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Objective To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care. Methods We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality). Results From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS. Conclusion There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.

Optic neuritis (ON) is associated with numerous immune-mediated inflammatory diseases. After presenting for the first time with undifferentiated ON, up to 50% per cent of patients are subsequently diagnosed with multiple sclerosis (MS), sometimes many years later. Differentiating MS-ON from non-MS-ON in the acute setting is challenging but important. Initial treatment of MS-ON and non-MS ON differs, with the latter often requiring urgent immunosuppression. Diagnostic delay in non-MS ON impacts final visual prognosis. Over 200 common genetic variants are associated with MS. We sought to establish whether integrating an MS genetic risk score (MS-GRS) improves prediction of future MS in undifferentiated ON. Using data from the United Kingdom Biobank we showed that combining MS-GRS with demographic risk factors significantly improves MS prediction in patients with undifferentiated ON. In a combined risk model including sex, age and MS-GRS, one standard deviation of MS risk score increased the Hazard of MS 1.3-fold (95% confidence interval 1.09-1.59, P

In 2021, WHO Member States endorsed a global target of a 40-percentage-point increase in effective refractive error coverage (eREC; with a 6/12 visual acuity threshold) by 2030. This study models global and regional estimates of eREC as a baseline for the WHO initiative.The Vision Loss Expert Group analysed data from 565 448 participants of 169 population-based eye surveys conducted since 2000 to calculate eREC (met need/[met need + undermet need + unmet need]). A binary logistic regression model was used to estimate eREC by Global Burden of Disease (GBD) Study super region among adults aged 50 years and older.In 2021, distance eREC was 79·1% (95% CI 72·4-85·0) in the high-income super region; 62·1% (54·7-68·8) in north Africa and Middle East; 49·5% (45·0-54·0) in central Europe, eastern Europe, and central Asia; 40·0% (31·7-48·2) in southeast Asia, east Asia, and Oceania; 34·5% (29·4-40·0) in Latin America and the Caribbean; 9·0% (6·5-12·0) in south Asia; and 5·7% (3·1-9·0) in sub-Saharan Africa. eREC was higher in men and reduced with increasing age. Global distance eREC increased from 2000 to 2021 by 19·0%. Global near vision eREC for 2021 was 20·5% (95% CI 17·8-24·4).Over the past 20 years, distance eREC has increased in each super region yet the WHO target will require substantial improvements in quantity and quality of refractive services in particular for near vision impairment.WHO, Sightsavers, The Fred Hollows Foundation, Fondation Thea, Brien Holden Vision Institute, Lions Clubs International Foundation.

BackgroundData on population-based self-reported dual vision and hearing impairment are sparse in Europe. We aimed to investigate self-reported dual sensory impairment (DSI) in European population.MethodsA standardised questionnaire was used to collect medical and socio-economic data among individuals aged 15 years or more in 29 European countries. Individuals living in collective households or in institutions were excluded from the survey.ResultsAmong 296 677 individuals, the survey included 153 866 respondents aged 50 years old or more. The crude prevalence of DSI was of 7.54% (7.36–7.72). Among individuals aged 60 or more, 9.23% of men and 10.94% of women had DSI. Eastern and southern countries had a higher prevalence of DSI. Multivariable analyses showed that social isolation and poor self-rated health status were associated with DSI with ORs of 2.01 (1.77–2.29) and 2.33 (2.15–2.52), while higher income was associated with lower risk of DSI (OR of 0.83 (0.78–0.89). Considering country-level socioeconomic factors, Human Development Index explained almost 38% of the variance of age-adjusted prevalence of DSI.ConclusionThere are important differences in terms of prevalence of DSI in Europe, depending on socioeconomic and medical factors. Prevention of DSI does represent an important challenge for maintaining quality of life in elderly population.

Purpose To identify and comprehensively evaluate studies capturing the experience of individuals affected by an inherited optic neuropathy (ION), focusing on patient-reported outcome measures (PROMs) and qualitative studies where the health status and quality of life (QoL) of these individuals have been explored. Methods Systematic review of five databases using a search strategy combining four concepts: (1) ION; (2) QoL and health status; (3) PROMs; and (4) qualitative research. Studies assessing the impact of ION on any QoL domain using a PROM or qualitative methodology were included and appraised, using criteria based on the COSMIN checklist (for PROM studies) and the CASP checklist (for qualitative studies). Results Of 1326 unique articles identified, six studies were included. Five PROMs were identified: Visual Function Index (VF-14); Hospital Anxiety and Depression Scale (HADS); a novel graphical online assessment tool (NGOAT) for reporting emotional response to vision loss; a new PROM informed by the DSM-V Criteria for Major Depressive Disorder; and an interpersonal and career ‘impact rating’ PROM. The psychometric performance of included PROMs were poorly described. Qualitative studies found that vision loss resulted in psychosocial losses including loss of social and communication skills and loss of independence and freedom. Factors that modified the response to vision loss were also identified. Conclusion The current PROMs used by individuals with ION have poor content coverage, primarily measuring activity limitation and emotional well-being, and insufficient reporting of psychometric performance. There is a need to develop a PROM for individuals ION to report their experiences of living with their condition.

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.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.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).We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.

This article, co-authored by a patient affected by bilateral, recurrent, atypical optic neuritis, and clinicians, discusses the mental burden of living with uncertainty and the possibility of further sight loss, along with the side effects of treatment. The patient shares some of the challenges, coping strategies, and the value they found in creating and participating in a patient support group. The physicians consider whether current clinical measures adequately capture the outcomes that matter to patients and discuss the role for patient-reported outcome measures (PROMs). We identify technological advances that are lowering traditional barriers to the use of PROMs in research and routine clinical care and look towards new PROM instruments enhancing shared patient-physician care in the future., Plain Language Summary In this patient-physician perspective article, we share the story of a patient affected by an autoimmune disease that attacks the nerves connecting the eyes and the brain and reflect back physicians’ perspectives on the disease and the patient’s experience of it. In a compelling account, we gain some understanding of what it might be like to live with the fear of unpredictable episodes of sudden, recurrent sight loss and the important impacts that this has on a patient’s life and mental wellbeing. We recognize that the outcome metrics that physicians usually focus on, such as measurement of vision and imaging of the optic nerve, do not fully capture the outcomes that most matter to the patient. We explore patient-reported outcome measures that go some way towards bridging this gap. Finally, we consider the technological advances that will make more comprehensive capture of the patient experience a reality in future clinical practice and research, supporting both patients and physicians to optimize shared care.

Background Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. Methods In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. Findings Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. Interpretation Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. Funding British Heart Foundation Data Science Centre, led by Health Data Research UK.

Case report - Introduction Bisphosphonates are known to rarely cause multi-system inflammation, including multiple cranial neuropathies. This is possibly via provoking transient cytokine storm. The literature reports bisphosphonate-associated orbital inflammatory syndrome, and one case of retrobulbar optic neuritis following zoledronate. Bisphosphonate manufacturers report conjunctivitis, blurred vision, scleritis, orbital inflammation, uveitis and episcleritis as ocular side effects. Separately, neurological sequalae, including cranial neuropathies, are reported following COVID-19 infection and vaccination. Here, we report the first case of cavernous sinus inflammation temporally related to both zoledronate infusion, and more remotely, to Pfizer-BioNTech COVID-19 vaccination. Case report - Case description A 76-year-old white man developed fever, bony leg pain – which rendered him unable to walk – and frontal headache, within 8 hours of his first zoledronate infusion for osteoporosis. A few weeks earlier he received his first Pfizer-BioNTech COVID-19 vaccine. His General Practitioner commenced a short course of low-dose oral prednisolone for the episode. One week later, off prednisolone, the headache localised around the left eye. He developed horizontal diplopia associated with abduction deficit. He was diagnosed with left VIth nerve palsy. He was started on high-dose steroids and clopidogrel (with PPI) with neuroimaging to exclude stroke or venous sinus thrombosis. Two weeks later, the diplopia worsened over 4 days, with new left adduction deficit (-2 limitation), left ptosis 1-2mm and anisocoria 0.5-1mm R>L suggestive of partial third nerve palsy and early Horner’s syndrome. Ocular and neurological examinations were otherwise normal. He wore varifocals and had migraines, osteoporosis, and asthma, for which he used inhalers. He worked in visual arts and was an ex-smoker (>50 years) with moderate alcohol intake. Blood results revealed CRP 38mg/L, but otherwise normal inflammation/vasculitis/infection screen; anti-thyroglobulin antibodies were >4000 U/ml; GQ1P, Creatinine Kinase, anti-ganglioside, and Anti-AChR/MuSK antibodies were normal. CT head and Optical Coherence Tomography were unremarkable. An enhanced MRI of the brain and orbits revealed abnormal thickening and T2 hyper-intensity of the left oculomotor nerve, most notably involving the left canalicular portion. The left cavernous sinus also appeared asymmetrically bulky with a rind of abnormal enhancing soft tissue in the left cavernous sinus. Subtle STIR hyper-intensity was also observed in the ipsilateral CN III-innervated extra-ocular muscles. After a 6-week course of tapering prednisolone, the vertical diplopia and leg swelling persisted; the horizontal diplopia and headaches had resolved. By 3 months, there was resolution with mild residual visual changes. Case report - Discussion We report a constellation of symptoms relating to multi-system inflammatory syndrome involving the cavernous sinus. There is a lack of epidemiological data on the incidence of this rare presentation in the population. This case has close temporal association to bisphosphonate infusion ( This case highlights a wider issue relating to the challenging possibility of ascertainment bias and increased ‘Yellow Card’ reporting of rare presentations during this historic global coronavirus pandemic, which may or may not have any true causal association to vaccination. There is difficulty in disentangling a true vaccine reaction from an unrelated presentation of a rare condition with an unknown baseline incidence rate. This is especially topical given that the majority of the population are receiving the coronavirus vaccination at this time. We also question what a plausible cut-off point would be to propose a temporal relationship for an adverse reaction; in the literature, adverse reactions have been postulated to develop beyond 1 month after the provoking agent. Case report - Key learning points

Eye health and vision have widespread and profound implications for many aspects of life, health, sustainable development, and the economy. Yet nowadays, many people, families, and populations continue to suffer the consequences of poor access to high-quality, affordable eye care, leading to vision impairment and blindness.\ud In 2020, an estimated 596 million people had distance vision impairment worldwide, of whom 43 million were blind. Another 510 million people had uncorrected near vision impairment, simply because of not having reading spectacles. A large proportion of those affected (90%), live in low-income and middle-income countries (LMICs). However, encouragingly, more than 90% of people with vision impairment have a preventable or treatable cause with existing highly cost-effective interventions. Eye conditions affect all stages of life, with young children and older people being particularly affected. Crucially, women, rural populations, and ethnic minority groups are more likely to have vision impairment, and this pervasive inequality needs to be addressed. By 2050, population ageing, growth, and urbanisation might lead to an estimated 895 million people with distance vision impairment, of whom 61 million will be blind. Action to prioritise eye health is needed now.\ud This Commission defines eye health as maximised vision, ocular health, and functional ability, thereby contributing to overall health and wellbeing, social inclusion, and quality of life. Eye health is essential to achieve many of the Sustainable Development Goals (SDGs). Poor eye health and impaired vision have a negative effect on quality of life and restrict equitable access to and achievement in education and the workplace. Vision loss has substantial financial implications for affected individuals, families, and communities. Although high-quality data for global economic estimates are scarce, particularly for LMICs, conservative assessments based on the latest prevalence figures for 2020 suggest that annual global productivity loss from vision impairment is approximately US$410·7 billion purchasing power parity. Vision impairment reduces mobility, affects mental wellbeing, exacerbates risk of dementia, increases likelihood of falls and road traffic crashes, increases the need for social care, and ultimately leads to higher mortality rates.\ud By contrast, vision facilitates many daily life activities, enables better educational outcomes, and increases work productivity, reducing inequality. An increasing amount of evidence shows the potential for vision to advance the SDGs, by contributing towards poverty reduction, zero hunger, good health and wellbeing, quality education, gender equality, and decent work. Eye health is a global public priority, transforming lives in both poor and wealthy communities. Therefore, eye health needs to be reframed as a development as well as a health issue and given greater prominence within the global development and health agendas.\ud Vision loss has many causes that require promotional, preventive, treatment, and rehabilitative interventions. Cataract, uncorrected refractive error, glaucoma, age-related macular degeneration, and diabetic retinopathy are responsible for most global vision impairment. Research has identified treatments to reduce or eliminate blindness from all these conditions; the priority is to deliver treatments where they are most needed. Proven eye care interventions, such as cataract surgery and spectacle provision, are among the most cost-effective in all of health care. Greater financial investment is needed so that millions of people living with unnecessary vision impairment and blindness can benefit from these interventions.\ud Lessons from the past three decades give hope that this challenge can be met. Between 1990 and 2020, the age-standardised global prevalence of blindness fell by 28·5%. Since the 1990s, prevalence of major infectious causes of blindness—onchocerciasis and trachoma—have declined substantially. Hope remains that by 2030, the transmission of onchocerciasis will be interrupted, and trachoma will be eliminated as a public health problem in every country worldwide. However, the ageing population has led to a higher crude prevalence of age-related causes of blindness, and thus an increased total number of people with blindness in some regions.\ud Despite this progress, business as usual will not keep pace with the demographic trends of an ageing global population or address the inequities that persist in each country. New threats to eye health are emerging, including the worldwide increase in diabetic retinopathy, high myopia, retinopathy of prematurity, and chronic eye diseases of ageing such as glaucoma and age-related macular degeneration. With the projected increase in such conditions and their associated vision loss over the coming decades, urgent action is needed to develop innovative treatments and deliver services at a greater scale than previously achieved.\ud Good eye health at the community and national level has been marginalised as a luxury available to only wealthy or urban areas. Eye health needs to be urgently brought into the mainstream of national health and development policy, planning, financing, and action.\ud The challenge is to develop and deliver comprehensive eye health services (promotion, prevention, treatment, rehabilitation) that address the full range of eye conditions within the context of universal health coverage. Accessing services should not bring the risk of falling into poverty and services should be of high quality, as envisaged by the WHO framework for health-care quality: effective, safe, people-centred, timely, equitable, integrated, and efficient. To this framework we add the need for services to be environmentally sustainable. Universal health coverage is not universal without eye care.\ud Multiple obstacles need to be overcome to achieve universal coverage for eye health. Important issues include complex barriers to availability and access to quality services, cost, major shortages and maldistribution of well-trained personnel, and lack of suitable, well maintained equipment and consumables. These issues are particularly widespread in LMICs, but also occur in underserved communities in high-income countries. Strong partnerships need to be formed with natural allies working in areas affected by eye health, such as non-communicable diseases, neglected tropical diseases, healthy ageing, children's services, education, disability, and rehabilitation. The eye health sector has traditionally focused on treatment and rehabilitation, and underused health promotion and prevention strategies to lessen the impact of eye disease and reduce inequality.\ud Solving these problems will depend on solutions established from high quality evidence that can guide more effective implementation at scale. Evidence-based approaches will need to address existing deficiencies in the supply and demand. Strategic investments in discovery research, harnessing new findings from diverse fields, and implementation research to guide effective scale up are needed globally. Encouragingly, developments in telemedicine, mobile health, artificial intelligence, and distance learning could potentially enable eye care professionals to deliver higher quality care that is more plentiful, equitable, and cost-effective.\ud This Commission did a Grand Challenges in Global Eye Health prioritisation exercise to highlight key areas for concerted research and action. This exercise has identified a broad set of challenges spanning the fields of epidemiology, health systems, diagnostics, therapeutics, and implementation. The most compelling of these issues, picked from among 3400 suggestions proposed by 336 people from 118 countries, can help to frame the future research agenda for global eye health.\ud In this Commission, we harness lessons learned from over two decades, present the growing evidence for the life-transforming impact of eye care, and provide a thorough understanding of rapid developments in the field. This report was created through a broad consultation involving experts within and outside the eye care sector to help inform governments and other stakeholders about the path forward for eye health beyond 2020, to further the SDGs (including universal health coverage), and work towards a world without avoidable vision loss.\ud The next few years are a crucial time for the global eye health community and its partners in health care, government, and other sectors to consider the successes and challenges encountered in the past two decades, and at the same time to chart a way forward for the upcoming decades. Moving forward requires building on the strong foundation laid by WHO and partners in VISION 2020 with renewed impetus to ultimately deliver high quality universal eye health care for all.

Purpose New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates. Methods Using standard systematic review methodology, we identified and tabulated the outcomes of studies reporting reliability and correlation between instrument-based measurements and clinician AC cell grading. Results From 3470 studies, 6 reported correlation between an instrument-based AC cell count to clinician grading. The two instruments were optical coherence tomography (OCT) and laser flare-cell photometry (LFCP). Correlation between clinician grading and LFCP was 0.66–0.87 and 0.06–0.97 between clinician grading and OCT. OCT volume scans demonstrated correlation between 0.75 and 0.78. Line scans in the middle AC demonstrated higher correlation (0.73–0.97) than in the inferior AC (0.06–0.56). Conclusion AC cell count by OCT and LFP can achieve high levels of correlation with clinician grading, whilst offering additional advantages of speed, automation, and objectivity.

This review article considers the rising demand for patient-reported outcome measures (PROMs) in modern ophthalmic research and clinical practice. We review what PROMs are, how they are developed and chosen for use, and how their quality can be critically appraised. We outline the progress made to develop PROMs in each clinical subspecialty. We highlight recent examples of the use of PROMs as secondary outcome measures in randomized controlled clinical trials and consider the impact they have had. With increasing interest in using PROMs as primary outcome measures, particularly where interventions have been found to be of equivalent efficacy by traditional outcome metrics, we highlight the importance of instrument precision in permitting smaller sample sizes to be recruited. Our review finds that while there has been considerable progress in PROM development, particularly in cataract, glaucoma, medical retina, and low vision, there is a paucity of useful tools for less common ophthalmic conditions. Development and validation of item banks, administered using computer adaptive testing, has been proposed as a solution to overcome many of the traditional limitations of PROMs, but further work will be needed to examine their acceptability to patients, clinicians, and investigators.

IntroductionOptic disc swelling (ODS) is a non-specific sign with clinical consequences ranging from benign to irreversible blindness. It is often a challenge to manage: patients present to different specialities and there is no unifying clinical pathway.Objectives/Aims1. to identify all patients presenting to King’s College Hospital with ODS using a translational informatics digital platform (Cogstack); 2. to develop an electronic care pathway with an integrated decision support tool.MethodWe used a digital translational informatics platform called Cogstack, developed in-house by King’s College London, to search 1.4billion EPR data files during a 12-week period. We engaged an MDT team to developed a clinical decision support tool, containing ‘red flag’ symptoms and signs for patients presenting with ODS.ResultsCogstack identified 407 patients with ODS in a 12-week period. Of these, 15% were new cases, 24% were not seen or referred to (neuro)/ophthalmology.The care pathway ensured that patients received timely investigation and initial management facilitated by transformative new technology. This translated into saving time, standardising care and enhanced patient safety.ConclusionThis technology-facilitated care pathway provides a proof of concept for other institutions. Its development supports the topical agenda of NHS improvement, to ‘Get it Right First Time’, and the aim to deliver a value-based healthcare.kitwu@doctors.org.uk

ObjectivesOphthalmic 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).DesignRetrospective cohort study.SettingPrimary care UK database.Participants38 805 subjects with an IAOI were identified (median age 51 (38–65), 57% women) and matched to 153 018 subjects without IAOI.MeasuresThe 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.Results213 (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), pWithin 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).ConclusionsSubjects 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.

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, Graphical abstract Image 1, Highlights • Here we present OcIMIDo, the first ontology of its kind in ophthalmology. • We developed the ontology using domain expertise and clinical guidelines. • Novel synonym extraction method with tf-idf to capture patient voice. • Facilitates analysis of unstructured text relating to ocular inflammatory diseases.

Purpose : This exploratory qualitative research was conducted to understand the quality of life (QoL) impacts of adult uveitis to develop a uveitis QoL item bank, and we present here the results of qualitative analysis of uveitis patient experience. Methods : A qualitative approach with phenomenological study design was employed to explore the common QoL domains in uveitis. Data were collected using focus groups and face-to-face interviews. The sessions were audio-recorded, transcribed verbatim, and analysed thematically. NViVo software was used to perform qualitative analysis. Results : Eight focus groups and 10 interviews were conducted with 41 patients with uveitis. Seven QoL domains were identified, namely symptoms, emotional, activity limitation, health concerns, convenience, social, and economic impact. Although these QoL domains have been previously identified in other eye diseases, the sub-themes within each QoL domain were unique to uveitis. Participants described a variety of symptoms including increased light sensitivity, blurred vision, pain, redness, and tearing. Participants repeatedly described feeling frustrated due to prognostic uncertainty and associated discomfort. Participants were concerned about the frequent relapses of inflammation, as well as side-effects from long-term systemic medications. Uveitis affected their ability to perform daily tasks such as using computers, driving, and reading books. Direct financial impacts included reduced work hours and the costs of treatment and specialist care. Conclusion : Participants with uveitis experience many symptoms in addition to medication-related inconveniences and activity limitations. The QoL issues identified will be used to develop a uveitis-specific QoL item bank. Refereed/Peer-reviewed

Background: Vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first approved on the 8th of December 2020. Though safe and effective, very rare side effects continue to be identified as global vaccination advances. They do not necessarily leave “a signal” in public registries if the incidence remains below previously reported total incidence levels. Optic neuritis (ON) is a rare but recognised adverse event after immunisation. The risk of post-vaccination ON and visual outcome in the context of global vaccination efforts against SARS-CoV-2 are not known. Methods: A global report on 73 deep-phenotyped individuals with post-SARS-CoV-2 vaccination ON observed in 15 of 55 countries with designated experts between 14 February to 18 July 2021. Statistical analyses were performed on type of vaccine, number of jabs, time to onset of ON, demographics, clinical features and treatment. Paraclinical data included immunological testing for autoantibodies against myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4, magnetic resonance imaging (MRI) of the brain and orbits, retinal optical coherence tomography (OCT). The primary outcome was the visual acuity (VA). Findings: The characteristics of the 69 individuals included, differed from pre-COVID whole population-based incidence studies in frequency of bilateral presentation, age distribution and radiological features more commonly found in immune-mediated ON. Most events (67%) occurred after vaccination with AstraZeneca, followed by Pfizer-BioNTech (26%) and Sinovac (7%). In 56 this was after the first and in 13 after the second jab with the same vaccine. Autoantibodies against MOG were present in 15 and not detected for aquaporin-4. The condition was steroid responsive in most (58/62), requiring plasma exchange in a few (5) with spontaneous recovery in the remainder (7). The incidence was highest in the UK (0.036 per 100,000 persons) where vaccination commenced earliest. Importantly, the pattern of presentation in time lagged about 1-5 weeks behind the pattern of national age group vaccination. The median VA at presentation was logMAR 1.0 and recovered to 0.0. Interpretation: Post-SARS-CoV-2 vaccination ON is an extremely rare adverse event with generally good outcome of visual function. The global incidence of post-vaccination ON (0.0017 per 100,000 persons) is lower than for ON (3.74 per 100,000 persons in the UK). A causal relationship is plausible, but the overall risk benefit balance is in favour of SARS-CoV-2 vaccination. Funding Information: None. Declaration of Interests: None. Ethics Approval Statement: Reporting of patients was approved by the Institutional Research Board at Moorfields Eye Hospital (study number CaRS_24).

BackgroundAge-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.AimsTo explore the relationship between metformin use and development of AMD among patients with type 2 diabetes in the UK.MethodsA 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.ResultsA 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.ConclusionWe found no evidence that metformin was associated with risk of AMD in primary care patients requiring treatment for type 2 diabetes.

OBJECTIVE To estimate 22-year trends in the prevalence and incidence of scleritis, and the associations of scleritis with infectious and immune-mediated inflammatory diseases (I-IMIDs) in the UK. METHODS The retrospective cross-sectional and population cohort study (1997-2018) included 10,939,823 patients (2,946 incident scleritis cases) in The Health Improvement Network, a nationally representative primary care records database. The case-control and matched cohort study (1995-2019) included 3,005 incident scleritis cases and 12,020 control patients matched by age, sex, region, and Townsend deprivation index. Data were analyzed using multivariable Poisson regression, multivariable logistic regression, and Cox proportional hazards multivariable models adjusted for age, sex, Townsend deprivation index, race/ethnicity, smoking status, nation within the UK, and body mass index. Incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) were calculated. RESULTS Scleritis incidence rates per 100,000 person-years declined from 4.23 (95% CI 2.16-6.31) to 2.79 (95% CI 2.19-3.39) between 1997 and 2018. The prevalence of scleritis per 100,000 person-years was 93.62 (95% CI 90.17-97.07) in 2018 (61,650 UK patients). Among 2,946 patients with incident scleritis, 1,831 (62.2%) were female, the mean ± SD age was 44.9 ± 17.6 years (range 1-93), and 1,257 (88.8%) were White. Higher risk of incident scleritis was associated with female sex (adjusted IRR 1.53 [95% CI 1.43-1.66], P < 0.001), Black race/ethnicity (adjusted IRR 1.52 [95% CI 1.14-2.01], P = 0.004 compared to White race/ethnicity), or South Asian race/ethnicity (adjusted IRR 1.50 [95% CI 1.19-1.90], P < 0.001 compared to White race/ethnicity), and older age (peak adjusted IRR 4.95 [95% CI 3.99-6.14], P < 0.001 for patients ages 51-60 years versus those ages ≤10 years). Compared to controls, scleritis patients had a 2-fold increased risk of a prior I-IMID diagnosis (17 I-IMIDs, P < 0.001) and significantly increased risk of subsequent diagnosis (13 I-IMIDs). The I-IMIDs most strongly associated with scleritis included granulomatosis with polyangiitis, Behcet's disease, and Sjogren's syndrome. CONCLUSION From 1997 through 2018, the UK incidence of scleritis declined from 4.23 to 2.79/100,000 person-years. Incident scleritis was associated with 19 I-IMIDs, providing data for rational investigation and cross-specialty engagement.

The integrity of ocular anatomy and physiology, the function of the visual system, and the perception of vision, our most prized sense, are intimately connected with our general health. Subtle visual signs and symptoms may therefore be the first manifestation of occult systemic disease. With a basic history and examination of the eyes and vision, the physician can narrow the differential diagnosis and ascertain whether there is any immediate threat to vision or even life. The major focus of this chapter is the eye in the context of a range of vascular, haematological, neoplastic, inflammatory, endocrine, genetic, metabolic, toxic, and nutritional disorders. This chapter also considers the leading causes of blindness globally, and common ocular presentations in primary care and general medical practice. Other isolated ocular conditions are excluded and neuro-ophthalmological conditions are referred to elsewhere in this book (Chapters 24.6.1 and 24.6.2).

Background: The Vision Loss Expert Group and Global Burden of Disease Study have extensively updated estimates of global vision loss burden in 2020, temporal changeover 3 decades and forecasts for 2050. Methods: A systematic review and meta-analysis was conducted of population-based datasets relevant to vision impairment (VI) from January 1980 to October 2018. Hierarchical models were fitted to estimate 2020 prevalence (with 95% uncertainty intervals, UI) of (1) mild VI (presenting visual acuity [PVA] 6/12). Findings: In 2020, an estimated 43.2 million (95% UI: 37.5-48.2 million; 55% female) people were blind, 295.3 (95% UI 267.0-325.5) million had MSVI, 257.3 (95% UI 232.2-284.7) million had mild VI, and 507.4 million (95% UI 369.3–663.8) were VI from uncorrected presbyopia. Globally among adults aged ≥50 years, age-standardised prevalence of blindness reduced by 29% between 1990 and 2020, while MSVI increased slightly (+2.4%). The number of blind people increased by 50.2% and MSVI by 91.6%. By 2050, we predict 895.5 million people blind/VI. Interpretation: It is encouraging that age-adjusted prevalence of blindness has reduced over the past 3 decades, yet due to population growth progress is not keeping pace with needs. We face enormous challenges in avoiding vision impairment as the global population grows and ages. Funding Statement: Brien Holden Vision Institute. Fondation Thea. Fred Hollows Foundation. Gates Foundation. Sightsavers International. University of Heidelberg. Declaration of Interests: A.M. Bron, Allergan (C) Baush and Lomb (C), Santen (C), Thea (C) - (C) stands for consultant. J Kempen: Consultant (DSMC Chair) for Gilead. Grants and contracts from National Institutes of Health/National Eye Institute; Sight for Souls; and Christoffel Blindenmission. No other authors had conflicts to declare.

BACKGROUND: Non‐infectious uveitis describes a heterogenous group of ocular disorders characterised by intraocular inflammation in the absence of infection. Uveitis is a leading cause of visual loss, most commonly due to uveitic macular oedema (UMO). Treatment is aimed at reducing disease activity by suppression of the intraocular inflammatory response. In the case of macular oedema, the aim is to restore macular architecture as quickly as possible, in order to prevent irreversible photoreceptor damage in this area. Acute exacerbations are typically managed with corticosteroids, which may be administered topically, locally or systemically. Whilst these are often rapidly effective in achieving disease control, long‐term use is associated with significant local and systemic side effects, and 'steroid sparing agents' are typically used to achieve prolonged control in severe or recalcitrant disease. Anti‐tumour necrosis factor (TNF) drugs block a critical cytokine in the inflammatory signalling process, and have emerged as effective steroid‐sparing immunomodulatory agents in a wide range of non‐ocular conditions. There is mechanistic data to suggest that they may provide a more targeted approach to disease control in UMO than other agents, but to date, these agents have predominantly been used 'off label' as the majority are not licensed for ocular use. This review aims to summarise the available literature reporting the use of anti‐TNF therapy in UMO, thus developing the evidence‐base on which to make future treatment decisions and develop clinical guidelines in this area. OBJECTIVES: To assess the efficacy of anti‐TNF therapy in treatment of UMO. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), which contains the Cochrane Eyes and Vision Trials Register; Ovid MEDLINE; Ovid Embase; LILACS; Web of Science Conference Proceedings Citation Index‐ Science (CPCI‐S); System for Information on Grey Literature in Europe (OpenGrey); the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 29 March 2018. SELECTION CRITERIA: We planned to include all relevant randomised controlled trials assessing the use of anti‐TNF agents in treatment of UMO. No limits were applied to participant age, gender or ethnicity. The primary comparisons of this review were: anti‐TNF versus no treatment or placebo; anti‐TNF versus another pharmacological agent; comparison of different anti‐TNF drugs; comparison of different doses and routes of administration of the same anti‐TNF drug. The primary outcome measure that we assessed for this review was best‐corrected visual acuity (BCVA) in the treated eye. Secondary outcome measures were anatomical macular change, clinical estimation of vitreous haze and health‐related quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts retrieved through the database searches. We retrieved full‐text reports of studies categorised as 'unsure' or 'include' after we had reviewed the abstracts. Two review authors independently reviewed each full‐text report for eligibility. We resolved discrepancies through discussion. MAIN RESULTS: We identified no completed or ongoing trial that was eligible for this Cochrane Review. AUTHORS' CONCLUSIONS: Our review did not identify any evidence from randomised controlled trials for or against the role of anti‐TNF agents in the management of UMO. Although there are a number of high‐quality randomised controlled trials that demonstrate the efficacy of anti‐TNF agents in preventing recurrence of inflammation in uveitis, the reported study outcomes do not include changes in UMO. As a result, there were insufficient data to conclude whether there was a significant treatment effect specifically for UMO. Future trials should be designed to include quantitative measures of UMO as primary study outcomes, for example by reporting the presence or absence of UMO, or by measuring central macular thickness for study participants. Furthermore, whilst UMO is an important complication of uveitis, we acknowledge that uveitis is associated with many significant structural and functional complications. It is not possible to determine treatment efficacy based on a single outcome measure. We recommend that future reviews of therapeutic interventions in uveitis should use composite measures of treatment response comprising a range of potential complications of disease.

Purpose: This paper describes the rationale, study design and procedures of the National Eye Survey of Trinidad and Tobago (NESTT). The main objective of this survey is to obtain prevalence estimates of vision impairment and blindness for planning and policy development.\ud \ud Methods: A population-based, cross-sectional survey was undertaken using random multistage cluster sampling, with probability-proportionate-to-size methods. Eligible participants aged 5 years and older were sampled from the non-institutional population in each of 120 cluster segments. Presenting distance and near visual acuity were screened in their communities. People aged 40 years and older, and selected younger people, were invited for comprehensive clinic assessment. The interview included information on potential risk factors for vision loss, associated costs and quality of life. The examination included measurement of anthropometrics, blood glucose, refraction, ocular biometry, corneal hysteresis, and detailed assessment of the anterior and posterior segments, with photography and optical coherence tomography imaging. Adult participants were invited to donate saliva samples for DNA extraction and storage.\ud \ud Results: The fieldwork was conducted over 13 months in 2013–2014. A representative sample of 10,651 individuals in 3410 households within 120 cluster segments identified 9913 people who were eligible for recruitment.\ud \ud Conclusion: The study methodology was robust and adequate to provide the first population-based estimates of the prevalence and causes of visual impairment and blindness in Trinidad and Tobago. Information was also gathered on risk factors, costs and quality of life associated with vision loss, and on normal ocular parameters for the population aged 40 years and older.

Purpose:\ud \ud To determine whether distance vision impairment (VI) (Logarithm of the Minimum Angle of Resolution (LogMAR) >0.30), or near VI (NVI) (LogMAR 0.32 to 1.30 at 40cm with 40 years.\ud \ud Methods:\ud \ud Responders rated general health level in the five dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) of the EQ-5D 5-level instrument. Multivariable regression analysis with robust standard error estimation explored the relationship between utility score and presenting vision.\ud \ud Main Outcome Measures:\ud \ud Utility value and Quality Adjusted Life Year (QALY) loss by vision category.\ud \ud Results:\ud \ud 62.4% (2658/4263) adults completed the EQ-5D-5L. Mean age was 58.4 (SD 11.8, range 40 to 103) years and 56.3% were female. Blindness had the largest independent effect on utility coefficient, at -0.140 (95% CI -0.092 to -0.192), with mean utility value 0.727 (95% CI 0.671-0.784) and mean EQ-VAS score 69.9 (95% CI 62.0-77.8). Near VI was also independently associated with utility loss of -0.012 (95% CI -0.004 to -0.021). Independent predictors of utility

AimTo estimate the prevalence, causes and risk factors for presenting distance and near vision impairment (VI) in Trinidad and Tobago.MethodsThis is a national, population-based survey using multistage, cluster random sampling in 120 clusters with probability-proportionate-to-size methods. Stage 1 included standardised, community-based measurement of visual acuity. Stage 2 invited all 4263 people aged ≥40 years for comprehensive clinic-based assessment. The Moorfields Eye Hospital Reading Centre graded fundus photographs and optical coherence tomography images independently.ResultsThe response rates were 84.2% (n=3589) (stage 1) and 65.4% (n=2790) (stage 2), including 97.1% with VI. The mean age was 57.2 (SD 11.9) years, 54.5% were female, 42.6% were of African descent and 39.0% were of South Asian descent. 11.88% (95% CI 10.88 to 12.97, n=468) had distance VI (logarithm of the minimum angle of resolution [logMAR] >0.30), including blindness (logMAR >1.30) in 0.73% (95% CI 0.48 to 0.97, n=31), after adjustment for study design, non-response, age, sex and municipality. The leading causes of blindness included glaucoma (31.7%, 95% CI 18.7 to 44.8), cataract (28.8%, 95% CI 12.6 to 45.1) and diabetic retinopathy (19.1%, 95% CI 4.2 to 34.0). The leading cause of distance VI was uncorrected refractive error (47.4%, 95% CI 43.4 to 51.3). Potentially avoidable VI accounted for 86.1% (95% CI 82.88 to 88.81), an estimated 176 323 cases in the national population aged ≥40 years. 22.3% (95% CI 20.7 to 23.8, n=695) had uncorrected near VI (logMAR >0.30 at 40 cm with distance acuity ConclusionsTrinidad and Tobago’s burden of avoidable VI exceeds that of other high-income countries. Population and health system priorities are identified to help close the gap.

Importance Epidemiologic data on optic neuritis (ON) incidence and associations with immune-mediated inflammatory diseases (IMIDs) are sparse. Objective To estimate 22-year trends in ON prevalence and incidence and association with IMIDs in the United Kingdom. Design, setting, and participants This cohort study analyzed data from The Health Improvement Network from January 1, 1995, to September 1, 2019. The study included 10 937 511 patients 1 year or older with 75.2 million person-years' follow-up. Annual ON incidence rates were estimated yearly (January 1, 1997, to December 31, 2018), and annual ON prevalence was estimated by performing sequential cross-sectional studies on data collected on January 1 each year for the same period. Data for 1995, 1996, and 2019 were excluded as incomplete. Risk factors for ON were explored in a cohort analysis from January 1, 1997, to December 31, 2018. Matched case-control and retrospective cohort studies were performed using data from January 1, 1995, to September 1, 2019, to explore the odds of antecedent diagnosis and hazard of incident diagnosis of 66 IMIDs in patients compared with controls. Exposures Optic neuritis. Main outcomes and measures Annual point prevalence and incidence rates of ON, adjusted incident rate ratios (IRRs) for risk factors, and adjusted odds ratios (ORs) and adjusted hazard ratios (HRs) for 66 IMIDs. Results A total of 10 937 511 patients (median [IQR] age at cohort entry, 32.6 [18.0-50.4] years; 5 571 282 [50.9%] female) were studied. A total of 1962 of 2826 patients (69.4%) with incident ON were female and 1192 of 1290 92.4%) were White, with a mean (SD) age of 35.6 (15.6) years. Overall incidence across 22 years was stable at 3.7 (95% CI, 3.6-3.9) per 100 000 person-years. Annual point prevalence (per 100 000 population) increased with database maturity, from 69.3 (95% CI, 57.2-81.3) in 1997 to 114.8 (95% CI, 111.0-118.6) in 2018. The highest risk of incident ON was associated with female sex, obesity, reproductive age, smoking, and residence at higher latitude, with significantly lower risk in South Asian or mixed race/ethnicity compared with White people. Patients with ON had significantly higher odds of prior multiple sclerosis (MS) (OR, 98.22; 95% CI, 65.40-147.52), syphilis (OR, 5.76; 95% CI, 1.39-23.96), Mycoplasma (OR, 3.90; 95% CI, 1.09-13.93), vasculitis (OR, 3.70; 95% CI, 1.68-8.15), sarcoidosis (OR, 2.50; 95% CI, 1.21-5.18), Epstein-Barr virus (OR, 2.29; 95% CI, 1.80-2.92), Crohn disease (OR, 1.97; 95% CI, 1.13-3.43), and psoriasis (OR, 1.28; 95% CI, 1.03-1.58). Patients with ON had a significantly higher hazard of incident MS (HR, 284.97; 95% CI, 167.85-483.81), Behcet disease (HR, 17.39; 95% CI, 1.55-195.53), sarcoidosis (HR, 14.80; 95% CI, 4.86-45.08), vasculitis (HR, 4.89; 95% CI, 1.82-13.10), Sjogren syndrome (HR, 3.48; 95% CI, 1.38-8.76), and herpetic infection (HR, 1.68; 95% CI, 1.24-2.28). Conclusions and relevance The UK incidence of ON is stable. Even though predominantly associated with MS, ON has numerous other associations with IMIDs. Although individually rare, together these associations outnumber MS-associated ON and typically require urgent management to preserve sight.

PubMed: 28779882, Background Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global estimates, trends, and projections of global blindness and vision impairment. Methods We did a systematic review and meta-analysis of population-based datasets relevant to global vision impairment and blindness that were published between 1980 and 2015. We fitted hierarchical models to estimate the prevalence (by age, country, and sex), in 2015, of mild visual impairment (presenting visual acuity worse than 6/12 to 6/18 inclusive), moderate to severe visual impairment (presenting visual acuity worse than 6/18 to 3/60 inclusive), blindness (presenting visual acuity worse than 3/60), and functional presbyopia (defined as presenting near vision worse than N6 or N8 at 40 cm when best-corrected distance visual acuity was better than 6/12). Findings Globally, of the 7·33 billion people alive in 2015, an estimated 36·0 million (80% uncertainty interval [UI] 12·9–65·4) were blind (crude prevalence 0·48%; 80% UI 0·17–0·87; 56% female), 216·6 million (80% UI 98·5–359·1) people had moderate to severe visual impairment (2·95%, 80% UI 1·34–4·89; 55% female), and 188·5 million (80% UI 64·5–350·2) had mild visual impairment (2·57%, 80% UI 0·88–4·77; 54% female). Functional presbyopia affected an estimated 1094·7 million (80% UI 581·1–1686·5) people aged 35 years and older, with 666·7 million (80% UI 364·9–997·6) being aged 50 years or older. The estimated number of blind people increased by 17·6%, from 30·6 million (80% UI 9·9–57·3) in 1990 to 36·0 million (80% UI 12·9–65·4) in 2015. This change was attributable to three factors, namely an increase because of population growth (38·4%), population ageing after accounting for population growth (34·6%), and reduction in age-specific prevalence (?36·7%). The number of people with moderate and severe visual impairment also increased, from 159·9 million (80% UI 68·3–270·0) in 1990 to 216·6 million (80% UI 98·5–359·1) in 2015. Interpretation There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world's population is causing a substantial increase in number of people affected. These observations, plus a very large contribution from uncorrected presbyopia, highlight the need to scale up vision impairment alleviation efforts at all levels. Funding Brien Holden Vision Institute. © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Background:\ud \ud The conduct of international collaborative genomics research raises distinct ethical challenges that require special consideration, especially if conducted in settings that are research-naïve or resource-limited. Although there is considerable literature on these issues, there is a dearth of literature chronicling approaches taken to address these issues in the field. Additionally no previous ethical guidelines have been developed to support similar research in Trinidad and Tobago.\ud \ud Methods:\ud \ud A literature review was undertaken to identify strategies used to address common ethical issues relevant to human genetics and genomics research in research-naïve or resource-limited settings. Strategies identified were combined with novel approaches to develop a culturally appropriate, multifaceted strategy to address potential challenges in the Genetics Substudy of the National Eye Survey of Trinidad and Tobago (GSNESTT).\ud \ud Results:\ud \ud Regarding the protection of study participants, we report a decision to exclude children as participants; the use of a Community Engagement and Sensitization Strategy to increase the genetic literacy of the target population; the involvement of local expertise to ensure cultural sensitivity and to address potential comprehension barriers in informed consent; and an audit of the informed consent process to ensure valid consent. Concerning the regulation of the research, we report on ethics approvals from relevant authorities; a Materials Transfer Agreement to guide sample ownership and export; and a Sample Governance Committee to oversee data use and data access. Finally regarding the protection of the interests of scientists from the host country, we report on capacity building efforts to ensure that local scientists have access to data collected through the project and appropriate recognition of their contributions in future publications.\ud \ud Conclusion:\ud \ud This paper outlines an ethical framework for the conduct of population-based genetics and genomics research in Trinidad and Tobago; highlights common issues arising in the field and strategies to address these.

IntroductionVision impairment (VI) places a burden on individuals, health systems and society in general. In order to support the case for investing in eye health services, an updated cost of illness study that measures the global impact of VI is necessary. To perform such a study, a systematic review of the literature is needed. Here we outline the protocol for a systematic review to describe and summarise the costs associated with VI and its major causes.Methods and analysisWe will systematically search in Medline (Ovid) and the Centre for Reviews and Dissemination database which includes the National Health Service Economics Evaluation Database. No language or geographical restriction will be applied. Additional literature will be identified by reviewing the references in the included studies and by contacting field experts. Grey literature will be considered. The review will include any study published from 1 January 2000 to November 2019 that provides information about costs of illness, burden of disease and/or loss of well-being in participants with VI due to an unspecified cause or due to one of the seven leading causes globally.Two reviewers will independently screen studies and extract relevant data from included studies. Methodological quality of economic studies will be assessed based on the British Medical Journal checklist for economic submissions adapted to costs of illness studies. This protocol has been prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocols and has been published prospectively in Open Science Framework.Ethics and disseminationFormal ethical approval is not required, as primary data will not be collected in this review. The findings of this study will be disseminated through peer-reviewed publications, stakeholder meetings and inclusion in the ongoing Lancet Global Health Commission on Global Eye Health.Registration detailshttps://osf.io/9au3w (DOI 10.17605/OSF.IO/6F8VM).

WOS: 000473042100004, PubMed: 30209083, Objective To estimate the prevalence and causes of blindness and vision impairment for distance and near in Latin America and the Caribbean (LAC) in 2015 and to forecast trends to 2020. Methods A meta-analysis from a global systematic review of 283 cross-sectional, population-representative studies from published and unpublished sources from 1980 to 2014 in the Global Vision Database included 17 published and 6 unpublished studies from LAC. Results In 2015, across LAC, age-standardised prevalence was 0.38% in all ages and 1.56% in those over age 50 for blindness; 2.06% in all ages and 7.86% in those over age 50 for moderate and severe vision impairment (MSVI); 1.89% in all ages and 6.93% in those over age 50 for mild vision impairment and 39.59% in all ages and 45.27% in those over 50 for near vision impairment (NVI). In 2015, 117.86 million persons were vision impaired; of those 2.34 million blind, 12.46 million with MSVI, 11.34 million mildly impaired and 91.72 million had NVI. Cataract is the most common cause of blindness. Undercorrected refractive-error is the most common cause of vision impairment. Conclusions These prevalence estimates indicate that one in five persons across LAC had some degree of vision loss in 2015. We predict that from 2015 to 2020, the absolute numbers of persons with vision loss will increase by 12% to 132.33 million, while the all-age age-standardised prevalence will decrease for blindness by 15% and for other distance vision impairment by 8%. All countries need epidemiologic research to establish accurate national estimates and trends. Universal eye health services must be included in universal health coverage reforms to address disparities, fragmentation and segmentation of healthcare, Brien Holden Vision Institute, This study was partially funded by the Brien Holden Vision Institute.

Avoidable blindness is an important global public health concern. This study aimed to assess Trinidad and Tobago's progress towards achieving the Pan American Health Organization, 'Strategic Framework for Vision 2020: The Right to Sight-Caribbean Region,' indicators through comprehensive review of the eyecare system, in order to facilitate health system priority setting. We administered structured surveys to six stakeholder groups, including eyecare providers, patients and older adult participants in the National Eye Survey of Trinidad and Tobago. We reviewed reports, registers and policy documents, and used a health system dynamics framework to synthesize data. In 2014, the population of 1.3 million were served by a pluralistic eyecare system, which had achieved 14 out of 27 Strategic Framework indicators. The Government provided free primary, secondary and emergency eyecare services, through 108 health centres and 5 hospitals (0.26 ophthalmologists and 1.32 ophthalmologists-in-training per 50 000 population). Private sector optometrists (4.37 per 50 000 population), and ophthalmologists (0.93 per 50 000 population) provided 80% of all eyecare. Only 19.3% of the adult population had private health insurance, revealing significant out-of-pocket expenditure. We identified potential weaknesses in the eyecare system where investment might reduce avoidable blindness. These included a need for more ophthalmic equipment and maintenance in the public sector, national screening programmes for diabetic retinopathy, retinopathy of prematurity and neonatal eye defects, and pathways to ensure timely and equitable access to subspecialized surgery. Eyecare for older adults was responsible for an estimated 9.5% (US$22.6 million) of annual health expenditure. This study used the health system dynamics framework and new data to identify priorities for eyecare system strengthening. We recommend this approach for exploring potential health system barriers to addressing avoidable blindness, and other important public health problems.

The association between socioeconomic position and morbidity and mortality has long been recognized. We evaluate the evidence for an association between multiple aspects of deprivation and ocular health in a global context. This is a systematic review of studies that evaluated deprivation in the adult population in the context of the major acquired causes of visual loss such as cataract, diabetic eye disease, glaucoma, age-related macular degeneration, and ocular trauma. The search strategy identified relevant studies reported between 1946 and August 2016, with randomized control trials, case-control, cohort, and cross-sectional study designs being selected for inclusion. The studies identified in this review from across the world demonstrate the extent to which the common themes such as low educational attainment and low income may be associated with increased incidence of various sight-threatening conditions and may adversely affect access to specialist assessment and delivery of treatment. Health inequality may always persist, but an increased recognition of the importance of the various impacts of deprivation may empower policy makers to target limited resources to the most vulnerable groups in order to deliver the greatest benefit.

The term autoimmune retinopathy encompasses a spectrum of rare autoimmune diseases that affect retinal function, often but not exclusively at the level of the photoreceptor. They typically present with painless visual loss, which may be accompanied by normal fundus examination. Some are progressive, often rapidly. They present a diagnostic challenge because there are no standardised clinical or laboratory based diagnostic criteria. Included within the spectrum are cancer-associated retinopathy, melanoma-associated retinopathy and presumed non-paraneoplastic autoimmune retinopathy. Differentiation from other retinopathies can be challenging, with overlap in symptoms, signs, and investigation findings, and an absence of pathognomonic features. However, technological developments in ophthalmic imaging and serological investigation over the past decade are adding novel dimensions to the investigation and classification of patients with these rare diseases. This review addresses the clinical, imaging, and serological features of the autoimmune retinopathies, and discusses the relative strengths and limitations of candidate diagnostic features.

Summary Background The UK has had universal free health care and public health programmes for more than six decades. Several policy initiatives and structural reforms of the health system have been undertaken. Health expenditure has increased substantially since 1990, albeit from relatively low levels compared with other countries. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to examine the patterns of health loss in the UK, the leading preventable risks that explain some of these patterns, and how UK outcomes compare with a set of comparable countries in the European Union and elsewhere in 1990 and 2010. Methods We used results of GBD 2010 for 1990 and 2010 for the UK and 18 other comparator nations (the original 15 members of the European Union, Australia, Canada, Norway, and the USA; henceforth EU15+). We present analyses of trends and relative performance for mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE). We present results for 259 diseases and injuries and for 67 risk factors or clusters of risk factors relevant to the UK. We assessed the UK's rank for age-standardised YLLs and DALYs for their leading causes compared with EU15+ in 1990 and 2010. We estimated 95% uncertainty intervals (UIs) for all measures. Findings For both mortality and disability, overall health has improved substantially in absolute terms in the UK from 1990 to 2010. Life expectancy in the UK increased by 4·2 years (95% UI 4·2–4·3) from 1990 to 2010. However, the UK performed significantly worse than the EU15+ for age-standardised death rates, age-standardised YLL rates, and life expectancy in 1990, and its relative position had worsened by 2010. Although in most age groups, there have been reductions in age-specific mortality, for men aged 30–34 years, mortality rates have hardly changed (reduction of 3·7%, 95% UI 2·7–4·9). In terms of premature mortality, worsening ranks are most notable for men and women aged 20–54 years. For all age groups, the contributions of Alzheimer's disease (increase of 137%, 16–277), cirrhosis (65%, −15 to 107), and drug use disorders (577%, 71–942) to premature mortality rose from 1990 to 2010. In 2010, compared with EU15+, the UK had significantly lower rates of age-standardised YLLs for road injury, diabetes, liver cancer, and chronic kidney disease, but significantly greater rates for ischaemic heart disease, chronic obstructive pulmonary disease, lower respiratory infections, breast cancer, other cardiovascular and circulatory disorders, oesophageal cancer, preterm birth complications, congenital anomalies, and aortic aneurysm. Because YLDs per person by age and sex have not changed substantially from 1990 to 2010 but age-specific mortality has been falling, the importance of chronic disability is rising. The major causes of YLDs in 2010 were mental and behavioural disorders (including substance abuse; 21·5% [95 UI 17·2–26·3] of YLDs), and musculoskeletal disorders (30·5% [25·5–35·7]). The leading risk factor in the UK was tobacco (11·8% [10·5–13·3] of DALYs), followed by increased blood pressure (9·0 % [7·5–10·5]), and high body-mass index (8·6% [7·4–9·8]). Diet and physical inactivity accounted for 14·3% (95% UI 12·8–15·9) of UK DALYs in 2010. Interpretation The performance of the UK in terms of premature mortality is persistently and significantly below the mean of EU15+ and requires additional concerted action. Further progress in premature mortality from several major causes, such as cardiovascular diseases and cancers, will probably require improved public health, prevention, early intervention, and treatment activities. The growing burden of disability, particularly from mental disorders, substance use, musculoskeletal disorders, and falls deserves an integrated and strategic response. Funding Bill & Melinda Gates Foundation.

Central retinal vein occlusion (CRVO) is a relatively common retinal vascular disorder in which macular oedema may develop, with a consequent reduction in visual acuity. Until recently there has been no treatment of proven benefit, but growing evidence supports the use of anti-vascular endothelial growth factor (anti-VEGF) agents.To investigate the effectiveness and safety of anti-VEGF therapies for the treatment of macular oedema secondary to CRVO.We searched CENTRAL (which contains the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 10), Ovid MEDLINE (January 1950 to October 2013), EMBASE (January 1980 to October 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2013), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to October 2013), OpenGrey, OpenSIGLE (January 1950 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and Web of Science Conference Proceedings Citation Index-Science (CPCI-S). There were no language or date restrictions in the electronic search for trials. The electronic databases and clinical trials registers were last searched on 29th October 2013.We considered randomised controlled trials (RCTs) that compared intravitreal anti-VEGF agents of any dose or duration to sham injection or no treatment. We focused on studies that included individuals of any age or gender and a minimum of six months follow-up.Two review authors independently assessed trial quality and extracted data. The primary outcome was the proportion of participants with a gain in best-corrected visual acuity (BCVA) from baseline of greater than or equal to 15 letters (3 lines) on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Secondary outcomes included the proportion of participants with a loss of 15 letters or more of BCVA, the mean change from baseline BCVA, the mean change in central retinal thickness (CRT), the number and type of complications or adverse outcomes, and the number of additional interventions administered. Where available, we also presented quality of life and economic data.We found six RCTs that met the inclusion criteria after independent and duplicate review of the search results. These RCTs included 937 participants and compared outcomes at six months to sham injection for four anti-VEGF agents: aflibercept (VEGF Trap-Eye, Eylea), bevacizumab (Avastin), pegaptanib sodium (Macugen) and ranibizumab (Lucentis). Three trials were conducted in Norway, Sweden and the USA, and three trials were multicentre, one including centres in the USA, Canada, India, Israel, Argentina and Columbia, a second including centres in the USA, Australia, France, Germany, Israel, and Spain, and a third including centres in Austria, France, Germany, Hungary, Italy, Latvia, Australia, Japan, Singapore and South Korea. We performed meta-analysis on three key visual outcomes, using data from up to six trials. High-quality evidence from six trials revealed that participants receiving intravitreal anti-VEGF treatment were 2.71 times more likely to gain at least 15 letters of visual acuity at six months compared to participants treated with sham injections (risk ratio (RR) 2.71; 95% confidence intervals (CI) 2.10 to 3.49). High-quality evidence from five trials suggested anti-VEGF treatment was associated with an 80% lower risk of losing at least 15 letters of visual acuity at six months compared to sham injection (RR 0.20; 95% CI 0.12 to 0.34). Moderate-quality evidence from three trials (481 participants) revealed that the mean reduction from baseline to six months in central retinal thickness was 267.4 µm (95% CI 211.4 µm to 323.4 µm) greater in participants treated with anti-VEGF than in participants treated with sham. The meta-analyses demonstrate that treatment with anti-VEGF is associated with a clinically meaningful gain in vision at six months. One trial demonstrated sustained benefit at 12 months compared to sham. No significant ocular or systemic safety concerns were identified in this time period.Compared to no treatment, repeated intravitreal injection of anti-VEGF agents in eyes with CRVO macular oedema improved visual outcomes at six months. All agents were relatively well tolerated with a low incidence of adverse effects in the short term. Future trials should address the relative efficacy and safety of the anti-VEGF agents and other treatments, including intravitreal corticosteroids, for longer-term outcomes.