PurposePatients with sight-threatening inflammatory eye disease (IED) are maintained on systemic immunosuppression whilst in long-term clinical remission. There are no clear guidelines on the duration of remission before implementing treatment withdrawal. We present a real-world analysis on the use of immunosuppression in IED in long-term remission and consider strategies for withdrawal.MethodsAdult IED patients on systemic immunosuppression were categorised into four disease groups: Corneal Transplant Survival Strategies (CTSS), Ocular Surface Disease (OSD), Non-infectious Uveitis (NIU) and Scleritis. Patients with Behcet's disease were excluded. Data on systemic immunosuppressants and biologics used; duration of treatment; reasons for drug discontinuation; disease activity/remission status; duration of clinical remission with an emphasis on patients who had been in remission for a minimum of 24 months were captured.ResultsOut of a total of 303 IED patients, 128 were on systemic immunosuppression with a clinical remission of their ocular disease for >= 24 months. The median duration of remission was 4-5 years with the longest duration of remission 22 years, and some patients on immunosuppression for up to 23 years. Sixty patients stopped at least one immunosuppressive agent without prior discussion with a health-care practitioner.ConclusionProgressive conditions, such as cicatrising conjunctivitis may require lifelong immunosuppression, but patients with NIU and Scleritis and those on CTSS, immunosuppression withdrawal should be considered if they remain in remission for 2 years. Any patient stopping a medication should be contacted immediately for counselling. These data will better inform patients, encourage adherence and aide formal guideline development.

PURPOSE:To assess the efficacy of treatment on acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and relentless placoid chorioretinopathy (RPC). METHODS:Cases were identified from three UK uveitis centers. Retrospective analysis of visual acuity recovery; OCT structural outcomes; and retinal lesion quantification in observed and treated cases of APMPPE/RPC. RESULTS:There were nine APMPPE and three RPC cases. Out of 12 patients, six were female. Median age: 26.5 years (range, 20-57 years). Four cases (six eyes) were observed, and eight cases (15 eyes) received corticosteroids ± immunosuppression. 4/4 observed and 6/10 treated foveal involving eyes regained 0.00 LogMAR vision. Observed lesions achieved more favorable anatomical outcomes. New lesions post-presentation developed in 1/6 (16%) observed eye versus 10/15 (66%) treated eyes. In three cases, a delayed, rebound lesion occurrence was observed post-high-dose corticosteroids. CONCLUSIONS:While subject to potential treatment bias, in this small case series, natural history alone appears non-inferior to corticosteroid treatment.

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

The management of uveitis in children can be extremely challenging as they constitute a unique population of patients. The aim of this review is to summarize current knowledge encompassing the clinical findings, diagnostic work-up, and therapeutic approach of uveitis in children. A thorough literature search was performed of PubMed. An additional search was made in Google Scholar to complete the collected items. Uveitis is less common in children than in adults, but it may be more complicated due to its often asymptomatic nature or due to the inability of children to express complaints. Uveitis in children can be chronic, persistent, recurrent, and resistant to conventional treatment. The most common type of uveitis in pediatric patients is anterior uveitis, whereas the prevalence of intermediate, posterior, and panuveitis depends on the ethnic group and geographical distribution. Although many cases of pediatric uveitis are idiopathic, the differential diagnosis requires awareness of etiologies, as uveitis in children may be associated with various systemic inflammatory disorders, infections, or masquerade syndromes. Ocular complications of uveitis include cataracts, synechiae formation, glaucoma or hypotony, band keratopathy, macular edema, epiretinal membrane, choroidal neovascular membranes, and retinal detachment. These complications are associated with not only the nature of the disease but also with the use of topical and systemic corticosteroids, leading to irreversible structural damage and visual loss. The therapeutic approach depends on the etiologic factor and the individual characteristics of each patient. Regular monitoring is crucial for early detection of any complications of uveitis or even adverse effects from treatments. Multidisciplinary management is also vital for providing more holistic care to young patients and their families ensuring a better quality of life. This study aims to review the current literature on the management of uveitis in pediatric patients.

Corneal transplantation is the most frequently performed transplantation in the UK. Despite this, the therapeutic value of matching human leukocyte antigen (HLA) subtypes for transplanted corneas remains controversial. Ocular immune privilege was originally deemed to render matching unnecessary; however, more recently, matching has demonstrated improved outcomes including graft success, amongst others. This systematic review aims to evaluate the effectiveness of major and minor antigen matching on graft outcomes in corneal transplantation. Standard systematic review methodology will be used to identify, select and extract data from observational studies and clinical trials assessing the effects of HLA matching on corneal graft outcomes. Bibliographic databases (Cochrane Library, EMBASE, MEDLINE, Web of Science, Scopus), clinical trial registers, abstract and conference proceedings, in addition to dissertation, thesis and grey literature will be searched. Neither date of publication nor language will be restricted, and non-English articles will be translated where necessary. The primary outcome will be to assess corneal graft success for different degrees of HLA matching/mismatching. The precise end outcome measure varies amongst studies and includes graft rejection, immunoreaction, failure and survival. Therefore, data will be extracted across all relevant outcome parameters and grouped for subsequent statistical tests. Risk of bias assessment will be completed, appropriate to each study design. Study selection, data extraction and risk of bias assessment will be independently completed by two reviewers. Data will be tabulated, and a narrative synthesis presented. Meta-analysis will be performed where there is sufficient homogeneity between studies to warrant its effective completion. Subgroup and sensitivity analysis will be undertaken if appropriate. Many studies have investigated the effectiveness of HLA matching for corneal transplantation. A systematic review is needed to collate and analyse this evidence. Findings of this systematic review may form the basis of evidence-based recommendations on pre-operative HLA typing and matching of corneal grafts for transplantation. PROSPERO reference CRD42020198882

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10-25% of patients laminin 332 is recognized. In 25-30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials.

Purpose To create a health utility value for birdshot chorioretinopathy (BCR) using Time Trade-Off (TTO) and Standard Gamble (SG) utilities. Method Adult BCR patients completed TTO, SG, EQ-5D-5L, and NEI VFQ-25 questionnaires and underwent a detailed history and clinical examination. Results 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 (p= .024) and NEI VFQ-25 composite score (p= .015). Conclusions 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 Non-infectious scleritis is a potentially sight-threatening condition in which the sclera, the white outer layer of the eye, becomes inflamed. Whilst scleritis can be infective, the majority of cases are due to non-infectious causes, often occurring in association with an underlying systemic autoimmune or auto-inflammatory condition. Thorough systemic work-up is crucial to identify disease aetiology and exclude infection; however, a significant proportion of disease remains idiopathic with the underlying cause unknown. Non-infectious scleritis is normally managed with systemic corticosteroid and immunosuppression, yet there is no widely agreed consensus on the most appropriate therapy, and no national or international guidelines exist for treatment of non-infectious scleritis. Methods Standard systematic review methodology will be used to identify, select and extract data from comparative studies of pharmacological interventions used to treat patients with non-infectious scleritis. Searches of bibliographic databases (Cochrane Library, MEDLINE, CINAHL and EMBASE) and clinical trial registers will be employed. No restrictions will be placed on language or date of publication. Non-English articles will be translated where necessary. The primary outcome of interest will be disease activity measured by reduction in scleritis grading according to standardised grading systems. Secondary outcomes will include change in best corrected visual acuity, reduction in concurrent dose of systemic corticosteroid, time to treatment failure, adverse events and health-related quality of life. Risk of bias assessment will be conducted appropriate to each study design. Study selection, data extraction and risk of bias assessment will be completed by two reviewers independently. Data will be presented in a table and a narrative synthesis will be undertaken. Meta-analysis will be performed where methodological and clinical homogeneity exists. Subgroup and sensitivity analysis will be undertaken if appropriate. Discussion Many studies have investigated the effectiveness of pharmacological agents used in the management of non-infectious scleritis. A systematic review is needed to collate and analyse this evidence. Findings of this systematic review will help guide ophthalmologists managing patients with non-infectious scleritis and may form the basis for evidence-based recommendations for future clinical practice and encourage standardisation of treatment protocols. Systematic review registration PROSPERO CRD42019125198

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.

Introduction: To report with multi-modal imaging the clinical course of 3 patients with new-onset uveitis following treatment with etanercept. Methods: Retrospective case-note reviews were conducted of 3 patients previously established on etanercept who developed new-onset acute uveitis. Results and Discussion: Three patients were assessed with a mean age of 44.3 (43-47). Etanercept was indicated for the treatment of ankylosing spondylitis in two patients and psoriatic arthritis in 1 patient. Duration of etanercept treatment ranged from 7 to 10 years; however, in two cases, treatment recently changed to an etanercept biosimilar agent. Two patients were diagnosed with bilateral panuveitis and one patient had chronic relapsing anterior uveitis. Infection screen was negative in all three patients. 2 patients developed cystoid macular oedema as viewed on Spectral Domain OCT. Fundus fluorescein angiography was performed in one patient who demonstrated bilateral retinal vasculitis. All three patients were started on systemic and topical treatment. One patient received sub-tenon triamcinolone injection. Etanercept was discontinued for all patients. 1 of 3 patients lost vision at 7 months. 2 patients demonstrated long-term remission and one patient required intravitreal steroid implantation to stabilize an ongoing intraocular inflammation. Two patients who had complete remission were commenced on Adalimumab while the third patient was commenced on Secukinumab. Conclusion: The clinical course of uveitis developing paradoxically following etanercept treatment is variable. Multi-modal imaging is useful for the clinician that helps in diagnosing and monitoring associated macular oedema and retinal ischaemia. Cessation of etanercept and systemic corticosteroid treatment are often required to prevent ocular morbidity.

Purpose Worldwide, as many as 6 million children annually sustain ocular trauma, with up to a quarter of a million children requiring hospitalization. Management of pediatric ocular trauma differs from that in adults, both in terms of initial assessment and acute intervention, with significant variation in practice between different centers. Patterns of healing and long-term outcomes are also very different for children compared to adults. In order to develop effective protocols for management, it is first necessary to understand current trends in presentation and treatment. Methods We conducted a prospective, observational study of pediatric ocular trauma presenting to UK-based ophthalmologists over a one-year period; reporting cards were distributed by the British Ophthalmic Surveillance Unit, and clinicians were asked to report cases of acute orbital and ocular trauma in children aged 16 years or less requiring inpatient or day-case admission. A validated, standardized questionnaire was sent to reporting ophthalmologists to collect data on clinical features and initial management of injury. Results Eighty-six episodes of pediatric ocular trauma were reported. Trauma involving the globe was reported in 66/86 patients (76.7%), of which 40/66 (60.1%) were open-globe. Trauma to the anterior segment was reported in 57/86 (66.3%), and posterior segment in 23/86 patients (26.7%). Twenty-five of 86 (29.1%) patients sustained severe trauma defined as having best-corrected visual acuity worse than 6/60 Snellen (incidence 0.19 per 100,000 population). Conclusions There has been no improvement in the incidence or severity of pediatric ocular injury rates over the past 25 years. Eye-care providers must be able to provide the necessary services for assessment and management of severe pediatric ocular trauma in the emergency setting.

Background: Childhood uveitis is a collection of chronic rare inflammatory eye disorders which result in visual loss in at least one eye of one fifth of affected children. Despite the introduction of novel systemic immunochemotherapies, it remains a blinding disease. We have undertaken a systematic review of outcome measures used in interventional trials of children with, or at risk of uveitis, in order to investigate metric quality and heterogeneity, as possible barriers to the translation of clinical research into improved outcomes. Methods: Systematic review of trials registered within databases approved by the International Committee of Medical Journal Editors (ICMJE). Eligible trials for were those which involved participants aged under 18 years with or at risk of non-infectious uveitis. Data on date of study commencement, uveitis site, inclusion age criteria, and outcome measure characteristics including type, dimension and quality were extracted independently by two authors. Quality was determined using the reproducibility, validity and age-appropriateness of the metric. Results: Of 917 identified trials, 57 were eligible for inclusion. Twenty different domains across five dimensions were used as primary outcome measures. The structure most commonly used was multiple separate outcome measures. In a quarter of studies, outcomes were assessed less than 3 months following the intervention. Disease activity was the most commonly assessed dimension, with only 30 studies (60%) using reproducible methodologies to assess activity. Only 2/12 (18%) studies on intermediate or posterior uveitis used reproducible activity grading schemes. Of 18 studies involving children aged under 6 years old which used outcome measures related to visual function, only 8/18 (44%) described the use of age-appropriate acuity assessment measures. None of the studies used a vision related quality of life metrics which had been validated for use in childhood. Conclusion: This review of outcome measures in childhood uveitis interventional trials has identified under-utilisation of reproducible or child appropriate measures, and considerable heterogeneity in metric type, and structure. Clinicians and researchers interested in improving outcomes for affected children must identify a patient and family centred core outcome set, and work to validate both objective and patient (or proxy) reported disease age appropriate outcome measures.

1Department of Ophthalmology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 2Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; 3Birmingham Institute for Glaucoma Research, Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 4Department of Ophthalmology, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK; 5Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Dundee, UK; 6Department of Ophthalmology, Ninewells Hospital and Medical School, Dundee, UK; 7University College London, London, UK; 8Centre for Health and Social Care Improvement, School of Health and Wellbeing, University of Wolverhampton, Wolverhampton, UK Purpose: Worldwide, as many as 6 million children annually sustain ocular trauma, with up to a

1Department of Ophthalmology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 2Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; 3Birmingham Institute for Glaucoma Research, Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 4Department of Ophthalmology, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK; 5Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Dundee, UK; 6Department of Ophthalmology, Ninewells Hospital and Medical School, Dundee, UK; 7University College London, London, UK; 8Centre for Health and Social Care Improvement, School of Health and Wellbeing, University of Wolverhampton, Wolverhampton, UK Purpose: Worldwide, as many as 6 million children annually sustain ocular trauma, with up to a

PURPOSE: To compare rates of visual field (VF) loss in uveitis patients with glaucoma against patients with primary open-angle glaucoma (POAG) and explore the association between intraocular pressure (IOP) and rate of VF loss. DESIGN: Retrospective cohort study. METHODS: Anonymized VFs and IOP measurements extracted from the electronic medical records of 5 regionally different glaucoma clinics in England. A total of 205 eyes with diagnosis of uveitis plus glaucoma were compared with 4600 eyes with POAG only. Minimum inclusion criteria were >= 4 visits within a 4-year window. Relative risk (RR) of being a "rapid progressor" (mean deviation [MD] loss >= 1.5 dB/year) was calculated. A mixed-effects model (MEM) and a pointwise VF progression analysis of pattern deviation were used to confirm differences between the groups. Longitudinal IOP mean, range, and variability were compared with rate of VF progression. RESULTS: Median (interquartile range) baseline MD in the uveitis and POAG groups was -3.8 (-8.7, -1.5) dB and -3.1 (-6.6, -1.2) dB, respectively. The uveitis and POAG groups had 23 of 205 (11%) and 331 of 4600 (7%) "rapidly progressing" eyes, respectively. Age-adjusted RR for "rapid progression" in uveitic vs POAG eyes was 1.9 (95% confidence interval: 1.8-2.0). The MEM confirmed that uveitic eyes (- 0.49 dB/year) showed higher rates of VF progression than the POAG group (- 0.37 dB/year; P < .01). IOP range and variability were higher in the "rapidly progressing" uveitic eyes. CONCLUSIONS: Our analysis suggests that VF loss occurs faster in glaucoma patients with uveitis than those without uveitis. The risk of progressing rapidly in glaucoma with uveitis is almost double than in those without uveitis. Early identification of "rapid progressors" may enable targeted intervention to preserve visual function in this high-risk group. (C) 2019 The Author(s). Published by Elsevier Inc.