KIR3DL1/S1 Allotypes Contribute Differentially to the Development of Behçet Disease.

Behçet disease is a chronic, relapsing-remitting autoinflammatory syndrome with a strong HLA-B*51 association. In this paper, we describe a human cohort of 267 individuals with Behçet disease and 445 matched controls from a tertiary referral center in the U.K. HLA-B*51 was confirmed as a genetic risk factor in this group (p = 0.0006, Bonferroni-Dunn correction for multiple testing [Pc] = 0.0192, odds ratio [OR] 1.92, 95% confidence interval [CI] 1.33-2.76). KIR3DL1/S1 allele-level analysis indicated that low-expressing KIR3DL1/S1 alleles in combination with KIR3DS1 increased the risk of developing Behçet disease (KIR3DL1LOW/KIR3DS1: p = 0.0004, Pc = 0.0040, OR 2.47, 95% CI 1.43-4.25), whereas high-expressing KIR3DL1/S1 alleles in combination with a null-expressing KIR3DL1 reduced the risk of disease (KIR3DL1HIGH/KIR3DL1NULL: p = 0.0035, Pc = 0.0350, OR 0.53, 95% CI 0.33-0.87). Behçet disease can manifest as a purely mucocutaneous disease or can involve other organ systems such as the eyes. In the U.K. cohort studied in this study, KIR3DL1LOW/KIR3DS1 increased the risk of ophthalmic disease (p = 1.2 × 10-5, OR 3.92, 95% CI 2.06-7.47), whereas KIR3DL1HIGH/KIR3DL1NULL reduced the risk of having purely mucocutaneous disease (p = 0.0048, OR 0.45, 95% CI 0.25-0.81). To our knowledge, this is the first analysis of KIR3DL1/S1 allelic variation in Behçet disease and may provide insight into the pathogenic role of HLA-B*51 and its interaction with KIR3DL1/S1.

RESCUE PNEUMATIC RETINOPEXY IN PATIENTS WITH FAILED PRIMARY RETINAL DETACHMENT SURGERY.

PURPOSE: To describe the outcome of a series of patients who underwent pneumatic retinopexy (PR) for recurrent retinal detachment after scleral buckling and vitrectomy. METHODS: This is a retrospective review of 42 consecutive cases who underwent secondary PR after either scleral buckling (n = 22) or vitrectomy (n = 20) between 1995 and 2011. Fisher's exact and nonparametric tests were used for comparison. RESULTS: Hundred percent of patients in the scleral buckle group and 90% of the vitrectomy group were repaired with 1 PR procedure (P = 0.67). The two patients in the vitrectomy group failed because of presumed new breaks and proliferative vitreoretinopathy. The median time between the primary procedure and PR was 8.5 days for the scleral buckle group (interquartile range, 5-55 days) and 31.5 days for the vitrectomy group (interquartile range, 21-52 days) (P = 0.003). Postoperative median visual acuity improved by more than 2 logMAR lines in both the scleral buckle group (P = 0.0008) and the vitrectomy group (P = 0.007), with no difference between groups (P = 0.19). The overall complication rate in our patients was 16%, including transient intraocular pressure rise and development of tears requiring further indirect laser retinopexy within 3 months. None of the patients had vitreous hemorrhage, subretinal gas, or endophthalmitis. CONCLUSION: Rescue PR seems to be a safe and effective method of treating recurrent retinal detachment after both unsuccessful scleral buckling and vitrectomy.

How should we approach management of childhood onset chronic anterior uveitis refractory to adalimumab?

INTRODUCTION: The management of refractory juvenile idiopathic associated uveitis (JIAU) or childhood-onset chronic anterior uveitis (CAU) is a challenge. There is no clear consensus or evidence base for to suggest the most appropriate therapy after primary or secondary failure of biweekly adalimumab. In this scenario, most clinicians advocate switching to another anti-tumor necrosis factor alpha inhibitor; however, there are a variety of other disease modifying agents to choose from albeit with a differing levels of evidence. AREAS COVERED: We discuss how to define nonresponse and potential treatment options for patients with JIAU and CAU refractory to biweekly adalimumab. EXPERT OPINION: Uncontrolled CAU and JIAU remain one of the most challenging diseases to manage and can lead to irreversible loss of vision in a third of those affected. Amongst the possible choices, weekly adalimumab, infliximab, tocilizumab and abatacept have more evidence to support their use. JAK inhibitors seem to be a promising option. Golimumab and Rituximab has also been thought to be partially effective in some refractory cases, whereas IL-17, IL-23, and IL-12 inhibition along with apremilast seem not to be a therapeutic option currently. The route of administration should also be considered as there can be significant pros and cons for different children.

Radius-Maumenee syndrome-associated glaucoma, a therapeutic challenge: A case report.

INTRODUCTION: Radius-Maumenee syndrome is a rare cause of open-angle glaucoma, secondary to elevated episcleral venous pressure (EVP) without any orbital or systemic abnormalities. CASE PRESENTATION: We present a case of a male patient in his mid-sixties, who presented with bilateral dilated episcleral vessels, bilateral glaucoma, chorioretinal folds in both maculae and choroidal effusion in his left eye. Our case highlights the differentials that should be considered and the systematic investigations that should be performed. We describe the clinical, optical coherence tomography and angiography findings of this patient and propose a potential pathophysiological mechanism leading to the propensity for perioperative complications. CONCLUSION: Radius-Maumenee syndrome should be a diagnosis of exclusion. Secondary glaucoma can remain refractory to medical treatment and filtering surgery carries the risk intra-operative or post-operative uveal effusions.

Show don't tell: assessing the impact of co-developed patient information videos in paediatric uveitis.

BACKGROUND/OBJECTIVES: There is a paucity of online educational content targeting children and young people with uveitis. We evaluated the impact of a co-designed patient education video on subjective and objective understanding of childhood uveitis. SUBJECTS/METHODS: Co-designed patient education media were produced in collaboration with the Childhood Uveitis Studies steering group and the Great Ormond Street Hospital Generation R Young People's Advisory Group and narrated by children. Patients managed within the Uveitis service at GOSH were invited to take part in a pre-post survey, undertaken immediately prior to and following viewing of a patient education video. RESULTS: Forty-three patients participated. These were stratified according to age, duration of disease, and treatment type for analysis. Self-rated knowledge improved across all groups (p = 0.001), particularly in those with a new diagnosis of uveitis (Z = -8.124, p < 0.001). Objective knowledge scores improved across all questions, especially in younger children, those with new disease, and those on steroid only treatment (Z = -3.847, p < 0.001, Z = -3.975, p < 0.001, Z = -3.448, p < 0.001; respectively). Most participants reported the videos to be easy to understand and with the right amount of information. All stated that they learned something new. CONCLUSIONS: Patient understanding of disease and treatment is crucial to achieving the best possible outcomes for this chronic, relapsing remitting and potentially blinding disorder. Our findings data shows the potential value of co-designed patient information videos, specifically in our study benefitting younger patients and those recently diagnosed. We suggest that other clinical teams could collaborate fruitfully with patient groups to develop similar videos to target possible misinformation and potentially improve patient outcomes.

Quality assessment of anterior segment OCT images: Development and validation of quality criteria.

BACKGROUND: The utility of medical imaging is dependant on image quality. We aimed to develop and validate quality criteria for ocular anterior segment optical coherence tomography (AS-OCT) images. METHODS: We undertook a cross-sectional study using AS-OCT images from patients aged 6-16. A novel three-level grading system (good, limited or poor) was developed based on the presence of image artefact (categorised as lid, eyelash, cropping, glare, or movement artefact). Three independent experts graded 2825 images, with agreement assessed using confusion matrices and intraclass correlation coefficients (ICC) for each parameter. RESULTS: There was very good inter-grader IQA agreement assessing image quality with ICC 0.85 (95 %CI: 0.84-0.87). The most commonly occurring artefact was eyelash artefact (1008/2825 images, 36 %). Graders labelled 621/2825 (22 %) images as good and 384 (14 %) as poor. There was complete agreement at either end of the confusion matrix with no 'good' images labelled as 'poor' by other graders, and vice versa. Similarly, there was very good agreement when assessing presence of lash (0.96,0.94-0.98), movement (0.97,0.96-0.99), glare (0.82,0.80-0.84) and cropping (0.90,0.88-0.92). CONCLUSIONS: The novel image quality assessment criteria (IQAC) described here have good interobserver agreement overall, and excellent agreement on the differentiation between 'good' and 'poor' quality images. The large proportion of images graded as 'limited' suggests the need for refine this classification, using the specific IQAC features, for which we also report high interobserver agreement. These findings support the future potential for wider clinical and community care implementation of AS-OCT for the diagnosis and monitoring of ocular disease.

A practical approach to uveitis screening in children with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA)-associated uveitis typically presents as a silent chronic anterior uveitis and can lead to blindness. Adherence to current screening guidelines is hampered by complex protocols which rely on the knowledge of specific JIA characteristics. The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to simplify screening to enable local eye care professionals (ECPs), who carry the main burden, to screen children with JIA appropriately and with confidence. METHODS: A consensus meeting took place in January 2023 in Barcelona, Spain, with an expert panel of 10 paediatric rheumatologists and 5 ophthalmologists with expertise in paediatric uveitis. A summary of the current evidence for JIA screening was presented. A nominal group technique was used to reach consensus. RESULTS: The need for a practical but safe approach that allows early uveitis detection was identified by the panel. Three screening recommendations were proposed and approved by the voting members. They represent a standardised approach to JIA screening taking into account the patient's age at the onset of JIA to determine the screening interval until adulthood. CONCLUSION: By removing the need for the knowledge of JIA categories, antinuclear antibody positivity or treatment status, the recommendations can be more easily implemented by local ECP, where limited information is available. It would improve the standard of care on the local level significantly. The proposed protocol is less tailored to the individual than the 'gold standard' ones it references and does not aim to substitute those where they are being used with confidence.

Patient-targeted mobile applications in healthcare.

There has been an increase in the number of healthcare-related applications targeted at patients for use on mobile phones. With an increasing proportion of the population using such applications, it is important to understand the associated limitations, safety concerns and challenges of legalisation. This article explores the impact of these applications on frontline care and patient wellbeing, evaluating the literature surrounding the benefits and challenges of patient-targeted mobile applications in health care and analysing the limitations of existing research. The proclaimed benefits of such applications are not always evidence based. Furthermore, many healthcare applications are created by laypeople and not validated by healthcare authorities, creating a potential to cause patient harm. Further research is needed to identify long-term effects on both healthcare systems and individuals' psychosocial wellbeing. However, research in this field often lacks a universal perspective and may be influenced by underlying financial motives to promote use of the applications.

The incidence, presenting clinical findings and treatment patterns of Birdshot Retinochoroiditis in a high-prevalence region: findings from Northern Ireland, England and Wales.

BACKGROUND: Birdshot Retinochoroiditis (BSRC) is a rare, chronic posterior uveitis that is strongly associated with HLA-A*29.2 positivity. To date, no robust incidence studies of BSRC have been undertaken. We present the first epidemiological study of BSRC in a high-prevalence region. METHODS: In collaboration with the British Ophthalmological Surveillance Unit, all new cases of BSRC between May 2017 and June 2019 were prospectively collected. Presenting demographics, symptoms, signs and treatment modalities were collected. A follow-up questionnaire twelve months later was also sent. RESULTS: Thirty-seven confirmed cases meeting the reporting criteria were identified. Twenty-three cases had both baseline and follow-up data. The total population incidence of BSRC was 0.035 cases per 100,000 person-years [95% CI 0.025-0.048 cases per 100 000 people]. 97.3% were HLA-A*29 positive. The median age was 46 years, with females making up 78% of patients. There were no significant differences in the latitudinal incidence of BSRC. At presentation, floaters were the most common symptom. Optic disc swelling was the most common sign. Mean presenting visual acuity was independent of symptom duration. Combined systemic corticosteroids and immunomodulatory therapy were the most common treatments at baseline and follow-up. Intravitreal steroids were equally popular at follow-up. CONCLUSIONS: This study provides the first nationwide estimate of the incidence of BSRC in a high-prevalence region. Cases were more common in females, with a broad range of presentation ages. No significant latitudinal effect of incidence was identified. Systemic therapy with steroids and IMT remain the most common treatments.

Hypotony in uveitis: an overview of medical and surgical management.

Hypotony is a well-recognised, sight-threatening complication of uveitis. It can also be the final common endpoint for a multitude of disease entities. Multiple mechanisms underlie hypotony, and meticulous clinical history alongside ocular phenotyping is necessary for choosing the best intervention and therapeutic management. In this narrative review, a comprehensive overview of medical and surgical treatment options for the management of non-surgically induced hypotony is provided. Management of ocular hypotony relies on the knowledge of the aetiology and mechanisms involved. An understanding of disease trajectory is vital to properly educate patients. Both anatomical and functional outcomes depend on the underlying pathophysiology and choice of treatment.

Quantitative and qualitative assessment of anterior segment optical coherence tomography capture of disease state in childhood anterior uveitis.

BACKGROUND/AIMS: Anterior segment optical coherence tomography (AS-OCT) assessment of anterior chamber inflammation is an emerging tool. We describe the performance of AS-OCT in a paediatric population. METHODS: A mixed-methods prospective study, using routine clinical assessment as reference standard, and AS-OCT, with Tomey CASIA2 or Heidelberg Spectralis HS1, as index test, with data collected on patient perceptions of imaging. Repeatability, diagnostic indices, responsiveness to clinical change and clinical correlations of imaging-based metrics (image cell count, size, density and brightness) were assessed, with construction of receiver operated characteristic curves. Exploratory thematic analysis of responses from families was undertaken. RESULTS: A total of 90 children (180 eyes) underwent imaging. Bland Altman limits of agreement for CASIA2 repeatability ranged from +17 cells (95% CI 13.6 to 21.1) to -19 cells (95% CI -15.6 to -23.2) and HS1 from +1 (95% CI 0.9 to 1.2) to -1.0 (-1.2 to -0.8) cells. CASIA2 imaging had higher sensitivity of 0.92 (95% CI 0.78 to 0.97) vs HS1 imaging 0.17 (95% CI 0.07 to 0.34), with positive correlation between clinical grade and CASIA2 cell count (coefficient 12.8, p=0.02, 95% CI 2.2 to 23.4). Change in clinical grade at follow-up examinations correlated with change in image based 'cell' count (r2=0.79, p<0.001). Patients reported a potential positive impact of seeing their disease activity. CONCLUSION: Our findings suggest that OCT-based imaging holds the promise of deeper understanding of disease, improved patient experience and more granular monitoring of activity with resultant improved outcomes, but further work is needed to refine acquisition and analysis protocols.

Ocular Inflammatory Events Following COVID-19 Vaccination in the Paediatric Population: A Multinational Case Series.

BACKGROUND: Ocular inflammatory events following COVID-19 vaccination have been reported in the adult population. METHODS: Multinational case series of patients under the age of 18 diagnosed with ocular inflammatory events within 28 days of COVID-19 vaccination. RESULTS: Twenty individuals were included. The most common event was anterior uveitis (n = 8, 40.0%), followed by intermediate uveitis (7 patients, 35%), panuveitis (4 patients, 20%), and posterior uveitis (1 patient, 5%). The event was noticed in the first week after vaccination in 11 patients (55.0%). Twelve patients (60.0%) had a previous history of intraocular inflammatory event. Patients were managed with topical corticosteroids (n = 19, 95.0%), oral corticosteroids (n = 10, 50.0%), or increased dose of immunosuppressive treatment (n = 6, 30.0%). Thirteen patients (65.0%) had a complete resolution of the ocular event without complications. All patients had a final visual acuity unaffected or less than three lines of loss. CONCLUSION: Ocular inflammatory events may happen in the paediatric population following COVID-19 vaccination. Most events were successfully treated, and all showed a good visual outcome.

New and Updated Recommendations for the Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis and Idiopathic Chronic Anterior Uveitis.

OBJECTIVE: The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to update the current guidelines, and the objective here was to produce this document to guide clinicians managing children with juvenile idiopathic arthritis-associated uveitis (JIAU) and idiopathic chronic anterior uveitis (CAU). METHODS: The group analyzed the literature published between December 2014 and June 2020 after a systematic literature review conducted by 2 clinicians. Pediatric rheumatologists were paired with ophthalmologists to review the eligible 37 publications. The search criteria were selected to reflect those used for the 2018 Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) recommendations, in order to provide an update, rather than a replacement for that publication. The summary of the current evidence for each SHARE recommendation was presented to the expert committee. These recommendations were then discussed and revised during a video consensus meeting on January 22, 2021, with 14 voting participants, using a nominal group technique to reach consensus. RESULTS: JIAU treatment was extended to include CAU. Fourteen recommendations regarding treatment of JIAU und CAU with >90% agreement were accepted. CONCLUSION: An update to the previous 2018 SHARE recommendations for the treatment of children with JIAU with the addition of CAU was created using an evidence-based consensus process. This guideline should help support clinicians to care for children and young people with CAU.

Optic disc assessment in the emergency department: a comparative study between the PanOptic and direct ophthalmoscopes.

Optic disc assessment is an essential part of the neurological examination of acutely unwell patients. This study compares the PanOptic ophthalmoscope with the direct ophthalmoscope for accuracy of diagnosis and ease of use. Patient satisfaction was also compared for the two instruments. A single-masked prospective observational study was carried out. The authors showed that the PanOptic ophthalmoscope was more sensitive (p=0.03) and specific (p=0.03) than the direct ophthalmoscope. The PanOptic ophthalmoscope was preferred by both doctors (p=0.001) and patients (p=0.04) in terms of comfort and ease of use.

Incidence of ophthalmic involvement in Behçet's disease in the United Kingdom: a British Ophthalmic Surveillance Unit (BOSU) study.

BACKGROUND: Behçet's disease (BD) is a relapsing-remitting vasculitis, which can manifest in different organ systems including the eyes. There is currently limited published data describing the incidence of ophthalmic disease within the United Kingdom. The primary aim of this study was to survey the incidence and manifestations of ophthalmic BD prospectively, with a secondary aim of reviewing treatment modalities initiated in first-line therapy. METHODS: Using the British Ophthalmic Surveillance Unit reporting system between October 2016 and November 2018, we prospectively surveyed the number of cases of BD presenting to UK ophthalmologists. A total of 89 cases of ophthalmic manifestations of BD were reported and complete information was collected on 58 patients. RESULTS: 93 eyes of 58 patients were affected. The median age of reported cases was 31 years (range 13-55 years) who were born in 15 different countries. Most cases (n = 35, 60%) had bilateral involvement. Vitritis was the most common ocular manifestation (68%; n = 63) followed by anterior uveitis (46%; n = 43). The greatest causes of visual morbidity were cystoid macular oedema, vitritis and retinal ischaemia. Most patients were prescribed either topical or oral corticosteroids (59%; n = 34), with some given intravitreal or intravenous corticosteroids. Five patients (8.6%) were initiated on disease-modifying anti-rheumatic drugs and one given an anti-TNF monoclonal antibody. CONCLUSIONS: This is the first prospective study to analyse the incidence of ophthalmic involvement in BD over a 2-year period, finding an annual incidence of 0.04 per 100,000 individuals in the UK.

Ibrutinib-related uveitis: A report of two severe cases.

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