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Background: Clinical trials of anti-inflammatories in schizophrenia do not show clear and replicable benefits, possibly because patients were not recruited based on elevated inflammation status. Interleukin 1-beta (IL-1β) mRNA and protein levels are increased in serum, plasma, cerebrospinal fluid, and brain of some chronically ill patients with schizophrenia, first episode psychosis, and clinical high-risk individuals. Canakinumab, an approved anti-IL-1β monoclonal antibody, interferes with the bioactivity of IL-1β and interrupts downstream signaling. However, the extent to which canakinumab reduces peripheral inflammation markers, such as, high sensitivity C-reactive protein (hsCRP) and symptom severity in schizophrenia patients with inflammation is unknown., Trial Design: We conducted a randomized, placebo-controlled, double-blind, parallel groups, 8-week trial of canakinumab in chronically ill patients with schizophrenia who had elevated peripheral inflammation., Methods: Twenty-seven patients with schizophrenia or schizoaffective disorder and elevated peripheral inflammation markers (IL-1β, IL-6, hsCRP and/or neutrophil to lymphocyte ratio: NLR) were randomized to a one-time, subcutaneous injection of canakinumab (150 mg) or placebo (normal saline) as an adjunctive antipsychotic treatment. Peripheral blood hsCRP, NLR, IL-1β, IL-6, IL-8 levels were measured at baseline (pre injection) and at 1-, 4- and 8-weeks post injection. Symptom severity was assessed at baseline and 4- and 8-weeks post injection., Results: Canakinumab significantly reduced peripheral hsCRP over time, F(3, 75) = 5.16, p = 0.003. Significant hsCRP reductions relative to baseline were detected only in the canakinumab group at weeks 1, 4 and 8 (p's = 0.0003, 0.000002, and 0.004, respectively). There were no significant hsCRP changes in the placebo group. Positive symptom severity scores were significantly reduced at week 8 (p = 0.02) in the canakinumab group and week 4 (p = 0.02) in the placebo group. The change in CRP between week 8 and baseline (b = 1.9, p = 0.0002) and between week 4 and baseline (b = 6.0, p = 0.001) were highly significant predictors of week 8 change in PANSS Positive Symptom severity scores. There were no significant changes in negative symptoms, general psychopathology or cognition in either group. Canakinumab was well tolerated and only 7 % discontinued., Conclusions: Canakinumab quickly reduces peripheral hsCRP serum levels in patients with schizophrenia and inflammation; after 8 weeks of canakinumab treatment, the reductions in hsCRP are related to reduced positive symptom severity. Future studies should consider increased doses or longer-term treatment to confirm the potential benefits of adjunctive canakinumab in schizophrenia. Australian and New Zealand Clinical Trials Registry number: ACTRN12615000635561., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to provide a retrospective analysis of the presentation, demographics, and treatment regimens for ocular toxoplasmosis at a large tertiary referral uveitis center., Design: Retrospective cohort study., Participants: A total of 48 patients with ocular toxoplasmosis who presented to Sydney Eye Hospital participated in this study., Methods: This is a retrospective review of patient files who presented to Sydney Eye Hospital between 2007 and 2016 with clinical features consistent with ocular toxoplasmosis. Baseline risk factors and treatment details were recorded and analyzed. Main outcome measures were visual acuity and relapse rate compared with other studies in ocular toxoplasmosis., Results: The median age was 35.5 (interquartile range 21-50) with 30 (60%) patients having no previous symptomatic episodes or evidence of chorioretinal scarring. Visual acuity at presentation was 0.51 or 6/19 (SE 0.096) and at follow-up 0.31 or 6/12 (SE 0.094). Nine patients experienced a recurrence during the period of observation with median time to recurrence 2.2 years (SE 0.45) and the relapse rate was 0.09/person-years. Location of lesion was predominantly within the vascular arcades (n = 44) with macular involvement in 9 patients. Most patients received clindamycin therapy (n = 34) with pyrimethamine and sulfadiazine was used for those with macula involvement., Conclusions: Patients with ocular toxoplasmosis had fewer recurrences compared with other published series and had better visual recovery. The majority of patients received clindamycin and oral prednisolone which were well tolerated with pyrimethazine and sulfadiazine reserved for those with macula-involving disease.

Aims: This study aimed to determine the incidence, clinical features and management of cicatrising conjunctivitis in Australia and New Zealand, also enabling comparison with data from the United Kingdom., Methods: A prospective surveillance study was conducted over 17 months via the Australian and New Zealand Ophthalmic Surveillance Unit with a one-year follow-up period. Practicing ophthalmologists on the Surveillance Unit's database were asked to report recently diagnosed cases of cicatrising conjunctivitis on a monthly basis. Initial and follow-up questionnaires were sent to ophthalmologists who had reported positive cases to obtain demographic and clinical data. The minimum incidence of cicatrising conjunctivitis was calculated based on cases reported during the study period and from population data., Results: During the 17-month study period (December 2011-April 2013), 56 cases of cicatrising conjunctivitis were reported. Data was obtained for 35 cases (62%) with a mean age of 74 years (range, 28-94 years). The most common aetiologies were ocular mucus membrane pemphigoid (n = 18 cases, 51.4%), Stevens-Johnson Syndrome (n = 3, 8.6%) and graft versus host disease (n = 3, 8.6%). The minimum incidence of cicatrising conjunctivitis in Australia and New Zealand was 1.5 per million, comparable to incidence data from the United Kingdom., Conclusions: This study is the first to prospectively record the incidence of cicatrising conjunctivitis in Australia and New Zealand and the second worldwide. It provides novel data on demographics and management of cicatrising conjunctivitis, as reported by treating ophthalmologists.

Sarcoidosis is a systemic disease of unknown aetiology, characterised by non-caseating granulomatous inflammation. It most commonly manifests in the lungs and intrathoracic lymph nodes but can affect any organ. This summary of an educational resource provided by the Thoracic Society of Australia and New Zealand outlines the current understanding of sarcoidosis and highlights the need for further research. Our knowledge of the aetiology and immunopathogenesis of sarcoidosis remains incomplete. The enigma of sarcoidosis lies in its immunological paradox of type 1 T helper cell-dominated local inflammation co-existing with T regulatory-induced peripheral anergy. Although specific aetiological agents have not been identified, mounting evidence suggests that environmental and microbial antigens may trigger sarcoidosis. Genome-wide association studies have identified candidate genes conferring susceptibility and gene expression analyses have provided insights into cytokine dysregulation leading to inflammation. Sarcoidosis remains a diagnosis of exclusion based on histological evidence of non-caseating granulomas with compatible clinical and radiological findings. In recent years, endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes has facilitated the diagnosis, and whole body positron emission tomography scanning has improved localisation of disease. No single biomarker is adequately sensitive and specific for detecting and monitoring disease activity. Most patients do not require treatment; when indicated, corticosteroids remain the initial standard of care, despite their adverse side effect profile. Other drugs with fewer side effects may be a better long term choice (eg, methotrexate, hydroxychloroquine, azathioprine, mycophenolate), while tumour necrosis factor-α inhibitors are a treatment option for patients with refractory disease.

Background: A healthy cornea is reliant on a distinct population of stem cells (SC) that replace damaged or aging epithelium throughout life. Depletion of the SC pool or damage to the niche can result in a blinding and painful condition known as limbal-SC deficiency (LSCD). Although current treatment strategies for reconstituting the ocular surface for patients suffering LSCD are promising, they are complicated by transferring autologous or allogeneic progenitors in the presence of animal, human, and synthetic products. We report on the safe and efficacy of a unique autologous SC transfer technique that utilizes an Food and Drug Administration-approved contact lens (CL) as the SC substrate and carrier for patients with LSCD., Methods: Three patients with LSCD due to aniridia (n=1) and posttreatment for recurrent ocular surface melanoma (n=2) were included. Limbal (n=2) or conjunctival biopsies (n=1) were harvested and progenitors expanded ex vivo on therapeutic CLs in the presence of autologous serum. Cell-laden CLs were transferred to the patient's corneal surface and clinical outcome measures were recorded (follow-up range, 8-13 months)., Results: A stable transparent corneal epithelium was restored in each patient. There was no recurrence of conjunctivalization or corneal vascularization, and a significant improvement in symptom score occurred in all patients. Best-corrected visual acuity was increased in all eyes after the procedure., Conclusion: Ex vivo expansion of ocular surface epithelium in the presence of autologous serum and transplantation with the aid of a soft CLs is a promising new technique capable of achieving ocular surface rehabilitation.

In our human psychoimmunological studies we have utilized a standardized assessment kit, the cell-mediated immunity (CMI) Multitest system, for determining delayed-type hypersensitivity (DTH) skin responses to a panel of ubiquitous antigens. Although the kit had been assessed in large populations of healthy controls in the U.S.A. and Europe, few data were available with regard to normative values in the Australian population. There are cogent reasons to suspect that results for the test will vary depending on geographical location, age cohort, compliance with specific immunization schedules and rates of natural exposure to certain diseases in differing populations. Most of our patient cohorts have a preponderance of female subjects and most standardization had been conducted in males. We tested medically and psychologically healthy males (n = 66) and females (n = 53). The percentage of positive responses to individual antigens was similar to other Australian studies but lower than that reported internationally. The mean number of positive responses was 3.7 for men and 2.8 for women, while the mean induration diameter was 17.5 mm for men and 12.2 mm for women. Three per cent of men and 5.6% of women were anergic (no positive responses), while a further 10.6% of men and 9.4% of women fell into the "hypoergic" category. These results, and those from other studies, indicate that the pattern of response to the CMI Multitest differs in healthy Australians. Therefore, researchers need to exercise caution when selecting patient and control samples (controlling for exposure factors), applying the test, reporting results (i.e. including all relevant parameters-with an emphasis on dimensional rather than categorical scores) and when designating subjects as having "impaired" responses.

Inflammatory eye disease (IED) is often the most severe manifestation of Behçet's syndrome (BS). This disease is a common cause of uveitis in Mediterranean countries, the Middle East and Japan. In order to ascertain the prevalence of this disease in Australia, we reviewed the aetiology of patients attending our uveitis clinic over a five-year period. Twelve of 426 patients with inflammatory eye disease had definite Behçet's syndrome. Four patients had anterior uveitis, four had posterior uveitis, four had retinal vasculitis and one also had optic neuritis. Although inflammatory eye disease was the initial clinical feature of Behçet's syndrome in only three of our patients, it was the feature that led to a definite diagnosis in all but one patient. The inflammatory eye disease of Behçet's syndrome was characteristically recurrent and severe with significantly decreased vision in 10 eyes, cataracts in six eyes, macula oedema in four eyes and glaucoma in two eyes. We conclude that Behçet's syndrome is a rare cause of inflammatory eye disease in Australia and is unlikely to be recognised as a distinct clinical entity prior to the onset of ocular involvement. The visual prognosis of ocular inflammation in Behçet's syndrome remains guarded despite the use of a variety of immunosuppressive agents.

Over a five-year period 245 patients with uveitis were investigated at the Uveitis Clinic, Sydney Eye Hospital, for possible aetiological and relevant disease associations. Uveitis was anterior in 75% of patients, posterior in 21% and generalized in 4%. Anterior uveitis (AU) was idiopathic in 52% of cases. In patients tested for the HLA-B27 antigen, 47% were HLA-B27 positive, including all cases of ankylosing spondylitis (8% of cases) and Reiter's syndrome (3% of cases). There was a marked male predominance in patients with AU, especially in HLA-B27 positive individuals. Posterior uveitis (PU) was most frequently unilateral, chronic and idiopathic (24% of cases), whilst recognizable aetiologies included toxoplasmosis (20%), Behcet's syndrome (14%), sarcoidosis (12%) and pars planitis (12%). The peak age of onset in patients presenting with AU was 30 to 40 years, whilst patients with PU presented a decade earlier. There were no major differences between males and females in the age of onset of their uveitis.

Infection due to yersinia enterocolitica is a common antecedent illness in patients with reactive arthritis in Scandinavia, but appears to be less frequent in other countries. In order to examine the frequency of yersinia infection in patients with seronegative arthritis in Australia we examined 22 patients, 15 with ankylosing spondylitis (AS) and seven with Reiter's syndrome (RS). A sensitive ELISA assay was used to detect serum antibodies to the most common serotypes. Six patients (29%) had positive yersinia serology, all were HLA B27 and four had a history of diarrhea preceding the onset of their disease. Four patients with positive yersinia serology had AS and two had RS. Antibodies were directed against Y. enterocolitica biotype 0:3 in three cases, Y. enterocolitica 0:9 in two cases and Y. enterocolitica 0:8 in one subject. Twenty-nine control subjects (13 HLA B27) had no serum antibodies to yersinia. The results of this study indicate that preceding yersinia infection occurs in a significant (p less than 0.05; compared to controls) proportion of patients with HLA B27 related seronegative arthropathies.

HLA antigens are associated with a number of inflammatory eye diseases, most notably HLA B2 with anterior uveitis (AU). This association varies between different populations and ethnic groups. The aim of this study was to investigate the relationship between uveitis and HLA A, B and DR locus antigens in an Australian population. Seventy-two consecutive patients with uveitis were studied (37 males and 35 females) over a 6 month period. Thirty-two percent of the AU patients were HLA B27+, as were 42% of males (19% females) with their first attack of AU compared with 60% of males (23% females) with recurrent AU. The only significant difference in etiology between males and females was the greatly increased incidence of rheumatic diseases in males, in whom 77% (10/13) had radiological evidence of sacroiliitis. Additional findings included a lack of association between the HLA B7 cross reactive group and DR locus antigens in AU as well as the lack of any HLA associations in the 13 patients with posterior uveitis (PU).