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To identify patient preference drivers related to the management of wet age-related macular degeneration (wet AMD).In this cross-sectional study, a self-explicated 'conjoint analysis' survey was administered online to eligible patients with wet AMD (receiving anti-vascular endothelial growth factor [VEGF] treatment for at least 12 months) from the USA, Canada, UK, France, Spain, Germany, Italy, Japan, Taiwan, and Australia. The survey consisted of six domains with 21 attributes, which were selected on the basis of a literature review, social media listening, and tele-interviews/discussions with patients, clinical experts, and patient groups. Utility and relative importance scores were generated for each attribute and utility difference significance testing was performed using 'unequal variances t tests'. The Patient Activation Measure (PAM-13) questionnaire was administered to assess patients' knowledge, skill, and confidence in self-management.A total of 466 patients (mean age, 68 years; women, 54%; binocular wet AMD, 28%) with an average anti-VEGF treatment duration of 3.9 years completed the survey. The most important preference domains were 'treatment effects on vision' (non-significant) and 'vision-related symptom burdens' (p 0.001), followed by 'treatment risk' (p 0.05), 'impact on daily activities' (p 0.05), 'burden of clinic/hospital visits' (p 0.001), and 'impact on psychological well-being'. The five most important attributes in order of importance were clarity of vision, treatment effect on symptoms, quality of vision, time to treatment effect, and time to re-administration. The two most important attributes globally were also in the top three attributes across countries. The majority of participants in the study were level 3 or level 4 of the PAM-13 questionnaire.This study identified the most important disease and treatment attributes to patients using patient-centred methods. The data showed the degree of harmonization of preferences across geographies and that participants actively adopt behaviours required for improved treatment outcomes. The identified preference drivers may inform future clinical development.

Untreated neovascular age-related macular degeneration (nAMD) can lead to severe and permanent visual impairment. The chronic nature of the disease can have a significant impact on patients' quality of life and an economic and time burden on medical retina (MR) services, with the care need outweighing the growth of resources that clinical services can access. The introduction of a new treatment into clinical services can be challenging, especially for services that are already under capacity constraints. Guidance for practical implementation is therefore helpful. Roundtable meetings, facilitated by Novartis UK, between a working group of MR experts with experience of leading and managing NHS retinal services in the intravitreal era were conducted between 2020 and 2021. These meetings explored various aspects and challenges of introducing a new anti-vascular endothelial growth factor (VEGF) therapy to the UK medical retina services. Provision of clear expert recommendations and practical guidance nationally, that can be adapted locally as required to support clinicians and healthcare professionals (HCPs), is valuable in supporting the introduction of a new anti-VEGF therapy within the NHS environment. The experts provide ophthalmologic HCPs with a collation of insights and recommendations to support the introduction and delivery of brolucizumab in their local service in the face of current and projected growth in demand for retina care.摘要: 未经治疗的新生血管年龄相关性黄斑变性(nAMD)可导致严重永久性的视力损害。该疾病的慢性进展性的临床特征会对患者的生活质量产生重大影响, 并对视网膜疾病的服务造成经济方面和时间方面的负担, 其护理需求超过了临床服务目前可获得的资源增速。在临床服务中引入一种新的治疗方法可能具有挑战性, 特别是对于已经受到限制的服务而言。因此, 对临床实践进行指导是非常有益的。在诺华英国公司的协助下, MR专家工作组在2020年至2021年期间召开了圆桌会议, 这些专家拥有在玻璃体腔注药时代领导和管理NHS视网膜服务的丰富经验。这些会议探讨了将一种新的抗血管内皮生长因子(VEGF)引入英国医疗视网膜服务的各个方面的问题和挑战。为了支持临床医生和医疗保健专业人员(healthcare professionals, HCPs), 对在全国范围内提供的明确的专家建议和实用指南, 可以根据需要在当地进行调整, 这对于支持在NHS环境中引入新的抗VEGF疗法非常有价值。面对当前和预计的视网膜护理需求增长, 专家们为眼科医务人员提供了一系列见解和建议, 以支持在他们的本地服务中引入和使用布洛赛珠单抗。.

IntroductionPatients with suspected inflammatory bowel disease (IBD) referred from primary care often face diagnostic and treatment delays. This study aimed to compare a novel direct-access IBD endoscopy pathway with the traditional care model.MethodSingle centre real-world study analysing primary care referrals with suspected IBD. Group A: patients triaged to direct-access IBD endoscopy. Group B: patients undergoing traditional outpatient appointments before the availability of direct-access IBD endoscopy. Demographics, fecal calprotectin (FCP), C-reactive protein (CRP), disease activity score, endoscopy findings, treatment and follow-up were collected and statistically analysed. Ranked semantic analysis of IBD symptoms contained within referral letters was performed.ResultsReferral letters did not differ significantly in Groups A and B. Demographic data, FCP and CRP values were similar. Referral to treatment time (RTT) at the time of IBD endoscopy was reduced from 177 days (Group B) to 24 days (Group A) (pConclusionOur novel pathway resulted in an 86% reduction in RTT with associated increased diagnostic yield while saving 100% of initial IBD consultant outpatient appointments. Replication in other trusts may improve patient experience and accelerate time to diagnosis/treatment while optimising the use of healthcare resources.

Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

PURPOSE: Management of neovascular age-related macular degeneration (nAMD) has evolved over the last decade with several treatment regimens and different medications. This study describes the treatment patterns and, importantly, visual outcomes over ten years in a large cohort of patients. DESIGN: Retrospective analysis of electronic health records from 27 National Health Service (NHS) secondary care healthcare providers in the UK. PARTICIPANTS: Treatment-naïve patients receiving at least three intravitreal anti-vascular endothelial growth factor (VEGF) injections for nAMD in their first six months of follow-up were included. Patients with missing data for age or gender and those aged less than 55 were excluded. METHODS: Eyes with at least three years of follow-up were grouped by years of treatment initiation, and three-year outcomes were compared between the groups. Data were generated during routine clinical care between 09/2008 and 12/2018. MAIN OUTCOME MEASURES: Visual acuity, number of injections, number of visits. RESULTS: A total of 15,810 eyes of 13,705 patients receiving 194,904 injections were included. Visual acuity (VA) improved from baseline during the first year, but dropped thereafter, resulting in loss of visual gains. This trend remained consistent throughout the past decade. Although an increasing proportion of eyes remained in the driving standard, this was driven by better presenting visual acuities over the decade. The number of injections dropped substantially between the first and subsequent years, from a mean of 6.25 in year 1 to 3 in year 2 and 2.5 in year 3, without improvement over the decade. In a multivariable regression analysis, final VA improved by 0.24 letters for each year since 2008, and younger age and baseline VA were significantly associated with VA at three years. CONCLUSION: Our findings show that despite improvement in functional VA over the years, primarily driven by improving baseline VA, patients continue to lose vision after the first year of treatment, with only marginal change over the past decade. The data suggest that these results may be related to suboptimal treatment patterns, which have not improved over the years. Rethinking treatment strategies may be warranted, possibly on a national level or through the introduction of longer-acting therapies.

Background Neovascular age-related macular degeneration (nAMD) presents a significant treatment burden for patients, carers and medical retina services. However, significant debate remains regarding how best to manage nAMD when assessing disease activity by optical coherence tomography (OCT), and particularly the significance of different types of fluid and how the understanding of anatomical efficacy can influence treatment strategies. This article provides opinion on the practical implications of anatomical efficacy and significance of fluid in the management of nAMD and proposes recommendations for healthcare professionals (HCPs) to improve understanding and promote best practice to achieve disease control. Methods An evidence-based review was performed and an expert panel debate from the Retina Outcomes Group (ROG), a forum of retinal specialists, provided insights and recommendations on the definition, role and practical implications of anatomical efficacy and the significance of fluid at the macula in the management of nAMD. Results The ROG has developed recommendations for achieving disease control through a zero-tolerance approach to the presence of fluid in nAMD as patients who avoid fluctuations in fluid at the macula have better visual outcomes. Recommendations cover five key areas: service protocol, training, regimen, multidisciplinary teams and engagement. This approach facilitates more standardised protocol-based treatment strategies. Conclusions Targeting a fluid-free macula and aiming for disease control are essential to improve outcomes. As new therapies and technologies become available, drying the macula and maintaining disease control will become even more achievable. The outlined recommendations aim to promote best practice among HCPs and medical retina services to improve patient outcomes.

Summary Background There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes. Methods The PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov , NCT04411784 . Findings We included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes. Interpretation The COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes. Funding None.

Purpose To evaluate the diagnostic accuracy of routinely used tests of visual function and retinal morphology compared with fundus fluorescein angiography (FFA) to detect onset of active macular neovascularization in unaffected fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD). Design Prospective diagnostic accuracy cohort study conducted in 24 eye clinics in the United Kingdom over 3 years. Participants Older adults (>50 years) with recently diagnosed unilateral nAMD with a fellow (study) eye free of nAMD. Methods Self-reported vision, Amsler, clinic-measured visual acuity (VA), fundus assessment, and spectral domain OCT. The reference standard is FFA. Main Outcome Measures Sensitivity and specificity of the 5 index tests. Results Of 552 participants monitored for up to 3 years, 145 (26.3%) developed active nAMD in the study eye, of whom 120 had an FFA at detection and constituted the primary analysis cohort. Index test positives at nAMD detection in those confirmed by FFA were self-reported vision much worse (5), distortion on Amsler (33), 10-letter decrease in acuity from baseline (36), fundus examination (64), and OCT (110). Percentage index test sensitivities were: self-reported vision 4.2 (95% confidence interval [CI], 1.6–9.8); Amsler 33.7 (95% CI, 25.1–43.5); VA 30.0 (95% CI, 22.5–38.7); fundus examination 53.8 (95% CI, 44.8–62.5); and OCT 91.7 (95% CI, 85.2–95.6). All 5 index test specificities were high at 97.0 (95% CI, 94.6–98.5), 81.4 (95% CI, 76.4–85.5), 66.3 (95% CI, 61.0–71.1), 97.6 (95% CI, 95.3–98.9), and 87.8 (95% CI, 83.8–90.9), respectively. The combination of OCT with one other index test that was a secondary outcome measure increased sensitivity marginally and decreased specificity for all combinations except fundus examination. Conclusions Tests of self-reported change in vision, unmasking of new distortion, measurements of acuity, and fundus checks to diagnose active nAMD performed poorly in contrast to OCT. Our findings support a change to guidelines in clinical practice to monitor for onset of nAMD.

Determine clinical-effectiveness, safety, and cost-effectiveness of subthreshold micropulse laser (SML), compared with standard laser (SL), for diabetic macular edema (DME) with central retinal thickness (CRT)400μ.Pragmatic, multicenter, allocation-concealed, double-masked, randomized, non-inferiority trial.Adults with400μ center-involved DME and best-corrected visual acuity (BCVA)24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in one/both eyes.Randomisation 1:1 to 577nm SML or SL; retreatments were allowed. Rescue with intravitreal anti-vascular endothelial growth factor therapies or steroids was permitted if10 ETDRS-letter-loss and/or CRT increased400μ.Primary: Mean change in BCVA in the study eye at 24 months (non-inferiority margin 5 ETDRS-letters). Secondary: mean change from baseline to month-24 in binocular BCVA; CRT and mean deviation (MD) of Humphrey 10-2 visual field in the study eye; percentage meeting driving standards; EuroQoL (EQ-5D-5L), National Eye Institute-Visual Function Questionnaire (NEI-VFQ25), and Vision and Quality of Life Index (VisQoL) scores; cost per quality-adjusted life year (QALY) gained; adverse effects; number of laser and rescue treatments.DIAMONDS recruited fully (n=266); 87% SML and 86% SL had primary outcome data. Mean BCVA change from baseline to month-24 was -2.43 (Standard Deviation [SD] 8.20) and -0.45 (SD 6.72) in SML and SL, respectively. SML was deemed not only non-inferior but also equivalent to SL as the 95% confidence interval (CI) (-3.9 to -0.04) lay wholly within both upper and lower margins of the permitted maximum difference (5 ETDRS-letters). There was no statistically significant difference in binocular BCVA (0.32 ETDRS letters; 95% CI -0.99, 1.64; p = 0.63), CRT (-0.64 microns; 95% CI -14.25, 12.98; p = 0.93), MD (0.39 dB; 95% CI -0.23, 1.02; p = 0.21), meeting driving standards (% point difference 1.6, 95% CI -25.3, 28.5; p=0.91), adverse effects (Risk Ratio 0.28, 95% CI 0.06, 1.34; p=0.11), rescue treatments (% point difference -2.8, 95% CI -13.1, 7.5; p=0.59) or EQ-5D/VFQ-25/VisQoL scores. Number of laser treatments was higher in SML (0.48; 95% CI 0.18, 0.79; p = 0.002). Base-case analysis indicated no differences in costs or QALYs.SML was equivalent to SL, requiring slightly higher laser treatments.

Purpose To estimate rates and risk factors for progression to geographic atrophy (GA) or choroidal neovascularization (CNV) among eyes diagnosed with early or intermediate age-related macular degeneration (AMD) in clinical practice. Design Retrospective cohort analysis of a multicenter electronic medical record (EMR) database from the United Kingdom. Participants Patients aged 50 years or more with diagnosis of early/intermediate AMD in at least 1 eye (the study eye) and no evidence of CNV or GA in the study eye, from 10 clinical sites using the EMR. Methods Anonymized data for 40 543 patients with a diagnosis of early/intermediate AMD were extracted between October 2000 and February 2016 from EMR database records held in the 10 sites. A sample of records randomly selected from each center was used to validate disease definitions. Records were analyzed by subgroup, based on the AMD status of the fellow eye. Multivariate Cox regression models identified other predictors of disease progression. Main Outcome Measures Progression rate (per 100 person-years) to GA or CNV in study eyes with early/intermediate AMD by fellow eye status and identified risk factors for progression. Results Study eyes with early/intermediate AMD and a diagnosis of CNV in the fellow eye progressed to CNV fastest (at a rate of 15.2 per 100 person-years), and those with a diagnosis of GA in the fellow eye progressed to GA fastest (11.2 per 100 person-years), compared with the rates per 100 person-years of progression to CNV (3.2–11.9) or GA (2.0–7.8) in the other subgroups. In individuals with bilateral early/intermediate AMD, rates of progression to GA or CNV were 2.0 and 3.2 per 100 person-years, respectively. In the multivariate model, age, female sex, and cardiovascular disease were associated with an increased risk for progression to advanced AMD, whereas diabetes and glaucoma were associated with a decreased rate of progression (hazard ratios, 0.45 and 0.64, respectively). Conclusions Progression to GA or CNV was observed frequently in eyes with early/intermediate AMD, with the status of the fellow eye affecting the rate of progression. Novel associations with risk factors were observed and require replication in other cohorts.

The management of diabetic retinopathy (DR) has evolved considerably over the past decade, with the availability of new technologies (diagnostic and therapeutic). As such, the existing Royal College of Ophthalmologists DR Guidelines (2013) are outdated, and to the best of our knowledge are not under revision at present. Furthermore, there are no other UK guidelines covering all available treatments, and there seems to be significant variation around the UK in the management of diabetic macular oedema (DMO). This manuscript provides a summary of reviews the pathogenesis of DR and DMO, including role of vascular endothelial growth factor (VEGF) and non-VEGF cytokines, clinical grading/classification of DMO vis a vis current terminology (of centre-involving [CI-DMO], or non-centre involving [nCI-DMO], systemic risks and their management). The excellent UK DR Screening (DRS) service has continued to evolve and remains world-leading. However, challenges remain, as there are significant variations in equipment used, and reproducible standards of DMO screening nationally. The interphase between DRS and the hospital eye service can only be strengthened with further improvements. The role of modern technology including optical coherence tomography (OCT) and wide-field imaging, and working practices including virtual clinics and their potential in increasing clinic capacity and improving patient experiences and outcomes are discussed. Similarly, potential roles of home monitoring in diabetic eyes in the future are explored. The role of pharmacological (intravitreal injections [IVT] of anti-VEGFs and steroids) and laser therapies are summarised. Generally, IVT anti-VEGF are offered as first line pharmacologic therapy. As requirements of diabetic patients in particular patient groups may vary, including pregnant women, children, and persons with learning difficulties, it is important that DR management is personalised in such particular patient groups. First choice therapy needs to be individualised in these cases and may be intravitreal steroids rather than the standard choice of anti-VEGF agents. Some of these, but not all, are discussed in this document.

An aging population leads to increasing demand for medical retina services with chronic diseases being managed in long-term care pathways. Many hospital services struggle to deliver efficient and effective MR care due, at least in part, to infrastructure that does not expand responsively enough to meet the increased demand. A steering committee of retinal specialists from a variety of UK NHS hospital ophthalmology departments with experience of leading and managing NHS retinal services in the intravitreal era came together for the generation of this document to review and compile key aspects that should be considered when optimising intravitreal treatment capacity within MR services. This article aims to provide a useful collation and signposting of key published evidence, consensus and insights on aspects of delivering an intravitreal service, including treatment regimens, virtual clinics, staff training and governance, telemedicine and information technology, and data collection and key performance indicators. The objective is to equip ophthalmologic healthcare professionals with the necessary tools to develop and adapt their local service in the face of current and projected increased demand.

Inflammatory bowel disease (IBD) clinical nurse specialists deliver a service that is highly valued by patients. Access to a specialist nurse-led IBD helpline forms part of the UK IBD consensus standards. This retrospective cohort study analyses the workload evolution of an IBD helpline and discusses its implications for the design of future services. Helpline activity was shown to increase significantly between 2016 and 2018. While largely due to appropriate increased patient demand for acute advice, significant inefficiencies were demonstrated. These are likely to be present in other comparable helpline services, alongside opportunities for making more efficient use of specialist nurse time. In addition, helpline activity was shown to generate a significant additional workload involving patient follow-up and results. Robust methods for capturing this workload could help units with similar services with service design, job planning and reimbursement.

Objectives This report aims to provide clear recommendations and practical guidance from a panel of UK retinal experts on an aflibercept treat-and-extend (T&E) pathway that can be implemented in clinical practice. These recommendations may help service providers across the NHS intending to implement a T&E approach, with the aim of effectively addressing the capacity and resource issues putting strain on UK neovascular age-related macular degeneration (nAMD) services while promoting patients’ best interests throughout. Methods Two structured roundtable meetings of retinal specialists were held in London, UK on 7 December 2018 and 1 March 2019. These meetings were organised and funded by Bayer. Results The panel provided recommendations for an aflibercept T&E pathway and developed specific criteria based on visual acuity, retinal morphology and optical coherence tomography imaging to guide reduction, maintenance and extension of injection intervals. They also discussed the extension of treatment intervals by 2- or 4-week adjustments to a maximum treatment interval of 16 weeks, the management of retinal fluid and the stopping of treatment. Conclusions The long-term benefits of implementing a T&E pathway may include superior visual outcomes compared with a pro re nata (PRN; as needed) protocol, and a lower treatment burden compared with a fixed protocol, which is likely to improve service capacity. Furthermore, the predictable nature of a T&E approach compared with a PRN service may aid capacity planning for the future nAMD treatment demand.

Objective To estimate the direct ophthalmic health care resource use in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Design Retrospective analysis of anonymized data derived from electronic medical records acquired at 10 clinical sites in the United Kingdom. Participants Patients aged ≥50 years with ≥1 eye with a clinical record of GA or, for comparison, bilateral early/intermediate AMD. Four subgroups were identified: GA in both eyes (GA : GA); GA in 1 eye, choroidal neovascularization (CNV) in the fellow eye (GA : CNV); GA in 1 eye with early or intermediate AMD in the fellow eye (GA : E); and early/intermediate AMD in both eyes (E : E). Methods Electronic medical records were analyzed to derive the median number of visits over the first 2 years following diagnosis of GA or early/intermediate AMD. Clinical tests recorded at visits were used to calculate estimated costs (payer perspective) of monitoring. Analyses were restricted to patients with an initial diagnosis on or after January 1, 2011 to represent present day monitoring and costs associated with AMD. Main Outcome Measures Median number of visits and estimated monitoring costs per patient (in £) over the first 2 years among patients with ≥2 years of follow-up and in the individual subgroups. Intravitreal treatment costs in the GA : CNV group were excluded. Results For all 3 GA subgroups (n = 1080), the median number of visits over the first 2 years was 5 and monitoring costs were £460.80 per patient. The GA : CNV subgroup (n = 355) had the highest number of visits (median, 15), with a cost of £1581, compared with the GA : E subgroup (n = 283; median 4 visits; cost ∼£369) and the GA : GA subgroup (n = 442; median 3 visits; cost ∼£277). Ophthalmic tests were conducted most frequently in the GA : CNV subgroup. Visits and costs in the E : E subgroup (n = 6079) were lower. Conclusions Resource use in patients with GA varies considerably and is strongly influenced by the concomitant presence of CNV and lack of monitoring strategies for GA.

ObjectiveTo understand the effectiveness of ustekinumab in treating Crohn’s disease (CD) in a UK real-world setting.DesignRetrospective cohort study using prospectively maintained clinical records.SettingSingle UK inflammatory bowel disease centre.PatientsAdult patients with an established diagnosis of CD prescribed ustekinumab outside of clinical trials at University Hospital Southampton (UHS).InterventionsUstekinumab, a monoclonal antibody to the shared p40 subunit of interleukin (IL) 12 and IL-23 as part of routine clinical care.Main outcome measuresEffectiveness as measured by an improvement in physician’s global assessment, drug persistence and improvement in biomarkers (C-reactive protein (CRP), albumin and calprotectin).Results84 patients were included, 72 had a postinduction review and 49 had 1-year data. At postinduction clinical review, clinical response occurred in 53% of patients and clinical remission occurred in 8%. For patients on ustekinumab at 1 year, clinical response occurred in 71% and remission in 14%. Adverse events included four patients with infections requiring admission, one drug-related rash, five CD surgeries and two CD exacerbations.ConclusionsUstekinumab was well tolerated in a complex UK CD population and demonstrated benefit to patients in terms of clinical response and improvement of biomarkers and with some patients attaining clinical remission. No unexpected safety signals were seen.

Background: Diabetic macular oedema (DMO) is effectively treated with ranibizumab but multiple injections are required. Where there is also peripheral ischaemia, it has been promoted that targeted panretinal photocoagulation (PRP) may reduce the number of injections. Method: Patients with optical coherence tomography confirmed DMO and Ultra-widefield Fundus Fluorescein Angiography confirmed peripheral retinal ischaemia were randomised to PRP plus ranibizumab or ranibizumab monotherapy. After three injections, repeat injections were given until the visual acuity was stable and the macula was dry. Re-treatment was given if there was a drop of visual acuity and/or a recurrence of intra-retinal fluid. The primary outcome was the number of repeat injections required after the first 6 months up until 1 year. Results: There were 49 patients, 25 in the ranibizumab only group and 24 in the ranibizumab + PRP group recruited at seven UK sites. The average number of injections in the ranibizumab-only arm was 6.84 over 1 year and 2.52 between months 6 and 12. The average number of injections in the combined arm was 6.67, with the number of injections in the second 6 months 1.92. For the primary outcome, comparing the number of 6- to 12-month injections, the result was not statistically significant (p = 0.33). Conclusion: The addition of targeted PRP to areas of non-perfusion in a patient with DMO does not reduce the number of injections required in the first year. It seems most likely that local VEGF at the macula is the main cause of DMO.

First-line treatment of centrally involved diabetic macular oedema (CI-DMO) is often with an anti-vascular endothelial growth factor (anti-VEGF) agent. Although this can provide efficacy in the majority of eyes, a sizeable proportion do not respond sufficiently and many continue to receive anti-VEGF therapy after it may be optimal. This imposes a treatment burden on both patients and clinicians and, most importantly of all, can be sight threatening. Changing treatment to an intravitreal corticosteroid implant at the appropriate time may help optimise patient outcomes and reduce injection frequency, thereby reducing treatment burden.Eight retina specialists convened to discuss how to ensure eyes with CI-DMO receiving intravitreal anti-VEGF therapy are evaluated for a potential change to intravitreal corticosteroid therapy at the most effective time in their treatment journey. They concluded that clear criteria on when to consider changing treatment would be helpful and so developed a consensus guideline covering key decision points such as when and how to assess response to anti-VEGF therapy, when to consider a change to corticosteroid therapy and when and how to assess the response to corticosteroid therapy.The guideline was developed before the COVID-19 pandemic but, with the additional challenges arising from this including even greater pressure on clinic capacity, it is more important than ever to reconsider current working practices and adopt changes to improve patient care while also easing pressure on clinic capacity, reducing hospital visits and maintaining patient safety. This publication therefore also includes suggestions for adapting the guidelines in the COVID-19 era.

Active inflammatory bowel disease (IBD), combined immunosuppression and corticosteroid therapy have all been identified as risk factors for a poor outcome in COVID-19 infection. The management of patients with both COVID-19 infection and active IBD is therefore complex. We present the case of a 31-year-old patient with Crohn’s disease, on dual immunosuppression with infliximab and mercaptopurine presenting with inflammatory small bowel obstruction and COVID-19 infection. The case highlights the use of nutritional therapy, which remains underused in the management of adults with IBD, to manage his flare acutely. Following negative SARS-CoV-2 PCR testing and SARS-CoV-2 IgG testing confirming an antibody response, ustekinumab (anti-interleukin 12/23) was prescribed for long-term maintenance.

Introduction Patients with suspected IBD referred by primary care (GP) are traditionally seen in gastroenterology outpatient clinics followed by endoscopic investigations. This 2 phase model leads to delay in diagnosis and treatment, increasing pressure on gastroenterology outpatient services while still requiring endoscopic intervention. Our novel pilot project compared outcomes between direct-access IBD physician-delivered endoscopy versus the traditional clinic model for patients with suspected IBD. Method A prospective cohort of consecutive patients referred by GP with suspected IBD were triaged either direct to IBD endoscopy (n=50) or to outpatient IBD clinic followed by IBD endoscopy (n=50) at the discretion of 10 gastroenterology consultants grading GP referrals. Data on demographics, faecal calprotectin, C-reactive protein, endoscopy outcomes, treatment, and follow up was collected. (Group A = direct to IBD endoscopy and Group B = IBD endoscopy via IBD clinic). Results Both groups were age and gender-matched. Group A had a higher mean calprotectin (1363 ug/g vs 302 ug/g) and a higher C-reactive protein (10.6 mg/l vs 4.5 mg/l). In Group A only 38% had a full colonoscopy versus 86% in Group B. Definitive diagnosis and treatment at time of IBD endoscopy took 27 days in Group A versus 212 days in Group B. Treatment with immunomodulators and biologics was similar in both groups but mesalazine and steroid use was higher in Group A due to more severe disease and higher rate of ulcerative colitis, table 1 shows the diagnostic breakdowns from both groups following endoscopy. The IBD pick up was significantly higher in Group A with 70% vs 42%. Endoscopy DNA rate was twice as high in Group B (n=6). The direct to IBD endoscopy pathway resulted in 50 less initial IBD consultant clinics (100% reduction) with a follow-up shift from IBD consultant to IBD nurse clinics. Conclusion Triaging patients referred with suspected IBD directly to IBD physician delivered endoscopy resulted in more than a 26-week reduction in time to diagnosis and treatment while saving 100% of initial IBD consultant clinics. IBD pick up was high at 70% in direct to IBD endoscopy group, identifying a higher-need IBD population. Triaging GP referrals with suspected IBD direct to IBD endoscopy delivers rapid assessment and treatment.

Purpose\ud To determine the time and risk factors for developing proliferative diabetic retinopathy (PDR) and vitreous hemorrhage (VH).\ud \ud Design\ud Multicenter, national cohort study.\ud \ud Methods\ud Anonymized data of 50 254 patient eyes with diabetes mellitus at 19 UK hospital eye services were extracted at the initial and follow-up visits between 2007 and 2014. Time to progression of PDR and VH were calculated with Cox regression after stratifying by baseline diabetic retinopathy (DR) severity and adjusting for age, sex, race, and starting visual acuity.\ud \ud Results\ud Progression to PDR in 5 years differed by baseline DR: no DR (2.2%), mild (13.0%), moderate (27.2%), severe nonproliferative diabetic retinopathy (NPDR) (45.5%). Similarly, 5-year progression to VH varied by baseline DR: no DR (1.1%), mild (2.9%), moderate (7.3%), severe NPDR (9.8%). Compared with no DR, the patient eyes that presented with mild, moderate, and severe NPDR were 6.71, 14.80, and 28.19 times more likely to develop PDR, respectively. In comparison to no DR, the eyes with mild, moderate, and severe NPDR were 2.56, 5.60, and 7.29 times more likely to develop VH, respectively. In severe NPDR, the eyes with intraretinal microvascular abnormalities (IRMA) had a significantly increased hazard ratio (HR) of developing PDR (HR 1.77, 95% confidence interval [CI] 1.25–2.49, P = .0013) compared with those with venous beading, whereas those with 4-quadrant dot-blot hemorrhages (4Q DBH) had 3.84 higher HR of developing VH (95% CI 1.39–10.62, P = .0095).\ud \ud Conclusions\ud Baseline severities and features of initial DR are prognostic for PDR development. IRMA increases risk of PDR whereas 4Q DBH increases risk of VH.

Contains fulltext : 174538.pdf (Publisher’s version ) (Closed access) Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder characterized by the abnormal development of the retinal vasculature. The majority of mutations identified in FEVR are found within four genes that encode the receptor complex (FZD4, LRP5, and TSPAN12) and ligand (NDP) of a molecular pathway that controls angiogenesis, the Norrin-beta-catenin signaling pathway. However, half of all FEVR-affected case subjects do not harbor mutations in these genes, indicating that further mutated genes remain to be identified. Here we report the identification of mutations in CTNNB1, the gene encoding beta-catenin, as a cause of FEVR. We describe heterozygous mutations (c.2142_2157dup [p.His720 *] and c.2128C>T [p.Arg710Cys]) in two dominant FEVR-affected families and a de novo mutation (c.1434_1435insC [p.Glu479Argfs *18]) in a simplex case subject. Previous studies have reported heterozygous de novo CTNNB1 mutations as a cause of syndromic intellectual disability (ID) and autism spectrum disorder, and somatic mutations are linked to many cancers. However, in this study we show that Mendelian inherited CTNNB1 mutations can cause non-syndromic FEVR and that FEVR can be a part of the syndromic ID phenotype, further establishing the role that beta-catenin signaling plays in the development of the retinal vasculature.

The management of diabetic retinopathy (DR) has evolved considerably over the past decade, with the availability of new technologies (diagnostic and therapeutic). As such, the existing Royal College of Ophthalmologists DR Guidelines (2013) are outdated, and to the best of our knowledge are not under revision at present. Furthermore, there are no other UK guidelines covering all available treatments, and there seems to be significant variation around the UK in the management of diabetic macular oedema (DMO). This manuscript provides a summary of reviews the pathogenesis of DR and DMO, including role of vascular endothelial growth factor (VEGF) and non-VEGF cytokines, clinical grading/classification of DMO vis a vis current terminology (of centre-involving [CI-DMO], or non-centre involving [nCI-DMO], systemic risks and their management). The excellent UK DR Screening (DRS) service has continued to evolve and remains world-leading. However, challenges remain, as there are significant variations in equipment used, and reproducible standards of DMO screening nationally. The interphase between DRS and the hospital eye service can only be strengthened with further improvements. The role of modern technology including optical coherence tomography (OCT) and wide-field imaging, and working practices including virtual clinics and their potential in increasing clinic capacity and improving patient experiences and outcomes are discussed. Similarly, potential roles of home monitoring in diabetic eyes in the future are explored. The role of pharmacological (intravitreal injections [IVT] of anti-VEGFs and steroids) and laser therapies are summarised. Generally, IVT anti-VEGF are offered as first line pharmacologic therapy. As requirements of diabetic patients in particular patient groups may vary, including pregnant women, children, and persons with learning difficulties, it is important that DR management is personalised in such particular patient groups. First choice therapy needs to be individualised in these cases and may be intravitreal steroids rather than the standard choice of anti-VEGF agents. Some of these, but not all, are discussed in this document.

An aging population leads to increasing demand for medical retina services with chronic diseases being managed in long-term care pathways. Many hospital services struggle to deliver efficient and effective MR care due, at least in part, to infrastructure that does not expand responsively enough to meet the increased demand. A steering committee of retinal specialists from a variety of UK NHS hospital ophthalmology departments with experience of leading and managing NHS retinal services in the intravitreal era came together for the generation of this document to review and compile key aspects that should be considered when optimising intravitreal treatment capacity within MR services. This article aims to provide a useful collation and signposting of key published evidence, consensus and insights on aspects of delivering an intravitreal service, including treatment regimens, virtual clinics, staff training and governance, telemedicine and information technology, and data collection and key performance indicators. The objective is to equip ophthalmologic healthcare professionals with the necessary tools to develop and adapt their local service in the face of current and projected increased demand.

Background/aimsThe RELIGHT clinical trial used an individualised treatment regimen of ranibizumab to treat diabetic macular oedema (DMO). We report findings from two patient-reported outcome instruments.MethodsThe National Eye Institute Visual Function Questionnaire (NEI-VFQ) was administered before starting treatment (M0) and at M6, 12 and 18. The Macular Disease Society Treatment Satisfaction Questionnaire (MacTSQ) was administered 1 month after treatment start (M1) and at M6, 12 and 18. Relationships between best-corrected visual acuity (BCVA) in the study eye (SE) and the status of the eye at baseline (as better or worse eye by BCVA) and the two instrument measures were investigated.ResultsBCVA in the SE correlated strongly with the NEI-VFQ composite scores and the majority of the subscales but not with the MacTSQ subscales. Statistically significant improvements were observed in the majority of the subscales of the NEI-VFQ at M6, 12 and 18. For the MacTSQ, improvements between baseline M6, 12 and 18 were seen for subscale 1 but only reached statistical significance at M12. In subscale 2, the changes in mean scores were statistically significant at all timepoints.ConclusionsAlthough ranibizumab treatment in DMO over an 18-month period resulted in improvements in visual functioning and patient satisfaction, no correlation was found between the instruments used to measure these outcomes. Our finding of a lack of correlation between BCVA and the MacTSQ suggests the presence of psychophysical factors not measured by traditional means.

Introduction Inflammatory bowel disease (IBD) patients calling our specialist nurse led IBD flare line with worsening symptoms were traditionally seen in outpatient clinics before being referred for endoscopy to evaluate disease activity. Non-IBD endoscopists often deferred treatment decisions until subsequent IBD outpatient appointments (OPA), leading to delays in treatment and pressure on IBD OPA workload. Methods In January 2016 “flare slots” on dedicated IBD endoscopy lists were introduced. Patients with flare symptoms submitted stool for enteric pathogen exclusion and those subsequently deemed suitable were directly booked to a flare slot on an IBD endoscopy list, if available. Anonymised data was systematically extracted from clinical systems for the first 6 months of 2016, 2017 and 2018 regarding endoscopy outcomes leading to change in treatment and number of OPA in the respective years. Change in treatment was defined as start/stop of medication, urgent investigation to guide treatment or admission to hospital. Results For the first six months of 2016, 2017 and 2018, data identified 90, 92 and 92 IBD flare line-triggered flexible sigmoidoscopies respectively. Overall 74.6% had ulcerative colitis and the remainder Crohn’s disease (22.3%) or IBDU (1.3%). In 2016, 63.3% of procedures were performed by IBD physicians, which increased to 77.2% and 79.3% in 2017 and 2018 respectively. IBD endoscopists initiated change in treatment following their procedures in 70.2% (2016), 74.7% (2017) and 84.9% (2018) of cases, compared to 9.1%, 14.3% and 5.3% of non-IBD endoscopist procedures over the same period. Total gastroenterology outpatient appointments within the year in this population were 232 (2016), 214 (2017) and 111 (2018); a 52.2% decrease from 2016 to 2018. Nurse-led outpatient appointments following IBD flare flexible sigmoidoscopy increased from 19 in 2016 to 51 in 2017 and 53 in 2018, when they constituted 47% of OPA in this group. This represented a 72.8% (155 OPA) reduction in consultant appointments from 2016 to 2018 (Figure1). Conclusion Changing the model of service delivery for acute IBD flares by combining IBD physician delivered endoscopy with proactive management decisions resulted in a change of management in 84.9% of patients. This reduced overall IBD OPA by 52.2%, while increasing nurse led follow up clinics in this cohort to 47% leading to a total 72.2% reduction in consultant OPA.

Introduction We present a data driven service evaluation of the use of an Inflammatory Bowel Disease (IBD) telephone helpline service at a single UK IBD centre (UHS). We demonstrate how such evaluation can highlight service improvement needs to maximise efficiency and improve patient care. Methods IBD patients at UHS can call our helpline and leave a message for one of our IBD specialist nurses to respond to the following working day. All helpline activity is electronically logged in the electronic health record. Anonymised data was systematically extracted for the first 6 months of 2016, 2017 and 2018. Calls were categorised as follows: 1) flare call – symptoms relating to IBD, 2) follow up call – following change in medication/results, 3) medication enquiries, 4) administrative calls and 5) unsuccessful unanswered calls. Results A total of 7,046 calls were analysed. Activity increased through the study period with 1627, 2676 and 2743 attempted/successful outgoing calls made to 598, 785 and 882 unique patients in the first six months of 2016, 2017, 2018 respectively (table 1). In total 28.5% of calls were unsucessful. The 416, 821 and 769 unsuccessful calls were made to 228, 388 and 384 unique patients respectively with associated preparation time of 19.7, 53.1 and 56.1 hours (hrs). Call success was similar for each weekday but showed a trend to improvement towards the end of each day (after 4pm). Administrative calls for 2016, 2017 and 2018 included patients requesting test results which generated 52 (10.5 hrs), 87 (20.0 hrs) and 105 (26.5 hrs) calls and appointment queries which generated 23 (4.1 hrs), 41 (7.9 hrs) and 21 (5.4 hrs) calls respectively. Conclusions Use of our IBD helpline has increased over time. When using incoming call requests as a marker of activity it is important to recognise that approximately half of these require follow-up calls to review results and treatment plans. This must be considered when designing services. Time wasted in unsuccessful calls is substantial and novel methods to reduce this are needed. Online access to results and appointments may reduce total calls. An online portal (My Medical Record) for medication information, results and admin queries as well as a pre-call text message are being introduced at UHS.

Introduction Glucocorticoids (GC) have been first line treatment for hospitalised IBD patients for over 60 years, despite the introduction of biologic therapy. IBD patients often have systemic inflammation complicated by malnutrition leading to metabolic stress. Frequency and risk factors for hyperglycaemia in hospitalised IBD patients receiving GC are unknown. Methods 112 consecutive IBD inpatients receiving intravenous hydrocortisone (IVH) for acute flares had capillary blood glucose (CBG) monitoring automatically triggered by the electronic prescription. CBG, biomarkers, IBD severity scores (Harvey Bradshaw, partial Mayo) and weight loss were prospectively recorded. Undiagnosed Diabetes Mellitus (DM) was defined as HbA1c >48 mmol/mol. Machine learning (random forest regressor, RFR) was applied to data to evaluate risk factors of hyperglycaemia. Results 51% of hospitalised IVH treated IBD patients met the WHO criteria of DM (CBG>11 mmol/L), while 20% and 6% had a CBG >14 mmol/l and >20 mmol/l, respectively. 8 patients had pre-existing DM, which was confirmed by admission HbA1c. RFR indicated disease severity score, duration of IVH, HbA1c and electrolyte imbalances (64%) were best predictors of hyperglycaemia. 49% were started on or switched biological therapy during admissions. 55% were discharged on prednisolone, 14% on budesonide and 34% on no GC. 48 patients had HbA1c checked at 3 month follow-up of which 4 were in the diabetic range. 1 was known DM with elevated CBG during admission whose insulin had been titrated, 2 had elevated CBG as inpatients with no prior DM discharged on gliclazide and insulin respectively and 1 was on long-term steroids for asthma who did not have CBG >11.0 mmol/L as inpatient. 4 other patients discharged on gliclazide for steroid induced DM had documented repeat HbA1c recorded, which were all in the normal range. Conclusions Our data demonstrates that hyperglycaemia is common in IVH treated inpatients, therefore CBG monitoring should be routine practice. Predictive modelling (RFR) identifies more severe disease activity, duration of IVH treatment and HbA1c as risk factors for hyperglycaemia. The importance of IVH duration suggests hyperglycaemia risk may be physician-modifiable. Alternative treatment strategies such as earlier introduction of biologics, rapid steroid taper and nutritional support could be used to minimise medication associated metabolic instability in high risk patients.

Introduction Ustekinumab (UST) is a human IgG1 kappa mAb to the shared p40 subunit of IL-12 and IL-23 which are involved in TH1 and TH17 mediated pathways of Crohn’s disease (CD) pathogenesis. NICE approved UST for CD in April 2017, but there is limited UK data on real-world effectiveness. We present clinical effectiveness, safety and drug persistence data from a complex UK cohort. Methods This was a retrospective observation cohort study of all CD patients treated with UST outside clinical trials in a single UK IBD centre. Physician’s global assessment (PGA) was recorded at baseline, post induction and 1 year. Primary outcome was clinical response defined by a fall in PGA. Secondary outcomes were drug persistence and fall in CRP or faecal calprotectin (FC). Statistical analysis was performed by Wilcoxon signed rank test in R v.3.4.4. Results 84 patients (mean age 42 years, sd 14.7, mean disease duration 12.3 years, sd 8.9) were treated to December 2018. 82 (98%) had previous exposure to anti-TNF therapy, 35 (42%) to both anti-integrin and anti-TNF and 2 were naive to biologics. 39 (46.4%) were on immunodulator co-therapy and 6 (7%) on steroids. Post-induction treatment was 12 weekly (9), 8 weekly (74) or 6 weekly (1). Post-induction (median 14.7 weeks, IQR 8.03) and 1 year (median 44.4 weeks, IQR 13.4) reviews were availiable for 72 and 47 patients respectively. Post-induction clinical response occurred in 38 (53%) and remission in 5 (7%). At 1 year response occurred in 34 (72%) and remission in 7 (15%). Of 15 non-responders post induction left on UST, 9 responded by 1 year. Steroid-free response occurred in 35 (48%) post-induction and 31 (65%) at 1 year. By 1 year 8 patients stopped UST (median 256 days, range 62–329); 1 cutaneous reaction, and 7 primary non-response or secondary loss of response. Only 1 of 8 given a second intravenous dose in an attempt to recapture response had a sustained benefit. For those with an elevated biomarker at baseline (CRP >10 or FC >250) and repeat meaurement post induction, mean CRP improved from 37 (11–96) to 28 (3.8–116) (p=0.074) and FC 2260 (292–6000) to 1152 (24–5084) (p=0.089). For paired results at baseline and 1 year mean CRP improved from 29 (11–96) to 19 (3–77) (p=0.045) and mean FC 2019 (823–6000) to 1070 (42–5528) (p=0.011). There was no significant change in normal baseline biomarkers. Conclusions UST was well tolerated in a complex UK CD cohort and demonstrated benefit in terms of clinical response, improvement of biomarkers and in some full clinical remission. Due to delayed response continuation beyond 3 months is justifiable in some non-responders. Reloading to recapture response as described elsewhere was of limited benefit.

Disclaimer This publication and the expert roundtable meeting on which the article is based were sponsored by Bayer plc. Prescribing information for Eylea® (aflibercept solution for injection) can be found at the end of the article., This report by a group of UK retina specialists and health professionals considers best practice recommendations for the management of sight-threatening neovascular age-related macular degeneration (nAMD), based on collective experience and expertise in routine clinical practice. The authors provide an update for ophthalmologists, allied healthcare professionals and commissioners on practice principles for optimal patient care and service provision standards. Refinement of care pathways for nAMD has improved access to intravitreal anti-vascular endothelial growth factor therapy but there are still variations in care and reported outcomes between clinic centres. Innovative organisational models of service provision allow providers to better match capacity with increasing demand. The authors review the recent NICE guideline for diagnosis and management of AMD, considerations for switching therapies and stopping treatment and need for regular monitoring of non-affected fellow eyes in patients with unilateral nAMD. Actions for delivery of high-quality care and to improve long-term patient outcomes are discussed. Local pathways need to detail nAMD target time to treat, maintenance of review intervals to ensure proactive treatment regimens are delivered on time and appropriate discharge for patients deemed low risk or no longer benefiting from treatment. Actual visual acuity outcomes achieved and maintenance of the level of vision when disease stability is achieved are considered good measures for judging the quality of care in the treatment of patients with nAMD. Robust community referral pathways must be in place for suspected reactivation of choroidal neovascularisation and rapid referral for second eye involvement. Practical considerations for intravitreal injection therapy are outlined.

Purpose To investigate if previous intravitreal therapy is a predictor of posterior capsule rupture (PCR) during cataract surgery. Design Multicenter, national electronic medical record (EMR) database study with univariate and multivariate regression modeling. Participants A total of 65 836 eyes of 44 635 patients undergoing cataract surgery. Methods Anonymized data were extracted for eyes undergoing cataract surgery from 20 hospitals using the same EMR for cases performed between 2004 and 2014. Variables included as possible risk indicators for PCR were age, sex, number of previous intravitreal injections, indication for intravitreal therapy, grade of healthcare professional administering intravitreal therapy, advanced cataract, and cataract surgeon grade. Main Outcome Measures Presence or absence of posterior capsular rupture during cataract surgery. Results Data were available on 65 836 cataract operations, of which 1935 had undergone previous intravitreal therapy (2.9%). In univariate regression analyses, patient age, advanced cataract, junior cataract surgeon grade, and number of previous intravitreal injections were significant predictors of PCR. By considering the number of previous intravitreal injections as a continuous variable, the odds ratio for PCR per intravitreal injection was 1.04 ( P = 0.016) after adjusting for age, advanced cataract, and cataract surgeon grade. Repeat analysis considering intravitreal injections as a categoric variable showed 10 or more previous injections were associated with a 2.59 times higher likelihood of PCR ( P = 0.003) after again adjusting for other significant independent predictors. Conclusions Previous intravitreal therapy is associated with a higher likelihood of PCR during cataract surgery. This study provides data to help inform surgeons and patients about the risk of complications when undergoing cataract surgery after multiple prior intravitreal injections. Further investigation is required to determine the cause behind the increased PCR risk.

BackgroundGlucocorticosteroids (GC) are long-established, widely used agents for induction of remission in inflammatory bowel disease (IBD). Hyperglycaemia is a known complication of GC treatment with implications for morbidity and mortality. Published data on prevalence and risk factors for GC-induced hyperglycaemia in the IBD population are limited. We prospectively characterise this complication in our cohort, employing machine-learning methods to identify key predictors of risk.MethodsWe conducted a prospective observational study of IBD patients receiving intravenous hydrocortisone (IVH). Electronically triggered three times daily capillary blood glucose (CBG) monitoring was recorded alongside diabetes mellitus (DM) history, IBD biomarkers, nutritional and IBD clinical activity scores. Hyperglycaemia was defined as CBG ≥11·1mmol/L and undiagnosed DM as HbA1c ≥48 mmol/mol. Random Forest regression models were used to extract predictor-patterns present within the dataset.Findings94 consecutive IBD patients treated with IVH were included. 60% (56/94) of the cohort recorded an episode of hyperglycaemia, including 57% (50/88) of those with no prior history of DM, of which 19% (17/88) and 5% (4/88) recorded a CBG ≥14mmol/L and ≥20mmol/L, respectively. The Random Forest models identified increased CRP followed by a longer IBD duration as leading risk predictors for significant hyperglycaemia.InterpretationHyperglycaemia is common in IBD patients treated with intravenous GC, therefore CBG monitoring should be included in routine clinical practice. Machine learning methods can identify key risk factors for clinical complications. Physicians should consider steroid-sparing strategies in high-risk patients such as those with high admission CRP or a longer IBD duration. There is an emergent case for research to explore steroid-free treatment regimens for hospitalised patients with severe IBD flares.Evidence before this studyGlucocorticosteroids (GC) are long-established induction agents in the management of inflammatory bowel disease (IBD). They are recommended first-line therapy in consensus guidelines and prescribing remains widespread, with an estimated 30% of IBD patients exposed annually. Hyperglycaemia is a known complication of GC and has been linked to increased length of hospital stay, morbidity and mortality. Small case series of GC treated medical patients suggest a higher risk of hyperglycaemia in the hospitalised population but have suffered from a lack of systematic blood glucose monitoring.Added value of this studyThis is the first study utilising prospective, systematic monitoring of capillary blood glucose (CBG) to determine the frequency of hyperglycaemia in a GC-treated hospitalised IBD population. We report that more than half of IBD patients without prior diabetes mellitus treated with intravenous hydrocortisone (IVH), will develop hyperglycaemia (CBG ≥11·1mmol/L). Random Forest regressors pinpointed CRP and IBD duration as the strongest predictor of this adverse outcome.Implications of all the available evidenceHyperglycaemia is a common complication of IVH therapy in hospitalised IBD patients, particularly in those with high inflammatory burden. The monitoring and management of this complication, which has potential implications for the morbidity, mortality and subsequent risk of diabetes diagnosis should become part of routine clinical practice.

Winfried Amoaku,1 Konstantinos Balaskas,2,3 Tomas Cudrnak,4 Louise Downey,5 Markus Groppe,6 Sajjad Mahmood,7 Hemal Mehta,8 Quresh Mohamed,9 Bushra Mushtaq,10 Philip Severn,11 Athanasios Vardarinos,12 Yit Yang,13 Saad Younis14 1Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK; 2NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and University College of London Institute of Ophthalmology, London, UK; 3University of Manchester, Manchester, UK; 4Royal Eye Infirmary, University Hospitals Plymouth NHS Trust, Plymouth, UK; 5Hull and East Yorkshire Eye Hospital, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK; 6Ophthalmology, Stoke Mandeville, Buckinghamshire Healthcare NHS Trust, Aylesbury, UK; 7Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; 8Royal Free London NHS Foundation Trust, London, UK; 9Gloucestershire Eye Unit, Cheltenham General Hospital, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK; 10Birmingham and Midland Eye Centre, Sandwell and West Birmingham NHS Trust, Birmingham, UK; 11South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK; 12Eye Treatment Centre, West Suffolk Hospital, West Suffolk NHS Foundation Trust, Bury St Edmunds, UK; 13Wolverhampton Eye Infirmary, The Royal Wolverhampton NHS Trust, Wolverhampton, UK; 14Ophthalmology, Western Eye Hospital, Imperial College Healthcare NHS Trust, London, UK Abstract: The treatment of neovascular (wet) age-related macular degeneration (AMD) with ranibizumab is now very well established in terms of efficacy and safety. Recent clinical trials and real-world studies have demonstrated the advantages of a Treat-and-Extend (T&E) regimen, and many hospital departments are now in the process of adopting this new regimen in favor of the pro re nata regimen for initiating and continuing ranibizumab therapy for patients with wet AMD. The comprehensive spectrum of issues related to implementation of the regimen is covered qualitatively in ten didactic topics provided by a group of clinicians with direct experience of this regimen in their department. The topics include definition, new and previously treated eyes, management of high-frequency injections, maximum extensions, discontinuing T&E, bilateral cases, clerical, audit, and patient counseling. This article aims to provide a useful resource for the implementation of the T&E regimen. A quantitative summary of the visual outcomes in key publications is also provided in this article. This article should be a valuable resource for staff training. Keywords: ranibizumab, age-related macular degeneration, nAMD, Treat and Extend, anti-VEGF treatment

Purpose: To understand levels of disease burden and progression in a real-world setting among patients from the United Kingdom with bilateral geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Design: Retrospective cohort analysis of a multicenter electronic medical record (EMR) database. Participants: Patients who were aged ≥50 years with bilateral GA and no history of choroidal neovascularization (CNV) and who attended 1 of 10 clinical sites using the EMR. Methods: A deidentified data set was constructed from the records held at the 10 sites. An algorithm was used to extract cases with a GA diagnosis, of which 1901 had bilateral GA and form the basis of this report. A sample of records randomly selected from each center was used to validate disease definitions. Main Outcome Measures: Progression to blindness (visual acuity [VA]

PURPOSE: To evaluate ranibizumab 0.5 mg using bimonthly monitoring and individualized re-treatment after monthly follow-up for 6 months in patients with visual impairment due to diabetic macular edema (DME). DESIGN: A phase IIIb, 18-month, prospective, open-label, multicenter, single-arm study in the United Kingdom. PARTICIPANTS: Participants (N = 109) with visual impairment due to DME. METHODS: Participants received 3 initial monthly ranibizumab 0.5 mg injections (day 0 to month 2), followed by individualized best-corrected visual acuity (BCVA) and optical coherence tomography-guided re-treatment with monthly (months 3-5) and subsequent bimonthly follow-up (months 6-18). Laser was allowed after month 6. MAIN OUTCOME MEASURES: Mean change in BCVA from baseline to month 12 (primary end point), mean change in BCVA and central retinal thickness (CRT) from baseline to month 18, gain of ≥10 and ≥15 letters, treatment exposure, and incidence of adverse events over 18 months. RESULTS: Of 109 participants, 100 (91.7%) and 99 (90.8%) completed the 12 and 18 months of the study, respectively. The mean age was 63.7 years, the mean duration of DME was 40 months, and 77.1% of the participants had received prior laser treatment (study eye). At baseline, mean BCVA was 62.9 letters, 20% of patients had a baseline BCVA of >73 letters, and mean baseline CRT was 418.1 μm, with 32% of patients having a baseline CRT

Objective: To explore factors that influence decision-making in relation to prenatal diagnostic testing (PDT) for inherited retinal disease (IRD). Method: Semi-structured interviews were conducted with 50 adults with IRD, selected from a larger sample to provide a diversity of backgrounds and opinions on genetic testing. Interviews were transcribed verbatim and analysed using thematic analysis. Results: Mostly participants supported PDT, believing that it would provide information to help them prepare for and plan the future care of the child and the potential for early access to emerging therapies. Opposition to PDT stemmed from its use to justify termination of pregnancy, with participants feeling that it was not justified as they retained a good quality of life despite their visual impairment. Participants raised concerns about the risk of PDT and the accuracy of the results. However, most suggested that it should be available as an option for others, but for specific reasons and not as a part of routine care. Conclusion: The variation in attitudes towards PDT and uncertainty about the risk and accuracy of results suggest that individuals at risk of having a child with IRD should have access to genetic counselling to support decision making.

AIM To assess the rate of 'treatment-requiring diabetic macular oedema (DMO)' in eyes for the two years before and after cataract surgery. METHODS Multicentre national diabetic retinopathy (DR) database study with anonymised data extraction across 19 centres from an electronic medical record system. INCLUSION CRITERIA eyes undergoing cataract surgery in patients with diabetes with no history of DMO prior to study start. The minimum dataset included: age, visual acuity (all time-points), injection episodes, timing of cataract surgery and ETDRS grading of retinopathy and maculopathy. MAIN OUTCOME MEASURE rate of developing first episode of treatment-requiring DMO in relation to timing of cataract surgery in the same eye. RESULTS 4850 eyes met the inclusion criteria. The rate of developing treatment-requiring DMO in this cohort was 2.9% in the year prior to surgery versus 5.3% in the year after surgery (p

PURPOSE To assess whether visual benefits exist in switching to aflibercept in patients who have been chronically treated with ranibizumab for neovascular age-related macular degeneration. METHODS A multicenter, national, electronic medical record database study was performed. Patients undergoing six continuous monthly ranibizumab injections and then switched to continuous aflibercept were matched to those on continuous ranibizumab therapy. Matching was performed in a 2:1 ratio and based on visual acuity 6 months before and at the time of the switch, and the number of previous ranibizumab injections. RESULTS Patients who were switched to aflibercept demonstrated transiently significant improvement in visual acuity that peaked at an increase of 0.9 Early Treatment Diabetic Retinopathy Study letters 3 months after the switch, whereas control patients continued on ranibizumab treatment showed a steady decline in visual acuity. Visual acuity differences between the groups were significant (P < 0.05) at 2, 3, and 5 months after the switch. Beginning at 4 months after the switch, the switch group showed a visual acuity decline similar to the control group. CONCLUSION Transient, nonsustained improvement in visual acuity occurs when switching between anti-vascular endothelial growth factor agents, which may have implications in treating patients on chronic maintenance therapy on one anti-vascular endothelial growth factor medication.

Introduction Ranibizumab is an inhibitor of vascular endothelial growth factor-A (anti-VEGF) approved for the treatment of neovascular age-related macular degeneration (nAMD). The treat and extend (T&E) regimen can potentially reduce the burden of clinic visits compared with a pro re nata (PRN) regimen. Retrospective, interim analyses of clinical effectiveness, treatment and resource use patterns were conducted using real-world data in England and Wales from the TERRA study. Methods Two cohorts, those switching from a PRN to a T&E regimen (‘prior PRN’) and those initiating ranibizumab on the T&E regimen as their first anti-VEGF therapy (‘anti-VEGF-naïve’) were enrolled in TERRA. Retrospective clinical assessments were gathered from medical records, while resource use patterns were collected via an operating cost questionnaire completed by each study site. Results At the interim analysis cut-off date (15 November 2016), 11 sites had enrolled 145 patients (prior PRN: n = 110; anti-VEGF-naïve: n = 35). Mean change from baseline (date of first injection) in visual acuity and central subfield retinal thickness to 12 months was +7.6 Early Treatment Diabetic Retinopathy Study letters [95% confidence interval (CI) 2.8, 12.4; p = 0.003; n = 27] and −67.7 μm (95% CI −106.5, −28.9; p = 0.001, n = 29), respectively, in the anti-VEGF-naïve cohort. Most T&E clinics were run as one-stop services (same-day monitoring and injection), whereas 4/10 PRN clinics were run as two-stop services (monitoring and injection on different days). In general, one-stop clinics used less staff resources and were likely to be shorter in duration for healthcare providers than the cumulative time spent for two-stop clinics. Conclusion This is the first real-world observational study conducted in England and Wales demonstrating the effectiveness of the ranibizumab T&E regimen in anti-VEGF-naïve patients. T&E is compatible with one-stop clinic services, which these real-world data suggest to be less resource intensive than two-stop clinic services, possibly providing a dosing regimen beneficial to both patients and resource burden in UK clinical practice. Funding: Novartis Pharmaceuticals UK Limited. Electronic supplementary material The online version of this article (doi:10.1007/s40123-017-0091-9) contains supplementary material, which is available to authorized users.