitis (AS) remains poorly understood, though Gram-negative bacteria and subclinical bowel inflammation are strongly implicated. Accumulating evidence from animal models and clinical studies supports several hypotheses, including HLA-B27-dependent dysbiosis, altered intestinal permeability, and molecular mimicry. However, the existing literature is hampered by inadequate studies designed to establish causation or uncover the role of viruses and fungi. Moreover, the unique disease model afforded by AAU to study the gut microbiota has been neglected. This review critically evaluates the current literature and prevailing hypotheses on the link between the gut microbiota and HLA-B27-associated disease. We propose a new potential role for HLA-B27-driven altered antibody responses to gut microbiota in disease pathogenesis and outline recommendations for future well-controlled human studies, focusing on AAU. Emerging human and animal studies of human leukocyte antigen (HLA)-B27-associated diseases have led to the development of several hypotheses for how HLA-B27 can influence the composition and function of the gut microbiota to mediate its disease associations. Shared metabolic dysregulations, despite the heterogenous taxa signatures observed, may underpin how the microbiome contributes to HLA-B27-associated disease, but it remains unclear if dysbiosis is directly driving disease. HLA-B27 transgenic rats that develop a spontaneous spondyloarthropathy-like illness do not develop disease when raised in a germ-free environment, but mono-association with Phocaeicola vulgatus is sufficient to induce disease. Progress in the field has been relatively slow due to the lack of integration between human studies and available animal models of disease, and increased attention should be paid to the microbiome in HLA-B27-associated acute anterior uveitis. [ABSTRACT FROM AUTHOR]

Acute anterior uveitis (AAU) is the most common form of uveitis, accounting for approximately 90% of all cases. Half of all cases of AAU are HLA-B27 positive. The disease is typically acute in onset, unilateral, nongranulomatous inflammation involving the iris and ciliary body, with a tendency to recurrent attacks. Approximately 50% of all patients with HLA-B27 AAU develop an associated seronegative arthritis (SNA), while approximately 25% of the patients initially diagnosed with HLA-B27 SNA develop AAU. Environmental factors play a critical role in the pathogenesis of AAU; in particular, bacterial triggers have been strongly implicated in the development of this disease. Topical corticosteroids and cycloplegic agents remain the cornerstones of treatment for AAU. Salazopirine and methotrexate are effective in decreasing recurrent attacks. Biological agents such as anti-TNF and anti-CD20 therapy may be effective in refractory severe AU but are rarely required. [ABSTRACT FROM AUTHOR]

The pathogenesis of acute and recurrent anterior uveitis is poorly understood. Here, recent evidence is presented for the hypothesis that this disease may be associated with activation of receptors of the innate immune system, such as Toll-like receptors, by pathogen associated molecule patterns, such as lipopolysaccharide, derived from triggering gram negative bacteria. Acute anterior uveitis results in ocular tissue damage and the release of endogenous molecules (damage associated molecular patterns), such as heat shock proteins and S100 proteins that can also activate Toll-like receptors and thus perpetuate or reactivate intraocular inflammation. [ABSTRACT FROM AUTHOR]

The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. The COTS consensus guidelines were generated based on the evidence from published literature, specialists' opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis. [ABSTRACT FROM AUTHOR]