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Purpose To determine classification criteria for Fuchs uveitis syndrome. Design Machine learning of cases with Fuchs uveitis syndrome and 8 other anterior uveitides. Methods Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand eighty-three cases of anterior uveitides, including 146 cases of Fuchs uveitis syndrome, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for Fuchs uveitis syndrome included unilateral anterior uveitis with or without vitritis and either: 1) heterochromia or 2) unilateral diffuse iris atrophy and stellate keratic precipitates. The overall accuracy for anterior uveitides was 97.5% in the training set (95% confidence interval [CI] 96.3, 98.4) and 96.7% in the validation set (95% CI 92.4, 98.6). The misclassification rates for FUS were 4.7% in the training set and 5.5% in the validation set, respectively. Conclusions The criteria for Fuchs uveitis syndrome had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.

Purpose To determine classification criteria for juvenile idiopathic arthritis (JIA)-associated chronic anterior uveitis (CAU). Design Machine learning of cases with JIA CAU and 8 other anterior uveitides. Methods Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand eighty-three cases of anterior uveitides, including 202 cases of JIA CAU, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for JIA CAU included 1) chronic anterior uveitis (or if newly diagnosed insidious onset) and 2) JIA, except for the systemic, rheumatoid factor-positive polyarthritis, and enthesitis related arthritis variants. The misclassification rates for JIA CAU were 2.4% in the training set and 0% in the validation set, respectively. Conclusions The criteria for JIA CAU had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.

Purpose To determine classification criteria for varicella zoster virus (VZV) anterior uveitis DESIGN: Machine learning of cases with VZV anterior uveitis and 8 other anterior uveitides. Methods Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand eighty-three cases of anterior uveitides, including 123 cases of VZV anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for VZV anterior uveitis included unilateral anterior uveitis with either 1) positive aqueous humor polymerase chain reaction assay for VZV; 2) sectoral iris atrophy in a patient ≥60 years of age; or 3) concurrent or recent dermatomal herpes zoster. The misclassification rates for VZV anterior uveitis were 0.9% in the training set and 0% in the validation set, respectively. Conclusions The criteria for VZV anterior uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

*Correspondence - Saaeha Rauz: s.rauz@bham.ac.uk OBJECTIVES: Mucous Membrane Pemphigoid is an orphan multi-system autoimmune scarring disease involving mucosal sites, including the ocular surface (OcMMP) and gut. The gut microbiome plays a critical role in the development of the immune system. This study examines the relationship between gut microbiome diversity and ocular inflammation in patients with OcMMP.Gut microbiome profiles between OcMMP patients (n=49) and healthy controls (n=40) were compared by extracting DNA from faecal samples and amplified for the V4 region of the 16S rRNA gene followed by Illumina Miseq platform sequencing. Sequencing reads were processed using the bioinformatics pipeline available in the mothur v.1.44.1 software.Using multivariable model and adjustment for participant factors, OcMMP cohort was found to be associated with lower number of operational taxonomic units (OTUs) and Shannon Diversity Index when compared to healthy controls. OcMMP OTUs were found to be significantly correlated with both the bulbar conjunctival inflammation score (p=0.03) and the current use of systemic immunotherapy (p=0.02). Linear discriminant analysis effect size scores found Streptococcus and Lachnoclostridium enriched in OcMMP. By contrast, healthy controls were enriched with Oxalobacter, Clostridia uncultured genus-level group (UCG) 014, Christensenellaceae R-7 group and butyrate-producing bacteria such as Ruminococcus, Lachnospiraceae, Coprococcus, Roseburia, Oscillospiraceae UCG 003, 005, NK4A214 group (Log10 LDA score2, FDR-adjusted p0.05).In conclusion, OcMMP patients have gut dysbiosis that correlated with bulbar conjunctival inflammation and the use of systemic immunotherapies. This provides a framework for future longitudinal deep phenotyping studies on the role of the gut microbiome in the pathogenesis of OcMMP.Low L, Suleiman K, Shamdas M, Bassilious K, Poonit N, Rossiter AE, Acharjee A, Loman N, Murray PI, Wallace GR, Rauz S. Gut dysbiosis in ocular mucous membrane pemphigoid.

To measure health utilities Time Trade-Off (TTO) and Standard Gamble (SG) in Behcet's disease (BD), and explore the interrelationships with EQ-5D-5L, disease activity, depression, anxiety and fatigue.TTO, SG, EQ-5D-5L, EQ VAS, depression (PHQ-9), anxiety (GAD-7) and fatigue (MAF) questionnaires were administered to 103 adult BD patients. Disease activity was assessed using the Behçet's Disease Activity Index (BDAI).Mean TTO was 0.72 ± SD 0.27, mean SG 0.70 ± SD 0.34, and mean EQ-5D-5L 0.519 ± SD 0.315. Moderate to severe depression was identified in 55.2%, moderate to severe anxiety in 35.1% and moderate to high fatigue in 97.7% patients. TTO correlated with SG (p 0.01), EQ-5D-5L (p 0.01) and negatively correlated with depression (p 0.01), anxiety (p 0.01) and fatigue (p 0.01). Multiple linear regression showed SG was the only predictor of TTO (p = 0.002). Cluster analysis revealed one cluster where psychological factors rather than disease activity may have influenced TTO and SG scores.TTO and SG show that BD patients would on average forgo 28% of their remaining life or run a 30% risk of death to avoid the condition. Complex interrelationships with depression, anxiety and fatigue appear to play an important role in their decision making.

OBJECTIVES: To ascertain adherence to an international consensus target of ≤7.5 mg/day of prednisolone for maintenance systemic corticosteroid (CS) prescribing in uveitis and report the frequency of courses of high-dose systemic CS in the UK. METHODS: We conducted a national, multicentre audit of systemic CS prescribing for uveitis at 11 UK sites between November 2018 and March 2019. High-dose CS was defined as (1) maintenance >7.5 mg prednisolone for >3 consecutive months, or (2) >1 course ≥40 mg oral CS or ≥500 mg intravenous (IV) methylprednisolone in the past 12 months. Case notes of patients exceeding threshold CS doses were reviewed by an independent uveitis specialist and judged as avoidable or not, based upon a scoring matrix. RESULTS: Of 667 eligible patients, 285 (42.7%) were treated with oral or IV CS over the preceding 12 months; 96 (33.7%) of these exceeded the threshold for high-dose CS. Twenty-five percent of prescribing in patients on excess CS was judged avoidable; attributed to either prescribing long-term CS without evidence of consideration of alternative strategies, prescribing error or miscommunication. More patients received immunomodulatory therapy (IMT) in the group treated with CS above threshold than below threshold (p

To create a health utility value for birdshot chorioretinopathy (BCR) using Time Trade-Off (TTO) and Standard Gamble (SG) utilities.Adult BCR patients completed TTO, SG, EQ-5D-5L, and NEI VFQ-25 questionnaires and underwent a detailed history and clinical examination.A total of 28 BCR patients (9 M, 19 F; mean age 62 years, range 47-83) were included. There were 22 patients with a logMAR vision of 0.3 or better in both eyes. Mean TTO was 0.90 ± SD 0.18 (range 0.33-1.0) and mean SG was 0.94 ± SD 0.14 (range 0.5-1.0). TTO correlated with EQ-5D-5L index value (Of 28 patients with BCR, 11 would trade remaining life (mean 5.4 years), and 6 would take a risk of immediate death (mean 28% risk), in return for perfect vision in both eyes for the rest of their life.

Mucous Membrane Pemphigoid is an orphan multi-system autoimmune scarring disease involving mucosal sites, including the ocular surface (OcMMP) and gut. Loss of tolerance to epithelial basement membrane proteins and generation of autoreactive T cell and/or autoantibodies are central to the disease process. The gut microbiome plays a critical role in the development of the immune system. Alteration in the gut microbiome (gut dysbiosis) affects the generation of autoreactive T cells and B cell autoantibody repertoire in several autoimmune conditions. This study examines the relationship between gut microbiome diversity and ocular inflammation in patients with OcMMP by comparing OcMMP gut microbiome profiles with healthy controls. DNA was extracted from faecal samples (49 OcMMP patients, 40 healthy controls), amplified for the V4 region of the 16S rRNA gene and sequenced using Illumina Miseq platform. Sequencing reads were processed using the bioinformatics pipeline available in the mothur v.1.44.1 software. After adjusting for participant factors in the multivariable model (age, gender, BMI, diet, proton pump inhibitor use), OcMMP cohort was found to be associated with lower number of operational taxonomic units (OTUs) and Shannon Diversity Index when compared to healthy controls. Within the OcMMP cohort, the number of OTUs were found to be significantly correlated with both the bulbar conjunctival inflammation score (p=0.03) and the current use of systemic immunotherapy (p=0.02). The linear discriminant analysis effect size scores indicated that Streptococcus and Lachnoclostridium were enriched in OcMMP patients whilst Oxalobacter, Clostridia uncultured genus-level group (UCG) 014, Christensenellaceae R-7 group and butyrate-producing bacteria such as Ruminococcus, Lachnospiraceae, Coprococcus, Roseburia, Oscillospiraceae UCG 003, 005, NK4A214 group were enriched in healthy controls (Log10 LDA score < 2, FDR-adjusted p

PurposeTo reassess the underlying pathophysiology of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and relentless placoid chorioretinitis (RPC) through comparison with the non-inoculated eye of the von Szily animal model of neurotropic viral retinal infection.MethodsNarrative review.ResultsLiterature reports of isolated neurotropic viral entities and rising serological viral titers in APMPPE after presentation support a potential direct infective etiology. In general, viral transport along axons results in mitochondrial stasis and disruption of axoplasmic flow. Clinical manifestations of axoplasmic flow disruption in APMPPE/RPC may signify the passage of virus along the neuronal pathway. From a case series of 11 patients, we demonstrate a timely, spatial, and proportional association of optic disc swelling with APMPPE lesion occurrence. Signs within the inner retina appear to precede outer retinal lesions; and acute areas of outer nuclear layer (ONL) hyperreflectivity appear to be the result of coalescence of multiple hyperreflective foci resembling axonal spheroids (which occur as a consequence of axoplasmic disruption) and follow the Henle fiber layer neurons. Underlying areas of retinal pigment epithelium (RPE) hyper-autofluorescence follow ONL hyperreflectivity and may signify localized infection. Areas of apparent choriocapillaris hypoperfusion mirror areas of RPE/Bruch’s membrane separation and appear secondary to tractional forces above. Increases in choroidal thickness with lesion occurrence and focal areas of choriocapillaris hypoperfusion are observed in both APMPPE/RPC and the von Szily model.ConclusionsThe neurotrophic infection model provides significant advantages over the existing primary choriocapillaris ischemia hypothesis to account for the range of imaging signs observed in APMPPE and RPC.

BackgroundOcular toxoplasmosis is common across all regions of the world. Understanding of the epidemiology and approach to diagnosis and treatment have evolved recently. In November 2020, an international group of uveitis-specialised ophthalmologists formed the International Ocular Toxoplasmosis Study Group to define current practice.Methods192 Study Group members from 48 countries completed a 36-item survey on clinical features, use of investigations, indications for treatment, systemic and intravitreal treatment with antiparasitic drugs and corticosteroids, and approach to follow-up and preventive therapy.ResultsFor 77.1% of members, unilateral retinochoroiditis adjacent to a pigmented scar accounted for over 60% of presentations, but diverse atypical presentations were also reported. Common complications included persistent vitreous opacities, epiretinal membrane, cataract, and ocular hypertension or glaucoma. Most members used clinical examination with (56.8%) or without (35.9%) serology to diagnose typical disease but relied on intraocular fluid testing—usually PCR—in atypical cases (68.8%). 66.1% of members treated all non-pregnant patients, while 33.9% treated selected patients. Oral trimethoprim–sulfamethoxazole was first-line therapy for 66.7% of members, and 60.9% had experience using intravitreal clindamycin. Corticosteroid drugs were administered systemically by 97.4%; 24.7% also injected corticosteroid intravitreally, almost always in combination with an antimicrobial drug (72.3%). The majority of members followed up all (60.4%) or selected (35.9%) patients after resolution of acute disease, and prophylaxis against recurrence with trimethoprim–sulfamethoxazole was prescribed to selected patients by 69.8%.ConclusionOur report presents a current management approach for ocular toxoplasmosis, as practised by a large international group of uveitis-specialised ophthalmologists.

Objective Ophthalmic complications in Systemic Lupus Erythematosus (SLE) are broad and can occur in up to a third of patients. The British Isles Lupus Assessment Group (BILAG) 2004 Index identifies 13 ocular manifestations of active SLE, as opposed to those related to previous disease activity and/or the consequences of therapy. We conducted a systematic review of published literature to determine the frequency of ophthalmic manifestations of active SLE. Methods A systematic literature search of Ovid MEDLINE and EMBASE from their respective inceptions to July 2020 was conducted to identify cohort, case–control and cross-sectional studies. Results 22 studies meeting eligibility criteria were included. Most studies featured small sample sizes and were judged to have a high risk of methodological bias. The number and quality of studies did not allow us to confidently estimate the incidence of the conditions. No studies reported epidemiological data for orbital inflammation/myositis/proptosis. The prevalence of each of the other ocular manifestations, with the exception of retinal vaso-occlusive disease, was consistently less than 5%. Retinal vasculitis, uveitis and isolated cotton wool spots tended to be associated with more active SLE disease. Conclusion The prevalence of eye disease due to SLE activity is uncommon, but clinicians should be aware that some conditions tend to be associated with more active systemic disease. Further studies to determine the incidence and risk factors for these ophthalmic manifestations are needed.

To evaluate the utility of nanopore sequencing for identifying potential causative pathogens in endophthalmitis, comparing culture results against full-length 16S rRNA nanopore sequencing (16S Nanopore), whole genome nanopore sequencing (Nanopore WGS), and Illumina (Illumina WGS).Cross-sectional diagnostic comparison.Patients with clinically suspected endophthalmitis underwent intraocular vitreous biopsy as per standard care. Clinical samples were cultured by conventional methods, together with full-length 16S rRNA and WGS using nanopore and Illumina sequencing platforms.Of 23 patients (median age 68.5 years [range 47-88]; 14 males [61%]), 18 cases were culture-positive. Nanopore sequencing identified the same cultured organism in all of the culture-positive cases and identified potential pathogens in two culture-negative cases (40%). Nanopore WGS was able to additionally detect the presence of bacteriophages in three samples. The agreements at genus level between culture and 16S Nanopore, Nanopore WGS, and Illumina WGS were 75%, 100%, and 78%, respectively.Whole genome sequencing has higher sensitivity and provides a viable alternative to culture and 16S sequencing for detecting potential pathogens in endophthalmitis. Moreover, WGS has the ability to detect other potential pathogens in culture-negative cases. Whilst Nanopore and Illumina WGS provide comparable data, nanopore sequencing provides potential for cost-effective point-of-care diagnostics.

Purpose: To study the complication rate of Nd:YAG laser posterior capsulotomy in patients with uveitis.Method: Retrospective case note analysis of pseudophakic uveitis patients having undergone Nd:...

Objective Behçet’s disease (BD) is a multisystem autoinflammatory disease characterised by mucosal ulceration, ocular, neural, joint and skin inflammation. The cause of BD is not known but there is a strong genetic association with HLA-B*51, IL10 and IL23R. Neutrophils are a first line of defence against invading pathogens and have been described as activated in patients with BD. Neutrophils can now be separated into different subsets, such as low density (LDN) and normal density (NDN) that have diverse functional roles. We wished to address neutrophil heterogeneity in patients with BD. MethodsPeripheral blood neutrophils were obtained from 32 BD patients and 37 healthy aged-matched controls. Percoll isolation was used to isolate all neutrophils, while Ficol-Hypaque was used to obtain LDN and NDN. Phagocytic capacity and production of reactive oxygen species (ROS), and neutrophil extracellular traps (NET) stimulated with phorbol 12-myristate 13-acetate (PMA) and Escherichia coli (E.coli) were assessed in both groups. Results We have demonstrated reduced phagocytic capacity and ROS production but greater NET production by total neutrophils stimulated with PMA or E.coli from BD patients in comparison with healthy controls. Patients with BD had elevated numbers of LDN and lower number of NDN compared with healthy controls. However, both neutrophil subsets showed the same reduced ROS production and phagocytic function as total neutrophils in both 41 groups. Conclusion Our novel findings indicate that the neutrophil population in BD is heterogeneous and the increased number of LDN in combination with greater NET production may contribute to the inflammatory response and pathogenesis.

BackgroundUveitis refers to a range of conditions that result in intraocular inflammation. Non-infectious Intermediate, posterior and panuveitis are the most serious forms of uveitis grouped as Non-Infectious Uveitis affecting the Posterior Segment (NIU-PS). To evaluate new and existing treatments trialists and clinicians aim to report certain measurements known as outcomes. The aim of this study was to understand the perspectives of healthcare professionals on what outcomes they thought important for adult patients with NIU-PS and their carers.MethodsTwelve semi-structured telephone interviews were undertaken to understand the perspectives of healthcare professionals - ophthalmologists (n=5), nurse practitioners (n=3) and health policy-makers/commissioners (n=4) on outcomes for NIU-PS. Interviews were audio recorded, transcribed and thematically analysed and a domain framework developed with focus group data from patients and carers applied to the data. Findings were compared with the views of patients and carers and outcomes abstracted from a previously published systematic review.ResultsEleven core domains were identified as important to healthcare professionals, which is broadly comparable to those previously identified by patients and carers: (1) visual function, (2) symptoms, (3) functional ability, (4) impact on relationships, (5) financial impact, (6) psychological morbidity and emotional well-being (7) psychosocial adjustment to uveitis, (8) doctor / patient / interprofessional relationships and access to health care, (9) treatment burden, (10) treatment side effects, (11) disease control. Healthcare professionals placed more emphasis on some items and identified additional outcomes, particularly in the disease control domain.ConclusionAlthough healthcare professionals recognise all of the same domains as patients/carers these findings are not yet implemented in practice or clinical research. These findings provide the basis to reflect on the nature of those outcomes at present used in uveitis clinical practice and clinical trials with those utilised in the development process of a core outcome set for NIU-PS.

PURPOSE: To determine classification criteria for cytomegalovirus (CMV) anterior uveitis DESIGN: Machine learning of cases with CMV anterior uveitis and 8 other anterior uveitides. METHODS: Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final datafubase was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. RESULTS: One thousand eighty-three of cases of anterior uveitides, including 89 cases of CMV anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for CMV anterior uveitis included unilateral anterior uveitis with a positive aqueous humor polymerase chain reaction assay for CMV. No clinical features reliably diagnosed CMV anterior uveitis. The misclassification rates for CMV anterior uveitis were 1.3 % in the training set and 0% in the validation set, respectively. CONCLUSIONS: The criteria for CMV anterior uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

PURPOSE: To determine classification criteria for herpes simplex virus (HSV) anterior uveitis DESIGN: Machine learning of cases with HSV anterior uveitis and 8 other anterior uveitides. METHODS: Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. RESULTS: One thousand eighty-three of cases of anterior uveitides, including 101 cases of HSV anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for HSV anterior uveitis included unilateral anterior uveitis with either 1) positive aqueous humor polymerase chain reaction assay for HSV; 2) sectoral iris atrophy in a patient ≤50 years of age; or 3) HSV keratitis. The misclassification rates for HSV anterior uveitis were 8.3% in the training set and 17% in the validation set, respectively. CONCLUSIONS: The criteria for HSV anterior uveitis had a reasonably low misclassification rate and appeared to perform well enough for use in clinical and translational research.

Background Microbial keratitis (MK) is the most common non-surgical ophthalmic emergency, and can rapidly progress, causing irreversible sight-loss. This study explored whether the COVID-19 (C19) national lockdown impacted upon the clinical presentation and outcomes of MK at a UK tertiary-care centre. Methods Medical records were retrospectively reviewed for all patients with presumed MK requiring corneal scrapes, presenting between 23rd March and 30th June in 2020 (Y2020), and the equivalent time windows in 2017, 2018 and 2019 (pre-C19). Results In total, 181 and 49 patients presented during the pre-C19 and Y2020 periods, respectively. In Y2020, concurrent ocular trauma (16.3% vs. 5.5%, p = 0.030) and immunosuppression use (12.2% vs 1.7%, p = 0.004) were more prevalent. Despite proportionately fewer ward admissions during the pandemic (8.2% vs 32.6%, p2, p = 0.520); or final VA (0.30 vs 0.30 LogMAR, p = 0.990). Whilst the overall rates of culture positivity were similar in Y2020 and pre-C19 (49.0% vs. 54.7%, p = 0.520), there were differences in the cultures isolated, with a lower rate of poly-microbial cultures in Y2020 (8.3% vs. 31.3%, p = 0.022). Conclusions Patient characteristics, MK severity and final visual outcomes did not appear to be affected in the first UK lockdown, despite fewer patients being admitted for care. Concurrent trauma and systemic immunosuppression use were greater than in previous years. The difference in spectra of isolated organisms may relate to behavioural changes, such as increased hand hygiene.

ObjectiveUveitis, a group of disorders characterised by intraocular inflammation, causes 10%–15% of total blindness in the developed world. The most sight-threatening forms of non-infectious uveitis are those affecting the posterior segment of the eye, collectively known as posterior segment-involving uveitis (PSIU). Numerous different clinical outcomes have been used in trials evaluating treatments for PSIU, but these may not represent patients’ and carers’ concerns. Therefore, the aims of this study were to understand the impact of PSIU on adult patients’ and carers’ lives and to explore what outcomes of treatment are important to them.Methods and AnalysisFour focus group discussions were undertaken to understand the perspectives of adult patients (=18) and carers (10) with PSIU. Participants were grouped according to whether or not their uveitis was complicated by the sight-threatening condition uveitic macular oedema. Discussions were audio-recorded, transcribed and analysed using the framework analytical approach. Outcomes were identified and grouped into outcome domains.ResultsEleven core domains were identified as important to patients and carers undergoing treatment for PSIU, comprising (1) visual function, (2) symptoms, (3) functional ability, (4) impact on relationships, (5) financial impact, (6) psychological morbidity and emotional well-being, (7) psychosocial adjustment to uveitis, (8) doctor/patient/interprofessional relationships and access to healthcare, (9) treatment burden, (10) treatment side effects, and (11) disease control.ConclusionThe domains identified represent patients’ and carers’ experience and perspectives and can be used to reflect on outcomes assessed in PSIU. They will directly inform the development of a core outcome set for PSIU clinical trials.

Purpose To determine classification criteria for spondyloarthritis/HLA-B27-associated anterior uveitis DESIGN: Machine learning of cases with spondyloarthritis/HLA-B27-associated anterior uveitis and 8 other anterior uveitides. Methods Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand eighty-three cases of anterior uveitides, including 184 cases of spondyloarthritis/HLA-B27-associated anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set (95% confidence interval [CI] 96.3, 98.4) and 96.7% in the validation set (95% CI 92.4, 98.6). Key criteria for spondyloarthritis/HLA-B27-associated anterior uveitis included 1) acute or recurrent acute unilateral or unilateral alternating anterior uveitis with either spondyloarthritis or a positive test for HLA-B27 or 2) chronic anterior uveitis with a history of the classic course and either spondyloarthritis or HLA-B27 or 3) anterior uveitis with both spondyloarthritis and HLA-B27. The misclassification rates for spondyloarthritis/HLA-B27-associated anterior uveitis were 0% in the training set and 3.6% in the validation set, respectively. Conclusions The criteria for spondyloarthritis/HLA-B27-associated anterior uveitis had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.

Purpose To develop an agreed upon set of outcomes known as a “core outcome set” (COS) for noninfectious uveitis of the posterior segment (NIU-PS) clinical trials. Design Mixed-methods study design comprising a systematic review and qualitative study followed by a 2-round Delphi exercise and face-to-face consensus meeting. Participants Key stakeholders including patients diagnosed with NIU-PS, their caregivers, and healthcare professionals involved in decision-making for patients with NIU-PS, including ophthalmologists, nurse practitioners, and policymakers/commissioners. Methods A long list of outcomes was developed based on the results of (1) a systematic review of clinical trials of NIU-PS and (2) a qualitative study of key stakeholders including focus groups and interviews. The long list was used to generate a 2-round Delphi exercise of stakeholders rating the importance of outcomes on a 9-point Likert scale. The proportion of respondents rating each item was calculated, leading to recommendations of “include,” “exclude,” or “for discussion” that were taken to a face-to-face consensus meeting of key stakeholders at which they agreed on the final COS. Main Outcome Measure Items recommended for inclusion in the COS for NIU-PS. Results A total of 57 outcomes grouped in 11 outcome domains were presented for evaluation in the Delphi exercise, resulting in 9 outcomes directly qualifying for inclusion and 15 outcomes being carried forward to the consensus meeting, of which 7 of 15 were agreed on for inclusion. The final COS contained 16 outcomes organized into 4 outcome domains comprising visual function, health-related quality of life, treatment side effects, and disease control. Conclusions This study builds on international work across the clinical trials community and our qualitative research to construct the world’s first COS for NIU-PS. The COS provides a list of outcomes that represent the priorities of key stakeholders and provides a minimum set of outcomes for use in all future NIU-PS clinical trials. Adoption of this COS can improve the value of future uveitis clinical trials and reduce noninformative research. Some of the outcomes identified do not yet have internationally agreed upon methods for measurement and should be the subject of future international consensus development.

Background/aimsTo measure health-related quality of life (HRQOL) in patients with uveitis using time trade-off (TTO) and standard gamble (SG) methods of direct utility analysis.MethodsConsecutive patients attending a tertiary referral uveitis clinic were administered standardised, interview-delivered TTO and SG questionnaires and completed the European Quality of Life Five Dimensions Five Level (EQ5D-5L) questionnaire. Clinical data recorded included best-corrected visual acuity, uveitis anatomical and clinical classifications, duration since diagnosis, disease activity, current medication and any ocular or systemic comorbidities.ResultsTwo hundred patients with uveitis (124 female, 76 male, median age 54 years) were included. Overall mean TTO utility was 0.831 (95% CI 0.802 to 0.860); mean SG utility was 0.868 (95% CI 0.840 to 0.896) and mean EQ5D-5L utility was 0.742 (95% CI 0.702 to 0.782). There was a negative correlation between visual acuity and mean HRQOL (6/12 or better: TTO 0.86, SG 0.893; 6/15–6/60: TTO 0.662, SG 0.742; worse than 6/60: TTO 0.608, SG 0.712). Poor vision in the better- seeing eye (p=0.004), bilateral disease (p=0.047) and concurrent glaucomatous optic neuropathy (p=0.005) were predictors of poor TTO HRQOL. No correlation was found between HRQOL and duration of diagnosis, a flare of uveitis or being on systemic therapy. Patients with uveitis with poor vision have a TTO value worse than patients with end-stage renal failure on haemodialysis or those with AIDS.ConclusionLoss of vision resulting from uveitis is associated with reduced HRQOL. The TTO and SG utility values appear directly dependent on the degree of vision loss and not on the duration of disease or systemic medications.

Purpose: To evaluate adherence to topical medication in patients with inflammatory eye disease.Methods: Questionnaire survey of patients attending inflammatory eye disease clinics. Treatment regimen was validated against hospital-generated clinic letters.Results: There were 86 patients (52 uveitis and 34 ocular surface disease) with 30% (26/86) failing to identify one or more of the medications they were using, and 28% (24/86) unable to offer the correct indication for their treatment. A total of 64% (55/86) failed to use their medication as advised (27% on a daily basis); the commonest reason being forgetfulness. In patients using multiple eye drops, 26% left insufficient time intervals between successive eye drops, and 58% (50/86) reported not being given any instruction on drop instillation.Conclusions: We highlight poor adherence to topical medication in patients with inflammatory eye disease. We recommend a dedicated practitioner providing a proactive approach to patient education to improve adherence.

To compare longitudinal changes in disease activity with quality of life and psychological status in patients with Behçet's disease (BD).Patients attending a National Centre of Excellence for BD over a two-year period had disease activity including clinician and patient perception of disease documented and completed a number of validated quality of life and psychological questionnaires. Some representative case-studies were examined in detail.102 patients were included. Disease activity weakly correlated with quality of life and psychological health. Clinician and patient perceptions strongly correlated with each other. Case-study analyses showed diverse, and sometimes incongruous, responses between, and in, individual patients.Changes in disease activity account for only a small proportion of changes in psychological status with intra-individual variation playing a large role. There is a complex relationship between psychological status and disease activity that cannot be explained by changes in disease activity alone.

Purpose: To conduct a systematic review of effectiveness of pharmacological therapies for treatment of Uveitic Macular Edema (UMO).Method/Design: Comparative studies of pharmacological therapies in patients with UMO were identified in Cochrane CENTRAL/MEDLINE/EMBASE/CINAHL/trials registers (February 2017). PROSPERO registration: CRD42015019170.Results: Thirty-one studies were included. Corticosteroids were the most frequently studied (n = 20). Corticosteroids (all forms) were consistently of greater/equal efficacy to active comparators; for anti-VEGF (n = 4) improvement, best-corrected visual acuity (BCVA) and central macular thickness (CMT) were mostly less than local corticosteroid injection; for interferon (n = 1) improvement BCVA and CMT were greater than the comparator of methotrexate; for topical indomethacin (n = 1) improvement, BCVA and CMT were greater than placebo. Non-steroidal anti-inflammatory drugs, carbonic anhydrase inhibitors, and vitamin E (n = 5) were not effective for these out...

ObjectiveTo evaluate whether topical therapy is linked to scores related to anxiety, depression and quality of life (QoL) in inflammatory eye disease (IED).Methods and analysisPatients with ocular surface disease (OSD, N=100) and Uveitis (N=100) completed self-administered validated questions on ocular symptoms and well-being, with supplemental questions on eye drop frequency.ResultsForty (20%) patients had scores consistent with depression and 33 (17%) anxiety. Anxiety, depression, QoL and OSD index (OSDI) scores did not differ significantly between OSD and Uveitis groups. In those with anxiety or depression, QoL was significantly reduced in all WHO Quality Of Life-BREF domains (all pConclusionA high proportion of patients with IED demonstrated scores indicative of anxiety and depression. Preliminary evidence suggests that the frequency of topical eye drops potentially plays a significant role in the psychological health status of patients with IED .

Background Microbial keratitis is a leading cause of preventable blindness worldwide. Conventional sampling and culture techniques are time-consuming, with over 40% of cases being culture-negative. Nanopore sequencing technology is portable and capable of generating long sequencing reads in real-time. The aim of this study is to evaluate the potential of nanopore sequencing directly from clinical samples for the diagnosis of bacterial microbial keratitis. Methods Using full-length 16S rRNA amplicon sequences from a defined mock microbial community, we evaluated and benchmarked our bioinformatics analysis pipeline for taxonomic assignment on three different 16S rRNA databases (NCBI 16S RefSeq, RDP and SILVA) with clustering at 97%, 99% and 100% similarities. Next, we optimised the sample collection using an ex vivo porcine model of microbial keratitis to compare DNA recovery rates of 12 different collection methods: 21-gauge needle, PTFE membrane (4 mm and 6 mm), Isohelix™ SK-2S, Sugi® Eyespear, Cotton, Rayon, Dryswab™, Hydraflock®, Albumin-coated, Purflock®, Purfoam and Polyester swabs. As a proof-of-concept study, we then used the sampling technique that provided the highest DNA recovery, along with the optimised bioinformatics pipeline, to prospectively collected samples from patients with suspected microbial keratitis. The resulting nanopore sequencing results were then compared to standard microbiology culture methods. Results We found that applying alignment filtering to nanopore sequencing reads and aligning to the NCBI 16S RefSeq database at 100% similarity provided the most accurate bacterial taxa assignment. DNA concentration recovery rates differed significantly between the collection methods (p < 0.001), with the Sugi® Eyespear swab providing the highest mean rank of DNA concentration. Then, applying the optimised collection method and bioinformatics pipeline directly to samples from two patients with suspected microbial keratitis, sequencing results from Patient A were in agreement with culture results, whilst Patient B, with negative culture results and previous antibiotic use, showed agreement between nanopore and Illumina Miseq sequencing results. Conclusion We have optimised collection methods and demonstrated a novel workflow for identification of bacterial microbial keratitis using full-length 16S nanopore sequencing.

Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis are associated with potentially sight-threatening inflammatory eye disease. Although the ocular manifestations associated with ankylosing spondylitis and psoriatic arthritis are similar, such as anterior uveitis, this differs from rheumatoid arthritis where dry eye, peripheral ulcerative keratitis and scleritis are the major ocular complications. Apart from causing sight loss, these conditions are painful, debilitating, often recurrent or chronic and may require long-term therapy. Treatments such as ocular lubricant, topical corticosteroid, systemic corticosteroid and systemic immunosuppression are often similar for the underlying systemic disease. Yet for the treatment of the ocular complications, the evidence base is weak. Close collaboration with a rheumatologist is often essential, particularly in the management of these patients.

To establish how much uveitis patients know about their own condition and to investigate the contribution of demographic factors to that knowledge.A self-designed questionnaire, comprising 20 questions about uveitis, was distributed to 200 consecutive patients attending a uveitis clinic. The questionnaire requested demographic details and required responses to uveitis-specific knowledge questions. Postcode was used to determine level of social deprivation using Index of Multiple Deprivation 2007. Univariate analyses with the Mann-Whitney test and Kruskal-Wallis test were utilized. Multivariable logistic regression was performed to simultaneously measure the independent influence of demographic variables on the level of patients' understanding of their condition.Of the respondents, 62% were female, 71% aged40 years and 67% of white ethnic origin, with 41% having been under the care of a uveitis specialist for10 years and 72% attending ≥3 clinic appointments in the preceding 12 months. Median questionnaire score (out of 60) was 27 (interquartile range, IQR 15). Females scored significantly higher than males (30 vs 24; p = 0.001), but there was no difference according to age, ethnicity, or social deprivation quintile, nor the duration patients had been under ophthalmic review or number of clinic attendances in the preceding 12 months. Multivariable analyses determined no independent influence of any of the factors on the uveitis questionnaire score.Uveitis patients' understanding of their condition is poor. This has relevance for adherence to treatment, follow-up clinic attendance, and eventual outcomes in these patients.

Background/aims To evaluate the vitreous signals obtained on spectral domain optical coherence tomography (SD-OCT) in patients with uveitic cystoid macular oedema (CMO) and compare these signals before and after sub-Tenon9s triamcinolone acetonide injection. Methods Retrospective study with standardised longitudinal imaging preintervention and postintervention. The study cohort comprises 22 patients (22 eyes) with uveitic CMO receiving a sub-Tenon9s triamcinolone acetonide (STTA) injection. Post hoc analysis of SD-OCT images using custom software provided an ‘absolute’ measurement of vitreous signal intensity, which was expressed as a ratio to the retinal pigment epithelium intensity (‘VIT/RPE-relative intensity’) in arbitrary units. Main outcome measure Difference in VIT/RPE-relative intensity before and after treatment. Results Treatment with STTA resulted in a significant reduction in VIT/RPE-relative intensity, which was associated with both a reduction in central retinal thickness (CRT) and improvement in visual acuity. Mean (SD) VIT/RPE-relative intensity pretreatment was 0.139 (0.074) versus 0.053 (0.028) post-treatment (p=3×10 −5 ). Mean (SD) CRT was 581 μm (119 μm) pretreatment versus 333 μm (95 μm) post-treatment (p=2×10 −8 ); the mean reduction in CRT was 248 (95% CI 189 to 306). The correlation coefficient between VIT/RPE-relative intensity and CRT was 0.534 (p=0.011) and between VIT/RPE-relative intensity and visual acuity was 0.702 (p=0.0001). Conclusions This study provides evidence that the OCT-derived VIT/RPE-relative intensity may be useful as a quantitative and objective marker of disease activity and treatment response in uveitis complicated by CMO. This first longitudinal study of this novel OCT parameter is an encouraging step in the development of sensitive objective OCT-based endpoints for trials of efficacy in uveitis.

Background: Direct ophthalmoscopy (DO) is an essential skill for medical graduates but there are multiple barriers to learning this. Medical students and junior doctors typically lack confidence in DO. Most students do not own an ophthalmoscope and learn via ward devices that vary in design and usability. The Arclight ophthalmoscope (AO) is an easy to use, low-cost and portable device that could help address device access. This study aimed to assess the impact of personal ownership of an AO on DO skill acquisition and competency amongst medical students in the clinical environment. Methods: Method comparison study with 42 medical students randomised to either traditional device ophthalmoscope (TDO) control or AO intervention group during an 18-week medical placement. Three objective assessments of DO competency were performed at the beginning and end of the placement: vertical cup to disc ratio (VCDR) measurement, fundus photo multiple-choice questions (F-MCQ) and model slide examination (MSE). DO examinations performed during the placement were recorded via an electronic logbook. Results: Students in both groups recorded a median number of six examinations each during an eighteen-week placement. There was no statistically significant difference between the groups in any of the objective assessment measures (VCDR p = 0.561, MCQ p = 0.872, Model p = 0.772). Both groups demonstrated a minor improvement in VCDR measurement but a negative performance change in F-MCQ and MSE assessments. Conclusions: Students do not practice ophthalmoscopy often, even with constant access to their own portable device. The lack of significant difference between the groups suggests that device access alone is not the major factor affecting frequency of DO performance and consequent skill acquisition. Improving student engagement with ophthalmoscopy will require a more wide-ranging approach. Publisher PDF