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Background Blau syndrome (BS) is a rare dominantly-inherited autoinflammatory disorder characterized by the triad of arthritis, uveitis and dermatitis that is consequence of gain-of-function NOD2 mutations. We describe the clinical features and genetic basis of a family with two affected members in consecutive generations affected with childhood onset arthritis and uveitis. Materials and methods Clinical features were retrospectively collected from clinical records. Genetic studies were performed using the Sanger method of DNA sequencing. Results The proband is a 44 years-old female, who was diagnosed with juvenile onset arthritis at the age of 9 years. She subsequently developed uveitis at age 12 and since then she was managed between the uveitis and rheumatology services. The proband's daughter developed episcleritis at the age of 7 years, and arthritis with bilateral intermediate uveitis two years later. NOD2 analyses revealed in both patients the heterozygous c.1494A>C transversion, predicted to lead the novel, missense p.E498D variant in the NOD2 protein. Additional studies including databases searches and in silico bioinformatic predictions strongly support the "likely pathogenic" classification for this novel variant. Conclusions We report a novel pathogenic NOD2 variant in a multiplex family with clinical features compatible with the BS diagnosis. This condition is inherited as a dominant trait in its familial form and should be considered in patients with granulomatous uveitis in association with arthritis and/or dermatitis. Further insight into NOD2 variants and their downstream effects may have implications in the treatment of BS and other inflammatory granulomatous diseases.

Management as an occupation has become increasingly feminised in Australia over the last two decades. This article focuses specifically on specialist managers, answering the question of where we are now in terms of gender equity. It charts the increasing but uneven growth of women’s employment among specialist management occupations. Women remain concentrated into a relatively small number of management specialisations and it is argued that there is a gendering of certain management roles which is reflected in the value attached to these roles. Using data sourced from the Australian Tax Office, the article shows that men earn higher income across all specialist management groups, including those that are highly feminised, and higher salary across all specialisations excepting one – childcare directors. Evidence is presented detailing the relativities between management specialisations, showing a variation between men and women in terms of rank. Women are much less valued in some management specialisations, such as finance. Men are much less valued in others, such as childcare. The article concludes by speculating how greater gender equity can be achieved among specialist managers but observes that ‘management’ and ‘male’ are still tightly connected.

Topic An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. Clinical relevance The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. Methods An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. Results Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. Discussion Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.

Topic 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). Clinical Relevance 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. Methods 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. Results 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. Discussion 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.

ObjectiveTo report the demographics and the clinical course of patients with multiple evanescent white dot syndrome (MEWDS) and to investigate for those factors which influence visual acuity (VA) recovery.MethodsThis is a retrospective single-centre observational study. Electronic medical records and retinal imaging of patients with a diagnosis of MEWDS with a minimum follow-up of 3 months were reviewed. Patients were categorised into three groups according to the VA at presentation and at the last visit: group 1 >0.48 logarithm of the minimum angle of resolution (LogMAR), group 2 ≤0.48 and ≥0.18 LogMAR and group 3 ResultsA total of 51 eyes from 51 patients (41 women, mean age 29.8±7.8 years) were included. Significantly more patients presented in the autumn (X2=8.69, p=0.034). The percentage of eyes recovering vision to 0.0 LogMAR or better was 80.3% (41/51). Worse presenting vision and young age at presentation were independent significant predictive variables for poorer final VA (p=0.002 and p=0.02, respectively). No imaging features were significantly predictive of complete versus incomplete recovery, but disc hyperfluorescence on fluorescein angiography was more common in those with incomplete recovery.ConclusionsAlthough the majority of cases have a benign prognosis, the clinical spectrum of MEWDS includes incomplete visual recovery. In our series, poor presenting VA and young age were associated with poor VA outcome. Further study is warranted to confirm these findings.

To compare functional and anatomical outcomes, rates of culture positivity and number of procedures in eyes with endophthalmitis following phacoemulsification surgery, treated with either primary vitrectomy and intravitreal antibiotics or vitreous tap and antibiotic injection (TI).Patients developing endophthalmitis after phacoemulsification surgery between 2007 and 2016 were identified, and outcomes were compared between the two treatment groups.19 patients underwent a primary vitrectomy and 22 underwent a TI. There was a significant improvement in visual acuity after TI (p=.003) and primary vitrectomy (p=.00005). The median improvement in visual acuity was significantly greater for the primary vitrectomy group than the TI group (p=.024). 64% of eyes were culture positive with the initial TI, and 63% with primary vitrectomy (p=1.00). Two eyes initially culture negative with a TI, and three eyes that were culture positive with a TI were subsequently culture positive with a vitrectomy 24-72 hours later. 68% of patients who underwent a TI required an additional procedure, compared to 26% of the vitrectomy group (p=.01). The TI group underwent a mean of 2.3 procedures each, and the primary vitrectomy group underwent 1.5 (p=.03).Eyes with endophthalmitis treated with a primary vitrectomy demonstrated greater visual improvement and needed fewer procedures than those initially treated with a TI. Viable bacteria were only seen in subsequent procedures in the TI group, indicating that primary vitrectomy was superior at sterilizing the eye.

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. Of the ...

To report a challenging case of unilateral choroidal effusion. A case report about patient who presented with unilateral choroidal effusion and who was taking sulfonamides. Patient has been under c...

The renaming of Accounting Business and Financial History to Accounting History Review in 2011 could, at face value, be taken as a narrowing of the journal’s focus toward accounting history. Rather...

International audience; Objective: To report the clinical features and treatment outcomes in immunocompetent patients with anterior segment inflammation (ASI) related to human cytomegalovirus (HCMV) depending on their ethnic origin.Material and Methods: Multicenter retrospective study of 38 patients with at least one test, either HCMV-positive PCR or GWc.Results: Features of Posner-Schlossman syndrome were observed in 50% of the eyes, Fuchs heterochromic iridocyclitis in 13% of the eyes, chronic nonspecific anterior uveitis in 21% of the eyes, and corneal endotheliitis in 18% of the eyes. PCR and GWc were positive for HCMV in 50% and 96.2% of the eyes, respectively. Glaucoma was diagnosed in 50% of eyes. Treatment was oral valganciclovir in about half of the patients. Other treatments were intravenous ganciclovir and/or ganciclovir topical ointment and/or intravitreal ganciclovir.Conclusions: No obvious association of specific clinical features with individual ethnicity could be identified. We found a high rate of glaucoma in all ethnic groups. There was a delay in diagnosis and specific treatment of HCMV in most patients.

Topic: Herpes simplex virus (HSV) and varicella zoster virus (VZV) are the most common ocular pathogens associated with infectious anterior uveitis. Currently, there are a number of antiviral agents administered to treat viral anterior uveitis (VAU). However, there is no consensus or guidelines about the most appropriate approach leading for the best treatment outcomes with fewer ocular complications.Clinical Relevance: To perform a systematic review and meta-analysis of the efficacy of different antiviral therapies in the management of anterior uveitis secondary to HSV and VZV.Methods: We searched PubMed, Web of Science, CINAHL, OVID, and Embase up to January 2020. Randomized trials, non-randomized intervention studies, controlled before and after studies and observational studies assessing the effect of oral and or topical treatments for VAU were considered. Data extraction and analysis with evaluation of the risk of bias in the included trials were performed.Results: Oral acyclovir demonstrated a statistically significant good treatment outcome in the management of VZV anterior uveitis (vs. placebo) (OR 0.26, 95% CI 0.11–0.59), but did not have similar effect in HSV anterior uveitis (OR 0.47, 95% CI 0.15–1.50). In the treatment of VZV anterior uveitis, there was significant superiority of oral acyclovir−7 day course—over topical acyclovir (OR 4.17, 95% CI 1.28–13.52). Whereas, there was no significant superiority of one of the following treatment regimens over the others: topical acyclovir over topical corticosteroids (OR 1.86, 95% CI 0.67–5.17), and oral acyclovir−7 day course—over oral acyclovir−14 day course—(OR 0.21, 95% CI 0.01–4.50) or oral valaciclovir (OR 1.40, 95% CI 0.48–4.07).Conclusion: Treatment of HSV and VZV anterior uveitis is currently based on individual experiences and limited literature, largely due to weak clinical trial evidence in this regard. Our results highlight the existence of a substantial gap in our evidence base. This finding might contribute to future research studies to ascertain the role of different antiviral therapies in the treatment of VAU.Systematic Review Registration: PROSPERO registration number: CRD420202 00404.

Aims: To evaluate the efficacy of tacrolimus in patients with noninfectious uveitis, as well as the usefulness of serum tacrolimus concentration measurements in predicting disease control.Methods: A retrospective review was carried out on 71 eligible patients from a single specialist uveitis center for minimum 1-year follow-up. Analysis was carried out on disease activity, visual acuity, and trough serum tacrolimus concentrations (STC).Results: At 1-year follow-up, disease control was achieved in 49 patients (69.0%), this was significantly more likely in patients with trough STC levels above 5 ng/mL (88% vs 53%, p = .002). There was a significant reduction in oral prednisolone (dose ≥7.5 mg, 86% vs 54%, p

To examine disease profile of tubercular uveitis (TBU) in Paediatric population. Among 945 patients of the retrospective multinational study by the Collaborative Ocular Tuberculosis Study (COTS)-1,...

PurposeTo report treatment outcomes and efficacy of the fluocinolone acetonide 0.19 mg intravitreal implant (Iluvien) in controlling retinal and choroidal inflammation in 11 patients with birdshot retinochoroiditis.MethodsA single-centre, retrospective, interventional case series. The primary efficacy end point was improvement in vascular leakage on fluorescein angiography (FA), effect on cystoid macular oedema (CMO) and resolution of hypofluorescent lesions on indocyanine green angiography (ICGA); secondary measures were improvements on pattern and full-field electroretinogram (PERG; ERG) parameters. Safety outcome measures were intraocular elevation and cataractogenesis.ResultsFifteen eyes received Iluvien implant with an average follow-up of 31 months (range 12–36 months). Prior to the implant, 5 (33.3%) eyes had received dexamethasone intravitreal implant 0.7 mg (Ozurdex). FA showed evidence of vascular leakage in all eyes at baseline. Between month 6 and 12, FA showed that 73.4% of eyes had no leakage, this increased to 84.6% by month 24. Three eyes in our study had CMO at baseline. 6 months after Iluvien implant, all eyes achieved complete CMO resolution. One year after insertion of the implant, the characteristic hypofluorescent lesions on ICGA were unchanged in all cases. There was baseline ERG evidence indicating a high incidence of peripheral cone system dysfunction and most showed PERG evidence of macular dysfunction. Retinal function improved and macular function improved or was stable in the majority following treatment.ConclusionsThe results show the possible therapeutic effect of Iluvien in the management of Birdshot-related vascular leakage, CMO and retinal dysfunction. However, choroidal lesions seem to persist with no detectable response to treatment.

This article explores how real estate investors and lenders can assess and manage the physical risks of climate change through well-established risk models and climate scenarios. The authors propose a methodology that real estate investors and lenders can use to improve their understanding and management of these risks. The methodology is applied to a sample of 12 real estate portfolios with a total market value in excess of £2 trillion, spread across Europe, North and South America, and Asia, investigating the impacts of climate change on losses from floods and winter storms (UK) as well as tropical cyclones (North America and the Pacific Rim). The estimated changes in risk, especially in the climate scenario most aligned with the current warming trajectory, raises important questions for investors, lenders, insurers, and policymakers as to how these new levels of risk can be managed in the most cost-effective manner. TOPICS:Real estate, private equity, ESG investing Key Findings • This paper shows how, in practice, insights from climate science and outputs from climate models can be used in combination with system risk models to assess changes in physical risk under different climate futures. • The results show that climate change could have large impacts on the losses that investors and lenders face from floods in the UK and tropical cyclones in North America and the Pacific Rim. The estimated changes in risk, especially in the climate scenario most aligned with the current warming trajectory, raise important questions for investors, lenders, insurers and policymakers. • Property-level adaptation measures can materially reduce climate change induced losses. They are most effective when combined appropriately with other adaptation responses and global efforts to reduce emissions. • There is a window of opportunity for investors, lenders and policymakers, working with insurers, developers and product providers, to promote property level adaptation to target those properties that benefit most.

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.

Aim of the study was to examine extent, natural history, and clinical features associated with visual impairment (VI) in patients diagnosed with ocular tuberculosis (OTB) by the Collaborative Ocula...

The Collaborative Ocular Tuberculosis Study (COTS) Group sought to address the diagnostic uncertainty through retrospective cohort analysis of treatment regimens and therapeutic outcomes for patien...

An international, expert led consensus initiative was set up by the Collaborative Ocular Tuberculosis Study (COTS) group to develop systematic, evidence, and experience-based recommendations for the treatment of ocular TB using a modified Delphi technique process. In the first round of Delphi, the group identified clinical scenarios pertinent to ocular TB based on five clinical phenotypes (anterior uveitis, intermediate uveitis, choroiditis, retinal vasculitis, and panuveitis). Using an interactive online questionnaires, guided by background knowledge from published literature, 486 consensus statements for initiating ATT were generated and deliberated amongst 81 global uveitis experts. The median score of five was considered reaching consensus for initiating ATT. The median score of four was tabled for deliberation through Delphi round 2 in a face-to-face meeting. This report describes the methodology adopted and followed through the consensus process, which help elucidate the guidelines for initiating ATT in patients with choroidal TB.

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 Collabora...

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.

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.

PurposeTo investigate the differences in demographics and clinical characteristics of patients diagnosed with ocular toxoplasmosis according to their IgM status.MethodsRetrospective case note analysis was carried out on patients who tested positive for serum Toxoplasma gondii-specific IgM antibodies (IgM+) as well as a comparator group who tested negative for serum IgM (IgM-), but positive for serum IgG. Patient demographics and clinical features were compared between the two groups to evaluate for any significant differences.ResultsOne hundred and six patients were included in the study between March 2011 and June 2018, consisting of 37 in the IgM +group and 69 in the IgM- group. Patients in the IgM +group were significantly older (51.1 vs 34.1 years, pConclusionsThis study demonstrated significant differences in clinical characteristics of ocular toxoplasmosis according to serum IgM status. IgM+ patients were older, less likely to report pain, had lower levels of intraocular inflammation, but were more likely to have macular involvement. We also found age to be correlated with larger and more peripheral lesions.

International audience; Purpose: To monitor perivascular sheathing during the course of retinal vasculitis by flood illumination adaptive optics ophthalmoscopy (AOO). Methods: Perivenous sheathing and venous diameters were quantitatively analyzed by semi-automatic segmentation of AOO images in 12 eyes of treatment-naive patients with retinal vasculitis. Results: The width of venous sheathing ranged from 45 to 225 µm (mean 101.0 µm ± 54.3). In 10 cases, the underlying vein showed focal narrowing (mean ± SD 14% ± 10). Focal narrowing of arteries was also present in one eye. At presentation, width of sheathing and vessel diameters were not correlated with fluorescein leakage. During follow-up, 5 eyes showed an increase in vein diameter or resolution of narrowing and in 10 eyes a thinning of vascular sheathing was observed (p= .003). Conclusions: Perivenous sheathing may be quantitatively analyzed and monitored by AOO. AOO may therefore contribute to monitor vascular sheathing during posterior uveitis.

Objective: Online data centers (ODCs) are becoming increasingly popular for making health-related data available for research. Such centers provide good privacy protection during analysis by trusted researchers, but privacy concerns may still remain if the system outputs are not sufficiently anonymized. In this article, we propose a method for anonymizing analysis outputs from ODCs for publication in academic literature. Methods: We use as a model system the Secure Unified Research Environment, an online computing system that allows researchers to access and analyze linked health-related data for approved studies in Australia. This model system suggests realistic assumptions for an ODC that, together with literature and practice reviews, inform our solution design. Results: We propose a two-step approach to anonymizing analysis outputs from an ODC. A data preparation stage requires data custodians to apply some basic treatments to the dataset before making it available. A subsequent output anonymization stage requires researchers to use a checklist at the point of downloading analysis output. The checklist assists researchers with highlighting potential privacy concerns, then applying appropriate anonymization treatments. Conclusion: The checklist can be used more broadly in health care research, not just in ODCs. Ease of online publication as well as encouragement from journals to submit supplementary material are likely to increase both the volume and detail of analysis results publicly available, which in turn will increase the need for approaches such as the one suggested in this paper.

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 ...

To evaluate the efficacy and safety of dexamethasone (DEX) implant compared with inferior fornix-based sub-Tenon triamcinolone injection (PSTA) for treatment of uveitis.A total of 48 eyes received DEX and 49 eyes received PSTA as the first treatment.A total of 31 eyes were implanted with DEX relapsed (64.5%) after the first injection, while 32 eyes were injected with PSTA as the first treatment relapsed (65.3%). Kaplan-Meier estimated survival to overall relapse after the first injection was a mean 20 months± 3.6 months for DEX (median,7) and 14 months± 1.9 months (median,9) for the PSTA (P = 0.505). Of 49 eyes receiving the PSTA implant as the first treatment, inflammation persisted in 14.3% after the first injection but persisted in none after the DEX injection (P = 0.005).DEX implantation achieved a higher rate of disease control in the initial 12 weeks postinjection with a relative equivalence in the duration of effect and relapse rates when compared with PSTA.

Objective: To present moxifloxacin as an alternative treatment option to ethambutol in an anti-tubercular therapy (ATT) regime in patients with presumed ocular tuberculosis (TB).Methods: We identified all cases in our hospital referred for treatment of presumed ocular TB between 2009 and 2013. Age, gender, ophthalmic examination, blood tests, treatment regimens, adverse drug reactions, and outcomes were collected and analyzed for the patients who had moxifloxacin as part of their ATT.Results: Forty-three cases of presumed ocular TB were treated with moxifloxacin as a part of ATT. Mean age was 44.18 ± 12.47 years; 62.8% were male. A response to treatment, with no evidence of disease recurrence, was seen in 72.1% of cases. Shortened ATT duration was associated with increased risk of treatment failure (p = 0.02, 95% CI: −0.77 to −0.00).Conclusions: Moxifloxacin can be considered as a safe and effective alternative to ethambutol for the treatment of presumed ocular TB.

The aim of this study is to characterise the choroidal features of patients diagnosed with sarcoid- and tuberculosis (TB)-associated granulomatous uveitis using spectral domain optical coherence tomography (OCT).Twenty-seven patients (27 eyes) diagnosed with sarcoid- (13 eyes) and TB (14 eyes)-related uveitis were included in this retrospective, cross-sectional study. Over a six-month period, patients diagnosed with sarcoid and TB granulomatous uveitis were scanned using enhanced depth imaging OCT. Clinical and demographical characteristics were recorded, including the method of diagnosis, disease activity, site of inflammation (anterior or posterior), treatments, and visual acuity (VA). Manual segmentation of the choroidal layers was performed using custom image analysis software.The main outcome measure was OCT-derived thickness measurements of the choroid and choroidal sublayers (Haller's large vessel and Sattler's medium vessel layers) at the macula region. The ratio of Haller's large vessel to Sattler's medium vessel layer was significantly different at the total macula circle in eyes diagnosed with TB uveitis (1.47 (=140.71/95.72 μm)) compared with sarcoid uveitis (1.07 (=137.70/128.69 μm)) (P=0.001). A thinner choroid was observed in eyes with a VA ≥0.3 LogMAR (Snellen 6/12; 198.1 μm (interquartile range (IQR)=147.0-253.4 μm) compared with those with VA0.3 LogMAR (292.4 μm (IQR=240.1-347.6 μm)) at the total macula circle (P=0.004). At the foveal central subfield, the median choroidal thickness was 336.8 μm (IQR=272.3-375.4 μm) in active compared with 239.3 μm (IQR=195.3-330.9 μm) in quiescent disease (P=0.04).A disproportionately enlarged Sattler's layer may indicate a diagnosis of sarcoid-related uveitis, and choroidal thickening may be a feature of active granulomatous uveitis.

The primary tumor side is emerging as a prognostic factor for patients with liver metastatic colorectal cancer (mCRC). In a combined analysis of data from 2 randomized studies, the addition of selective internal radiation therapy to first-line chemotherapy in patients with mCRC was associated with statistically and clinically significant overall survival gains for patients with a right-sided primary tumor. Background: The primary tumor side is emerging as a major prognostic factor for patients with metastatic colorectal cancer (mCRC). We examined the survival data from 2 randomized studies to determine whether the outcomes differ between patients with mCRC with right-sided primary (RSP) tumors and those with left-sided primary (LSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy, versus chemotherapy alone. Patients and Methods: Separate and combined analyses were performed on the data from the SIRFLOX and FOXFIRE global trials, which compared chemotherapy plus SIRT with chemotherapy alone for patients with mCRC liver metastases. The primary tumor side data were prospectively collected. The principal outcome measure was overall survival (OS) stratified by treatment and primary tumor side. Results: In the combined analysis of all 739 patients enrolled, SIRT had no effect on OS (median OS, 24.3 vs. 24.6 months; hazard ratio [HR], 1.021; P = .810). For the 179 patients (24.2%) with a RSP tumor, OS was improved with the addition of SIRT (median, 22.0 vs. 17.1 months HR, 0.641; P = .008). The addition of SIRT was not associated with a significant difference in OS among the 540 patients with a LSP tumor (median, 24.6 vs. 26.6 months; HR, 1.120; P = .264). A test of treatment interaction by primary tumor side was statistically significant for RSP and SIRT (P = .002). Conclusion: The addition of SIRT for patients with RSP tumors, but not for those with LSP tumors, was associated with a statistically and clinically significant OS gain. (C) 2018 Elsevier Inc. All rights reserved.

To investigate deterioration in serial Humphrey visual fields (HVFs) using pointwise linear regression (PLR) analysis in patients with birdshot chorioretinopathy (BCR) monitored with full field electroretinography (ERG).Retrospective review of the case notes, HVFs and ERG of patients under treatment for BCR at Moorfields Eye Hospital between 1998 and 2014. Eyes with ERG recorded using protocols to incorporate International Society for Clinical Electrophysiology of Vision standards and at least five reliable Swedish Interactive Testing Algorithm standard 24-2 HVFs were included. HVFs were analysed by PLR analysis of luminance sensitivity using the Progressor software and linear regression analysis of mean deviation (MD).202 HVFs from 31 eyes of 16 patients were analysed. Mean follow-up was 60.25 months. MD remained stable in all eyes. PLR analysis detected progressive field loss in 10 eyes (seven patients). The mean (SD) slope of change at progressing points was -1.83 (0.90) db/year (p0.05). ERG worsened in 3 of the 10 eyes with field loss. Although there was no clear relationship between patterns of field loss and electrophysiological dysfunction, more extensive field loss was associated with more marked ERG abnormalities and rod system involvement.This study demonstrates that PLR analysis can identify field loss despite a stable MD and stable and even normal electrophysiology in BCR, thus establishing a role for regular standardised monitoring of visual fields as an adjunct to electrophysiology in order to facilitate more accurate characterisation of retinal dysfunction and hence enabling better-informed treatment decisions and monitoring of treatment efficacy.

Objective: To analyze the factors affecting the treatment outcome in patients with presumed ocular tuberculosis on anti-tubercular therapy (ATT).Methods: Retrospective chart review of patients with presumed ocular tuberculosis seen at a tertiary referral eye care center in the United Kingdom. Failure was defined as recurrence of inflammation within 6 months of completion of ATT.Results: There were a total of 175 patients with presumed ocular tuberculosis who had ATT. Patients with intermediate uveitis or panuveitis and those on immunosuppressive therapy had higher odds of treatment failure (p

In studying airspace it is necessary to have a model of how and when two aircraft come into proximity. There are two components: a kinematic description of the aircraft in flight, and a set of rules for deciding whether proximity has occurred. The focus in this paper is on the rules with the kinematics kept as simple as possible by utilizing the crossing track model. The aircraft are assumed to be flying straight-line paths at constant speed in a common plane towards a common waypoint A where the paths intersect. The kinematics is completely determined once the initial positions and the velocity vectors are known. A set of proximity rules are described which then permit partitioning of a constrained mathematical model for proximity. The partitioning is a function of parameter values derived from the proximity rules. It follows that the region where all constraints are satisfied defines a Feasible Design Space (FDS), and a different set of design variables is identified for describing the kinematics than is commonly used in current practice. The Compromise Decision Support methodology constructs permit the formalization of the analysis of how different designs for airspace management and communication might affect the occurrence of proximity between aircraft. The existence of proximity can be determined analytically once the kinematic variables are known. The use of the new FDS is applicable hierarchically from strategic planning through to real-time adaption required in actual in-flight operations. It is important as a visualization tool for simulation studies and decision support analyses.

ObjectiveRecent growth in the number of population health researchers accessing detailed datasets, either on their own computers or through virtual data centers, has the potential to increase privacy risks. In response, a checklist for identifying and reducing privacy risks in population health analysis outputs has been proposed for use by researchers themselves. In this study we explore the usability and reliability of such an approach by investigating whether different users identify the same privacy risks on applying the checklist to a sample of publications.MethodsThe checklist was applied to a sample of 100 academic population health publications distributed among 5 readers. Cohen’s κ was used to measure interrater agreement.ResultsOf the 566 instances of statistical output types found in the 100 publications, the most frequently occurring were counts, summary statistics, plots, and model outputs. Application of the checklist identified 128 outputs (22.6%) with potential privacy concerns. Most of these were associated with the reporting of small counts. Among these identified outputs, the readers found no substantial actual privacy concerns when context was taken into account. Interrater agreement for identifying potential privacy concerns was generally good.ConclusionThis study has demonstrated that a checklist can be a reliable tool to assist researchers with anonymizing analysis outputs in population health research. This further suggests that such an approach may have the potential to be developed into a broadly applicable standard providing consistent confidentiality protection across multiple analyses of the same data.

AimEvaluation of the use of tacrolimus in the treatment of birdshot retinochoroiditis (BRC) at a tertiary referral centre with the aim to describe its safety and efficacy.MethodsThe medical records of 25 patients diagnosed with BRC at uveitis service, Moorfields Eye Hospital, and who had received tacrolimus treatment were retrospectively reviewed. The main outcome measures of the study were (1) safety of tacrolimus in terms of side effects and (2) efficacy, as measured both by control of inflammation and visual function assessed by Humphrey visual fields and electrophysiological testing over at least 6 months and then 1 year.ResultsTacrolimus was commenced in 25 patients (mean age 50.4±10.8 years) and was well tolerated in 21 patients (84%). It was necessary to stop the tacrolimus in four patients. No patient showed major changes in renal function: 3/21 patients (14.28%) showed slightly abnormal (less than 30%) function at the end of the first month of treatment; 1/21 (4.76%) patients at 3 months, but at the end of a 6-month treatment period only 1/21 patients (4.76%) showed minor abnormality in renal function. The mean daily prednisolone dose was 19.7 mg at the beginning of the study, which had fallen to 6.9 mg at the end (t=5.071, p=0.001). Visual acuity mostly remained stable. Visual fields improved over time (mean improvement in Humphrey mean deviation, right eye=1.8±2.4 dB, t=3.821, p=0.004; left eye=1.9±2.7, dB, t=3.06, p=0.007). Electrophysiological function showed improvement in 10 patients, and in four patients an initial deterioration in function improved following tacrolimus dose adjustment.ConclusionTacrolimus has a good safety profile for long-term use in patients with BRC as a second-line agent enabling steroid sparing and visual function stabilisation or improvement.

Purpose To perform qualitative and quantitative analyses of retinal and choroidal morphology in patients with punctate inner choroidopathy (PIC) using enhanced depth imaging optical coherence tomography (EDI-OCT). Design Cross-sectional, consecutive series. Participants A total of 2242 patients attending 2 tertiary referral uveitis clinics at Moorfields Eye Hospital were screened; 46 patients with PIC diagnosis were identified, and 35 eyes (35 patients) had clinically inactive PIC had EDI-OCT images that met the inclusion criteria. Methods Punctate inner choroidopathy lesions were qualitatively assessed for retinal features, such as (1) focal elevation of the retinal pigment epithelium (RPE), (2) focal atrophy of the outer retina/RPE, and (3) presence of sub-RPE hyperreflective deposits and choroidal features: (a) presence of focal hyperreflective dots in the inner choroid and (b) focal thinning of the choroid adjacent to PIC lesions. Quantitative analyses of the retina, choroid, and choroidal sublayers were performed, and associations with clinical and demographic data were examined. Main Outcome Measures Prevalence of each lesion pattern and thickness of retinal and choroidal layers. Results A total of 90 discrete PIC lesions were captured; 46.6% of PIC lesions consisted of focal atrophy of the outer retina and RPE; 34.4% consisted of sub-RPE hyperreflective deposits; and 18.8% consisted of localized RPE elevation with underlying hyporeflective space. Focal hyperreflective dots were seen in the inner choroid of 68.5% of patients, with 17.1% of eyes presenting focal choroidal thinning underlying PIC lesions. By excluding high myopes, patients with "atypical" PIC had reduced retinal thickness compared with patients with "typical" PIC (246.65±30.2 vs. 270.05±24.6 μm; P = 0.04), and greater disease duration was associated with decreases in retinal thickness ( r = −0.53; P = 0.01). A significant correlation was observed between best-corrected visual acuity and foveal retinal thickness ( r = −0.40; P = 0.03). Conclusions In a large series of patients with clinically inactive PIC, one fifth of the lesions analyzed revealed RPE elevation with underlying hyporeflective space, described before as a sign of activity and suggesting subclinical inflammation. Retinal thickness seems to be associated with disease type and duration of disease in non–highly myopic eyes. Improved visualization of the inner choroid using EDI-OCT may allow noninvasive assessment of inflammatory status.

The incidence of kidney cancer in the United States is rising because the increased use of cross-sectional imaging is resulting in more tumors being detected and because the population is aging. In addition, a stage migration in kidney cancer has been observed—again because of improved detection—with an increase in stage T1 tumors and a concomitant decrease in the number of stage T2 to T4 tumors. Recent studies have shown that up to 80% of small renal tumors (SRTs) either have an indolent course or are histologically benign. These fndings raise the question of what the optimal management of SRTs should be. Radical nephrectomy, the traditional, most aggressive, and still most frequently used extirpative surgery, has been shown to increase the risk of chronic kidney disease. Therefore, during the past 2 decades there has been a shift toward nephron-sparing surgery in carefully selected patients as such procedures have demonstrated equivalent oncologic outcomes with a decrease in long-term renal-induced morbidities. More recently, thermal ablative techniques have evolved as a reliable minimally invasive option for SRTs that can provide adequate oncologic control with minimal morbidity. Finally, in patients with limited life expectancies, active surveillance may be a reasonable approach given the slow median growth rate of SRTs. In evaluating patients with SRTs, percutaneous renal biopsies are being used safely and with increasing accuracy, providing valuable histologic information that can be used to guide the management of SRTs. This article will explore the approaches to managing and treating this growing cohort of patients with SRTs, which are usually incidentally identifed.

Idiopathic panuveitis is a diagnosis of exclusion that lacks distinguishing features on fluorescein and indocyanine green angiography. Choroidal hypoperfusion or ischaemia has been implicated in panuveitis of different aetiologies. In this study, we use enhanced depth imaging optical coherence tomography (OCT) to examine the choroid and its vasculature in patients with this disease. In this retrospective, cross-sectional study, OCT-derived measurements of retinal and choroidal thickness were obtained after manual segmentation using custom software. Choroidal measurements were further subdivided into Haller’s large vessel layer (HLVL) and Sattler’s medium vessel layer (SMVL), and correlated with clinical parameters. Twenty-one eyes from 21 patients were included. A reduction in hypo-reflective spaces, corresponding to vascular lumens, was observed in HLVL. The mean thickness of both the choroid (233.7 ± 73.3 μm), and HLVL (167.8 ± 53.7 μm), was less than that previously reported for normal eyes. Choroidal thickness expressed as a ratio to retina thickness showed significant correlation to visual acuity (r = 0.58, p = 0.006). This correlation was maintained in the ratio between HLVL and retinal thickness (r = 0.56, p = 0.009), but not in SMVL to retinal thickness (r = 0.352, p = 0.12). This study reports novel OCT-derived parameters in patients with idiopathic panuveitis. We noted loss of hyporeflectivity in HLVL, and thinning of both HLVL and the choroid as a whole. The observed correlation between visual acuity and the ratio of choroidal to retinal thickness is a strong enhanced depth imaging (EDI)-OCT derived candidate for prospective validation in future studies.

Background To evaluate the contribution made to the diagnostic work-up for patients with suspected ocular tuberculosis (TB) by QuantiFERON-TB Gold In-Tube (QFT) tests using latent class analysis model. Methods A single centre retrospective cohort study. A Bayesian latent class model was constructed on the basis of demographics, phenotypes and test results from patients attending a tertiary referral center in the UK. This estimated the probability of ocular TB for each patient in two versions, first with and then without QFT. The estimated probability of ocular TB was compared with treatment failure. Results From a database of 365 patients with clinical signs suggestive of ocular TB, 267 patients who had QFT and complete data were evaluated. Mean age was 45.0 ± 15.4 years with 141 (52.9%) male and 148 (50.5%) of Asian ethnicity. QFT was positive in 208 (70.1%) patients and ATT was instituted in 145 (49.5%) patients with 100 (34.1%) patients also having concurrent systemic corticosteroid therapy. The best estimate of a QFT level separating TB-positive and TB-negative patients was extremely low. This weak discrimination between TB and non-TB groups was reflected in poor positive and negative predictive values for treatment failure. Conclusions The latent class model did not successfully predict treatment failure, despite taking all variables into account. The threshold between TB and non-TB in QFT values was implausibly low and removing QFT from the model made prediction slightly worse. A larger prospective study is required to establish the role of all tests, demographics and phenotypes in diagnosis. Electronic supplementary material The online version of this article (10.1186/s12886-017-0597-x) contains supplementary material, which is available to authorized users.

Purpose: To target the use of two biologic tests in the diagnostic of viral Herpesviridae anterior uveitis (AC) by the consideration of clinical behavior and delay of intraocular sampling.Methods: Aqueous humor samples were collected from 42 patients suspected of having AU of infectious origin at presentation. The diagnosis of infectious uveitis was confirmed by quantification of antibodies with the Goldmann-Witmer coefficient (GWC) and/or detection of Herpesviridae genomes with PCR. The data were compared with data of 16 uveitis control samples used to calculate the specificity of the tests.Results: Sixteen out of 42 eyes (38%) had a final diagnosis of anterior segment infectious uveitis of viral origin (Herpesviridae) confirmed by PCR positive result (5/14 eyes; 14 of the 16 eyes were tested by PCR) and/or specific intraocular antibody synthesis (14/16 eyes).Conclusions: While the GWC is progressively less often performed, these findings suggest that it still has a role in AU suspected of herpesvirus et...

Purpose To report a rare case of transthyretin (TTR) familial amyloid cardiomyopathy with retinal microangiopathy and vitreous amyloid as the initial manifestation. Methods A 54-year-old woman presented with bilateral retinal microangiopathy, presumed idiopathic retinal vasculitis. She subsequently developed retinal ischemia associated vitreous hemorrhage and was treated with panretinal laser photocoagulation. Clinical eye signs remained stable for 6 years with the absence of overt inflammation. However, the patient developed chest pain and atrial flutter and underwent echocardiography, cardiac magnetic resonance imaging, and Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy to investigate possible cardiac amyloidosis. Sequencing of the TTR gene was conducted and a rectal biopsy performed for tissue diagnosis. A full neurologic screen was also conducted. Results Cardiac investigations were highly suggestive of an amyloid cardiomyopathy. The rectal biopsy stained positive for Congo red with demonstration of apple green birefringence, confirming amyloid, and immunostaining confirmed the TTR subtype. Gene sequencing revealed heterozygous TTR mutation encoding E89K variant. No significant neuropathy could be detected. Conclusion Amyloid should be considered as a masquerade diagnosis in cases of retinal microangiopathy, especially in the absence of inflammation. Liaising with physicians for systemic evaluation and TTR gene sequencing is essential for early diagnosis and management of this rare condition.

PurposeTo determine visual acuity and rates of post-operative cystoid macular oedema (CMO) in an ethnically diverse and predominantly diabetic population.MethodsThe study was undertaken over a one year period. Snellen visual acuity (VA) was measured pre and 4-8 weeks post-operatively and optical coherence topography (OCT) was performed at baseline and post-operatively. No eyes received prophylactic non-steroidal anti-inflammatory drugs (NSAIDs) prior to or after surgery.ResultsOut of 262 eyes, 59% were in the Black, Asian and minority ethnic group (BAME), 57% had a history of diabetes mellitus and 34% had pre-existing diabetic retinopathy. 76% of all eyes achieved 6/12 post-operative VA at the first postoperative review and the incidence of post-operative CMO within the study population was 7.6%. In patients with a history of diabetes mellitus the incidence of post-operative CMO was 10.7% compared to 3.5% in those without diabetes. This was found to be clinically significant (P=0.0297).ConclusionWe believe this is the first study to benchmark standards for care in this demographic of patients. A history of diabetes mellitus, irrespective of whether there is diabetic retinopathy or not, is an independent risk factor for the development of post-operative CMO in patients undergoing cataract surgery (P=0.0297). Ethnicity is not an independent risk factor for the development of post-operative CMO.

Purpose Describe the clinical features and outcomes of patients with peripheral retinal vasculitis (RV) and describe clinical characteristics of presumed tubercular RV in a nonendemic setting. Methods Retrospective cohort study of 110 consecutive patients with peripheral RV at a tertiary referral eye care center in the United Kingdom. Retinal vasculitis was defined as RV with vitritis associated with peripheral retinal ischemia. Patients who also had positive Quantiferon Gold in Tube test, positive tuberculin skin test, and/or other evidence of systemic tuberculosis such as biopsy were labeled with presumed tubercular RV. Treatment success was defined as resolution of inflammation, and successful tapering of oral corticosteroids to less than 10 mg/day or topical steroids to less than twice a day. Results Mean age of the study population was 42.69 ± 14.95 years. Patients were predominantly Asian (49.1%) and Male (67.0%). A total of 73.2% had bilateral involvement. Sixty-nine (62.72%) patients had presumed tubercular RV. A total of 52.8% patients received antitubercular therapy, 65.5% received oral corticosteroids, and 17.3% required steroid-sparing oral immunosuppressive agents. A total of 85.19% of patients with presumed tubercular RV achieved treatment success with concurrent antitubercular therapy as against 75.61% of patients with nontubercular RV. Conclusion This is the largest study of the epidemiology, clinical features, and outcomes of both peripheral RV and presumed tubercular RV to date. Presumed tubercular RV commonly seems to affect young males of Asian descent and had vitreous hemorrhage as common clinical findings and also demonstrated a good treatment outcome with antitubercular therapy.

Institutions of the state, in the form of industrial tribunals, were in the past entrenched in the development of the detailed labour process in Australian workplaces. This paper explores a case where the NSW Industrial Commission came to actively structure the contours of the effort bargain at a NSW oil refinery in the late 1970s. Importantly the activities of the tribunal influenced the deliberate choices of management and workers at the refinery resulting in a particular type of conflict taking shape at this workplace. There emerged a set of polarised industrial tactics centred on the assertion of 'workers control' by the operator's union and moves to restrict this control by company management. These tactics provided limited scope for genuine co-operation between management and workers at this workplace. The presence of the industrial tribunal was not merely a mediating factor in the development of these industrial tactics and consequently the particular nature of conflict that emerged. Rather the New South Wales Industrial Commission came to be an important determinant in shaping conflict and co-operation at the refinery. The evidence from this case suggests that, in particular places at particular historical moments, the activities of the state actively structure the detailed labour process and the contours of conflict at work.

As air traffic management systems have evolved and traffic flows have increased, communications protocols have become more complex. Extra frequencies have been introduced, resulting in different frequencies being assigned to adjacent airspace volumes around airports. Consequently, pilots in close spatial proximity might not be operating on a common frequency. This could fatally inhibit timely exchange of information critical to successful avoidance of a mid-air collision. This paper considers the physical feasibility of communication between aircraft when they operate near radio frequency boundaries. It uses a simple but revealing model of aircraft operation within a multiple radio frequency structure. The model allows comprehensive descriptions of operational and failure modes once parameters such as aircraft velocities, radio frequency structures and communication transmission lengths are specified. The paper uses a novel form of nested plot for high-dimensional data to show how the failure modes are influenced by the parameters. An important conclusion is that circumstances in which problems can arise are not easily predicted during flight. Thus operational experience is not necessarily a good basis for evaluating the safety of communication system design. The model is not intended to be complete or exhaustive; its role is to demonstrate design principles and processes.

The aim of this work was to determine the diagnostic performance of real-time polymerase chain reaction (RT-PCR) and to assess intraocular specific antibody secretion (Goldmann-Witmer coefficient) on samples from patients with signs of posterior uveitis presumably of infectious origin and to target the use of these two biologic tests in the diagnostic of Toxoplasma/viral Herpesviridae posterior uveitis by the consideration of clinical behavior and delay of intraocular sampling.Aqueous humour and/or vitreous fluid were collected from patients suspected of having posterior uveitis of infectious origin at presentation (140 samples). The diagnosis was confirmed by quantification of antibodies with the Goldmann-Witmer coefficient (GWC) and for detection of Herpesviridae and Toxoplasma gondii genomes with RT-PCR. Forty-one patients had final diagnosis of uveitis of non-Toxoplasma/non-viral origin and 35 among them constituted the control group. The main outcome measures were sensitivity, specificity, and positive and negative predictive values (PPV and NPV).When pre-intraocular testing indication was compared with final diagnosis, GWC was a more sensitive and specific method than RT-PCR, and was successful in detecting T. gondii, especially if the patient is immunocompetent and the testing is carried out later in the disease course, up to 15 months. For viral Herpesviridae uveitis, the sensitivity and PPV of PCR evaluation was higher than detected with GWC with respectively 46% compared with 20% for sensitivity and 85% versus 60% for PPV. In either viral retinitis or toxoplasmosis infection, RT-PCR results were positive from 24 h, although GWC was not significant until 1 week after the onset of signs. In toxoplasmosis patients, positive RT-PCR results were statistically correlated with the chorioretinitis area (more than three disc areas; p = 0.002), with the age older than 50 (p = 0.0034) and with a clinical anterior inflammation (Tyndall ≥1/2+) and panuveitis; (p = 0.0001).For the diagnosis of viral or toxoplasmosis-associated intraocular inflammation, the usefulness of laboratory diagnosis tools (RT-PCR and GWC) depends on parameters other than the sensitivity of the tests. Certain patient characteristics such as the age of the patients, immune status, duration since the onset of symptoms, retinitis area, predominant site and extent of inflammation within the eye should orientate the rational for the choice of laboratory testing in analysis of intraocular fluids.