Publications by authors named "Alastair K Denniston"

163 Publications

Building trust in real-world data: lessons from INSIGHT, the UK's health data research hub for eye health and oculomics.

Curr Opin Ophthalmol 2022 Sep;33(5):399-406

INSIGHT Health Data Research hub for Eye Health.

Purpose Of Review: In this review, we consider the challenges of creating a trusted resource for real-world data in ophthalmology, based on our experience of establishing INSIGHT, the UK's Health Data Research Hub for Eye Health and Oculomics.

Recent Findings: The INSIGHT Health Data Research Hub maximizes the benefits and impact of historical, patient-level UK National Health Service (NHS) electronic health record data, including images, through making it research-ready including curation and anonymisation. It is built around a shared 'north star' of enabling research for patient benefit. INSIGHT has worked to establish patient and public trust in the concept and delivery of INSIGHT, with efficient and robust governance processes that support safe and secure access to data for researchers. By linking to systemic data, there is an opportunity for discovery of novel ophthalmic biomarkers of systemic diseases ('oculomics'). Datasets that provide a representation of the whole population are an important tool to address the increasingly recognized threat of health data poverty.

Summary: Enabling efficient, safe access to routinely collected clinical data is a substantial undertaking, especially when this includes imaging modalities, but provides an exceptional resource for research. Research and innovation built on inclusive real-world data is an important tool in ensuring that discoveries and technologies of the future may not only favour selected groups, but also work for all patients.
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http://dx.doi.org/10.1097/ICU.0000000000000887DOI Listing
September 2022

Symptoms and risk factors for long COVID in non-hospitalized adults.

Nat Med 2022 Jul 25. Epub 2022 Jul 25.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.
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http://dx.doi.org/10.1038/s41591-022-01909-wDOI Listing
July 2022

UK National Screening Committee's approach to reviewing evidence on artificial intelligence in breast cancer screening.

Lancet Digit Health 2022 07;4(7):e558-e565

Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.

Artificial intelligence (AI) could have the potential to accurately classify mammograms according to the presence or absence of radiological signs of breast cancer, replacing or supplementing human readers (radiologists). The UK National Screening Committee's assessments of the use of AI systems to examine screening mammograms continues to focus on maximising benefits and minimising harms to women screened, when deciding whether to recommend the implementation of AI into the Breast Screening Programme in the UK. Maintaining or improving programme specificity is important to minimise anxiety from false positive results. When considering cancer detection, AI test sensitivity alone is not sufficiently informative, and additional information on the spectrum of disease detected and interval cancers is crucial to better understand the benefits and harms of screening. Although large retrospective studies might provide useful evidence by directly comparing test accuracy and spectrum of disease detected between different AI systems and by population subgroup, most retrospective studies are biased due to differential verification (ie, the use of different reference standards to verify the target condition among study participants). Enriched, multiple-reader, multiple-case, test set laboratory studies are also biased due to the laboratory effect (ie, radiologists' performance in retrospective, laboratory, observer studies is substantially different to their performance in a clinical environment). Therefore, assessment of the effect of incorporating any AI system into the breast screening pathway in prospective studies is required as it will provide key evidence for the effect of the interaction of medical staff with AI, and the impact on women's outcomes.
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http://dx.doi.org/10.1016/S2589-7500(22)00088-7DOI Listing
July 2022

Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.

Nat Med 2022 05 18;28(5):924-933. Epub 2022 May 18.

Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.

A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico evaluation, but few have yet demonstrated real benefit to patient care. Early-stage clinical evaluation is important to assess an AI system's actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use and pave the way to further large-scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multi-stakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two-round, modified Delphi process to collect and analyze expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 pre-defined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation & Elaboration (E&E) sections were refined based on feedback from a qualitative evaluation process. In total, 123 experts participated in the first round of Delphi, 138 in the second round, 16 in the consensus meeting and 16 in the qualitative evaluation. The DECIDE-AI reporting guideline comprises 17 AI-specific reporting items (made of 28 subitems) and ten generic reporting items, with an E&E paragraph provided for each. Through consultation and consensus with a range of stakeholders, we developed a guideline comprising key items that should be reported in early-stage clinical studies of AI-based decision support systems in healthcare. By providing an actionable checklist of minimal reporting items, the DECIDE-AI guideline will facilitate the appraisal of these studies and replicability of their findings.
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http://dx.doi.org/10.1038/s41591-022-01772-9DOI Listing
May 2022

Risk of a subsequent diagnosis of inflammatory bowel disease in subjects with ophthalmic disorders associated with inflammatory bowel disease: a retrospective cohort analysis of UK primary care data.

BMJ Open 2022 05 11;12(5):e052833. Epub 2022 May 11.

Gastroenterology, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK.

Objectives: Ophthalmic conditions including anterior uveitis (AU), episcleritis and scleritis may occur in association with the inflammatory bowel diseases (IBD) as ophthalmic extraintestinal manifestations. The aim of this study was to assess the risk of a later IBD diagnosis in those presenting with IBD associated ocular inflammation (IAOI).

Design: Retrospective cohort study.

Setting: Primary care UK database.

Participants: 38 805 subjects with an IAOI were identified (median age 51 (38-65), 57% women) and matched to 153 018 subjects without IAOI.

Measures: The risk of a subsequent diagnosis of IBD in subjects with IAOIs compared with age/sex matched subjects without IAOI. HRs were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, baseline axial arthropathy, diarrhoea, loperamide prescription, anaemia, lower gastrointestinal bleeding and abdominal pain.Logistic regression was used to produce a prediction model for a diagnosis of IBD within 3 years of an AU diagnosis.

Results: 213 (0.6%) subsequent IBD diagnoses (102 ulcerative colitis (UC) and 111 Crohn's disease (CD)) were recorded in those with IAOIs and 329 (0.2%) (215 UC and 114 CD) in those without. Median time to IBD diagnosis was 882 (IQR 365-2043) days in those with IAOI and 1403 (IQR 623-2516) in those without. The adjusted HR for a subsequent diagnosis of IBD was 2.25 (95% CI 1.89 to 2.68), p<0.001; for UC 1.65 (95% CI 1.30 to 2.09), p<0.001; and for CD 3.37 (95% CI 2.59 to 4.40), p<0.001 in subjects with IAOI compared with those without.Within 3 years of an AU diagnosis, 84 (0.5%) subjects had a recorded diagnosis of IBD. The prediction model performed well with a C-statistic of 0.75 (95% CI 0.69 to 0.80).

Conclusions: Subjects with IAOI have a twofold increased risk of a subsequent IBD diagnosis. Healthcare professionals should be alert for potential signs and symptoms of IBD in those presenting with ophthalmic conditions associated with IBD.
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http://dx.doi.org/10.1136/bmjopen-2021-052833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096531PMC
May 2022

Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension.

Br J Clin Pharmacol 2022 Apr 27. Epub 2022 Apr 27.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Aims: Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK.

Methods: In this study, 53 832 and 43 106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD.

Results: During a median follow-up of 2 years (interquartile range 1-5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2-2.6) and 2.2 (2.0-2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90-1.27] and 0.87 [0.71-1.07], respectively).

Conclusion: We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.
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http://dx.doi.org/10.1111/bcp.15366DOI Listing
April 2022

Therapies for Long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study).

BMJ Open 2022 04 26;12(4):e060413. Epub 2022 Apr 26.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Introduction: Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.

Methods And Analysis: A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.

Ethics And Dissemination: Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.

Trial Registration Number: 1567490.
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http://dx.doi.org/10.1136/bmjopen-2021-060413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044550PMC
April 2022

Outreach screening to address demographic and economic barriers to diabetic retinopathy care in rural China.

PLoS One 2022 20;17(4):e0266380. Epub 2022 Apr 20.

The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou City, China.

Importance: Poor access to existing care for diabetic retinopathy (DR) limits effectiveness of proven treatments.

Objectives: We examined whether outreach screening in rural China improves equity of access.

Design, Setting And Participants: We compared prevalence of female sex, age > = 65 years, primary education or below, and requiring referral care for DR between three cohorts with diabetes examined for DR in neighboring areas of Guangdong, China: passive case detection at secondary-level hospitals (n = 193); persons screened during primary-level DR outreach (n = 182); and individuals with newly- or previously-diagnosed diabetes in a population survey (n = 579). The latter reflected the "ideal" reach of a screening program.

Results: Compared to the population cohort, passive case detection reached fewer women (50·8% vs. 62·3%, p = 0·006), older adults (37·8% vs. 51·3%, p < 0·001), and less-educated persons (39·9% vs. 89·6%, p < 0·001). Outreach screening, compared to passive case detection, improved representation of the elderly (49·5% vs. 37·8%, p = 0·03) and less-educated (70·3% vs. 39·9%, p<0·001). The proportion of women (59.8% vs 62.3%, P>0.300) and persons aged > = 65 years (49.5% vs 51.3%, p = 0.723) in the outreach screening and population cohorts did not differ significantly. Prevalence of requiring referral care for DR was significantly higher in the outreach screening cohort (28·0%) than the population (14·0%) and passive case detection cohorts (7·3%, p<0·001 for both).

Conclusions And Relevance: Primary-level outreach screening improves access for the poorly-educated and elderly, and removes gender inequity in access to DR care in this setting, while also identifying more severely-affected patients than case finding in hospital.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266380PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020743PMC
April 2022

Opportunities and Risks of UK Medical Device Reform.

Ther Innov Regul Sci 2022 07 13;56(4):596-606. Epub 2022 Apr 13.

Birmingham Health Partners Centre for Regulatory Science and Innovation, University of Birmingham, Birmingham, UK.

Objectives: To identify the potential opportunities and risks around future UK regulatory reform of medical devices.

Design: A mixed methods approach, comprising a rapid literature review, one-to-one, semi-structured interviews with key stakeholders, a multidisciplinary stakeholder workshop, and a post-workshop survey.

Setting: United Kingdom.

Participants: 32 key stakeholders across the medical device sector were identified both from the public and private sectors.

Results: Opportunities relating to regulatory independence were identified, including the potential to create and implement a regulatory framework that ensures availability of medical devices; innovation and investment potential; and safety to the citizens of the UK. The most significant risks identified included threats to the safety of individual patients and the wider health system arising from the delay in awaiting regulatory approval due to the shortage of approved bodies; and reduced competitiveness of UK market and device manufacturers. Recommendations were identified to mitigate risks, centred on harnessing broader cross-sector collaborations, promoting patient and public partnership, and maximizing international engagement.

Conclusions: The UK's medical device sector is at a time-critical juncture to construct a regulatory framework to navigate its exit of Europe and respond to Europe's transition to new medical device regulations whilst also addressing the ongoing demand for rapid approval for new devices in response to the global pandemic. Investment, capacity-building, and international engagement will play a central role in mitigating risks and maximizing opportunities for medical device regulation.
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http://dx.doi.org/10.1007/s43441-022-00394-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007047PMC
July 2022

Measuring Inflammation in the Vitreous and Retina: A Narrative Review.

Ocul Immunol Inflamm 2022 Apr 12:1-10. Epub 2022 Apr 12.

Ophthalmology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

Uveitis consists of a group of syndromes characterised by intraocular inflammation, accounting for up to 15% of visual loss in the western world and 10% worldwide. Assessment of intraocular inflammation has been limited to clinician-dependent, subjective grading. Developments in imaging technology, such as optical coherence tomography (OCT), have enabled the development of objective, quantitative measures of inflammatory activity. Important quantitative metrics including central macular thickness and vitreous signal intensity allow longitudinal monitoring of disease activity and can be used in conjunction with other imaging modalities enabling holistic assessment of ocular inflammation. Ongoing work into the validation of instrument-based measures alongside development of core outcome sets is crucial for standardisation of clinical trial endpoints and developing guidance for quantitative multi-modal imaging approaches. This review outlines methods of grading inflammation in the vitreous and retina, with a focus on the use of OCT as an objective measure of disease activity.
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http://dx.doi.org/10.1080/09273948.2022.2049316DOI Listing
April 2022

The medical algorithmic audit.

Lancet Digit Health 2022 05 5;4(5):e384-e397. Epub 2022 Apr 5.

Australian Institute for Machine Learning, University of Adelaide, Adelaide, SA, Australia. Electronic address:

Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.
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http://dx.doi.org/10.1016/S2589-7500(22)00003-6DOI Listing
May 2022

AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353 157 patients in London, UK.

BMJ Open 2022 03 16;12(3):e058552. Epub 2022 Mar 16.

Institute of Ophthalmology, University College London, London, UK

Purpose: Retinal signatures of systemic disease ('oculomics') are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.

Participants: Between 1 January 2008 and 1 April 2018, 353 157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.

Findings To Date: Among the 353 157 individuals, 186 651 had a total of 1 337 711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12 022 patients with myocardial infarction, 11 735 with all-cause stroke and 13 363 with all-cause dementia. A total of 6 261 931 retinal images of seven different modalities and across three manufacturers were acquired from 1 54 830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).

Future Plans: AlzEye combines the world's largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.
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http://dx.doi.org/10.1136/bmjopen-2021-058552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928293PMC
March 2022

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

Br J Ophthalmol 2022 Feb 23. Epub 2022 Feb 23.

Population, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health Population Policy and Practice, London, UK

Background/aims: Anterior segment optical coherence tomography (AS-OCT) assessment of anterior chamber inflammation is an emerging tool. We describe the performance of AS-OCT in a paediatric population.

Methods: A mixed-methods prospective study, using routine clinical assessment as reference standard, and AS-OCT, with Tomey CASIA2 or Heidelberg Spectralis HS1, as index test, with data collected on patient perceptions of imaging. Repeatability, diagnostic indices, responsiveness to clinical change and clinical correlations of imaging-based metrics (image cell count, size, density and brightness) were assessed, with construction of receiver operated characteristic curves. Exploratory thematic analysis of responses from families was undertaken.

Results: A total of 90 children (180 eyes) underwent imaging. Bland Altman limits of agreement for CASIA2 repeatability ranged from +17 cells (95% CI 13.6 to 21.1) to -19 cells (95% CI -15.6 to -23.2) and HS1 from +1 (95% CI 0.9 to 1.2) to -1.0 (-1.2 to -0.8) cells. CASIA2 imaging had higher sensitivity of 0.92 (95% CI 0.78 to 0.97) vs HS1 imaging 0.17 (95% CI 0.07 to 0.34), with positive correlation between clinical grade and CASIA2 cell count (coefficient 12.8, p=0.02, 95% CI 2.2 to 23.4). Change in clinical grade at follow-up examinations correlated with change in image based 'cell' count (r=0.79, p<0.001). Patients reported a potential positive impact of seeing their disease activity.

Conclusion: Our findings suggest that OCT-based imaging holds the promise of deeper understanding of disease, improved patient experience and more granular monitoring of activity with resultant improved outcomes, but further work is needed to refine acquisition and analysis protocols.
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http://dx.doi.org/10.1136/bjophthalmol-2021-320448DOI Listing
February 2022

Consensus-based recommendations for optical coherence tomography angiography reporting in uveitis.

Br J Ophthalmol 2022 Feb 8. Epub 2022 Feb 8.

Ophthalmology, Inselspital, University Hospital Bern, Bern, Switzerland.

Background/aims: To establish a consensus in the nomenclature for reporting optical coherence tomography angiography (OCTA findings in uveitis.

Methods: The modified Delphi process consisted of two rounds of electronic questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-one items were included for discussion. The three main areas of discussion were: wide field OCTA (WF-OCTA), nomenclature of OCTA findings and OCTA signal attenuation assessment and measurement. Seventeen specialists in uveitis and retinal imaging were selected by the executive committee to constitute the OCTA nomenclature in Uveitis Delphi Study Group. The study endpoint was defined by the degree of consensus for each question: 'strong consensus' was defined as >90% agreement, 'consensus' as 85%-90% and 'near consensus' as >80% but <85%.

Results: There was a strong consensus to apply the term 'wide field' to OCTA images measuring over 70° of field of view, to use the terms 'flow deficit' and 'non-detectable flow signal' to describe abnormal OCTA flow signal secondary to slow flow and to vessels displacement respectively, to use the terms 'loose' and 'dense' to describe the appearance of inflammatory choroidal neovascularisation, and to use the percentage of flow signal decrease to measure OCTA ischaemia with a threshold greater than or equal to 30% as a 'large area'.

Conclusions: This study sets up consensus recommendations for reporting OCTA findings in uveitis by an expert panel, which may prove suitable for use in routine clinical care and clinical trials.
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http://dx.doi.org/10.1136/bjophthalmol-2021-320021DOI Listing
February 2022

Metformin and risk of age-related macular degeneration in individuals with type 2 diabetes: a retrospective cohort study.

Br J Ophthalmol 2022 Feb 3. Epub 2022 Feb 3.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Background: Age-related macular degeneration (AMD) in its late stages is a leading cause of sight loss in developed countries. Some previous studies have suggested that metformin may be associated with a reduced risk of developing AMD, but the evidence is inconclusive.

Aims: To explore the relationship between metformin use and development of AMD among patients with type 2 diabetes in the UK.

Methods: A large, population-based retrospective open cohort study with a time-dependent exposure design was carried out using IQVIA Medical Research Data, 1995-2019. Patients aged ≥40 with diagnosed type 2 diabetes were included.The exposed group was those prescribed metformin (with or without any other antidiabetic medications); the comparator (unexposed) group was those prescribed other antidiabetic medications only. The exposure status was treated as time varying, collected at 3-monthly time intervals.Extended Cox proportional hazards regression was used to calculate the adjusted HRs for development of the outcome, newly diagnosed AMD.

Results: A total of 173 689 patients, 57% men, mean (SD) age 62.8 (11.6) years, with incident type 2 diabetes and a record of one or more antidiabetic medications were included in the study. Median follow-up was 4.8 (IQR 2.3-8.3, range 0.5-23.8) years. 3111 (1.8%) patients developed AMD. The adjusted HR for diagnosis of AMD was 1.02 (95% CI 0.92 to 1.12) in patients prescribed metformin (with or without other antidiabetic medications) compared with those prescribed any other antidiabetic medication only.

Conclusion: We found no evidence that metformin was associated with risk of AMD in primary care patients requiring treatment for type 2 diabetes.
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http://dx.doi.org/10.1136/bjophthalmol-2021-319641DOI Listing
February 2022

Teleophthalmology-enabled and artificial intelligence-ready referral pathway for community optometry referrals of retinal disease (HERMES): a Cluster Randomised Superiority Trial with a linked Diagnostic Accuracy Study-HERMES study report 1-study protocol.

BMJ Open 2022 Feb 1;12(2):e055845. Epub 2022 Feb 1.

NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London, London, UK

Introduction: Recent years have witnessed an upsurge of demand in eye care services in the UK. With a large proportion of patients referred to Hospital Eye Services (HES) for diagnostics and disease management, the referral process results in unnecessary referrals from erroneous diagnoses and delays in access to appropriate treatment. A potential solution is a teleophthalmology digital referral pathway linking community optometry and HES.

Methods And Analysis: The HERMES study (Teleophthalmology-enabled and artificial intelligence-ready referral pathway for community optometry referrals of retinal disease: a cluster randomised superiority trial with a linked diagnostic accuracy study) is a cluster randomised clinical trial for evaluating the effectiveness of a teleophthalmology referral pathway between community optometry and HES for retinal diseases. Nested within HERMES is a diagnostic accuracy study, which assesses the accuracy of an artificial intelligence (AI) decision support system (DSS) for automated diagnosis and referral recommendation. A postimplementation, observational substudy, a within-trial economic evaluation and discrete choice experiment will assess the feasibility of implementation of both digital technologies within a real-life setting. Patients with a suspicion of retinal disease, undergoing eye examination and optical coherence tomography (OCT) scans, will be recruited across 24 optometry practices in the UK. Optometry practices will be randomised to standard care or teleophthalmology. The primary outcome is the proportion of false-positive referrals (unnecessary HES visits) in the current referral pathway compared with the teleophthalmology referral pathway. OCT scans will be interpreted by the AI DSS, which provides a diagnosis and referral decision and the primary outcome for the AI diagnostic study is diagnostic accuracy of the referral decision made by the Moorfields-DeepMind AI system. Secondary outcomes relate to inappropriate referral rate, cost-effectiveness analyses and human-computer interaction (HCI) analyses.

Ethics And Dissemination: Ethical approval was obtained from the London-Bromley Research Ethics Committee (REC 20/LO/1299). Findings will be reported through academic journals in ophthalmology, health services research and HCI.

Trial Registration Number: ISRCTN18106677 (protocol V.1.1).
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http://dx.doi.org/10.1136/bmjopen-2021-055845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808461PMC
February 2022

Comparison of colour contrast sensitivity in eyes at high risk of neovascular age-related macular degeneration with and without subsequent choroidal neovascular membrane development.

Eye (Lond) 2022 Jan 20. Epub 2022 Jan 20.

Aston University, School of Life and Health Sciences, Birmingham, UK.

Background: Neovascular age-related macular degeneration (nAMD) is a leading cause of blind registrations in the elderly. Unfortunately, it is difficult to detect the early stage of the disease, when treatment is more likely to be successful. Subjects with very early disease are likely to have abnormal macular function, even in the pre-symptomatic stage. In this study, colour vision was evaluated to establish if subjects at high risk of developing nAMD can be identified, thus allowing earlier diagnosis and possible treatment.

Methods: Colour contrast sensitivity (CCS) was evaluated over time in the fellow unaffected eye of subjects with unilateral nAMD. Participants were divided into Group 1 (182 participants) or Group 2 (15 participants) according to whether nAMD did not or did develop in the study period respectively and the two groups were compared.

Results: CCS was increased (i.e. worse colour vision) compared with the age-matched reference range in a high proportion of fellow eyes in both Groups 1 and 2. Global mean CCS values did not show statistically significant differences between the two groups. However, there was a statistically significant difference between mean Group 1 CCS values and the last CCS value prior to nAMD diagnosis from Group 2 subjects.

Conclusion: This study shows that in patients with unilateral nAMD, colour vision is frequently abnormal in the fellow unaffected eye. Abnormal CCS does not predict the development of nAMD within the 12 month period of the study and therefore it is not a viable screening tool for this pathology.
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http://dx.doi.org/10.1038/s41433-021-01875-6DOI Listing
January 2022

Development and external validation of prognostic models for COVID-19 to support risk stratification in secondary care.

BMJ Open 2022 01 17;12(1):e049506. Epub 2022 Jan 17.

Institute of Applied Health Research, University of Birmingham, Birmingham, UK.

Objectives: Existing UK prognostic models for patients admitted to the hospital with COVID-19 are limited by reliance on comorbidities, which are under-recorded in secondary care, and lack of imaging data among the candidate predictors. Our aims were to develop and externally validate novel prognostic models for adverse outcomes (death and intensive therapy unit (ITU) admission) in UK secondary care and externally validate the existing 4C score.

Design: Candidate predictors included demographic variables, symptoms, physiological measures, imaging and laboratory tests. Final models used logistic regression with stepwise selection.

Setting: Model development was performed in data from University Hospitals Birmingham (UHB). External validation was performed in the CovidCollab dataset.

Participants: Patients with COVID-19 admitted to UHB January-August 2020 were included.

Main Outcome Measures: Death and ITU admission within 28 days of admission.

Results: 1040 patients with COVID-19 were included in the derivation cohort; 288 (28%) died and 183 (18%) were admitted to ITU within 28 days of admission. Area under the receiver operating characteristic curve (AUROC) for mortality was 0.791 (95% CI 0.761 to 0.822) in UHB and 0.767 (95% CI 0.754 to 0.780) in CovidCollab; AUROC for ITU admission was 0.906 (95% CI 0.883 to 0.929) in UHB and 0.811 (95% CI 0.795 to 0.828) in CovidCollab. Models showed good calibration. Addition of comorbidities to candidate predictors did not improve model performance. AUROC for the International Severe Acute Respiratory and Emerging Infection Consortium 4C score in the UHB dataset was 0.753 (95% CI 0.720 to 0.785).

Conclusions: The novel prognostic models showed good discrimination and calibration in derivation and external validation datasets, and performed at least as well as the existing 4C score using only routinely collected patient information. The models can be integrated into electronic medical records systems to calculate each individual patient's probability of death or ITU admission at the time of hospital admission. Implementation of the models and clinical utility should be evaluated.
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http://dx.doi.org/10.1136/bmjopen-2021-049506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764710PMC
January 2022

OCT Assisted Quantification of Vitreous Inflammation in Uveitis.

Transl Vis Sci Technol 2022 01;11(1)

Academic Unit of Ophthalmology, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, UK.

Purpose: Vitreous haze (VH) is a key marker of inflammation in uveitis but limited by its subjectivity. Optical coherence tomography (OCT) has potential as an objective, noninvasive method for quantifying VH. We test the hypotheses that OCT can reliably quantify VH and the measurement is associated with slit-lamp based grading of VH.

Methods: In this prospective study, participants underwent three repeated OCT macular scans to evaluate the within-eye reliability of the OCT vitreous intensity (VI). Association between OCT VI and clinical findings (including VH grade, phakic status, visual acuity [VA], anterior chamber cells, and macular thickness) were assessed.

Results: One hundred nineteen participants were included (41 healthy participants, 32 patients with uveitis without VH, and 46 patients with uveitis with VH). Within-eye test reliability of OCT VI was high in healthy eyes and in all grades of VH (intraclass correlation coefficient [ICC] > 0.79). Average OCT VI was significantly different between healthy eyes and uveitic eyes without and uveitic eyes with VH, and was associated with increasing clinical VH grade (P < 0.05). OCT VI was significantly associated with VA, whereas clinical VH grading was not. Cataract was also associated with higher OCT VI (P = 0.03).

Conclusions: OCT VI is a fast, noninvasive, objective, and automated method for measuring vitreous inflammation. It is associated with clinician grading of vitreous inflammation and VA, however, it can be affected by media opacities.

Translational Relevance: OCT imaging for quantifying vitreous inflammation shows high within-eye repeatability and is associated with clinical grading of vitreous haze. OCT measurements are also associated with visual acuity but may be affected by structures anterior to the acquisition window, such as lens opacity and other anterior segment changes.
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http://dx.doi.org/10.1167/tvst.11.1.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742534PMC
January 2022

The Cellular Composition of the Uveal Immune Environment.

Front Med (Lausanne) 2021 29;8:721953. Epub 2021 Oct 29.

The Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.

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.
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http://dx.doi.org/10.3389/fmed.2021.721953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586083PMC
October 2021

Characteristics of publicly available skin cancer image datasets: a systematic review.

Lancet Digit Health 2022 01 9;4(1):e64-e74. Epub 2021 Nov 9.

Department of Dermatology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic address:

Publicly available skin image datasets are increasingly used to develop machine learning algorithms for skin cancer diagnosis. However, the total number of datasets and their respective content is currently unclear. This systematic review aimed to identify and evaluate all publicly available skin image datasets used for skin cancer diagnosis by exploring their characteristics, data access requirements, and associated image metadata. A combined MEDLINE, Google, and Google Dataset search identified 21 open access datasets containing 106 950 skin lesion images, 17 open access atlases, eight regulated access datasets, and three regulated access atlases. Images and accompanying data from open access datasets were evaluated by two independent reviewers. Among the 14 datasets that reported country of origin, most (11 [79%]) originated from Europe, North America, and Oceania exclusively. Most datasets (19 [91%]) contained dermoscopic images or macroscopic photographs only. Clinical information was available regarding age for 81 662 images (76·4%), sex for 82 848 (77·5%), and body site for 79 561 (74·4%). Subject ethnicity data were available for 1415 images (1·3%), and Fitzpatrick skin type data for 2236 (2·1%). There was limited and variable reporting of characteristics and metadata among datasets, with substantial under-representation of darker skin types. This is the first systematic review to characterise publicly available skin image datasets, highlighting limited applicability to real-life clinical settings and restricted population representation, precluding generalisability. Quality standards for characteristics and metadata reporting for skin image datasets are needed.
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http://dx.doi.org/10.1016/S2589-7500(21)00252-1DOI Listing
January 2022

An informatics consult approach for generating clinical evidence for treatment decisions.

BMC Med Inform Decis Mak 2021 10 12;21(1):281. Epub 2021 Oct 12.

Institute of Health Informatics, University College London, London, UK.

Background: An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis.

Methods: We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems.

Results: We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39-1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49-0.76) and ischaemic stroke (HR = 0.27, CI 0.08-0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results.

Conclusion: We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on 'patients like me'. We identify the key challenges in offering such an Informatics Consult as a service.
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http://dx.doi.org/10.1186/s12911-021-01638-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506488PMC
October 2021

Predicting the immediate impact of national lockdown on neovascular age-related macular degeneration and associated visual morbidity: an INSIGHT Health Data Research Hub for Eye Health report.

Br J Ophthalmol 2021 Sep 13. Epub 2021 Sep 13.

Genentech Inc, South San Francisco, California, USA.

Objective: Predicting the impact of neovascular age-related macular degeneration (nAMD) service disruption on visual outcomes following national lockdown in the UK to contain SARS-CoV-2.

Methods And Analysis: This retrospective cohort study includes deidentified data from 2229 UK patients from the INSIGHT Health Data Research digital hub. We forecasted the number of treatment-naïve nAMD patients requiring anti-vascular endothelial growth factor (anti-VEGF) initiation during UK lockdown (16 March 2020 through 31 July 2020) at Moorfields Eye Hospital (MEH) and University Hospitals Birmingham (UHB). Best-measured visual acuity (VA) changes without anti-VEGF therapy were predicted using post hoc analysis of Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD trial sham-control arm data (n=238).

Results: At our centres, 376 patients were predicted to require anti-VEGF initiation during lockdown (MEH: 325; UHB: 51). Without treatment, mean VA was projected to decline after 12 months. The proportion of eyes in the MEH cohort predicted to maintain the key positive visual outcome of ≥70 ETDRS letters (Snellen equivalent 6/12) fell from 25.5% at baseline to 5.8% at 12 months (UHB: 9.8%-7.8%). Similarly, eyes with VA <25 ETDRS letters (6/96) were predicted to increase from 4.3% to 14.2% at MEH (UHB: 5.9%-7.8%) after 12 months without treatment.

Conclusions: Here, we demonstrate how combining data from a recently founded national digital health data repository with historical industry-funded clinical trial data can enhance predictive modelling in nAMD. The demonstrated detrimental effects of prolonged treatment delay should incentivise healthcare providers to support nAMD patients accessing care in safe environments.

Trial Registration Number: NCT00056836.
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http://dx.doi.org/10.1136/bjophthalmol-2021-319383DOI Listing
September 2021

Stability of OCT and OCTA in the Intensive Therapy Unit Setting.

Diagnostics (Basel) 2021 Aug 23;11(8). Epub 2021 Aug 23.

Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.

To assess the stability of retinal structure and blood flow measures over time and in different clinical settings using portable optical coherence tomography angiography (OCTA) as a potential biomarker of central perfusion in critical illness, 18 oesophagectomy patients completed retinal structure and blood flow measurements by portable OCT and OCTA in the eye clinic and intensive therapy unit (ITU) across three timepoints: (1) pre-operation in a clinic setting; (2) 24-48 h post-operation during ITU admission; and (3) seven days post-operation, if the patient was still admitted. Blood flow and macular structural measures were stable between the examination settings, with no consistent variation between pre- and post-operation scans, while retinal nerve fibre layer thickness increased in the post-operative scans (+2.31 µm, = 0.001). Foveal avascular zone (FAZ) measurements were the most stable, with an intraclass correlation coefficient of up to 0.92 for right eye FAZ area. Blood flow and structural measures were lower in left eyes than right eyes. Retinal blood flow assessed in patients before and during an ITU stay using portable OCTA showed no systematic differences between the clinical settings. The stability of retinal blood flow measures suggests the potential for portable OCTA to provide clinically useful measures in ITU patients.
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http://dx.doi.org/10.3390/diagnostics11081516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394026PMC
August 2021

Developing a reporting guideline for artificial intelligence-centred diagnostic test accuracy studies: the STARD-AI protocol.

BMJ Open 2021 06 28;11(6):e047709. Epub 2021 Jun 28.

Division of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Introduction: Standards for Reporting of Diagnostic Accuracy Study (STARD) was developed to improve the completeness and transparency of reporting in studies investigating diagnostic test accuracy. However, its current form, STARD 2015 does not address the issues and challenges raised by artificial intelligence (AI)-centred interventions. As such, we propose an AI-specific version of the STARD checklist (STARD-AI), which focuses on the reporting of AI diagnostic test accuracy studies. This paper describes the methods that will be used to develop STARD-AI.

Methods And Analysis: The development of the STARD-AI checklist can be distilled into six stages. (1) A project organisation phase has been undertaken, during which a Project Team and a Steering Committee were established; (2) An item generation process has been completed following a literature review, a patient and public involvement and engagement exercise and an online scoping survey of international experts; (3) A three-round modified Delphi consensus methodology is underway, which will culminate in a teleconference consensus meeting of experts; (4) Thereafter, the Project Team will draft the initial STARD-AI checklist and the accompanying documents; (5) A piloting phase among expert users will be undertaken to identify items which are either unclear or missing. This process, consisting of surveys and semistructured interviews, will contribute towards the explanation and elaboration document and (6) On finalisation of the manuscripts, the group's efforts turn towards an organised dissemination and implementation strategy to maximise end-user adoption.

Ethics And Dissemination: Ethical approval has been granted by the Joint Research Compliance Office at Imperial College London (reference number: 19IC5679). A dissemination strategy will be aimed towards five groups of stakeholders: (1) academia, (2) policy, (3) guidelines and regulation, (4) industry and (5) public and non-specific stakeholders. We anticipate that dissemination will take place in Q3 of 2021.
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http://dx.doi.org/10.1136/bmjopen-2020-047709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240576PMC
June 2021

Development and application of the ocular immune-mediated inflammatory diseases ontology enhanced with synonyms from online patient support forum conversation.

Comput Biol Med 2021 08 8;135:104542. Epub 2021 Jun 8.

University Hospitals Birmingham NHS Foundation Trust, UK; Institute of Applied Health Research, University of Birmingham, UK; The Medical Eye Unit, St Thomas' Hospital NHS Foundation Trust, London, UK.

Background: Unstructured text created by patients represents a rich, but relatively inaccessible resource for advancing patient-centred care. This study aimed to develop an ontology for ocular immune-mediated inflammatory diseases (OcIMIDo), as a tool to facilitate data extraction and analysis, illustrating its application to online patient support forum data.

Methods: We developed OcIMIDo using clinical guidelines, domain expertise, and cross-references to classes from other biomedical ontologies. We developed an approach to add patient-preferred synonyms text-mined from oliviasvision.org online forum, using statistical ranking. We validated the approach with split-sampling and comparison to manual extraction. Using OcIMIDo, we then explored the frequency of OcIMIDo classes and synonyms, and their potential association with natural language sentiment expressed in each online forum post.

Findings: OcIMIDo (version 1.2) includes 661 classes, describing anatomy, clinical phenotype, disease activity status, complications, investigations, interventions and functional impacts. It contains 1661 relationships and axioms, 2851 annotations, including 1131 database cross-references, and 187 patient-preferred synonyms. To illustrate OcIMIDo's potential applications, we explored 9031 forum posts, revealing frequent mention of different clinical phenotypes, treatments, and complications. Language sentiment analysis of each post was generally positive (median 0.12, IQR 0.01-0.24). In multivariable logistic regression, the odds of a post expressing negative sentiment were significantly associated with first posts as compared to replies (OR 3.3, 95% CI 2.8 to 3.9, p < 0.001).

Conclusion: We report the development and validation of a new ontology for inflammatory eye diseases, which includes patient-preferred synonyms, and can be used to explore unstructured patient or physician-reported text data, with many potential applications.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404035PMC
August 2021

Structural Endpoints and Outcome Measures in Uveitis.

Ophthalmologica 2021 1;244(5):465-479. Epub 2021 Jun 1.

Department of Ophthalmology, University Hospital Bonn, Bonn, Germany.

Most uveitis entities are rare diseases but, taken together, are responsible for 5-10% of worldwide visual impairment which largely affects persons of working age. As with many rare diseases, there is a lack of high-level evidence regarding its clinical management, partly due to a dearth of reliable and objective quantitative endpoints for clinical trials. This review provides an overview of available structural outcome measures for uveitis disease activity and damage in an anatomical order from the anterior to the posterior segment of the eye. While there is a multitude of available structural outcome measures, not all might qualify as endpoints for clinical uveitis trials, and thorough testing of applicability is warranted. Furthermore, a consensus on endpoint definition, standardization, and "core outcomes" is required. As stipulated by regulatory agencies, endpoints should be precisely defined, clinically important, internally consistent, reliable, responsive to treatment, and relevant for the respective subtype of uveitis. Out of all modalities used for assessment of the reviewed structural outcome measures, optical coherence tomography, color fundus photography, fundus autofluorescence, and fluorescein/indocyanine green angiography represent current "core modalities" for reliable and objective quantification of uveitis outcome measures, based on their practical availability and the evidence provided so far.
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http://dx.doi.org/10.1159/000517521DOI Listing
November 2021
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