A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution.

Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most fibrotic diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTKlowCD48+ macrophages and MERTK + LYVE1 + MRC1+ macrophages enriched for negative regulators of inflammation which co-exist in frozen shoulder capsule tissues. Micro-cultures of patient-derived cells identify integrin-mediated cell-matrix interactions between MERTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in frozen shoulder resolution. Cross-tissue analysis reveals a shared gene expression cassette between shoulder capsule MERTK+ macrophages and a respective population enriched in synovial tissues of rheumatoid arthritis patients in disease remission, supporting the concept that MERTK+ macrophages mediate resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identify MERTK + LYVE1 + MRC1+ macrophages and DKK3+ and POSTN+ fibroblast populations analogous to those in frozen shoulder, suggesting that the template to resolve fibrosis is established during shoulder development. Crosstalk between MerTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts could facilitate resolution of frozen shoulder, providing a basis for potential therapeutic resolution of persistent fibrotic diseases.

Ocular Lichen Planus: A clinicopathologic review.

Lichen planus is a chronic inflammatory dermatosis that can affect the skin, mucous membranes and nails. Cutaneous lichen planus lesions are best described by the "six Ps" - purple pruritic polygonal planar papules and plaques. Mucous membrane lesions are commonly associated with cutaneous lichen planus. Ocular involvement with lichen planus is rare and conjunctival involvement usually predominates, it can however be visually devastating. Ocular lichen planus often progresses to extensive conjunctival scarring which can be impossible to distinguish clinically from other cicatrising conjunctivitis, requiring histopathological confirmation. Here we review the ocular pathology of this condition.

Systematic review of clinical practice guidelines for uveitis.

To facilitate the integration of eye care into universal health coverage, the WHO is developing a Package of Eye Care Interventions (PECI). Development of the PECI involves the identification of evidence-based interventions from relevant clinical practice guidelines (CPGs) for uveitis.A systematic review of CPGs published on uveitis between 2010 and March 2020 was conducted. CPGs passing title and abstract and full-text screening were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool and data on recommended interventions extracted using a standard data extraction sheet.Of 56 CPGs identified as potentially relevant from the systematic literature search, 3 CPGs underwent data extraction following the screening stages and appraisal with the AGREE II tool. These CPGs covered screening for, monitoring and treating juvenile idiopathic arthritis (JIA)-associated uveitis, the use of adalimumab and dexamethasone in treating non-infectious uveitis, and a top-level summary of assessment, differential diagnosis and referral recommendations for uveitis, aimed at primary care practitioners. Many of the recommendations were based on expert opinion, though some incorporated clinical study and randomised controlled trial data.There is currently sparse coverage of the spectrum of disease caused by uveitis within CPGs. This may partially be due to the large number of conditions with diverse causes and clinical presentations covered by the umbrella term uveitis, which makes numerous sets of guidelines necessary. The limited pool of CPGs to select from has implications for clinicians seeking guidance on clinical care strategies for uveitis.

The Cellular Composition of the Uveal Immune Environment.

The uveal tract consists of the iris, the ciliary body and the choroid; these three distinct tissues form a continuous layer within the eye. Uveitis refers to inflammation of any region of the uveal tract. Despite being grouped together anatomically, the iris, ciliary body and choroid are distinct functionally, and inflammatory diseases may affect only one part and not the others. Cellular structure of tissues direct their function, and understanding the cellular basis of the immune environment of a tissue in health, the "steady state" on which the perturbations of disease are superimposed, is vital to understanding the pathogenesis of those diseases. A contemporary understanding of the immune system accepts that haematopoietic and yolk sac derived leukocytes, though vital, are not the only players of importance. An array of stromal cells, connective tissue cells such as fibroblasts and endothelial cells, may also have a role in the inflammatory reaction seen in several immune-mediated diseases. In this review we summarise what is known about the cellular composition of the uveal tract and the roles these disparate cell types have to play in immune homeostasis. We also discuss some unanswered questions surrounding the constituents of the resident leukocyte population of the different uveal tissues, and we look ahead to the new understanding that modern investigative techniques such as single cell transcriptomics, multi-omic data integration and highly-multiplexed imaging techniques may bring to the study of the uvea and uveitis, as they already have to other immune mediated inflammatory diseases.

Using the West Midlands CONCERT to characterise regional incidence of acute-onset post cataract surgery endophthalmitis.

BACKGROUND: Whilst research and innovation is embedded within the UK's National Health Service (NHS) constitution, Doctors-in-training have little opportunity to contribute to designing, leading and recruiting into clinical trials or cohort studies. We formed the West Midlands Collaborative Ophthalmology Network for Clinical Effectiveness & Research by Trainees (The West Midlands CONCERT) and undertook a characterisation of post cataract surgery endophthalmitis as a proof-of-concept study to test the feasibility of the CONCERT model. METHODS: Doctors-in-training formed a collaborative working group to test the concept of delivering a pan-regional clinical effectiveness study across multiple hospital sites by performing retrospective analyses of post cataract endophthalmitis over a 6-year period. RESULTS: Overall, 157,653 cataract surgeries were performed by participating centres accredited to deliver the Royal College of Ophthalmologists training curriculum. Thirty-eight cases of post cataract endophthalmitis were identified, giving an incidence of 2.41 per 10,000 cases (0.0241%). A further 15 endophthalmitis cases presented who had surgery in non-training centres, giving a total of 53 cases. The most common organisms were S. epidermidis (14 (51.9%)) and P. aeruginosa (5 (18.5%)). Anterior-chamber and vitreous sampling yielded positive culture in 33.3% (6/18) and 50.9% (27/53), respectively. At 6 months follow-up, 19 (51.4%) patients achieved visual acuities of ≤0.5 LogMAR. Repeat intravitreal injections (11 (20.8%)) and vitrectomy (n = 22 (41.5%)) were not associated with better outcomes. CONCLUSIONS: Using post cataract endophthalmitis as a pilot cohort, this study highlights the feasibility of using the CONCERT model for studies across multiple sites. A UK-CONCERT could provide a powerful infrastructure enabling characterisation of patient cohorts and a platform for high-quality interventional studies, improving patient care.

Hepatitis E infection in stem cell and solid organ transplantpatients: A cross-sectional study: The importance of HEV RNA screening in peri-transplant period.

BACKGROUND: Hepatitis E Virus (HEV) is a common cause of acute viral hepatitis worldwide. Typically associated with a self-limiting illness, infection may persist in immunosuppressed populations with significant morbidity and mortality. Based on clinical data published world-wide, UK blood safety guidance recommends the universal screening for HEV RNA of blood donors and donors of tissue, organs and stem cells. OBJECTIVES: This cross-sectional study aimed to determine the point prevalence of HEV viraemia and clinical course of viraemic patients in the peri-transplant period in solid organ transplant (SOT) and haematopoietic stem cell transplant (HSCT) recipients transplanted over a 3-year period (2013-2015). STUDY DESIGN: Nucleic acid extracts of whole blood from patients undergoing SOT or HSCT were tested by an in-house real-time reverse-transcriptase polymerase chain reaction assay for HEV RNA. Samples were tested at baseline (time of transplant), 30, 60 and 90 days post-transplant. RESULTS: 870 patients (259 HSCT, 262 liver and 349 kidney transplant) were included with 2554 samples meeting the inclusion criteria. No kidney transplant patients had HEV viraemia at time of testing. One HSCT and three liver transplant patients were found to be HEV RNA positive. Overall this represented 0.46% of the patients testing positive for HEV viraemia. CONCLUSIONS: Prevalence of HEV viraemia in SOT and HSCT patients in U.K. although higher than in the general population is low at baseline and remains low throughout the early post-transplant phase. Clearance of viraemia can be maintained despite ongoing immunosuppression. Prospective U.K. studies are necessary to inform screening policies in this population.

VITRECTOMY FOR PHACOANAPHYLACTIC GLAUCOMA SECONDARY TO POSTERIOR CAPSULAR RUPTURE IN AN ADULT WITH PERSISTENT HYPERPLASTIC PRIMARY VITREOUS.

PURPOSE: Persistent hyperplastic primary vitreous (PHPV) is a developmental anomaly in which the normal regression of the primary vitreous and hyaloid vasculature does not occur. In the literature, there are a few cases of PHPV in adulthood. We report the novel presentation of phacoanaphylactic glaucoma secondary to posterior capsular rupture in an adult with PHPV. We discuss the best management of this condition with a review of the literature on this topic. METHODS: Case report and literature review. RESULTS: Medical management was unsuccessful in this case and vitrectomy and fragmatome lensectomy improved vision from PL to counting fingers. CONCLUSION: This case is unusual in the age of the patient in question as PHPV usually presents in childhood, as such there are few accounts in the literature to guide optimum management of adult PHPV. We suggest that surgical management of late-presenting PHPV should be considered to improve functional outcome.

Use of Lumbar Punctures in the Management of Ocular Syphilis.

PURPOSE: Ocular syphilis has become rare in the developed world, but is a common presentation to ophthalmology departments in South Africa. We investigated the proportion of patients diagnosed with ocular syphilis who went on to receive lumbar punctures, and determined the fraction of these who had cerebrospinal fluid findings suggestive of neurosyphilis. We aimed to determine whether the use of lumbar punctures in ocular syphilis patients was beneficial in picking up cases of neurosyphilis. METHODS: Retrospective study of case notes of patients admitted to two district hospitals in Durban, South Africa, with ocular syphilis over a 20-month period. RESULTS: A total of 31 of 68 ocular syphilis patients underwent lumbar puncture, and of these, eight (25.8%) had findings suggestive of neurosyphilis. CONCLUSIONS: Lumbar puncture in ocular syphilis patients should continue to be a routine part of the investigation of these patients; a large proportion of ocular syphilis patients show cerebrospinal fluid findings suggestive of neurosyphilis, are at risk of the complications of neurosyphilis, and should be managed accordingly.

Efficacy and safety of bimatoprost in glaucoma and ocular hypertension in non-responder patients.

AIM: To establish the efficacy and safety of bimatoprost 0.03% monotherapy in glaucoma and ocular hypertension (OHT) patients with inadequate intraocular pressure (IOP)on current therapy. METHODS: Pre- and post-switch IOPs were analyzed for 59 consecutive patients who were switched from current therapy to bimatoprost monotherapy between 2011-2015. Demographic information, diagnosis, and any adverse events were recorded. Change in IOP post-pre switch was analyzed using a 2-sided Student's paired t-test at the 5% significance level. RESULTS: There was a statistically significant mean reduction in IOP at the first follow up visit, which was maintained at subsequent follow up visits for patients regardless of diagnosis, or pre-switch treatment (P<0.001). Subgroup analysis also demonstrated a statistically significant mean reduction in IOP when looking at OHT patients only, as well as patients with any diagnosis switched from latanoprost monotherapy to bimatoprost monotherapy (P<0.001). CONCLUSION: This is the largest independent data set which supports switching glaucoma patients with poor response to current treatment onto bimatoprost monotherapy before considering other adjuvant medical or more invasive therapy.

Vitrectomy, Inner Limiting Membrane Peel, and Gas Tamponade in the Management of Traumatic Paediatric Macular Holes: A Case Series of 13 Patients.

PURPOSE: To review the outcomes of pars plana vitrectomy, internal limiting membrane (ILM) peel, and gas tamponade in the management of traumatic paediatric macular holes. METHODS: Retrospective case series of children undergoing vitrectomy, ILM peel, and gas tamponade for traumatic macular hole between March 2007 and July 2014. Main outcome measures were postoperative visual acuity at 3 and 12 months, anatomic closure rate, and surgical complications. RESULTS: Anatomic macular hole closure was achieved in 12 (92.3%) of 13 cases. Mean preoperative logMAR visual acuity was 0.91 (95% CI 0.65-1.17) with improvement postoperatively to 0.54 (95% CI 0.43-0.64) at 3 months (p = 0.002) and 0.50 (95% CI 0.39-0.60) at 12 months (p = 0.002). There were no perioperative complications. CONCLUSION: Pars plana vitrectomy and ILM peel is an effective management option for paediatric macular holes.

The role of day one postoperative review of intraocular pressure in modern vitrectomy surgery.

BACKGROUND: With the introduction of sutureless 23-gauge (23G) vitrectomy, the risks for elevated intraocular pressure (IOP) and the need for day 1 review of IOP are less certain. AIMS: To assess current practice for postoperative review in the vitreoretinal service at a large tertiary referral centre; to assess whether day 1 review detected complications altering patient management; to identify risk factors for IOP spikes postvitrectomy. METHODS: Retrospective, consecutive case note review of all patients undergoing 23G vitrectomy at the study institution between April and June 2013. Patients had assessment at either day 1, week 2 and month 2 or week 2 and month 2. Linear regression analysis was performed to identify risk factors for IOP elevation. RESULTS: 200 (89%) cases met inclusion criteria. Of these, 176 (89.3%) had day 1 review, 24 (12%) were seen at week 2. Mean follow-up was 120 days (range 20-360). Two cases (1%) required urgent surgical intervention due to early IOP complications. Combined laser was the only risk factor for a day 1 IOP spike (p=0.005). In total, 44 patients (22%) were treated for elevated IOP within 2 weeks following vitrectomy. No long-term complications were detected in these patients. CONCLUSIONS: Day 1 review detected adverse events in 0.5% of study patients. No long-term complications were reported in the 22% of patients who received treatment for early postoperative IOP elevation. This observation has led to the removal of routine day 1 review from the surgical care pathway following routine uncomplicated vitrectomy at the study institution.

Notch cooperates with Lozenge/Runx to lock haemocytes into a differentiation programme.

The diverse functions of Notch signalling imply that it must elicit context-specific programmes of gene expression. With the aim of investigating how Notch drives cells to differentiate, we have used a genome-wide approach to identify direct Notch targets in Drosophila haemocytes (blood cells), where Notch promotes crystal cell differentiation. Many of the identified Notch-regulated enhancers contain Runx and GATA motifs, and we demonstrate that binding of the Runx protein Lozenge (Lz) is required for enhancers to be competent to respond to Notch. Functional studies of targets, such as klumpfuss (ERG/WT1 family) and pebbled/hindsight (RREB1 homologue), show that Notch acts both to prevent the cells adopting alternate cell fates and to promote morphological characteristics associated with crystal cell differentiation. Inappropriate activity of Klumpfuss perturbs the differentiation programme, resulting in melanotic tumours. Thus, by acting as a master regulator, Lz directs Notch to activate selectively a combination of target genes that correctly locks cells into the differentiation programme.