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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.

Background 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. Methods Peripheral 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 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.

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 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.

ObjectiveThis study aimed to explore the British public’s healthcare-seeking beliefs concerning eye symptoms, and assess how the first COVID-19 lockdown influenced these.Methods and analysisAn anonymous web-based survey was disseminated through mailing lists and social media between June and August 2020. The survey sought participants’ views on the severity and urgency of the need for medical review for four ophthalmic and two general medical scenarios on a five-point scale. Participants were asked to answer questions twice: once ignoring the COVID-19 pandemic, and once taking this into account, with additional questions asked to identify factors influencing the decision to seek medical attention and ward admission.ResultsA total of 402 participants completed the survey (mean age 61.6 years, 63.1% female and 87.7% of white ethnicity). Scores for symptom severity and urgency of medical review increased significantly with the severity of the clinical scenario (both pConclusionsDuring the first UK lockdown of the COVID-19 pandemic, reduced urgency of medical review for ocular and systemic pathologies was reported in response to the pandemic, which represents a barrier to healthcare-seeking behaviour. This has the potential to critically delay medical review and timely management, negatively impacting patient outcomes.

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

Systemic lupus erythematosus (SLE) is a life-threatening multisystem inflammatory condition that may affect almost any part of the eye. We provide an update for the practicing ophthalmologist comprising a systematic review of the recent literature presented in the context of current knowledge of the pathogenesis, diagnosis, and treatment of this condition. We review recent advances in the understanding of the influence of genetic and environmental factors on the development of SLE. Recent changes in the diagnostic criteria for SLE are considered. We assess the potential for novel molecular biomarkers to find a clinical application in disease diagnosis and stratification and in the development of therapeutic agents. We discuss limited forms of SLE and their differentiation from other collagen vascular disorders and review recent evidence underlying the use of established and novel therapeutics in this condition, including specific implications regarding monitoring for ocular toxicity associated with antimalarials.

Transforming growth factor β (TGFβ) is an important immunoregulatory cytokine in regulatory T cell (Treg) and Th17-mediated pathology, including uveitis due to Behçet's disease (BD). Of the three isoforms, TGFβ2 is found at highest levels in the aqueous humour of uninflamed eyes. TGFβ signals through a cell-surface receptor comprising three subunits (TGFBR1, 2 and 3). TGFBR3 is considered necessary for TGFβ2 signal transduction, but not for other isoforms. A polymorphism in TGFBR3 (rs1805110) has previously been identified in Han Chinese patients with BD. We investigated the frequency of this polymorphism in a Caucasian population with BD and idiopathic intermediate uveitis (IIU).The single-nucleotide polymorphism (SNP) rs1805110 in TGFBR3 was genotyped in 75 BD patients, 92 IIU disease controls and 85 disease-free controls. The association with both diseases was analysed using Fisher's exact test.No significant difference in rs1805110 allele or genotype frequency was observed. A low frequency of the T allele was observed (5.88% control, 9.33% BD, 10.33% IIU) with the TT genotype absent in patients with BD and IIU (1.18% control, 0% BD and 0% IIU). Stratification analysis according to clinical features of BD did not associate with the tested SNP.RS1805110 is not associated with BD or IIU in Caucasian patients. The T allele frequency is consistent with that presented for Caucasian populations in the HapMap database (p0.05). Our results differ from the previous analysis in Han Chinese patients (p0.0001), however, the possibility of having a much smaller effect due to the low minority frequency cannot be excluded.

BackgroundThe diagnosis of primary vitreoretinal lymphoma (PVRL) poses significant difficulties; presenting features are non-specific and confirmation usually necessitates invasive vitreoretinal biopsy. Diagnosis is often delayed, resulting in increased morbidity and mortality. Non-invasive imaging modalities such as spectral domain optical coherence tomography (SD-OCT) offer simple and rapid aids to diagnosis. We present characteristic SD-OCT images of patients with biopsy-positive PVRL and propose a number of typical features, which we believe are useful in identifying these lesions at an early stage.MethodsMedical records of all patients attending Moorfields Eye Hospital between April 2010 and April 2016 with biopsy-positive PVRL were reviewed. Pretreatment SD-OCT images were collected for all eyes and were reviewed independently by two researchers for features suggestive of PVRL.ResultsPretreatment SD-OCT images of 32 eyes of 22 patients with biopsy-proven PVRL were reviewed. Observed features included hyper-reflective subretinal infiltrates (17/32), hyper-reflective infiltration in inner retinal layers (6/32), retinal pigment epithelium (RPE) undulation (5/32), clumps of vitreous cells (5/32) and sub-RPE deposits (3/32). Of these, the hyper-reflective subretinal infiltrates have an appearance unique to PVRL, with features not seen in other diseases.ConclusionWe have identified a range of SD-OCT features, which we believe to be consistent with a diagnosis of PVRL. We propose that the observation of hyper-reflective subretinal infiltrates as described is highly suggestive of PVRL. This case series further demonstrates the utility of SD-OCT as a non-invasive and rapid aid to diagnosis, which may improve both visual outcomes and survival of patients with intraocular malignancies such as PVRL.

Background/AimHistoric data suggest that open globe injuries should be repaired within 12–24 hours to reduce the risk of endophthalmitis. However, endophthalmitis is uncommon when systemic antibiotic prophylaxis is given. It is not clear whether delayed primary repair impacts visual outcomes in other ways or what is the optimum time to repair. We aimed to examine the effect of time to primary repair on visual outcomes.MethodsThis is a retrospective comparative case series including all open globe injuries presenting to the Birmingham Midland Eye Centre between 1 January 2014 and 15 March 2016. Presenting features, mechanism of injury, visual acuity at 6–12 months and demographic data were examined.Results56 open globe injuries were repaired, of which sufficient data for analysis were available on 52 cases. The mean time to primary repair was 1 day after injury (range 5 hours to 7 days). Final visual acuity at 6–12 months was related to the presenting visual acuity and the Ocular Trauma Score and to the time between injury and primary repair, with a reduction in predicted visual acuity of logarithm of the minimum angle of resolution of 0.37 for every 24 hours of delay (95% CI 0.14 to 0.6).DiscussionOpen globe injuries should be repaired promptly. Presenting visual acuity remains the strongest predictor of outcome; however, delay to primary repair also reduced final visual acuity, and any significant delay from injury to repair is likely to negatively impact final visual outcome.

Non-infectious uveitis represents a sub-type of intraocular inflammation often associated with disorders of immune dysregulation. If untreated, the intraocular inflammation may progress to severe visual impairment and blindness. Current treatment is heavily reliant on systemic corticosteroid, often at doses associated with severe side effects. There is a need for efficacious corticosteroid-sparing immunomodulatory therapy for these patients. Current immunomodulators include various immunosuppressants and biologics but mammalian target of rapamycin (mTOR) inhibitors (such as sirolimus and everolimus) may also be contenders for this role. The systematic review proposed here will evaluate the evidence for the use of sirolimus and everolimus in the context of non-infectious uveitis.Standard systematic review methodology will be used to identify, select and extract data from any comparative or non-comparative study of mTOR inhibitors in patients with non-infectious uveitis excluding case reports. Searches of bibliographic databases (MEDLINE, EMBASE, The Cochrane Library and CINAHL) and clinical trials registers will be performed, with no restriction on language or date of publication. Translation of non-English language articles will be undertaken where necessary. The primary outcome of interest will be uveitis activity as measured by vitreous haze. Secondary outcomes will include other pre-specified measures of uveitis activity (such as anterior chamber cells or central macular thickness) best corrected visual acuity, heath-related quality of life, requirement for concurrent treatment and adverse events. Risk of bias assessment will be performed appropriate to each study design. Study selection, data extraction and risk of bias assessment will be undertaken by two reviewers independently. Data will be grouped, tabulated and narratively synthesised. Meta-analysis will be undertaken where appropriate clinical and methodological homogeneity exists. The review will be published according to PRISMA guidance.Studies of various designs have investigated the clinical use of mTOR inhibitors for non-infectious uveitis, and a large international randomised controlled trail of sirolimus for non-infectious uveitis is due to report. The findings of this systematic review will help inform ophthalmologists and aid the improvement of treatment protocols for non-infectious uveitis with regard to the use of mTOR inhibitors.PROSPERO CRD42017056390.

Purpose: The authors report a case of a 60-year-old Caucasian male with a background of treated Chronic Lymphocytic Leukaemia (CLL) with secondary hypogammaglobulinaemia present with toxoplasma chorioretinitis and negative serum toxoplasma serology on presentation and on subsequent reactivation.Methods: Retrospective case notes review with fundal photographs.Results: In this case, on initial presentation and on recurrence, the patient’s serum anti-Toxoplasma IgG remained negative. The diagnosis was made on quantitative PCR of vitreous initially and aqueous humor on reactivation.Conclusions: Despite negative serology, one must still consider ocular toxoplasmosis especially in CLL patients where the clinical picture could be compatible. Hypogammaglobulinaemia, the inability to produce IgG antibodies, is a well-recognized complication of CLL. Intraocular fluid sampling is essential in these cases where the sensitivity of PCR on either aqueous or vitreous humor has been shown to be higher in immunocom...

BACKGROUND Non-infectious uveitis describes a heterogenous group of ocular disorders characterised by intraocular inflammation in the absence of infection. Uveitis is a leading cause of visual loss, most commonly due to uveitic macular oedema (UMO). Treatment is aimed at reducing disease activity by suppression of the intraocular inflammatory response. In the case of macular oedema, the aim is to restore macular architecture as quickly as possible, in order to prevent irreversible photoreceptor damage in this area. Acute exacerbations are typically managed with corticosteroids, which may be administered topically, locally or systemically. Whilst these are often rapidly effective in achieving disease control, long-term use is associated with significant local and systemic side effects, and 'steroid sparing agents' are typically used to achieve prolonged control in severe or recalcitrant disease. Anti-tumour necrosis factor (TNF) drugs block a critical cytokine in the inflammatory signalling process, and have emerged as effective steroid-sparing immunomodulatory agents in a wide range of non-ocular conditions. There is mechanistic data to suggest that they may provide a more targeted approach to disease control in UMO than other agents, but to date, these agents have predominantly been used 'off label' as the majority are not licensed for ocular use. This review aims to summarise the available literature reporting the use of anti-TNF therapy in UMO, thus developing the evidence-base on which to make future treatment decisions and develop clinical guidelines in this area. OBJECTIVES To assess the efficacy of anti-TNF therapy in treatment of UMO. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), which contains the Cochrane Eyes and Vision Trials Register; Ovid MEDLINE; Ovid Embase; LILACS; Web of Science Conference Proceedings Citation Index- Science (CPCI-S); System for Information on Grey Literature in Europe (OpenGrey); the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 29 March 2018. SELECTION CRITERIA We planned to include all relevant randomised controlled trials assessing the use of anti-TNF agents in treatment of UMO. No limits were applied to participant age, gender or ethnicity. The primary comparisons of this review were: anti-TNF versus no treatment or placebo; anti-TNF versus another pharmacological agent; comparison of different anti-TNF drugs; comparison of different doses and routes of administration of the same anti-TNF drug. The primary outcome measure that we assessed for this review was best-corrected visual acuity (BCVA) in the treated eye. Secondary outcome measures were anatomical macular change, clinical estimation of vitreous haze and health-related quality of life. DATA COLLECTION AND ANALYSIS Two review authors independently screened titles and abstracts retrieved through the database searches. We retrieved full-text reports of studies categorised as 'unsure' or 'include' after we had reviewed the abstracts. Two review authors independently reviewed each full-text report for eligibility. We resolved discrepancies through discussion. MAIN RESULTS We identified no completed or ongoing trial that was eligible for this Cochrane Review. AUTHORS' CONCLUSIONS Our review did not identify any evidence from randomised controlled trials for or against the role of anti-TNF agents in the management of UMO. Although there are a number of high-quality randomised controlled trials that demonstrate the efficacy of anti-TNF agents in preventing recurrence of inflammation in uveitis, the reported study outcomes do not include changes in UMO. As a result, there were insufficient data to conclude whether there was a significant treatment effect specifically for UMO. Future trials should be designed to include quantitative measures of UMO as primary study outcomes, for example by reporting the presence or absence of UMO, or by measuring central macular thickness for study participants. Furthermore, whilst UMO is an important complication of uveitis, we acknowledge that uveitis is associated with many significant structural and functional complications. It is not possible to determine treatment efficacy based on a single outcome measure. We recommend that future reviews of therapeutic interventions in uveitis should use composite measures of treatment response comprising a range of potential complications of disease.

ᅟ: Behçet's disease (BD) is a systemic vasculitis characterised by a relapsing remitting course, affecting multiple organ systems. In the eye, it is a cause of potentially blinding inflammation in the form of uveitis. Management of uveitis in BD often requires the use of systemic immunosuppression, in order to reduce disease activity and prevent accumulation of irreversible damage. Whilst corticosteroids remain the mainstay of treatment, long-term use is limited by the development of adrenocorticotrophic side effects. There has therefore been significant interest in the use of corticosteroid-sparing immunosuppressive agents, and more recently, biologic therapies. Recent publications have demonstrated biologic therapy to have beneficial effects both on overall disease control, and quality of life for patients with BD. Widespread use of such agents is however limited, partly by the lack of high quality research evidence, and partly by the prohibitive cost of biologic treatments. In this review, we discuss the most recent research investigating the use of biologic therapy in uveitis due to BD, with consideration of health economics and quality of life outcomes.

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.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare oculorenal inflammatory condition that was first described in 1975. In 2001 a major review identified 133 cases in the world literature and proposed key diagnostic criteria for the condition. Although acknowledged as rare, the limited data available prevented reliable estimates of the prevalence of the condition, and hampered elucidation of the relationship between genetic and environmental factors that contribute to its pathogenesis. In this review we have performed a systematic search on the epidemiology, demographics and proposed risk factors for TINU. Estimates of prevalence based on studies that explicitly report TINU cases suggest that it is diagnosed in 0.2–2% of patients attending specialist uveitis services, with variation reflecting a number of factors including level of diagnostic certainty required. The prevalence of uveitis in patients with tubulointerstitial nephritis (TIN) may be higher than currently recognised, particularly in the paediatric population. The prevalence of TINU is higher in younger age groups and there is a female preponderance although this gender effect appears weaker than suggested by early studies. Although important genetic contributions have been proposed, the small size of studies and variation between reports currently preclude identification of a ‘pro-TINU’ haplotype. Drugs and infections have been proposed as the leading acquired risk factors for the development of TINU; whilst the small size of TINU cohorts and issues of study design limit interpretation of many studies. Larger datasets from the renal literature suggest that the majority of these cases are precipitated by a drug-induced hypersensitivity reaction; however in many ophthalmic cases no clear precipitant is identified.

Eye disease can be devastating. The most feared impact is sight loss, but in a number of ophthalmic conditions, there can be wide-ranging systemic, psychological, emotional and social effects of both the disease and its treatment. External tests of visual function, such as visual acuity, are inadequate to understand the overall impact of ophthalmic disease on a patient’s functional vision or daily life. This can lead to a discordance between the patient’s priorities and perspective on the one hand and the efforts of clinicians and other stakeholders on the other hand. In this review, we discuss how the patient is uniquely placed to understand the impact of the disease and can use that position to transform ophthalmic care at the individual and collective level, from research to care delivery. We highlight how the “patient voice” can contribute to key areas, including priority setting in the research agenda, communicating the wide-ranging impact of disease and its treatment as assessed through qualitative research, identifying the outcome measures that matter to the patient through core outcome set development and reporting these outcomes through appropriate patient-reported outcome measures. We also consider the increasing power of the patient voice on health institutions, ranging from broadcasting an individual’s experience of care he/she has received to patient societies influencing future health policy. Finally, we reflect on the challenges that need to be overcome for the patient voice to increasingly influence and improve the delivery of eye care in the future.

Purpose Unifying terminology for the description of ocular surface disease (OSD) is vital for determining treatment responses and ensuring robust clinical trial outcomes. To date, there are no agreed parameters describing ‘activity' and ‘damage' phases of disease. Methods A working group of international experts in OSD, oculoplastics, and uveitis from a range of backgrounds (university, teaching, district general and private hospitals) participated in a modified Delphi consensus-building exercise (October 31, 2011 to March 20, 2015). Two steering group meetings took place in which factors based upon published literature were discussed and supplemented with anonymous web-based questionnaires to refine clinical indices according to ‘activity' (reversible changes resulting directly from the inflammatory process) and/or ‘damage' (persistent, >6 months duration) changes resulting from previously active disease that are cumulative and irreversible). Results The recommended set of clinical parameters for the assessment of OSD encompasses 68 clinical indices and 22 ancillary grading tools (in parenthesis) subdivided by anatomical domain as follows: 4(4) tear-film, eyelid 21(3), 17(3) conjunctiva, 15(10) cornea and 11(2) Anterior Chamber/Sclera. Of these; 17(2) were considered as measures of clinical activity, 27(3) as damage, 1(8) as measures of both activity and damage. Twenty-three clinical descriptors and 9 tools did not reach the threshold for inclusion into the main standard set. These were defined as ‘second tier' parameters for use in special clinical settings. Conclusion These core parameters provide the first description of ‘activity' and ‘damage' relevant to OSD and provide a platform for the future development of scoring scales for each parameter.

Background: Anterior chamber paracentesis is a valuable diagnostic tool in the management of uveitis, but may be underutilized because of concerns over its safety. We evaluated the safety profile of anterior chamber paracentesis performed at the slit lamp as an outpatient procedure. Design: Retrospective, observational case series in a single tertiary centre. Participants: Five hundred and sixty patients with uveitis undergoing anterior chamber paracentesis. Methods: All anterior chamber paracenteses performed at the slit lamp for diagnostic or research purposes between January 1997 and June 2009 were analysed with regard to adverse events and pipet/syringe used. Procedures were included whether carried out on undilated or dilated pupils. Main Outcome Measures: Adverse events and serious adverse events. Results: Out of 560 paracenteses, 510 were performed with a 27-gauge fixed-needle tuberculin syringe, and 50 using an O'Rourke aqueous pipet. All patients were prescribed a short course of topical antibiotic and examined post-procedure and 1–2 weeks later. Out of 560 procedures there were four complications (0.7%). Two patients had inadvertent injection of sterile air into the anterior chamber but with spontaneous resolution and no adverse outcome (O'Rourke pipet for both). One patient had anterior lens capsule touch that was self-sealing and left a tiny localized opacity (tuberculin syringe). One patient had an allergic reaction to povidone iodine. No patients reported pain, and there were no cases of iris trauma, entry site leak, hypotony, hyphaema or endophthalmitis. Conclusion: Anterior chamber paracentesis can be performed safely as an outpatient procedure at the slit lamp following adequate aseptic precaution, and appropriate counselling.

Changes in the UK undergraduate medical curriculum mean that a clinical placement in ophthalmology is no longer a requirement. An ophthalmic assessment is necessary for a full physical examination and failure to elicit and interpret signs could mean missing sight and life-threatening pathology. This study was to investigate current undergraduate ophthalmology teaching. An email questionnaire, about the content and delivery of the ophthalmology teaching, was sent to each UK medical school in 2007/2008. The response rate was 83%. Nineteen (79%) medical schools had a compulsory attachment to the ophthalmology department with an average length of 7.6 days (range 3.5-15 days). There was variation as to how ophthalmology was included in the curriculum. Teaching methods and standards also varied. Finally, assessments ranged from formal written and practical exams in some medical schools to informal or non-existent ones in others. The most striking finding was the variation in ophthalmology education a student may receive, with some students receiving none. It is necessary to improve the profile of ophthalmology and ensure that all students achieve a minimum basic standard.

Aqueous humor (AqH) has been shown to have significant immunosuppressive effects on APCs in animal models. We wanted to establish whether, in humans, AqH can regulate dendritic cell (DC) function and to identify the dominant mechanism involved. Human AqH inhibited the capacity of human peripheral blood monocyte-derived DC to induce naive CD4+ T cell proliferation and cytokine production in vitro, associated with a reduction in DC expression of the costimulatory molecule CD86. This was seen both for DC cultured under noninflammatory conditions (immature DC) and for DC stimulated by proinflammatory cytokines (mature DC). DC expression of MHC classes I/II and CD83 was reduced (mature DC only). Myeloid DC from peripheral blood were similarly sensitive to the effects of human AqH, but only under inflammatory conditions. The addition of α-melanocyte stimulating hormone and vasoactive intestinal peptide did not cause significant inhibition at physiological levels. However, the addition of exogenous cortisol at physiological levels recapitulated the AqH-induced reduction in CD86 and inhibition of DC-induced T cell proliferation, and blockade of cortisol in AqH partially reversed its suppressive effects. TGF-β2 had an additional effect with cortisol, and although simultaneous blockade of cortisol and TGF-β2 in AqH reduced its effectiveness, there was still a cortisol- and TGF-β–independent component. In humans, AqH regulates DC maturation and function by the combined actions of cortisol and TGF-β2, a pathway that is likely to contribute to the maintenance of immune privilege in the eye.

Summary Subjective visual perceptions during intraocular ophthalmic surgery under regional anaesthesia are now well recognised. They range from simple light perception to seeing vivid colours, intricate movements, flashes and instruments. Surgeons, anaesthetists and patients should be aware of these phenomena. Although the majority of the patients find visual perceptions bearable some may be frightened. Preoperative counselling should therefore be offered to patients. This article reviews the range and clinical implications of subjective visual perceptions during intraocular surgery and explores the mechanisms behind their genesis.

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is regarded with other molecules such as HLA, PTPN22 and CARD15 as genetic master switches of autoimmunity. Single nucleotide polymorphisms (SNPs) in the genes encoding these molecules have been associated with autoimmune conditions. We analysed the SNPs -318C/T and 49A/G in CTLA-4 in patients with Behcet's disease (BD), patients with intermediate uveitis and appropriate controls. Blood was collected from 236 patients with BD from the UK and the Middle East (ME), all fulfilling the International Study Group criteria for the diagnosis of BD, and 143 patients with idiopathic intermediate uveitis were recruited from the Medical Eye Unit at St Thomas' Hospital. Samples from healthy individuals from each geographical centre were used as controls. DNA was prepared by standard methods, and SNPs -318 and 49 in CTLA-4 were detected by a polymerase chain reaction-sequence specific primers (PCR-SSP) assay using primer mixes. The results showed that there was no association with either polymorphism in patients with BD from the UK or the ME. Similarly, there was no association in patients with intermediate uveitis. Moreover, there was no association with SNP in CTLA-4 and disease manifestations in BD or outcome in patients with intermediate uveitis. Both BD and intermediate uveitis have HLA associations, but there is no difference in distribution of CTLA-4 polymorphisms that are associated with other autoimmune diseases. The lack of association with polymorphisms in CTLA-4 and other master controlling genes of autoimmunity suggests that mechanisms that mediate such a description for BD and intermediate uveitis have still to be elucidated.

In the elderly, uveitis can present de novo after the age of 60 years or may represent a process earlier in life continuing after the age of 60 years, although many cases will have become quiescent by that time.