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Necrotizing scleritis is the most destructive and vision-threatening form of scleritis. Necrotizing scleritis can occur in systemic autoimmune disorders and systemic vasculitis, as well as following microbial infection. Rheumatoid arthritis and granulomatosis with polyangiitis remain the commonest identifiable systemic diseases associated with necrotising scleritis. Pseudomonas species is the most common organism causing infectious necrotizing scleritis, with surgery the most common risk factor. Necrotizing scleritis has the highest rates of complications and is more prone to secondary glaucoma and cataract than other phenotypes of scleritis. The differentiation between non-infectious and infectious necrotizing scleritis is not always easy but is critical in the management of necrotizing scleritis. Non-infectious necrotizing scleritis requires aggressive treatment with combination immunosuppressive therapy. Infectious scleritis is often recalcitrant and difficult to control, requiring long-term antimicrobial therapy and surgical debridement with drainage and patch grafting due to deep-seated infection and the avascularity of the sclera. [ABSTRACT FROM AUTHOR]

To report an atypical case of bilateral syphilitic chorioretinitis. A case report. A young male presented with bilateral pigmentary retinal changes along with multifocal chorioretinal lesions along the blood vessels giving a "beaded pearl" appearance. He was a hitherto undiagnosed case of human immunodeficiency virus infection and was diagnosed to have syphilis. He had a favourable visual and anatomical outcome following treatment. Multifocal chorioretinal lesions along blood vessels forming a "beaded pearls" appearance can be a rare and unique presentation of syphilis. [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]

Ocular involvement is a rare manifestation of tuberculosis. Four key issues historically faced by clinicians when diagnosing and treating ocular tuberculosis – diagnostic uncertainty, naturally heterogeneous presentations, limitations of existing laboratory diagnostic tools, and non-uniform treatment guidelines – continue to test today's physicians. Unparalleled scientific and clinical developments over the past century have greatly expanded the knowledge surrounding this challenging ophthalmic condition. Experience with large volumes of cases at tuberculosis-endemic centres has led to recent growth in knowledge and physician experience, perhaps more so in developing countries. Looking forward, the role of diverse new technologies, including artificial intelligence and proteomics, will advance ocular tuberculosis research. Efforts have been made to address the lack of standardized nomenclature, diagnostic uncertainty, and unvalidated, geographically variable treatment guidelines. [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]

Purpose: Tubercular intermediate uveitis (TIU) and panuveitis (TBP) are difficult to manage because of limitations in diagnostic tools and lack of evidence-based treatment guidelines. The Collaborative Ocular Tuberculosis Study (COTS) analyzed treatment regimens and therapeutic outcomes in patients with TIU and TBP. Methods: Multicentre retrospective analysis. Results A total of 138 TIU and 309 TBP patients were included. A total of 382 subjects received antitubercular therapy (ATT) (n = 382/447; 85.4%) and 382 received corticosteroids (n = 382/447; 85.4%). Treatment failure was observed in 78 individuals (n = 78/447; 17.4%), occurring less frequently in patients receiving ATT (n = 66/382; 17.2%) compared to those who did not (n = 12/65; 18.5%). The study did not show any statistically significant therapeutic effect of ATT in patients with TIU and TBP. Conclusion Taking into account the limitations of the retrospective, non-randomized study design, resultant reliance on reported data records, and unequal size of the samples, the current study cannot provide conclusive evidence on the therapeutic benefit of ATT in TIU and TBP. [ABSTRACT FROM AUTHOR]

Purpose: To report the clinical findings, anatomical features, and treatment outcomes in subjects with ocular tuberculosis (OTB) at 24 months in the Collaborative Ocular Tuberculosis Study (COTS)-1. Methods: Of the 945 subjects included in COTS-1, those who completed a 24-month follow-up after completion of treatment were included. The main outcome measure was a number of patients with treatment failure (TF). Results: 228 subjects (120 males; mean age of 42.82 ± 14.73 years) were included. Most common phenotype of uveitis was posterior (n = 81; 35.53%), and panuveitis (n = 76; 33.33%). Fifty-two patients (22.81%) had TF. On univariable analysis, odds of high TF was observed with bilaterality (OR: 3.46, p =.003), vitreous haze (OR: 2.14, p =.018), and use of immunosuppressive therapies (OR: 5.45, p =.003). However, only bilaterality was significant in the multiple regression model (OR: 2.84; p =.02). Conclusions: Majority of subjects (>75%) achieved cure in the COTS-1 at 24-month follow-up. The concept of "cure" may be a valuable clinical endpoint in trials for OTB. [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]

Purpose: To contribute a global description of the spectrum of choroidal involvement in tubercular uveitis (TBU).Methods: Retrospective cohort study of TBU patients with choroidal involvement from 25 centers between January 2004 and December 2014. Medical records of patients with a minimum follow-up of 1 year were reviewed.Results: 245 patients were included. The phenotypic variations included serpiginous-like choroiditis (SLC) (46%), tuberculoma (13.5%), multifocal choroiditis (MFC) (9.4%), ampiginous choroiditis (9%), among others. 219 patients were treated with anti-tubercular therapy (ATT) (n = 219/245, 89.38%), 229 patients with steroids (n = 229/245, 93.47%) and 28 patients with immunosuppressive agents (n = 28/245, 11.42%). Treatment failure was noted in 38 patients (n = 38/245, 15.5%). Patients with SLC and ampiginous choroiditis appeared to have superior outcomes on survival analysis (p = 0.06).Conclusion: This study provides a comprehensive description of choroidal involvement in TBU. Patients with SLC and ampiginous choroiditis may have better clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To standardize a nomenclature system for defining clinical phenotypes, and outcome measures for reporting clinical and research data in patients with ocular tuberculosis (OTB).Methods: Uveitis experts initially administered and further deliberated the survey in an open meeting to determine and propose the preferred nomenclature for terms related to the OTB, terms describing the clinical phenotypes and treatment and reporting outcomes.Results: The group of experts reached a consensus on terming uveitis attributable to tuberculosis (TB) as tubercular uveitis. The working group introduced a SUN-compatible nomenclature that also defines disease "remission" and "cure", both of which are relevant for reporting treatment outcomes.Conclusion: A consensus nomenclature system has been adopted by a large group of international uveitis experts for OTB. The working group recommends the use of standardized nomenclature to prevent ambiguity in communication and to achieve the goal of spreading awareness of this blinding uveitis entity. [ABSTRACT FROM AUTHOR]

Purpose: To compare clinical features, complications, and outcomes of CMV retinitis in non-HIV immunocompromised patients with HIV infected patients.Methods: A retrospective study of patients diagnosed with CMV retinitis with or without HIV infection was performed. Results: Thirty-five eyes from 27 patients (median follow up 26 months) were included. Six patients had HIV infection, the others were immunocompromised from a range of causes. The baseline visual acuity (VA) was similar in the two groups. Prevalence of different types of retinitis (fulminant/indolent) was similar in the two groups. Presence of vitreous haze ≥1+ (p = .041), presence of arteritis, (p = .016) and widespread vascular occlusion (p = .003) were more common in the non-HIV group.Conclusion: CMV retinitis can present with different features depending on the cause of immunocompromise. Evidence of intraocular inflammation such as vitritis, retinal arteritis, and vascular occlusions was more common in HIV-negative subjects. [ABSTRACT FROM AUTHOR]

Purpose: To examine the spectrum of scleritis in four tertiary institutions across the Asia-Pacific. Methods: Clinical records from 354 patients were reviewed from centers in Australia, Singapore, and India, excluding those with insufficient data (n = 24). Results: Indian patients presented younger (41.5 ± 13.4 years) than Australians (50.8 ± 17.5) and Singaporeans (48.6 ± 15.9), with fewer women (49% vs 62%/57%). Diffuse disease was universally most common. Autoimmune and infectious disease proportions were similar in Australia (31%/10.3%) and Singapore (27.5%/8.3%) but reversed in India (8.3%/30%). Necrotizing scleritis was most frequently associated with infection (27.3%). Presumed ocular tuberculosis accounted for 75% of infectious cases in India. Posterior scleritis had the highest complication rate (82.4%) and immunosuppressants used per patient (0.98 ± 0.31 95% CI). Conclusions: Clinical presentations of scleritis vary across the Asia-Pacific, particularly in endemic regions for tuberculosis such as India, where it affects younger men with a predominance of nodular and infectious disease. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy and tolerability of interferon (IFN) alpha-2a in post-infectious uveitis secondary to presumed intraocular tuberculosis (IOTB). Methods: Patients with chronic uveitis secondary to presumed IOTB who, after completing an antitubercular treatment, showed poor response to treatments or recurred after tapering oral corticosteroids to ≤7.5 mg/day were enrolled. All patients were treated with IFN alpha-2a subcutaneous injections. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and inflammatory signs were compared between baseline and follow-up visits up to six months. Results: Twelve eyes (six patients) were enrolled. Mean BCVA improved from 0.64 ± 0.55 logMAR at baseline to 0.32 ± 0.31 logMAR at 6 months (p = 0.03). Mean CRT decreased from 372 ± 132.2 μm to 274.66 ± 34.9 μm at six months (p = 0.01). Inflammatory signs (vitritis, vasculitis) also decreased overtime. No major complications or tuberculosis reactivations were recorded. Conclusions: IFN alpha-2a was efficacious and safe in treating chronic post-infectious uveitis secondary to presumed IOTB. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To report the pattern of uveitis in patients attending a tertiary uveitis service in Sydney, Australia. Methods: The charts of patients seen between January 2009 and December 2015 were retrospectively reviewed. Data pertaining to patient demographics, eye examination on presentation, work-up and final diagnoses were collected. Results: The total number of patients with uveitis seen over this period was 1165. There were 650 males (56%) and 515 females (44%). There were 838 patients aged 17–60 years (72%) and 327 patients aged >60 years (28%). Uveitis was anterior in 735 patients (63%), posterior in 234 patients (20%), pan in 109 patients (9%), and intermediate in 87 patients (8%). The most common associations were HLA-B27+ve (264 patients; 22.8%), sarcoidosis (78 patients; 6.7%) and Fuchs (33 patients; 2.8%), while VZV (51 patients; 4.4%), HSV (49 patients; 4.2%), tuberculosis (49 patients; 4.2%) and toxoplasmosis (48 patients; 4.1%) were the most common infectious causes of uveitis. No identifiable association was found in 389 patients (33.4%). HLA-B27 was more common in the younger age group compared with the older age group (p<0.001, χ2-test), but there was no difference between the age groups for no identifiable cause (p value 0.24) and sarcoidosis (p value 0.08). Conclusions: This retrospective case review reveals a broad spectrum of uveitis in a tertiary referral service in Sydney, Australia. It is comparable with other major studies around the world. [ABSTRACT FROM AUTHOR]

Purpose: To assess the vision-related (VR) and health-related (HR) quality-of-life (QoL) of patients with uveitis.Methods: In total, 60 patients with uveitis, 81 patients with diabetic retinopathy (DR), and 70 healthy subjects completed the National Eye Institute Visual Functioning Questionnaire and the Medical Outcome Study 36-Item Short Form.Results: Patients with uveitis reported lower HR- and VR-QoL than healthy subjects (p<0.05) and lower VR-QoL (p<0.001) than patients with DR. For patients with uveitis, multiple linear regression analyses indicated that lower HR-QoL scores were predicted by younger age (p<0.01), while lower VR-QoL scores were predicted by poorer visual acuity (p<0.001), ocular comorbidities (p<0.05), and female sex (p<0.05).Conclusions: Patients with uveitis have significantly poorer VR- and HR-QoL than healthy control subjects. Uveitis has a more debilitating impact on VR-QoL than DR. [ABSTRACT FROM AUTHOR]

Purpose: To explore the unmet needs in the management of patients with severe inflammatory eye disease (IED), future directions for research and therapy, and to develop and facilitate access and delivery of better medical care to patients with severe IED.Methods: The unmet needs and future directions in inflammatory eye disease were identified and discussed by experts in relevant disciplines at a recent international conference.Results: A total of 14 major unmet needs were identified and discussed by experts in the areas of ophthalmology, rheumatology, infectious disease, and internal medicine, at an international conference. The major areas discussed are summarized in this review.Conclusions: Identification of unmet needs in IED is seen as a first step in implementing changes in the way we diagnose and treat patients with these sight-threatening IEDs. [ABSTRACT FROM AUTHOR]

Systemic corticosteroids (CS) are an essential, frequently used therapy for patients with a variety of sight-threatening inflammatory eye diseases (IEDs). While there are notable differences between patients with RA and those who require systemic CS treatment for IED, this article highlights several important points. Long-term exposure to medium-dose glucocorticoid therapy associates with hypertension in patients with rheumatoid arthritis. [Extracted from the article]

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]

An introduction is presented in which editor discusses various articles within the issue on topics including features of patients diagnosed with posterior scleritis, use of enhanced depth anterior segment optical coherence tomography and use of oral flurbiprofen to treat patients of scleritis.

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]

Inflammatory eye diseases (IED) such as uveitis affect females and males in the prime of their reproductive life. Despite their propensity to lead to significant visual loss, there have been very few studies of the management of patients with IED who are pregnant or plan a pregnancy during the course of therapy. The first trimester and postpartum period may be associated with an exacerbation of IED and it is important to have available medications that control the disease and do not cause miscarriage or fetal abnormalities. Several immunosuppressive drugs are contraindicated in pregnancy (methotrexate and alkylating agents), whil e others (corticosteroids, azathioprine, and cyclosporin) may be considered for use in pregnancy. Most drugs are excluded from use in pregnancy not because of proven teratogenicity but because of the lack of available evidence of their safety for the fetus. [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]