Search

Introduction: Ibrutinib is a small-molecule drug approved for the treatment of haematological disorders and is known to be associated with visual disturbances, but uveitis has not yet been reported as an adverse effect of this medication. We present two cases of ibrutinib-associated severe uveitis in patients with chronic lymphocytic leukaemia. Case description: Our first case is a 65-year-old woman who presented with acute onset of bilateral fibrinous anterior uveitis 1 day after starting ibrutinib. Her vision was hand movements in the right eye and 20/120 in the left with hyperaemic discs and subretinal fluid. Ibrutinib was stopped and she experienced a significant improvement under local and oral steroid treatment. The second case is a 64-year-old male with subacute onset of bilateral hypertensive anterior uveitis with pupillary seclusion and right eye hyphaema. He was on ibrutinib for the past 9 months. His vision at presentation was 20/80 and 20/60 for the right and left eye, respectively. He responded poorly to local steroid treatment until ibrutinib was stopped due to cardiac side-effects, after which his uveitis resolved and treatment was stopped. Conclusion: The temporal association between changes in ibrutinib treatment and our patients’ ocular inflammation suggests a causative link. Ibrutinib increases Th1-based immune responses which is proposed as a mechanism for drug-induced uveitis. Its antiplatelet effect may explain the fibrinous nature of the inflammation and hyphaema.

Objectives The West London lung screening pilot aimed to identify early-stage lung cancer by targeting low-dose CT (LDCT) to high risk participants. Successful implementation of screening requires maximising participant uptake and identifying those at highest risk. As well as reporting pre-specified baseline screening metrics, additional objectives were to 1) compare participant uptake between a mobile and hospital-based CT scanner and 2) evaluate the impact on cancer detection using two lung cancer risk models. Methods From primary care records, ever-smokers aged 60–75 were invited to a lung health check at a hospital or mobile site. Participants with PLCOM2012 6-yr risk ≥1.51 % and/or LLPv2 5-yr risk ≥2.0 % were offered a LDCT. Lung cancer detection rate, stage, and recall rates are reported. Participant uptake was compared at both sites (chi-squared test). LDCT eligibility and cancer detection rate were compared between those recruited under each risk model. Results Of 8366 potential participants invited, 1047/5135 (20.4 %) invitees responded to an invitation to the hospital site, and 702/3231 (21.7 %) to the mobile site (p = 0.14). The median distance travelled to the hospital site was less than to the mobile site (3.3 km vs 6.4 km, p Conclusion Targeted screening is effective in detecting early-stage lung cancer. Similar levels of participant uptake at a mobile and fixed site scanner were demonstrated, indicating that uptake was driven by factors in addition to scanner location. The LLPv2 model was more permissive; recruitment with PLCOM2012 alone would have missed several cancers.

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 ...

Alcoholic hepatitis (AH) is an acute inflammatory liver condition with high early mortality rate. Steroids improve short-term survival but nonresponders have the worst outcomes. There is a clinical need to identify these high-risk individuals at the time of presentation. T cells are implicated in AH and steroid responsiveness. We measured ;ex vivo T cell cytokine expression as a candidate biomarker of outcomes in patients with AH. Consecutive patients (bilirubin >80 μmol/L and ratio of aspartate aminotransferase to alanine aminotransferase >1.5 who were heavy alcohol consumers with discriminant function [DF] ≥32), were recruited from University Hospitals Plymouth NHS Trust. T cells were obtained and stimulated ;ex vivo. Cytokine expression levels were determined by flow cytometry and protein multiplex analysis. Twenty-three patients were recruited (10 male; median age 51 years; baseline DF 67; 30% 90-day mortality). Compared to T cells from nonsurvivors at day 90, T cells from survivors had higher baseline baseline intracellular interleukin (IL)-10:IL-17A ratio (0.43 vs 1.20, p=0.02). Multiplex protein analysis identified interferon γ (IFNγ) and tumor necrosis factor-α (TNF-α) as independent predictors of 90-day mortality (p=0.04, p=0.01, respectively). The ratio of IFNγ to TNF-α was predictive of 90-day mortality (1.4 vs 0.2, p=0.03). These data demonstrate the potential utility of T cell cytokine release assays performed on pretreatment blood samples as biomarkers of survival in patients with severe AH. Our key findings were that intracellular IL-10:IL-17A and IFNγ:TNF-α in culture supernatants were predictors of 90-day mortality. This offers the promise of developing T cell-based diagnostic tools for risk stratification.

Susac syndrome is a rare condition presumed to be immune-mediated occlusion of small arterial vasculature principally of the brain, inner ear, and retina. Clinically, the syndrome manifests as a pathognomonic triad of encephalopathy, hearing loss, and branch retinal artery occlusion. Early recognition and diagnosis is important as delayed treatment may be profound and result in deafness, blindness, dementia, and other neurological deficits. The plethora of imaging technology, including magnetic resonance imaging, retinal fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography, allows deeper and more discrete anatomical-physiological correlation of underlying pathology, early diagnosis, and imaging biomarkers for early detection of relapse during follow-up. We highlight the current clinical classification of Susac syndrome, available investigations, treatment, and care pathways.

Background/Aim To report the efficacy and tolerability of antitumour necrosis factor-alpha therapy (TNF inhibitors [TNFi]) in the management of non-infectious ocular inflammation, including uveitis and scleritis, in adult patients over an 8-year period.Materials and methods This is a prospective cohort study of infliximab and adalimumab in the treatment of non-infectious ocular inflammatory disease. 43 of 85 adult patients on TNFi (34 infliximab, 9 adalimumab) for ≥1 year with non-infectious uveitis or scleritis were followed from 2006 to 2014. Clinical assessments, medication, adverse events and history of steroid rescues were collected at 6 monthly intervals. General quality of life (Short Form Health Survey (SF-36)) and visual quality of life (Vision-related quality of life Core Measure (VCM1)) were assessed annually. Outcome measures included rate of sustained remission, rate of relapse, systemic corticosteroid reduction, adverse events, and VCM1 and SF-36 scores.Results The median time on infliximab was 3.2 years (IQR 4.3) and on adalimumab was 2.4 years (IQR 1.8). Sustained remission was induced in 39 patients (91%) (0.5 per patient year) after a median of 1.2 years on a TNFi. 22 (51%) experienced one relapse, and 5 (12%) had two relapses. 23 (54%) had at least one adverse event; serious adverse events necessitating hospitalisation or cessation of medication occurred in four (9%) patients. 10 patients (23%) switched from the initiation of TNFi, at 1.7 years after starting, to another TNFi or another class of biologic therapy.Conclusion TNFi treatment is associated with long-term drug-induced remission of ocular inflammation, visual stability and corticosteroid reduction. Adverse events were common and no new safety signals occurred. Relapse of inflammation occurs in half of the treated population.This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Early cancer diagnosis is a clinical and research priority of the UK government. Earlier cancer diagnosis should enable identification of cancers at an earlier stage, leading to improved outcomes.1 This must be balanced with the potential physical and psychological harms of over-investigation and over-diagnosis. The ‘two-week wait’ (2WW) referral pathway represents the most common route to cancer diagnosis. However, only 39% of cancer diagnoses were made via 2WW pathways in 2017, while significant proportions of diagnoses are made via other outpatient clinics (32%) or emergency presentation (19%), representing potentially missed diagnostic opportunities.2 Approximately 50% of cancer patients present with non-specific but concerning symptoms of cancer (NSCS).3 Compared to ‘alarm symptoms’ these have low predictive values for cancer and are less indicative of site-specific disease; consequently, they are not reflected in 2WW referral criteria.3 These patients frequently are referred later for specialist investigation and have more advanced disease.4 A principal goal for the new NHS Rapid Diagnostic Centres (RDCs) is to provide a pathway for patients with NSCS to detect cancer earlier, where treatment outcomes are more favourable.1 NHS England aims to provide full population coverage with RDCs by 2024.5 Despite their low predictive value and association with multiple diseases, many NSCS are considered as characteristic warning signs of cancer. These include unexpected weight loss, malaise, unexplained pain, new dyspnoea, and persistently abnormal blood tests.4,6,7 Unexpected weight loss was the most common symptom seen within an RDC pilot (66%) between 2016 and 2018;7 however, it has a relatively low predictive value for cancer.6,8,9 While patients with weight loss in isolation may not warrant further investigation, considering other clinical variables …

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,...

[No abstract]

Background: Uveitis associated with juvenile idiopathic arthritis is a cause of major ocular morbidity. A substantial proportion of children are refractory to systemic methotrexate and TNF inhibitors. Our aim was to study the safety and efficacy of tocilizumab in children with juvenile idiopathic arthritis-associated uveitis refractory to both methotrexate and TNF inhibitors.Methods: This multicentre, single-arm, phase 2 trial was done following a Simon's two-stage design at seven tertiary hospital sites in the UK. Patients aged 2-18 years with active juvenile idiopathic arthritis-associated uveitis were eligible. All patients had been on a stable dose of methotrexate for at least 12 weeks and had not responded to treatment with a TNF inhibitor. Patients weighing 30 kg or more were treated with 162 mg subcutaneous tocilizumab every 2 weeks for 24 weeks, and participants weighing less than 30 kg were treated with 162 mg every 3 weeks for 24 weeks. The primary outcome was treatment response defined as a two-step decrease, or decrease to zero, from baseline in the level of inflammation (anterior chamber cells) at week 12, per the standardisation of uveitis nomenclature criteria. A phase 3 trial would be justified if more than seven patients responded to treatment. An interim analysis was planned to assess whether the trial would be stopped for futility, with futility defined as two or fewer treatment responses among ten participants. Adverse events were collected up to 30 calendar days after treatment cessation. The primary analysis was done in the intention-to-treat population and the safety analysis was done in all patients who started the treatment. This trial is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN95363507) and EU Clinical Trials Register (EudraCT 2015-001323-23).Findings: 22 participants were enrolled to the trial between Dec 3, 2015, and March 9, 2018, and 21 participants received treatment. One participant was found to be ineligible immediately after enrolment and was therefore withdrawn. Seven of 21 (median unbiased estimate of proportion 34% [95% CI 25-57]) responded to treatment (p=0·11). Safety results were consistent with the known safety profile of tocilizumab.Interpretation: The primary endpoint was not met, and thus the results do not support a phase 3 trial of tocilizumab in patients with juvenile idiopathic arthritis-associated uveitis. Importantly, data on the use of tocilizumab in clinical practice is now captured in national registries. Despite this trial not meeting the threshold required to justify a larger phase 3 trial, several patients responded to treatment; as such, tocilzumab might still be a therapeutic option in some children with uveitis refractory to anti-TNF drugs, given the absence of other treatment options.Funding: Versus Arthritis and the National Institute for Health Research Clinical Research Network: Children.

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.

PurposeThe aim of this study was to determine a sequence of structural changes in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using optical coherence tomography-angiography (OCT-A) and comparing with other imaging modalities.Patients and methodsPatients with a new diagnosis of acute-onset APMPPE referred to a regional specialist centre from October 2015 to October 2016 were included. Multimodal imaging employed on all patients from diagnosis included the following: fundus fluorescein angiography, indocyanine green angiography, fundus autofluorescence, spectral domain-OCT (SD-OCT), and OCT-A. All non-invasive imaging processes were repeated during follow-up.ResultsTen eyes of five patients were included in the study, three males and two females, with a mean age of 26.2 years (range: 21–32) and a mean follow-up of 6.4 months (range: 2.6–13.3). All patients presented with bilateral disease and macular involving lesions. OCT-A imaging of the choriocapillaris was supportive of hypoperfusion at the site of APMPPE lesions during the acute phase of this condition with normalisation of choroidal vasculature during follow-up. Multimodal imaging consistently highlighted four sequential phases from presentation to resolution of active disease.ConclusionsMultimodal imaging in patients with APMPPE in acute and long-term follow-up demonstrates a reversible choroidal hypoperfusion supporting the primary inciting pathology as a choriocapillaritis. The evolution shows resolution of the ischaemia through a defined sequence that results in persistent changes at the level of the retinal pigment epithelium and outer retina. OCT-A was able to detect preclinical changes and chart resolution at the level of the choriocapillaris.

Since lung cancer (LC) is still the leading cause of cancer deaths worldwide [1], early detection through screening represents an important opportunity to improve LC survival and is a priority area for cancer care. The National Lung Screening Trial (NLST) aimed to compare low-dose helical computed tomography (LDCT) with chest radiography in LC screening of current or former heavy smokers. The trial found a relative reduction in mortality from LC of 20% in those who had undergone LDCT screening. LC screening has regained prominence in the thoracic oncology literature with the completion of NELSON and other European trials, which support the role of LC screening in achieving early diagnosis and reducing mortality. A growing number of implementation pilots are providing an impetus towards organised, national programmes for LC screening, which are in need of long-term follow-up data such as those presented in this study., The extended follow-up of the NLST represents a timely and important update to the NLST data, alongside full results of the NELSON and the LUSI trials, as Europe begins to set out a vision for lung cancer screening. http://bit.ly/2MYXedI

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.

It is not currently possible to reliably visualise and track immune cells in the human central nervous system or eye. Previous work demonstrated that indocyanine green (ICG) dye could label immune cells and be imaged after a delay during disease in the mouse retina. We report a pilot study investigating if ICG can similarly label immune cells within the human retina. Twelve adult participants receiving ICG angiography as part of routine standard of care were recruited. Baseline retinal images were obtained prior to ICG administration then repeated over a period ranging from 2 hours to 9 days. Matched peripheral blood samples were obtained to examine systemic immune cell labelling and activation from ICG by flow cytometry with human macrophage cultures as positive controls. Differences between the delayed near infrared ICG imaging and 488 nm autofluorescence was observed across pathologies, likely arising from the retinal pigment epithelium (RPE). Only one subject demonstrated ICG signal on peripheral blood myeloid cells and only three distinct cell-sized signals appeared over time within the retina of three participants. No significant increase in immune cell activation markers were detected after ICG administration. ICG accumulated in the endosomes of macrophage cultures and was detectable above a minimum concentration, suggesting cell labelling is possible. ICG can label RPE and may be used as an additional biomarker for RPE health across a range of retinal disorders. Standard clinical doses of intravenous ICG do not lead to robust immune cell labelling in human blood or retina and further optimisation in dose and route are required.

Graves orbitopathy, also known as thyroid eye disease or thyroid-associated orbitopathy, is visually disabling, cosmetically disfiguring and has a substantial negative impact on a patient’s quality of life. There is increasing awareness of the need for early diagnosis and rapid specialist input from endocrinologists and ophthalmologists. Glucocorticoids are the mainstay of treatment; however, recurrence occurs frequently once these are withdrawn. Furthermore, in >60% of cases, normal orbital anatomy is not restored, and skilled rehabilitative surgery is required. Clinical trials have shown that considerable benefit can be derived from the addition of antiproliferative agents (such as mycophenolate or azathioprine) in preventing deterioration after steroid cessation. In addition, targeted biologic therapies have shown promise, including teprotumumab, which reduces proptosis, rituximab (anti-CD20), which reduces inflammation, and tocilizumab, which potentially benefits both of these parameters. Other strategies such as orbital radiotherapy have had their widespread role in combination therapy called into question. The pathophysiology of Graves orbitopathy has also been revised with identification of new potential therapeutic targets. In this Review we provide an up-to-date overview of the field, outline the optimal management of Graves orbitopathy and summarize the research developments in this area to highlight future research questions and direct future clinical trials.

Introduction The NLST and NELSON studies demonstrated lung cancer mortality reduction from low-dose CT (LDCT) lung cancer screening. Local implementation pilots of ‘Lung Health Checks’ indicate feasibility in the NHS. NHS England will now fund 10 aligned projects for a national Lung Health Check pilot as a major centre-piece of the early diagnosis agenda of the NHS Long Term Plan. We report on methodological approaches to deliver this project and progress towards deployment. Methods Sites selected from Clinical Commissioning Groups in 10 Cancer Alliances had highest incidence and mortality from lung cancer, excluding those where screening pilots or research projects were already underway. Approximately 600,000 individuals will be invited with an expected 200,000 scans over the next four years, including baseline and 24 month incident round scanning. To support quality and governance, NHS England published a National Protocol (January 2019), are developing a Quality Assurance Framework, minimum dataset, Incidental Findings Protocol and Research Standard (assisted by CRUK). NHSE are supported by the CT Screening Advisory Committee, a sub-group of the Clinical Expert Group for Lung Cancer, NHSE. Cancer Alliances are being assisted in developing detailed delivery plans by the National Cancer Programme team. Results Detailed delivery plans have been provided by all regions. 47 radiologists will attend a national education program with clearly defined metrics for a national quality assurance training standard including volumetry and computer-aided detection. Standard participant materials are in production and QA evaluator appointed. Data on infrastructure readiness, progress against delivery milestones and final supporting documents relating to quality and governance will be presented. Conclusions The Lung Health Check program will be a major national flagship for respiratory medicine and a key component of the Long Term Plan aspirations to achieve early stage diagnosis in 75% of cancer cases. The program will inform the international literature on implementation of potentially revolutionary lung cancer screening but careful adherence to QA and demonstration of efficacy through appropriate evaluation is critical. Potential barriers include participant uptake; workforce capacity and data flow/information governance. The Standard Protocol is already being used by several European countries as a template for local protocol development. On behalf of the CT Screening Advisory Group, Clinical Expert Group for Lung Cancer and NHS England National Cancer Team.

Purpose To investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design. Design Randomized, double-masked, 36-week, 3-period crossover clinical trial. Participants Fifty-six subjects with DME involving the center of the macula in one or both eyes. Methods Monthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg). Main Outcome Measures Comparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model. Results Based on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was −89 μm for bevacizumab and −137 μm for ranibizumab (difference, 48 μm; P Conclusions This trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab, ranibizumab, and aflibercept for DME. The 3-period crossover design allowed for meaningful and efficient comparison, suggesting that this approach may be useful for future comparative efficacy studies of anti–vascular endothelial growth factor drugs for DME.

Highlights • The immediate morbidity from COVID-19 is high in UK thoracic cancer patients. • Mortality, hospitalisation and treatment interruption rates were high. • All patients who died were current or ex-smokers., Background UK COVID-19 mortality rates are amongst the highest globally. Controversy exists on the vulnerability of thoracic cancer patients. We describe the characteristics and sequelae of patients with thoracic cancer treated at a UK cancer centre infected with COVID-19. Methods Patients undergoing care for thoracic cancer diagnosed with COVID-19 (RT-PCR/radiology/clinically) between March-June 2020 were included. Data were extracted from patient records. Results Thirty-two patients were included: 14 (43%) diagnosed by RT-PCR, 18 (57%) by radiology and/or convincing symptoms. 88% had advanced thoracic malignancies. Eleven of 14 (79%) patients diagnosed by RT-PCR and 12 of 18 (56%) patients diagnosed by radiology/clinically were hospitalised, of which four (29%) and 2 (11%) patients required high-dependency/intensive care respectively. Three (21%) patients diagnosed by RT-PCR and 2 (11%) patients diagnosed by radiology/clinically required non-invasive ventilation; none were intubated. Complications included pneumonia and sepsis (43% and 14% respectively in patients diagnosed by RT-PCR; 17% and 11% respectively in patients diagnosed by radiology/clinically). In patients receiving active cancer treatment, therapy was delayed/ceased in 10/12 (83%) and 7/11 (64%) patients diagnosed by RT-PCR and radiology/clinically respectively. Nine (28%) patients died; all were smokers. Median time from symptom onset to death was 7 days (range 3–37). Conclusions The immediate morbidity from COVID-19 is high in thoracic cancer patients. Hospitalisation and treatment interruption rates were high. Improved risk-stratification models for UK cancer patients are urgently needed to guide safe cancer-care delivery without compromising efficacy.

Purpose To determine longer-term outcomes of participants enrolled from a single center in the SYCAMORE trial, a randomized placebo-controlled trial of adalimumab versus placebo in children with juvenile idiopathic arthritis-associated uveitis (JIA-U) uncontrolled on methotrexate. Design Retrospective interventional case series. Methods Medical records of all 28 SYCAMORE participants recruited at the Bristol Eye Hospital were reviewed at approximately 3-monthly intervals up to 5 years from the trial randomization date. Uveitis activity, treatment course, visual outcomes, ocular complications and adverse events were recorded. Data are presented using summary statistics. Results Following withdrawal of the investigational medicinal product (IMP), 25 of the 28 participants were started on adalimumab for active juvenile idiopathic arthritis-associated uveitis (JIA-U). Of the 12 participants in the active treatment arm of the SYCAMORE study, 11 (92%) were restarted on adalimumab after withdrawal of the IMP for active JIA-U (median time to flare 188 days (range 42-413)). Two participants stopped adalimumab for uncontrolled JIA-U. One participant had a reduction in vision to 0.3 due to cataract. Mean visual acuity for the remaining 27 participants was -0.04 (right eye) and -0.05 (left eye). Conclusions Drug-induced remission of JIA-U did not persist when adalimumab was withdrawn after 1-2 years treatment. Adalimumab was well tolerated and visual acuity outcomes were excellent.

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 ...

Background: Standard treatment for thyroid eye disease is with systemic corticosteroids. We aimed to establish whether orbital radiotherapy or antiproliferative immunosuppression would confer any additional benefit. Methods: CIRTED was a multicentre, double-blind, randomised controlled trial with a 2 × 2 factorial design done at six centres in the UK. Adults with active moderate-to-severe thyroid eye disease associated with proptosis or ocular motility restriction were recruited to the trial. Patients all received a 24 week course of oral prednisolone (80 mg per day, reduced to 20 mg per day by 6 weeks, 10 mg per day by 15 weeks, and 5 mg per day by 21 weeks) and were randomly assigned via remote computerised randomisation to receive either radiotherapy or sham radiotherapy and azathioprine or placebo in a 2 × 2 factorial design. Randomisation included minimisation to reduce baseline disparities in potential confounding variables between trial interventions. Patients and data analysts were masked to assignment, whereas trial coordinators (who monitored blood results), pharmacists, and radiographers were not. The radiotherapy dose was 20 Gy administered to the retrobulbar orbit in ten to 12 fractions over 2 to 3 weeks. Azathioprine treatment was provided for 48 weeks at 100–200 mg per day (dispensed as 50 mg tablets), depending on bodyweight (100 mg for interaction=0·86). The adjusted odds ratio (ORadj) for improvement in the binary clinical composite outcome measure was 2·56 (95% CI 0·98–6·66, p=0·054) for azathioprine and 0·89 (0·36–2·23, p=0·80) for radiotherapy. In a post-hoc analysis of patients who completed their allocated therapy the ORadj for improvement was 6·83 (1·66–28·1, p=0·008) for azathioprine and 1·32 (0·30–4·84, p=0·67) for radiotherapy. The ophthalmopathy index, clinical activity score, and numbers of adverse events (161 with azathioprine and 156 with radiotherapy) did not differ between treatment groups. In both groups, the most common adverse events were mild infections. No patients died during the study. Interpretation: In patients receiving oral prednisolone for 24 weeks, radiotherapy did not have added benefit. We also did not find added benefit for addition of azathioprine in the primary analysis; however, our conclusions are limited by the high number of patients who withdrew from treatment. Results of post-hoc analysis of those who completed the assigned treatment suggest improved clinical outcome at 48 weeks with azathioprine treatment. Funding: National Eye Research Centre, Above and Beyond, and Moorfields Eye Charity.

Purpose: To report a case of juxtafoveal choroidal neovascularization in a patient with candida chorioretinitis successfully treated with intravitreal bevacizumab. Methods: Case report. Results: A 45-year-old woman previously treated for candida chorioretinitis was presented with reduced vision in the left eye. The patient was investigated with ophthalmoscopy, fluorescein angiography, and optical coherence tomography (OCT). Following initial treatment, fundus examination, fluorescein angiography, and OCT of the right eye revealed a secondary juxtafoveal classic choroidal neovascularization. Following a single intravitreal injection of bevacizumab, the patient had excellent visual recovery, with absence of subretinal or intraretinal fluid in the OCT. Conclusions: Bevacizumab was effective in treatment of choroidal neovascularization associated with candida chorioretinitis.

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.

Cardiac emergencies in pregnancy and the postpartum period are rare but often life-threatening. An emergency physician’s differential diagnosis for chest pain in the peripartum patient often includes serious etiologies such as pulmonary embolism or myocardial infarction (MI). A lesser-known but important consideration on the differential for MI is that of a spontaneous coronary artery dissection (SCAD). SCAD is defined as an intramural hematoma within the coronary artery that compresses the true lumen. Expansion by increased pressures may lead to subsequent myocardial ischemia and infarction. This condition is the most common cause of pregnancy-associated MI and is reported as the cause of MI in 24% to 35% of all women younger than 50 years. This condition is predominately seen in young healthy females with no traditional risk factors for coronary artery or cardiac disease, and typically in the postpartum period. SCAD in the peripartum period is defined as pregnancy-associated spontaneous coronary artery dissection (PASCAD). Abnormal ECG changes, elevated troponins, and regional wall motional abnormalities on echocardiography are all diagnostic findings of SCAD, which can be ultimately confirmed with coronary angiography. Failure to immediately address this condition can lead to acute heart failure, cardiogenic shock, and death. Thrombolytic treatment may be harmful and is not recommended, and percutaneous coronary intervention can result in the iatrogenic propagation of further coronary dissection. As a result, the management for suspected SCAD involves emphasis on urgent transfer and urgent coronary artery angiography to determine appropriate treatment modalities.

Thyroid eye disease (TED) is a potentially sight-threatening and cosmetically disfiguring condition arising in 25–50% of patients with Graves’ hyperthyroidism. CIRTED is the first study to evaluate the long-term role of radiotherapy and prolonged immunosuppression with azathioprine in treating TED, one aim of which was to validate the use of the English version of GO-QOL in an UK population with TED. In a three stage design over a 48 week period, the GO-QOL was tested and compared to a general measure of quality of life (WHOQOL-Bref). In stage 1 utilising a standard 14 day test-retest design both GO-QOL subscales achieved Cronbach’s alphas demonstrating excellent validity and internal reliability (Visual Function 0.929 and 0.931; Appearance 0.888 and 0.906). In stage 2, Repeated Measures ANOVA demonstrated longitudinal validity, with both subscales of the GO-QOL showing significant change over time (Visual Function, η2 = 0.114, p < .001; Appearance, η2 = 0.069, p < .002). In stage 3 the GO-QOL showed discriminant validity at the week 48 time point, with the visual function subscale being able to detect changes in groups identified by clinicians (using BCCOM ratings of improvement or deterioration), while both subscales could detect group differences when based on participants’ subjective ratings of TED noticeability and severity. The results of this project provide support for the English translation of the GO-QOL as an outcome measure for patients with moderately severe active Graves’ orbitopathy/TED

Background Bronchiectasis is a chronic lung condition commonly affecting adults in middle to later years. Quality of life can be poor with a chronic, productive cough, dyspnoea and significant fatigue. Treatments aim to reduce symptoms, exacerbation frequency and severity, preserve lung function and improve health related quality of life. Regular, often twice daily nebulised antibiotics are commonly used in managing bronchiectasis. This patient population typically has severe bronchiectasis requiring multiple other medications. Little is known on patients’ views and preferences for such therapies. We aimed to assess this and define patient preferences and experiences. Methods We conducted three focus groups and three single interviews to define patients’ experience of nebulised antibiotics. 19 patients and/or carers attended focus groups providing in-depth information of lived experience using inhaled antibiotics. Thematic data analysis (TA) was used to derive a patient experience survey and a further 120 adult bronchiectasis patients completed surveys. Results Thematic analysis of the focus group data identified that many patients found nebulised therapy an imposition on their daily routine and this impaired adherence. Reducing treatment burden/time administering therapy was important. Others reported that nebulisation time was a period of rest, often incorporated into daily routines. The survey data showed although 70% of those currently taking nebulised antibiotics found them easy/very easy to administer, 10% found these hard/very hard to administer. 20% found taking the nebuliser in front of others “uncomfortable”. When nebulising, 47% excluded themselves in a separate room on a daily basis. 53% stopped nebulised therapy during vacations. If an inhaler that was as effective as nebulised therapy at preventing exacerbations was available 76% strongly agreed/agreed that they preferred an antibiotic delivered by an inhaler over a nebuliser if it was as effective at preventing exacerbations. 16% stated a preference for nebulised. Notably, only 10% wished to remain on nebulised therapy. Conclusions Bronchiectasis patients do not fully adhere with current treatments based upon treatment burden, life experience and lay knowledge. Inhaled antibiotics via dry power devices are quicker and easier to use and preferred by patients providing they were at least as effective as current nebulised treatments.

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.

Purpose To obtain measurements of vitreous signal intensity from optical coherence tomography (OCT) image sets in patients with uveitis, with the aim of developing an objective, quantitative marker of inflammatory activity in patients with this disease. Design Retrospective, observational case-control series. Participants Thirty patients (30 eyes) with vitreous haze secondary to intermediate, posterior, or panuveitis; 12 patients (12 eyes) with uveitis but without evidence of vitreous haze; and 18 patients (18 eyes) without intraocular inflammation or vitreoretinal disease. Methods Clinical and demographic characteristics were recorded, including visual acuity (VA), diagnosis, and anatomic type of uveitis. In each eye, the anterior chamber (AC) was graded for cellular activity and flare according to standardized protocols. The presence and severity of vitreous haze were classified according to the National Eye Institute system. Spectral-domain OCT images were analyzed using custom software. This software provided an "absolute" measurement of vitreous signal intensity, which was then compared with that of the retinal pigment epithelium (RPE), generating an optical density ratio with arbitrary units ("VIT/RPE-Relative Intensity"). Main Outcome Measures Correlation between clinical vitreous haze scores and OCT-derived measurements of vitreous signal intensity. Results The VIT/RPE-Relative Intensity was significantly higher in uveitic eyes with known vitreous haze (0.150) than in uveitic eyes without haze or in healthy controls (0.0767, P = 0.0001). The VIT/RPE-Relative Intensity showed a significant, positive correlation with clinical vitreous haze scores ( r = 0.566, P = 0.0001). Other ocular characteristics significantly associated with VIT/RPE-Relative Intensity included VA ( r = 0.573, P = 0.0001), AC cells ( r = 0.613, P = 0.0001), and AC flare ( r = 0.385, P = 0.003). Measurement of VIT/RPE-Relative Intensity showed a good degree of intergrader reproducibility (95% limits of agreement, −0.019 to 0.016). Conclusions These results provide preliminary evidence that OCT-derived measurements of vitreous signal intensity may be useful as an outcome measure in patients with uveitis. If validated in future studies, such measures may serve as an objective, quantitative disease activity end point, with the potential to improve the "signal:noise" ratio of clinical trials in this area, thus enabling smaller studies for the same power. The incorporation of automated vitreous analysis in commercial OCT systems may, in turn, facilitate monitoring and re-treatment of patients with uveitis in clinical practice.

The term autoimmune retinopathy encompasses a spectrum of rare autoimmune diseases that affect retinal function, often but not exclusively at the level of the photoreceptor. They typically present with painless visual loss, which may be accompanied by normal fundus examination. Some are progressive, often rapidly. They present a diagnostic challenge because there are no standardised clinical or laboratory based diagnostic criteria. Included within the spectrum are cancer-associated retinopathy, melanoma-associated retinopathy and presumed non-paraneoplastic autoimmune retinopathy. Differentiation from other retinopathies can be challenging, with overlap in symptoms, signs, and investigation findings, and an absence of pathognomonic features. However, technological developments in ophthalmic imaging and serological investigation over the past decade are adding novel dimensions to the investigation and classification of patients with these rare diseases. This review addresses the clinical, imaging, and serological features of the autoimmune retinopathies, and discusses the relative strengths and limitations of candidate diagnostic features.

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.

PURPOSE: To report the clinical outcomes of adalimumab therapy in cases of birdshot chorioretinitis (BCR) with cystoid macular edema (CME) refractory to conventional immunotherapy.METHODS: This is a retrospective case series of three BCR patients treated with adalimumab for refractory CME. The main outcome measure was central subfield thickness (CST) on optical coherence tomography. Any patients treated with local steroids and/or receiving systemic steroids higher than 40 mg prednisolone daily during adalimumab therapy were excluded.RESULTS: At baseline, all patients were receiving systemic corticosteroids and two second-line immunosuppressive agents. The mean duration of treatment with adalimumab was 31.2 months (range 17.2-52). The mean CST was 327 ± 112.7 μm (mean ± SD) at baseline and 256.2 ± 39.7 μm at 6 months and 235.5 ± 32.5 μm at 12 months. Adalimumab permitted cessation or reduction in the daily dose of oral prednisolone plus withdrawal of a second-line agent in all patients.CONCLUSIONS: In these patients, adalimumab was effective in the treatment of refractory CME.

Background: Twice daily nebulised antibiotics are used in 10-20% of patients with bronchiectasis. This patient population typically has severe bronchiectasis requiring multiple treatments. Methods: 16 patients and/or carers attended focus groups providing in-depth information of lived experience using nebulised antibiotics. Thematic data analysis (TA) allowed questionnaire development that was applied to a larger group of users. Results: TA of the focus group data identified that many patients found nebulised therapy an imposition on their daily routine and impaired adherence. Reducing treatment burden / time taken was important. Others reported that nebulisation time was a period of rest, incorporated into fixed daily routines. Data from questionnaires showed 70% of patients currently taking nebulised antibiotics found them easy/very easy to administer, 10% found these hard/very hard to administer. 20% found taking the nebuliser in front of others “uncomfortable”. When nebulising, 47% excluded themselves in a separate room. 53% stopped nebulised therapy during vacations. If an inhaler was available, that was as effective as nebulised therapy at preventing exacerbations, 53% strongly agreed/agreed that they preferred an antibiotic delivered by an inhaler over a nebuliser. 16% stated a preference for nebulised. 10% wished to remain on nebulised therapy. Conclusions: Bronchiectasis patients do not fully adhere with their treatments citing treatment burden, lay knowledge and previous experience. Clinicians should recognise challenges to adherence and act in partnership to promote treatment options that facilitate concordance.

© 2016 PUBLISHED BY ELSEVIER INC. Purpose To develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts. Design Modified Delphi process. Methods A survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement. Results There was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies. Conclusions Consensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study.

The ophthalmic manifestations of dengue fever include a visually impairing maculopathy, where patients are left with a central or paracentral relative scotoma. The authors present a case of a 26-year-old female patient returning from Thailand with unilateral reduction in visual acuity and a central scotoma associated with dengue fever. The authors report the use of the optical coherence tomography angiography (OCTA) as a noninvasive imaging platform to demonstrate its value in showing the persistent changes corresponding to the functional central scotoma in dengue-related maculopathy, which often cannot be visualized clinically or by standard OCT and fundus fluorescein angiography. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:1057–1060.]

Purpose\ud \ud The purpose of the study was to report a case of multiple sclerosis (MS)-associated uveitis refractory to conventional immunosuppressants, with subsequent remission following treatment with alemtuzumab.\ud \ud \ud Methods\ud \ud Case report Patient was treated with intravenous alemtuzumab, a lymphocyte depleting anti-CD52 monoclonal antibody that has recently been approved for use in relapsing MS.\ud \ud \ud Results\ud \ud A 17-year-old female presented with bilateral optic neuritis and subsequently bilateral intermediate uveitis and secondary macular oedema. She was diagnosed with active relapsing MS for which she received treatment with alemtuzumab. The intraocular inflammation previously refractory to conventional immunosuppressants responded to alemtuzumab, inducing remission.\ud \ud \ud Conclusions\ud \ud To our knowledge, this is the first such report of alemtuzumab treatment in MS-associated ocular inflammatory disease and may demonstrate a potential utility for this drug in related conditions.

Pleuritic pain, a sharp discomfort near the chest wall exacerbated by inspiration is associated with a number of pathologies. Pulmonary embolus and infection are two common causes but diagnosis can often be challenging, both for experienced physicians and trainees. The underlying anatomy and pathophysiology of such pain and the most common aetiologies are presented. Clinical symptoms and signs that may arise alongside pleuritic pain are then discussed, followed by an introduction to the diagnostic tools such as the Wells’ score and current guidelines that can help to select the most appropriate investigation(s). Management of pulmonary embolism and other common causes of pleuritic pain are also discussed and highlighted by a clinical vignette.

Purpose To compare tacrolimus monotherapy with tacrolimus and prednisone therapy for the maintenance of disease remission in subjects with noninfectious posterior segment intraocular inflammation (PSII). Design Randomized, controlled, phase 2b, open-label, dual-center noninferiority trial. Participants Fifty-eight patients with sight-threatening PSII. Methods Patients requiring a second-line systemic immunosuppressive agent to control their PSII were treated with therapeutic doses of oral tacrolimus. Those subjects who subsequently were able to taper their prednisone dose to 10 mg daily without disease reactivation were assigned randomly either to stop prednisone or to continue 7.5 to 10 mg prednisone daily for 9 months. Main Outcome Measures Change in logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) and rate of patient withdrawal resulting from treatment inefficacy or intolerance. Results Thirty-five patients successfully tapered their prednisone to 10 mg daily. Of these, 16 were allocated randomly to receive tacrolimus monotherapy and 19 to continue taking prednisone and tacrolimus dual therapy. The difference in the mean change in VA for monotherapy compared with the dual therapy group was less than 1 logMAR letter (logMAR, −0.008; 95% confidence interval, −0.108 to 0.092; P = 0.870). The proportion of patients who tolerated treatment and maintained disease remission for 9 months after randomization also was similar in both groups (monotherapy, 62.5%; dual therapy, 68.4%; P = 0.694). All monotherapy treatment failures were the result of disease reactivation, whereas 50% of dual-therapy failures were the result of drug intolerance. Conclusions This study provides preliminary evidence that corticosteroids can be withdrawn in tacrolimus-treated patients who are able to achieve control of PSII with 10 mg prednisone daily, and any advantage of dual therapy in the prevention of disease reactivation was offset by its greater treatment intolerance. These findings support the further evaluation of corticosteroid-free treatment in future phase 3 trials (International Standard Randomised Controlled Trial Number Register identification, ISRCTN46576063). Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

The term pulmonary renal vasculitis syndrome describes a clinical syndrome of diffuse alveolar haemorrhage (DAH) complicating acute glomerulonephritis that often heralds severe, life-threatening systemic vasculitis requiring urgent, aggressive therapy. "Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis" and glomerular basement membrane ("Goodpasture's") disease are the commonest causes but other pathologies including systemic lupus erythematosus and the anti-phospholipid syndrome are also implicated. Such patients hence present most commonly to rheumatologists and nephrologists but usually require input from a number of specialties, respiratory and critical care medicine in particular. Such care is typically provided in specialist centres able to offer plasma exchange and experience in the use of immunosuppressants. We review clinical features, advances in therapy and understanding of pathophysiology.