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Patient portals allowing access to electronic health care records and services can inform and empower but may widen existing sociodemographic inequities. We aimed to describe associations between activation of a paediatric patient portal and patient race/ethnicity, socioeconomic status and markers of previous engagement with health care. A retrospective single site cross-sectional study was undertaken to examine patient portal adoption amongst families of children receiving care for chronic or complex disorders within the United Kingdom. Descriptive and multivariable regression analysis was undertaken to describe associations between predictors (Race/Ethnicity, age, socio-economic deprivation status based on family residence, and previous non-attendance to outpatient consultations) and outcome. A sample of 3687 children, representative of the diverse 'real world' patient population, was identified. Of these 37% (1364) were from a White British background, 71% (2631) had English as the primary family spoken language (PSL), 14% (532) lived in areas of high deprivation, and 17% (643) had high (>33%) rates of non-attendance. The families of 73% (2682) had activated the portal. In adjusted analyses, English as a PSL (adjusted odds ratio [aOR] 1.58, 95% confidence interval 1.29-1.95) and multi-morbidity (aOR 1.26, 1.22-1.30) was positively associated with portal activation, whilst families from British Black African backgrounds (aOR 0.68, 0.50-0.93), and those with high rates of non-attendance (aOR 0.48, 0.40-0.58) were less likely to use the portal. Family race/ethnicity and previous low engagement with health care services are potentially key drivers of widening inequity in access to health care following the implementation of patient portals, a digital health innovation intended to inform and empower. Health care providers should be aware that innovative human-driven engagement approaches, targeted towards previously underserved communities, are needed to ensure equitable access to high quality patient-centred care., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Solebo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: We investigated the impact of operator parameters on the diagnostic performance of danterior segment optical coherence tomography (AS-OCT) in anterior uveitis., Design: Prospective comparative diagnostic analysis., Methods: Setting: Single site., Study Population: Children aged under 18 years with anterior uveitis, recruited consecutively., Observation Procedures: Index testing: Optovue RTVue80 AS-OCT using 'low-volume' (LV, horizontal and vertical cross-sections) and 'high-volume' (HV, 68 horizontal cross-sections) protocols. Reference testing: slit lamp examination with anterior chamber inflammation graded using standardisation of uveitis nomenclature (SUN)., Main Outcome Measure: Index test performance metrics (sensitivity, specificity, likelihood ratios), utility for 'ruling-in' and 'ruling-out' disease (positive / negative predictive values, PPV/NPV), receiver operating characteristic (ROC) curves to explore the impact of different imaging derived metrics, multivariable multilevel regression analyses to quantify correlation of index to reference testing, and repeatability indices across protocols., Results: 40 children (77 eyes: 51 eyes at SUN grade 0, 10 at SUN0.5+, 8 at SUN1+, 8 SUN≥2+ or higher) were included. There was high repeatability across protocols (0.98, p<0.001, 95% CI 0.75-1.0). OCT resulted in strong predictive values for 'ruling-out' (LV-scan NPV 82.9%, 95% CI 71.5 - 90.4%; HV-scan NPV 100%, 95% CI 3% to 100%), and but less predictive value for 'ruling-in' SUN≥0.5+ (LV-scan PPV 52.8% 95% CI 41.5 - 63.7%; HV-scan PPV 34.2%, 95% CI 33.3 to 35.1%). Detection of more than 1 cell within a cross sectional scan was strongly suggestive of clinical activity, with area under the curve of 0.76 (95% CI 0.62 - 0.89) for SUN≥0.5+, and 0.85 (95% CI 0.73- 0.98), for the detection of SUN≥1+. Cell count correlated with SUN grades at higher levels of inflammation (SUN≥2+ both protocols, SUN≥1+ HV-scans). There was an independent positive association between age and AS-OCT cell (adjusted correlation coefficient 0.2 cells for each additional year of age)., Conclusions: Operator dependent factors impact the diagnostic and quantification performance of AS-OCT for anterior chamber inflammation. However, the strong, 'dose-respondent' correlation of low-volume protocols with SUN grading promises clinical utility without the storage and analysis burden of high-volume approaches. Further work will involve exploration of the need for age-specific image metric interpretation., (Copyright © 2024. Published by Elsevier Inc.)

Background/aims: Evaluation of telemedicine care models has highlighted its potential for exacerbating healthcare inequalities. This study seeks to identify and characterise factors associated with non-attendance across face-to-face and telemedicine outpatient appointments., Methods: A retrospective cohort study at a tertiary-level ophthalmic institution in the UK, between 1 January 2019 and 31 October 2021. Logistic regression modelled non-attendance against sociodemographic, clinical and operational exposure variables for all new patient registrations across five delivery modes: asynchronous, synchronous telephone, synchronous audiovisual and face to face prior to the pandemic and face to face during the pandemic., Results: A total of 85 924 patients (median age 55 years, 54.4% female) were newly registered. Non-attendance differed significantly by delivery mode: (9.0% face to face prepandemic, 10.5% face to face during the pandemic, 11.7% asynchronous and 7.8%, synchronous during pandemic). Male sex, greater levels of deprivation, a previously cancelled appointment and not self-reporting ethnicity were strongly associated with non-attendance across all delivery modes. Individuals identifying as black ethnicity had worse attendance in synchronous audiovisual clinics (adjusted OR 4.24, 95% CI 1.59 to 11.28) but not asynchronous. Those not self-reporting their ethnicity were from more deprived backgrounds, had worse broadband access and had significantly higher non-attendance across all modes (all p<0.001)., Conclusion: Persistent non-attendance among underserved populations attending telemedicine appointments highlights the challenge digital transformation faces for reducing healthcare inequalities. Implementation of new programmes should be accompanied by investigation into the differential health outcomes of vulnerable populations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Evidence on the socioeconomic burden associated with childhood visual impairment, severe visual impairment and blindness (VI/SVI/BL) is needed to inform economic evaluations of existing and emerging interventions aimed at protecting or improving vision. This study aimed to evaluate the quantity and quality of literature on resource use and/or costs associated with childhood VI/SVI/BL disorders., Methods: PubMed, Web of Science (Ovid), the National Health Service (NHS) Economic Evaluation Database and grey literature were searched in November 2020. The PubMed search was rerun in February 2022. Original articles reporting unique estimates of resource use or cost data on conditions resulting in bilateral VI/SVI/BL were eligible for data extraction. Quality assessment (QA) was undertaken using the Drummond checklist adapted for cost-of-illness (COI) studies., Results: We identified 31 eligible articles, 27 from the peer-reviewed literature and four from the grey literature. Two reported on resource use, and 29 reported on costs. Cerebral visual impairment and optic nerve disorders were not examined in any included studies, whereas retinopathy of prematurity was the most frequently examined condition. The quality of studies varied, with economic evaluations having higher mean QA scores (82%) compared to COI studies (77%). Deficiencies in reporting were seen, particularly in the clinical definitions of conditions in economic evaluations and a lack of discounting and sensitivity analyses in COI studies., Conclusions: There is sparse literature on resource use or costs associated with childhood visual impairment disorders. The first step in addressing this important evidence gap is to ensure core visual impairment outcomes are measured in future randomised control trials of interventions as well as cohort studies and are reported as a discrete health outcome., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The utility of medical imaging is dependant on image quality. We aimed to develop and validate quality criteria for ocular anterior segment optical coherence tomography (AS-OCT) images., Methods: We undertook a cross-sectional study using AS-OCT images from patients aged 6-16. A novel three-level grading system (good, limited or poor) was developed based on the presence of image artefact (categorised as lid, eyelash, cropping, glare, or movement artefact). Three independent experts graded 2825 images, with agreement assessed using confusion matrices and intraclass correlation coefficients (ICC) for each parameter., Results: There was very good inter-grader IQA agreement assessing image quality with ICC 0.85 (95 %CI: 0.84-0.87). The most commonly occurring artefact was eyelash artefact (1008/2825 images, 36 %). Graders labelled 621/2825 (22 %) images as good and 384 (14 %) as poor. There was complete agreement at either end of the confusion matrix with no 'good' images labelled as 'poor' by other graders, and vice versa. Similarly, there was very good agreement when assessing presence of lash (0.96,0.94-0.98), movement (0.97,0.96-0.99), glare (0.82,0.80-0.84) and cropping (0.90,0.88-0.92)., Conclusions: The novel image quality assessment criteria (IQAC) described here have good interobserver agreement overall, and excellent agreement on the differentiation between 'good' and 'poor' quality images. The large proportion of images graded as 'limited' suggests the need for refine this classification, using the specific IQAC features, for which we also report high interobserver agreement. These findings support the future potential for wider clinical and community care implementation of AS-OCT for the diagnosis and monitoring of ocular disease., Competing Interests: Declaration of Competing Interest No conflicting relationship exists for any author., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Periodontitis, a ubiquitous severe gum disease affecting the teeth and surrounding alveolar bone, can heighten systemic inflammation. We investigated the association between very severe periodontitis and early biomarkers of age-related macular degeneration (AMD), in individuals with no eye disease., Design: Cross-sectional analysis of the prospective community-based cohort United Kingdom (UK) Biobank., Participants: Sixty-seven thousand three hundred eleven UK residents aged 40 to 70 years recruited between 2006 and 2010 underwent retinal imaging., Methods: Macular-centered OCT images acquired at the baseline visit were segmented for retinal sublayer thicknesses. Very severe periodontitis was ascertained through a touchscreen questionnaire. Linear mixed effects regression modeled the association between very severe periodontitis and retinal sublayer thicknesses, adjusting for age, sex, ethnicity, socioeconomic status, alcohol consumption, smoking status, diabetes mellitus, hypertension, refractive error, and previous cataract surgery., Main Outcome Measures: Photoreceptor layer (PRL) and retinal pigment epithelium-Bruch's membrane (RPE-BM) thicknesses., Results: Among 36 897 participants included in the analysis, 1571 (4.3%) reported very severe periodontitis. Affected individuals were older, lived in areas of greater socioeconomic deprivation, and were more likely to be hypertensive, diabetic, and current smokers (all P < 0.001). On average, those with very severe periodontitis were hyperopic (0.05 ± 2.27 diopters) while those unaffected were myopic (-0.29 ± 2.40 diopters, P < 0.001). Following adjusted analysis, very severe periodontitis was associated with thinner PRL (-0.55 μm, 95% confidence interval [CI], -0.97 to -0.12; P  = 0.022) but there was no difference in RPE-BM thickness (0.00 μm, 95% CI, -0.12 to 0.13; P  = 0.97). The association between PRL thickness and very severe periodontitis was modified by age ( P < 0.001). Stratifying individuals by age, thinner PRL was seen among those aged 60 to 69 years with disease (-1.19 μm, 95% CI, -1.85 to -0.53; P < 0.001) but not among those aged < 60 years., Conclusions: Among those with no known eye disease, very severe periodontitis is statistically associated with a thinner PRL, consistent with incipient AMD. Optimizing oral hygiene may hold additional relevance for people at risk of degenerative retinal disease., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Purpose: Anterior segment optical coherence tomography (AS-OCT) is an emerging diagnostic and monitoring tool for anterior uveitis. We investigated AS-OCT findings in the eyes of a large, diverse population of children free of uveitis to establish its potential to "rule out" accurately those without disease., Methods: In this cross-sectional observational study, image acquisition was performed with swept source AS-OCT (Heidelberg Anterion), using a protocol of 13 B-scans per volume, from 217 children (434 eyes) aged 5 to 15 years, with analysis of acquired images (identification of apparent inflammatory cells, or "cell events") by multiple graders. Outcomes of interest were median and maximum cell event count (MEDCC, MAXCC) per B-scan from each eye and the total cell event count (TCC) per volume scan., Results: At least one cell event was detected in volume scans of 76% of eyes (329/434) and 87% of children (189/217). The maximum number (MAXCC) per scan ranged from 0 to 6 (median, 2). There was a strong positive association between increasing age (years) and the number of cell events detected within a volume scan following adjustment for gender and iris color (adjusted regression coefficient for TCC 0.5; P < 0.0001; 95% confidence interval, 0.4-0.7)., Conclusions: Our findings demonstrate that apparent inflammatory cells are detectable on AS-OCT in the apparently healthy eyes of children and furthermore suggest early life developmental changes in blood-iris barrier stability that merit further exploration. We provide the foundation for the normative data set necessary for establishing the clinical utility of AS-OCT for surveillance of children with inflammatory eye diseases.

Background/aims: To investigate if impaired vision adversely impacts the intentions/ambitions of adolescents concerning their future education, careers and social outcomes., Methods: Population-based birth cohort study in the UK comprising 9273 participants from the Millennium Cohort Study who were followed up to age 17 years. Children were classified as having normal vision or unilateral or bilateral impaired vision caused by significant eye conditions based on detailed parental-structured questionnaire data on sight problems and treatment coded by clinicians. Ten domains covering education, career and social outcomes by age 30 were investigated., Results: Adjusted regression models showed few differences by vision status. Bilateral impaired vision was associated with increased odds of intending to remain in full-time education after statutory school age (adjusted OR (aOR) 2.00, 95% CI 1.08 to 3.68) and of home ownership at age 30 (aOR 1.83, 95% CI 1.01 to 3.32). Impaired vision was not associated with intending to attend university. A significantly higher proportion of parents of children with bilateral or unilateral impaired vision thought that their child would not get the exam grades required to go to university than parents of those with normal vision (29% or 26% vs 16%, p= 0.026)., Conclusion: Adolescents with impaired vision have broadly the same intentions/ambitions regarding future education, careers and social outcomes as their peers with normal vision. The known significant gaps in attainment in these domains among young adults with vision impairment are therefore likely to be due to barriers that they face in achieving their ambitions. Improved implementation of existing interventions is necessary to ensure equality of opportunities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: Addressing childhood visual disability is an international priority, with data on causes needed to plan, implement and evaluate public health and clinical care. We have examined the contribution of 'avoidable' blinding disorders to childhood visual impairment, severe visual impairment and blindness (VI/SVIBL) in the UK., Methods: National prospective observational longitudinal study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), of children (aged 18 years or under) newly diagnosed with vision worse than 0.48 logMAR (logarithm of the minimum angle of resolution) or equivalent in both eyes. Proportions of children with an 'avoidable' disorder comprising either a potentially preventable (isolated disorders with an effective intervention which reduces disease incidence) or treatable (isolated eye or vision disorders for which there are routinely available effective interventions able to improve vision or halt progressive visual loss) are reported., Results: Of the 784 children within BCVIS2, isolated potentially preventable disorders were present in only 17% (132/784) and treatable disorders in an additional 13% (99/784). The most common treatable causes were cataract, retinopathy of prematurity and glaucoma. Of the 132 children with potentially preventable disease, 64 had hypoxic-ischaemic encephalopathy. Non-accidental injury accounted for almost two-thirds (11/16, 69%) of those with VI/SVIBL due to injury., Conclusion: Despite significant progress in the past decades in high-income countries, there remains a need to be vigilant about implementing preventive strategies and treatments. Attention to disorders that are currently neither preventable nor treatable remains a priority in these settings and will become increasingly important in lower-income and middle-income countries undergoing economic transition., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Cadaveric studies have shown disease-related neurodegeneration and other morphological abnormalities in the retina of individuals with Parkinson disease (PD); however, it remains unclear whether this can be reliably detected with in vivo imaging. We investigated inner retinal anatomy, measured using optical coherence tomography (OCT), in prevalent PD and subsequently assessed the association of these markers with the development of PD using a prospective research cohort., Methods: This cross-sectional analysis used data from 2 studies. For the detection of retinal markers in prevalent PD, we used data from AlzEye, a retrospective cohort of 154,830 patients aged 40 years and older attending secondary care ophthalmic hospitals in London, United Kingdom, between 2008 and 2018. For the evaluation of retinal markers in incident PD, we used data from UK Biobank, a prospective population-based cohort where 67,311 volunteers aged 40-69 years were recruited between 2006 and 2010 and underwent retinal imaging. Macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GCIPL), and inner nuclear layer (INL) thicknesses were extracted from fovea-centered OCT. Linear mixed-effects models were fitted to examine the association between prevalent PD and retinal thicknesses. Hazard ratios for the association between time to PD diagnosis and retinal thicknesses were estimated using frailty models., Results: Within the AlzEye cohort, there were 700 individuals with prevalent PD and 105,770 controls (mean age 65.5 ± 13.5 years, 51.7% female). Individuals with prevalent PD had thinner GCIPL (-2.12 μm, 95% CI -3.17 to -1.07, p = 8.2 × 10 -5 ) and INL (-0.99 μm, 95% CI -1.52 to -0.47, p = 2.1 × 10 -4 ). The UK Biobank included 50,405 participants (mean age 56.1 ± 8.2 years, 54.7% female), of whom 53 developed PD at a mean of 2,653 ± 851 days. Thinner GCIPL (hazard ratio [HR] 0.62 per SD increase, 95% CI 0.46-0.84, p = 0.002) and thinner INL (HR 0.70, 95% CI 0.51-0.96, p = 0.026) were also associated with incident PD., Discussion: Individuals with PD have reduced thickness of the INL and GCIPL of the retina. Involvement of these layers several years before clinical presentation highlight a potential role for retinal imaging for at-risk stratification of PD., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background : Childhood uveitis is a rare inflammatory eye disease which is typically chronic, relapsing-remitting in nature, with an uncertain aetiology (idiopathic). Visual loss occurs due to structural damage caused by uncontrolled inflammation. Understanding of the determinants of long term outcome is lacking, including the predictors of therapeutic response or how to define disease control. Aims : To describe disease natural history and outcomes amongst a nationally representative group of children with non-infectious uveitis, describe the impact of disease course on quality of life for both child and family, and identify determinants of adverse visual, structural and developmental outcomes. Methods : UNICORNS is a prospective longitudinal multicentre cohort study of children newly diagnosed with uveitis about whom a core minimum clinical dataset will be collected systematically. Participants and their families will also complete patient-reported outcome measures annually from recruitment. The association of patient (child- and treatment- dependent) characteristics with outcome will be investigated using logistic and ordinal regression models which incorporate adjustment for within-child correspondence between eyes for those with bilateral disease and repeated outcomes measurement. Discussion: Through this population based, prospective longitudinal study of childhood uveitis, we will describe the characteristics of childhood onset disease. Early (1-2 years following diagnosis) outcomes will be described in the first instance, and through the creation of a national inception cohort, longer term studies will be enabled of outcome for affected children and families., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Kellett S et al.)

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 2 =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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: Understanding temporal trends in childhood visual disability is necessary for planning and evaluating clinical services and health policies. We investigate the changing epidemiology of severe visual impairment (SVI) and blindness (BL) in children in the UK in the 21st century., Methods: Comparative analysis of two national population-based epidemiological studies of incident childhood SVI/BL (ICD-10 definition; visual acuity worse than 1.0 LogMAR in the better eye). We carry out comparative analysis of studies conducted in 2000 and 2015 using identical methods., Results: Overall annual and cumulative incidence rates remained broadly stable in 2015 at 0.38 per 10 000 (95% CI 0.34 to 0.41) for 0-15 years old and 5.65 per 10 000 (5.16 to 6.18) by 16 years, respectively, and with annual incidence in infancy (3.52 per 10 000, 3.13 to 3.97) remaining considerably higher than any other age. Mortality among children diagnosed in infancy declined (from 61.4 to 25.6 per 1000), despite an increase (from 77% to 84%, p=0.037) in the overall proportion with significant non-ophthalmic impairments/disorders. The relative contribution of all the main groups of disorders increased over time, most notably cerebral visual impairment (from 50% to 61%). Aetiological factors operating prenatally continued to predominate, with an increased relative contribution of hereditary conditions in all children (from 35% to 57%, p<0.001). The substantially elevated rates for any ethnic minority group and those born preterm were unchanged, with amplification of increased rates associated with low birth weight., Conclusion: The changing landscape of healthcare and increased survival of affected children, is reflected in increasing clinical complexity and heterogeneity of all-cause SVI/BL alongside declining mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The potential association of schizophrenia with distinct retinal changes is of clinical interest but has been challenging to investigate because of a lack of sufficiently large and detailed cohorts., Objective: To investigate the association between retinal biomarkers from multimodal imaging (oculomics) and schizophrenia in a large real-world population., Design, Setting, and Participants: This cross-sectional analysis used data from a retrospective cohort of 154 830 patients 40 years and older from the AlzEye study, which linked ophthalmic data with hospital admission data across England. Patients attended Moorfields Eye Hospital, a secondary care ophthalmic hospital with a principal central site, 4 district hubs, and 5 satellite clinics in and around London, United Kingdom, and had retinal imaging during the study period (January 2008 and April 2018). Data were analyzed from January 2022 to July 2022., Main Outcomes and Measures: Retinovascular and optic nerve indices were computed from color fundus photography. Macular retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (mGC-IPL) thicknesses were extracted from optical coherence tomography. Linear mixed-effects models were used to examine the association between schizophrenia and retinal biomarkers., Results: A total of 485 individuals (747 eyes) with schizophrenia (mean [SD] age, 64.9 years [12.2]; 258 [53.2%] female) and 100 931 individuals (165 400 eyes) without schizophrenia (mean age, 65.9 years [13.7]; 53 253 [52.8%] female) were included after images underwent quality control and potentially confounding conditions were excluded. Individuals with schizophrenia were more likely to have hypertension (407 [83.9%] vs 49 971 [48.0%]) and diabetes (364 [75.1%] vs 28 762 [27.6%]). The schizophrenia group had thinner mGC-IPL (-4.05 μm, 95% CI, -5.40 to -2.69; P = 5.4 × 10-9), which persisted when investigating only patients without diabetes (-3.99 μm; 95% CI, -6.67 to -1.30; P = .004) or just those 55 years and younger (-2.90 μm; 95% CI, -5.55 to -0.24; P = .03). On adjusted analysis, retinal fractal dimension among vascular variables was reduced in individuals with schizophrenia (-0.14 units; 95% CI, -0.22 to -0.05; P = .001), although this was not present when excluding patients with diabetes., Conclusions and Relevance: In this study, patients with schizophrenia had measurable differences in neural and vascular integrity of the retina. Differences in retinal vasculature were mostly secondary to the higher prevalence of diabetes and hypertension in patients with schizophrenia. The role of retinal features as adjunct outcomes in patients with schizophrenia warrants further investigation.

Background: We describe an investigation of temporal trends in the incidence of childhood uveitis-related hospital admissions, hospitalization being a robust indicator of disease severity., Methods: A population-based retrospective study using a hospitalization database, the Hospital Episode Statistics (HES) dataset, capturing data on care between 2013 and 2020. Primary outcomes were rates of pediatric hospital admissions for uveitis-related disorders., Results: During the study period, there were 3,258 reported uveitis-related hospital admissions of children aged 0 to 14 years, comprising 19% of all-age uveitis-related admissions. Anterior uveitis was the most common diagnosis. The annual incidence of childhood uveitis-related hospitalizations declined year on year from a peak incidence of 5.4 per 100,000 children (95% confidence interval 5.0-5.9) in 2015-2016 to 3.3 per 100,000 (95% CI 3.0-3.6) in 2019-2020. Over the same period, the national incidence of juvenile arthropathy-related admissions stayed stable., Conclusion: The decline in admissions nationally may reflect reduced incidence of uveitis complications with increasing use of immunosuppressive therapies.

Purpose: Genetic variants identified through population-based genome-wide studies are generally of high frequency, exerting their action in the central part of the refractive error spectrum. However, the power to identify associations with variants of lower minor allele frequency is greatly reduced, requiring considerable sample sizes. Here we aim to assess the impact of rare variants on genetic variation of refractive errors in a very large general population cohort., Methods: Genetic association analyses of non-cyclopaedic autorefraction calculated as mean spherical equivalent (SPHE) used whole-exome sequence genotypic information from 50,893 unrelated participants in the UK Biobank of European ancestry. Gene-based analyses tested for association with SPHE using an optimised SNP-set kernel association test (SKAT-O) restricted to rare variants (minor allele frequency < 1%) within protein-coding regions of the genome. All models were adjusted for age, sex and common lead variants within the same locus reported by previous genome-wide association studies. Potentially causal markers driving association at significant loci were elucidated using sensitivity analyses by sequentially dropping the most associated variants from gene-based analyses., Results: We found strong statistical evidence for association of SPHE with the SIX6 (p-value = 2.15 x 10-10, or Bonferroni-Corrected p = 4.41x10-06) and the CRX gene (p-value = 6.65 x 10-08, or Bonferroni-Corrected p = 0.001). The SIX6 gene codes for a transcription factor believed to be critical to the eye, retina and optic disc development and morphology, while CRX regulates photoreceptor specification and expression of over 700 genes in the retina. These novel associations suggest an important role of genes involved in eye morphogenesis in refractive error., Conclusion: The results of our study support previous research highlighting the importance of rare variants to the genetic risk of refractive error. We explain some of the origins of the genetic signals seen in GWAS but also report for the first time a completely novel association with the CRX gene., Competing Interests: NO

Background: Patient-reported outcome measures (PROMs) are increasingly used in paediatric ophthalmology. However, little is known about the distribution of PROM scores among children and young people with visual impairment., Aim: To investigate the distributions and predictors of scores on the VQoL&#95;CYP ( measuring vision-related quality of life ) and FVQ&#95;CYP ( measuring functional vision )., Methods: Children and young people aged 8-18 years, with visual impairment/blindness (logarithm of the minimum angle of resolution (LogMAR) worse than 0.48 in the better eye, and/or eligible visual field restriction) completed the VQoL&#95;CYP and FVQ&#95;CYP at home or Great Ormond Street Hospital, London, UK. Associations between VQoL&#95;CYP and FVQ&#95;CYP scores and sociodemographic and clinical factors were analysed using multiple linear regression models., Results: Among 93 participants, VQoL&#95;CYP scores ranged from 36.6 to 78.2 (mean=57.9, SD=8.1). FVQ&#95;CYP scores ranged from 23.5 to 70.3 (mean=48.3, SD=10.1). Only 0.4% of the variation in VQoL&#95;CYP scores was explained, with no associations with the variables of interest. By contrast, 21.6% of the variation in FVQ&#95;CYP scores was explained, with a gradient of worse acuity (p<0.001) and female gender (p=0.04) associated with worse self-rated functional vision. Age, ethnicity, time of onset and stability/progression of visual impairment were not associated., Discussion: Self-rated vision-related quality of life and functional vision are not readily predicted from sociodemographic or clinical characteristics that ophthalmologists measure/record. Routine use of PROMs in clinical practice can offer important insights. Use in research can provide valuable measures of effectiveness of interventions. The reference values provided will aid interpretation in both settings., Competing Interests: Competing interests: This study was funded by the Great Ormond Street Hospital Charity (V0418). It was undertaken at UCL Great Ormond Street (GOS) Institute of Child Health/Great Ormond Street Hospital, which receive a proportion of funding from the Department of Health’s National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme. Members of the team are also supported by the Ulverscroft Foundation. Professor Rahi is an NIHR Senior Investigator. Professor Jugnoo Rahi had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Refractive errors, particularly myopia, are the most common eye conditions, often leading to serious visual impairment. The age of onset is correlated with the severity of refractive error in adulthood observed in epidemiological and genetic studies and can be used as a proxy in refractive error genetic studies. To further elucidate genetic factors that influence refractive error, we analysed self-reported age of refractive error correction data from the UK Biobank European and perform genome-wide time-to-event analyses on the age of first spectacle wear (AFSW). Genome-wide proportional hazards ratio analyses were conducted in 340 318 European subjects. We subsequently assessed the similarities and differences in the genetic architectures of refractive error correction from different causes. All-cause AFSW was genetically strongly correlated (rg = -0.68) with spherical equivalent (the measured strength of spectacle lens required to correct the refractive error) and was used as a proxy for refractive error. Time-to-event analyses found genome-wide significant associations at 44 independent genomic loci, many of which (GJD2, LAMA2, etc.) were previously associated with refractive error. We also identified six novel regions associated with AFSW, the most significant of which was on chromosome 17q (P = 3.06 × 10-09 for rs55882072), replicating in an independent dataset. We found that genes associated with AFSW were significantly enriched for expression in central nervous system tissues and were involved in neurogenesis. This work demonstrates the merits of time-to-event study design in the genetic investigation of refractive error and contributes additional knowledge on its genetic risk factors in the general population., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Perimetry is important in the management of children with glaucoma, but there is limited evidence-based guidance on its use. We report an expert consensus-based study to update guidance and identify areas requiring further research., Methods: Experts were invited to participate in a modified Delphi consensus process. Panel selection was based on clinical experience of managing children with glaucoma and UK-based training to minimise diversity of view due to healthcare setting. Questionnaires were delivered electronically, and analysed to establish 'agreement'. Divergence of opinions was investigated and resolved where possible through further iterations., Results: 7/9 experts invited agreed to participate. Consensus (≥5/7 (71%) in agreement) was achieved for 21/26 (80.8%) items in 2 rounds, generating recommendations to start perimetry from approximately 7 years of age (IQR: 6.75-7.25), and use qualitative methods in conjunction with automated reliability indices to assess test quality. There was a lack of agreement about defining progressive visual field (VF) loss and methods for implementing perimetry longitudinally. Panel members highlighted the importance of informing decisions based upon individual circumstances-from gauging maturity/capability when selecting tests and interpreting outcomes, to accounting for specific clinical features (e.g. poor IOP control and/or suspected progressive VF loss) when making decisions about frequency of testing., Conclusions: There is commonality of expert views in relation to implementing perimetry and interpreting test quality in the management of children with glaucoma. However, there remains a lack of agreement about defining progressive VF loss, and utilising perimetry over an individuals' lifetime, highlighting the need for further research., (© 2021. The Author(s).)

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., Competing Interests: Competing interests: SKW is funded through a Medical Research Council Clinical Research Training Fellowship (MR/TR000953/1). NP is funded by a Moorfields Eye Charity Career Development Award (R190031A). HM is supported by the National Institute for Health Research’s (NIHR) Comprehensive Biomedical Research Centre (BRC) at University College London Hospitals. SEP receives support from the NIHR BRC at Barts. KB has received speaker fees from Novartis, Bayer, Alimera, Allergan, Roche and Heidelberg; meeting or travel fees from Novartis and Bayer; compensation for being on an advisory board from Novartis and Bayer; consulting fees from Novartis and Roche and research support from Apellis, Novartis and Bayer. AP receives financial support from the NIHR BRC based at Moorfields Eye Hospital (MEH) NHS Foundation Trust and UCL Institute of Ophthalmology; is part of the Steering Committee of the Advanced Nerve and Glaucoma Imaging (ANGI) network which is sponsored by ZEISS and Steering Committee of the OCTiMS Study which is sponsored by Novartis and reports speaker fees from Heidelberg Engineering. JSR receives support from the NIHR as a senior investigator and via the NIHR BRCs at MEH and Great Ormond Street Hospital. AKD is director of INSIGHT, the HDRUK Health Data Research Hub for Eye Health. PAK is supported by a Moorfields Eye Charity Career Development Award (R190028A) and a UK Research & Innovation Future Leaders Fellowship (MR/T019050/1); receives research support from Apellis; is a consultant for DeepMind, Roche, Novartis, Apellis and Bitfount; is an equity owner in Big Picture Medical and has received speaker fees from Heidelberg Engineering, Topcon, Allergan, Roche and Bayer, meeting or travel fees from Novartis and Bayer and compensation for being on an advisory board from Novartis and Bayer., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study investigated temporal trends in the epidemiology of primary myopia and associations with key environmental risk factors in a UK population. Data were collected at recruitment (non-cycloplegic autorefraction, year of birth, sex, ethnicity, highest educational attainment, reason and age of first wearing glasses and history of eye disease) from 107,442 UK Biobank study participants aged 40 to 69 years, born between 1939 and 1970. Myopia was defined as mean spherical equivalent (MSE) ≤-1 dioptre (D). Temporal changes in myopia frequency by birth cohort (5-year bands using date of birth) and associations with environmental factors were analysed, distinguishing both type (childhood-onset, <18 years versus adult-onset) and severity (three categories: low -1.00 to -2.99D, moderate -3.00 to -5.99D or high ≥-6.00D). Overall myopia frequency increased from 20.0% in the oldest cohort (births 1939-1944) to 29.2% in the youngest (1965-1970), reflecting a relatively higher increase in frequency of adult-onset and low myopia. Childhood-onset myopia peaked in participants born in 1950-54, adult-onset myopia peaked in the cohort born a decade later. The distribution of MSE only shifted for childhood-onset myopia (median: -3.8 [IQR -2.4, -5.4] to -4.4 [IQR -3.0, -6.2]). The magnitude of the association between higher educational attainment (proxy for educational intensity) and myopia overall increased over time (adjusted Odds Ratio (OR) 2.7 [2.5, 2.9] in the oldest versus 4.2 [3.3, 5.2] in the youngest cohort), being substantially greater for childhood-onset myopia (OR 3.3 [2.8, 4.0] to 8.0 [4.2, 13]). Without delineating childhood-onset from adult-onset myopia, important temporal trends would have been obscured. The differential impact of educational experience/intensity on both childhood-onset and high myopia, amplified over time, suggests a cohort effect in gene-environment interaction with potential for increasing myopia frequency if increasing childhood educational intensity is unchecked. However, historical plateauing of myopia frequency does suggest some potential for effective intervention., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Air pollution is associated with chronic diseases of later life. Cataract is the most common cause of blindess globally. It is biologically plausible that cataract risk is increased by pollution exposure. Therefore, the relationship between air pollution and incident cataract surgery was examined., Methods: This was a prospective, observational study involving 433,727 UK Biobank participants. Ambient air pollution measures included particulates, nitrogen dioxide (NO2) and nitrogen oxides (NOx). Outdoor air pollution was estimated based on land use regression models. Participants undergoing cataract surgery in either eye were ascertained via data linkage to the National Health Service procedure statistics. Those undergoing cataract surgery within 1 year of baseline assessment and those reporting cataract at baseline were excluded. Cox proportional hazards models were used to examine the associations between air pollutants and incident cataract surgery, adjusting for sociodemographic and lifestyle factors., Results: There were 16,307 incident cases of cataract surgery. Higher exposure to PM2.5 was associated with a 5% increased risk of incident cataract surgery (per interquartile range [IQR] increase). Compared to the lowest quartile, participants with exposures to PM2.5, NO2, and NOx in the highest quartile were 14%, 11%, and 9% more likely to undergo cataract surgery, respectively. A continuous exposure-response relationship was observed, with the likelihood of undergoing cataract surgery being progressively higher with greater levels of PM2.5, NO2, and NOx (P for trend P < 0.001)., Conclusions: Although the results of our study showed a 5% increased risk of future cataract surgery following an exposure to PM2.5, NO2, and NOx, the effect estimates were relatively small. Further research is required to determine if the associations identified are causal.

Objectives: This study aimed to investigate associations between persisting amblyopia into adulthood and its "real-life" impacts and inform the current debate about the value of childhood vision screening programs., Methods: Associations between persisting amblyopia and diverse socioeconomic, health, and well-being outcomes were investigated in multivariable-adjusted (sex, age, ethnicity, deprivation) regression models, with 126 400 participants (aged 40-70 years) of the UK Biobank with complete ophthalmic data. Analysis by age group (cohort 1, 60-70 years; cohort 2, 50-59 years; cohort 3, 40-49 years) assessed temporal trends., Results: Of 3395 (3%) participants with confirmed amblyopia, overall 77% (2627) had persisting amblyopia, declining from 78% in cohort 1 to 73% in cohort 3. The odds of persisting amblyopia were 5.91 (5.24-6.66) and 2.49 (2.21-2.81) times greater in cohort 1 and cohort 2, respectively, than cohort 3. The odds were also higher for more socioeconomically deprived groups and for white ethnicity. Reduced participation in sport, adverse general and mental health, and well-being were all independently associated with persisting amblyopia, with the strongest associations in the youngest cohorts. Associations with lower educational attainment and economic outcomes were only evident in the oldest cohort., Conclusions: There has been a decline in the overall frequency of persisting amblyopia since the introduction of universal child vision screening in the United Kingdom. Nevertheless, most adults treated for amblyopia in childhood have persisting vision deficits. There was no evidence that persisting amblyopia has vision-mediated effects on educational, employment-related, or economic outcomes. The observed adverse outcomes were largely those not directly mediated by vision. Patients undergoing treatment should be counseled about long-term outcomes., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate disagreement between children's self-reported vision-related quality of life (VQoL) and functional vision (FV) and their parents' proxy-reports., Design: Cross-sectional study., Methods: A total of 152 children aged 7-18 years with visual impairment (VI) (defined by the World Health Organization), and their parents, were recruited from 22 National Health Service (NHS) ophthalmology departments in the United Kingdom. Age-appropriate versions of 2 vision-specific instruments, capturing VQoL and FV, were administered to children alongside modified versions for completion by parents on behalf of their child (ie, parent proxy-report). Disagreement between self-report and parent proxy-report was examined using the Bland-Altman (BA) method and a threshold of disagreement based on 0.5 standard deviation. Disagreement was analyzed according to participants' age, sex, and clinical characteristics, using logistic regression analyses., Results: Children rated themselves as having better outcomes than their parents did, although parents both under- and overestimated their child's VQoL (mean score difference = 7.7). With each year of increasing age, there was a 1.18 (1.04-1.35) higher odds of children self-rating their VQoL better than their parents (P = .013). Although parents consistently underestimated their child's FV (mean score difference = -4.7), no characteristics were significantly associated with differences in disagreement., Conclusions: Disagreement between child self-report on the impact of VI and their parents' proxy-reports varies by age. This implies that self-report from children must remain the gold standard. Where self-reporting is not possible, parent proxy-reports may provide useful insights, but they must be interpreted with caution., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Childhood visual impairment (VI) has a profound impact on many aspects of childhood and adolescence. This is well-documented in cross-sectional and/or quantitative studies utilizing self-report instruments which compare children with and without VI. Young people's views on the experience of growing up with VI as a developmental, change-driven process remain largely unexplored., Methods: As part of our broader research programme on quality of life of visually impaired children and young people in the United Kingdom, in-depth, semi-structured interviews were conducted between March and June 2015, with a stratified sample of 17 young people with VI, aged 16-19 years. An age-sensitive, empirically-based topic guide encouraged retrospective reflections on participants' experiences of growing up with VI, including age-normative and vision-specific challenges., Results: Descriptions of growing up with VI largely centered on an overarching higher-order theme labelled becoming me. Four themes representing everyday activities, attitudes, preferences and perceptions in relation to i) social relationships, ii) independence and responsibilities, iii) the future, and iv) rising to challenges emerged and were used by participants in their description of three stages in which they developed a sense of self: i) laying the foundations, ii) testing the waters, and iii) this is me. Differences in manifestation of VI influenced how young people made sense of their experiences and their sense of self., Conclusions: Findings are discussed in relation to normative and vision-specific changes in psychosocial development during adolescence, including the development of identity. They highlight the need for ongoing monitoring of subjective well-being in a clinical population with a unique early life course trajectory., Competing Interests: The authors have declared that no competing interests exist.

Background: We investigated the incidence and causes of sight-threatening diabetes-related eye disease in children living with diabetes in the UK, to inform the national eye screening programme and enable monitoring of trends., Methods: We undertook a prospective active national surveillance via the British Ophthalmic Surveillance Unit. Eligible cases were children aged 18 years or younger, with type 1 or 2 diabetes, newly diagnosed between January 2015 and February 2017 with sight-threatening diabetic eye disease., Results: Eight children were reported. The annual incidence of all sight-threatening diabetes-related eye disease requiring referral to an ophthalmologist among children living with diabetes (n=8) in the UK was 1.21 per 10 000 person-years (95% CI 0.52 to 2.39) and was largely attributable to cataract (n=5) 0.76 per 10 000 person-years (95% CI 0.25 to 1.77). The incidence of sight-threatening diabetic retinopathy (n=3) among those eligible for screening (12 to 18 year-olds living with diabetes) was 1.18 per 10 000 person-years (95% CI 0.24 to 3.46). No subjects eligible for certification as visually impaired or blind were reported., Conclusions: Secondary prevention of visual disability due to retinopathy is currently the sole purpose of national eye screening programmes globally. However, the rarity of treatment-requiring retinopathy in children/young people living with diabetes, alongside growing concerns about suboptimal screening uptake, merit new consideration of the utility of screening for primary prevention of diabetes-related morbidity by using the screening event and findings as a catalyst for better diabetes self-management., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.

Background: The WHO VISION 2020 global initiative against blindness, launched in 2000, prioritised childhood visual disability by aiming to end avoidable childhood blindness by 2020. However, progress has been hampered by the global paucity of epidemiological data concerning childhood visual disability. The British Childhood Visual Impairment and Blindness Study 2 (BCVIS2) was done to address this evidence gap., Methods: BCVIS2 was a prospective UK-wide, cross-sectional, observational study to establish an inception cohort of children newly diagnosed with visual impairment. Opthalmologists and paediatricians reported cases from 89 hospitals and community centres across the UK. We included children aged 18 years or younger who were newly diagnosed with any condition causing impaired visual acuity to a level of 0·5 logMAR or worse (worse than 6/18 Snellen) in each eye, or equivalent vision as assessed by standard qualitative measures, between Oct 1, 2015, and Nov 1, 2016. Eligible children were notified simultaneously but independently by their managing ophthalmologists and paediatricians via the two national active surveillance schemes, the British Ophthalmological Surveillance Unit and the British Paediatric Surveillance Unit. Standardised detailed demographic, socioeconomic, and clinical data about detection, management, and treatment were collected at diagnosis and 1 year later. We calculated incidence estimates and relative rates by key sociodemographic factors. We did descriptive analyses of underlying ophthalmic disorders and non-ophthalmic comorbidities., Findings: 61 (7%) of 845 eligible children initially notified were ineligible at follow-up because of improved vision after treatment. Thus, the study sample comprised 784 children with permanent newly-diagnosed all-cause visual impairment, severe visual impairment, or blindness. 559 (72%) of 778 children had clinically significant non-ophthalmic impairments or conditions. 28 (4%) of 784 children died within a year after diagnosis of visual disability (all had underlying systemic disorders). Incidence of visual disability in the first year of life was 5·19 per 10 000 children (95% CI 4·71-5·72), almost ten times higher than among 1-to-4-year-olds and between 20 times and 100 times higher than in the older age groups. The overall cumulative incidence (or lifetime risk) of visual impairment, severe visual impairment, or blindness was 10·03 per 10 000 children (9·35-10·76). Incidence rates were higher for those from any ethnic minority group, the lowest quintile of socioeconomic status, and those born preterm or with low birthweight. 345 (44%) of 784 children had a single affected anatomical site. Disorders of the brain and visual pathways affected 378 (48%) of 784 children., Interpretation: BCVIS2 provides a contemporary snapshot of the heterogeneity, multi-morbidity, and vulnerability associated with childhood visual disability in a high-income country. These findings could facilitate developing and delivering health care and planning of interventional research. Our findings highlight the importance of including childhood visual disability as a sentinel event and metric in global child health initiatives., Funding: Fight for Sight, National Institute for Health Research, and Ulverscroft Foundation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Refractive errors, particularly myopia, are common and a leading cause of blindness. This study aimed to explore associations between medications and refractive error in an aging adult cohort and to determine whether childhood-onset refractive errors predict future medication use to provide novel insights into disease mechanisms., Methods: The study compared the spherical equivalent values measured in 102,318 UK Biobank participants taking the 960 most commonly used medications. The strengths of associations were evaluated against the self-reported age of spectacle wear. The causality of refractive error changes was inferred using sensitivity and Mendelian randomization analyses., Results: Anti-glaucoma drugs were associated with 1 to 2 diopters greater myopic refraction, particularly in subjects who started wearing correction in the first two decades of life, potentially due to the association of higher intraocular pressure since early years with both myopia and, later in life, glaucoma. All classes of pain-control medications, including paracetamol, opiates, non-steroidal antiinflammatory drugs, and gabapentinoids, were associated with greater hyperopia (+0.68-1.15 diopters), after correction for deprivation, education, and polypharmacy and sensitivity analyses for common diagnoses. Oral hypoglycemics (metformin, gliburonide) were associated with myopia, as was allopurinol, and participants using bronchodilators (ipratropium and salbutamol) were more hyperopic., Conclusions: This study finds for the first time, to our knowledge, that medication use is associated with refractive error in adults. The novel finding that analgesics are associated with hyperopic refraction, and the possibility that multisite chronic pain predisposes to hyperopia, deserves further research. Some drugs, such as antihyperglycemic or bronchodilators, may directly alter refractive error. Intraocular pressure appears causative for myopia.

Objective: Children with juvenile idiopathic arthritis (JIA) need regular examinations for uveitis to avoid visual morbidity from the most common extraarticular manifestation of disease. This study was undertaken to investigate the feasibility, acceptability, and performance of optical coherence tomography (OCT) imaging-based diagnosis of uveitis., Methods: This observational cross-sectional study included children with and those without uveitis. The children underwent routine clinical examinations and anterior segment OCT scanning of intraocular inflammatory cells. Acceptability of image acquisition was assessed using a visual analog scale and length of time needed to acquire images. Interobserver and intraobserver variability of manual counting of acquired images (Bland-Altman limits of agreement), correlation between imaging and routine assessment, and sensitivity and specificity of anterior segment OCT detection of active inflammation were assessed., Results: Of the 26 children ages 3-15 years (median age 8 years) who underwent imaging, 12 had active inflammation. All patients rated the acceptability of image acquisition as at least 8.5 on a scale of 0-10. Time taken to acquire images ranged from 1.5 minutes to 22 minutes (median time 8 minutes). There was good positive correlation between clinical assessment and image-based cell quantification (R 2 = 0.63, P = 0.002). Sensitivity of anterior segment OCT manual image cell count for diagnosis of active inflammation was 92% (95% confidence interval [95% CI] 62-99%), specificity was 86% (95% CI 58-98%), and negative predictive value (ruling out uveitis) was 92% (95% CI 65-99%)., Conclusion: Non-contact, high-resolution imaging for JIA uveitis surveillance is feasible, acceptable to patients, and holds the promise of transforming pediatric practice. Further work is needed to determine the analytic and clinical validity of anterior segment OCT quantification of active inflammation, and the clinical utility and cost-effectiveness of imaging-based disease monitoring., (© 2020, American College of Rheumatology.)

Background/objectives: Routine use of patient-reported outcome measures (PROMs) to assess quality of health care systems is mandated in many countries and has been implemented successfully in many specialities. Ophthalmology currently lags behind. To support and inform future implementation, we investigated paediatric ophthalmic clinicians' experience of, and future training needs for, using child-appropriate vision PROMs and their views about the barriers and enablers to future routine implementation in clinical practice., Methods: We conducted a pilot study, using an online survey to elicit the experience, attitudes, training needs and perceptions of barriers and enablers to routine PROMs use of ophthalmic health professionals in the Paediatric Ophthalmology Department at Great Ormond Street Hospital, London. A focus-group was undertaken to discuss survey results and preferences regarding presentation of PROM data. Analysis comprised descriptive statistics, presented alongside complementary qualitative data., Results: Eighteen clinicians in the department completed the survey. Twenty-seven took part in the focus group. Clinicians had limited experience of using PROMs but high confidence in the potential positive impact on communication with patients, monitoring chronic conditions and clinical decision-making. Clinicians identified operational issues (collection and analysis of data) and impact (interpretation and application of data) as the two key areas for consideration. Training and information requirements before implementation were clearly articulated, alongside the benefits of using digital/electronic data capture ahead of consultations to allow efficiency and automated analysis, and presentation in an appropriate visual format alongside clinical data to ensure meaningful use., Conclusion: The findings of this pilot study of ophthalmic clinicians working in a specialist paediatric ophthalmology department, suggest that ophthalmic clinicians recognise the potential benefits of routine PROMs use in clinical practice. Together with existing literature outside ophthalmology relating to overcoming barriers and exploiting enablers to routine implementation, findings may be applicable in planning routine PROM implementation in paediatric ophthalmology., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To develop age-appropriate extensions of a patient-reported outcome measure for capturing the functional impact of visual impairment on daily activities of children and young people aged 8 up to 18 years., Design: Questionnaire development and validation study., Methods: Pediatric Ophthalmology departments at Great Ormond Street Hospital and Moorfields Eye Hospital, and, in the final study phase, 20 further UK hospitals. Children and young people (aged 6-19 years) with visual impairment (acuity of the logarithm of the minimum angle of resolution (LogMAR) worse than 0.50 in the better eye) due to any cause but without significant non-ophthalmic impairments. We used our prototype FVQ&#95;CYP for 10-15 year olds as the foundation. Twenty-nine semi-structured interviews confirmed relevance of existing, and identified new, age-specific items. Twenty-eight cognitive interviews captured information regarding comprehensibility and format. The FVQ&#95;Child (8-12 years) and FVQ&#95;Young Person (13-18 years) were evaluated with a national sample of 113 children and 96 young people using Rasch analysis., Results: Issues emerging from interviews with children and young people were largely congruent with those elicited originally with 10-15 year olds. The 28-item FVQ&#95;Child and 38-item FVQ&#95;Young Person versions have goodness-of-fit statistics within the interval 0.5, 1.5 and person separation values of 5.87 and 6.09 respectively. Twenty-four overlapping "core" items enabled their calibration on the same measurement scale. Correlations with acuity (r = 0.47) demonstrated construct validity., Conclusions: The FVQ&#95;C and FVQ&#95;Young Person are robust age-appropriate versions of the FVQ&#95;CYP which can be used cross-sectionally or sequentially/longitudinally across the age range of 8 up to 18 years in clinical practice and research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: We investigated glaucoma related adverse events, predictors and impact at 5 years following surgery in the IoLunder2 cohort METHODS: Population based observational cohort study of children undergoing cataract surgery aged 2 years or under between January 2009 and December 2010. Glaucoma was defined using internationally accepted taxonomies based on the consequences of elevated intraocular pressure (IOP). Glaucoma related adverse events were any involving elevated IOP. Multivariable analysis was undertaken to investigate potential predictors of secondary glaucoma with adjustment for within-child correlation in bilateral cataract. Unilateral and bilateral cataract were analysed separately., Results: Complete follow-up data were available for 235 of 254, 93% of the inception cohort. By 5 years after primary cataract surgery, 20% of children with bilateral cataract and 12% with unilateral had developed secondary glaucoma. Glaucoma related complications had been diagnosed in 24% and 36% of children, respectively. Independent predictors of glaucoma were younger age at surgery (adjusted OR for reduction of week in age: 1.1, 95%C I 1.1 to 1.2, p<0.001); the presence of significant ocular comorbidity (adj OR 3.2, 95% CI 1.1 to 9.6, p=0.01); and shorter axial length (adj OR for each mm 1.7, 95% CI 10.0 to 1, p=0.05) for bilateral cataract. Shorter axial length was the single independent factor in unilateral disease (adj OR 9.6, 95% CI 1.7 to 52, p=0.009) CONCLUSIONS: Both younger age at surgery (the strongest marker of ocular 'immaturity') and smaller ocular size (a marker of both immaturity and developmental vulnerability) can be used to identify those at greatest risk of glaucoma due to early life cataract surgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (area under the curve (AUC) = 0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes that participate in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may enable the prediction of refractive error and the development of personalized myopia prevention strategies in the future.

Purpose: Developmentally sensitive measures of vision-related quality of life (VQoL) are needed to capture age-specific concerns about the impact of living with visual impairment (VI) in children and young people. Our objective was to use our validated VQoL instrument for children and young people 10 to 15 years of age (the VQoL&#95;CYP) as the foundation for development of age-specific extensions., Design: Questionnaire development., Participants: A representative sample of children and young people 6 to 19 years of age with VI, defined as visual acuity worse than 0.50 logarithm of the minimum angle of resolution in the better eye. They were recruited from pediatric ophthalmology clinics at Great Ormond Street Hospital and Moorfields Eye Hospital and, in the final phase of the study, from 20 additional United Kingdom hospitals., Methods: Standard instrument development processes were followed across 4 phases. Twenty-nine semistructured interviews with children and young people permitted draft age-appropriate extensions. Twenty-eight cognitive interviews informed items and response options. Age-appropriate extensions were prepiloted with 49 participants to ensure feasibility and administered via a postal survey to a national sample of 160 participants for psychometric evaluation using Rasch analysis. Construct validity was evaluated through correlations with the Pediatric Quality of Life Inventory., Main Outcome Measures: Psychometric indices of validity and reliability of the instrument versions., Results: Interviews confirmed that the existing VQoL&#95;CYP content and format were relevant across a wider age range. Age-appropriate extensions were drafted for children (8-12 years) and young people (13-17 years). Psychometric item reduction produced 20-item child and 22-item young person versions, each with acceptable fit values, no notable differential item functioning, good measurement precision, ordered response categories and acceptable targeting, and no notable differential item functioning on items common to both. Construct validity was demonstrated through correlations with health-related quality of life (r = 0.698)., Conclusions: Using an efficient child- and young person-centered approach, we developed 2 robust, age-appropriate versions of an instrument capturing VQoL that can be used cross-sectionally or sequentially across the age range of 8 to 17 years in research and clinical practice. This approach may be applicable in other rare childhood ophthalmic disorders., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background/aims: There is a paucity of high-level evidence to support the management of childhood uveitis, particularly for those children without juvenile idiopathic arthritis uveitis (JIA). We undertook a modified Delphi consensus exercise to identify agreement in the management of chronic anterior uveitis (CAU), the most common manifestation of childhood disease., Methods: A four-round, two-panel process was undertaken between June and December 2017. Paediatric uveitis specialists identified through multiple sources, including a multicentre network (the Paediatric Ocular Inflammation Group), were invited to participate. They were asked whether they agreed with items derived from existing guidelines on the management of JIA-U when extrapolated to the population of all children with CAU. Consensus was defined as agreement greater than or equal to 75% of respondents., Results: 26 of the 38 (68%) invited specialists participated with the exercise, and response rates were 100% for rounds one to three, and 92% for round four. Consensus was reached on 23 of the 44 items. Items for which consensus was not reached included management at presentation, use of systemic and periocular steroids for children with severe disease and the role of conventional steroid sparing immunosuppressants beyond methotrexate., Conclusion: The areas of management uncertainty at the level of the group, as indicated by absence of consensus, reflect the areas where the evidence base is particularly poor. Our findings identify the key areas for the future research needed to ensure better outcomes for this blinding childhood ocular inflammatory disorders., Competing Interests: Competing interests: AV Ramanan is Co-Chief Investigator of the Sycamore study which is funded by NIHR and ARUK, and has received Honoraria/Consultancy and speaker fees from Abbvie, Lilly, UCB, SOBI and Novartis. C Guly and JA have received fees from AbbVie (as speaker and advisory board member)., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To assess cross-cultural validity between Dutch and English versions of the FVQ&#95;CYP, a patient-reported outcome measure developed in the United Kingdom (UK) for children and adolescents with (severe) visual impairment or blindness (VI for brevity) to measure functional vision., Methods: The 36-item FVQ&#95;CYP was translated and adapted into Dutch using standard guidelines. The questionnaire was administered to Dutch children and adolescents aged 7-17 years (N = 253) with impaired vision (no restrictions regarding acuity). Data were compared to existing UK data of children and adolescents aged 10-15 years (N = 91) with VI (acuity LogMar worse than 0.48). As with the original UK FVQ&#95;CYP validation, a rating scale model (RSM) was applied to the Dutch data., Results: Minor adaptations were needed in translation-rounds. Significant differences in item responses were found between the Dutch and UK data. Item response theory assumptions were met, but fit to the RSM was unsatisfactory. Therefore, psychometric properties of the Dutch FVQ&#95;CYP were analysed irrespective of the original model and criteria used. A graded response model led to the removal of 12 items due to missing data, low information, overlapping content and limited relevance to Dutch children. Fit indices for the remaining 24 items were adequate., Conclusions: Differences in population characteristics, distribution of responses, non-invariance at the model level and small sample sizes challenged the cross-cultural validation process. However, the Dutch adapted FVQ&#95;CYP showed high measurement precision and broad coverage of items measuring children's functional vision. The underlying reasons for differences between countries in instrument performance are discussed with implications for future studies.

Background: Children and young people (CYP) living with diabetes require integrated child-centered care. We hypothesized that suboptimal uptake to diabetic retinopathy screening in CYP may be partly related to the degree of services integration. We investigated the structure of the current pediatric diabetic eye care pathway and associations between service-level characteristics and screening uptake., Methods: A quality improvement project between January and May 2017 comprising a survey of practice of all 158 pediatric diabetes services (pediatric diabetes units, PDUs) across England and secondary data analysis of routinely collected service data. Generalized linear models for proportional responses were fitted to investigate associations between reported PDU characteristics and screening uptake., Results: 124 PDUs (78%) responded. In 67% (n = 83), patients could be referred directly to screening programs; the remainder relied on primary care for onward referral. 97% (n = 120) considered eye screening results useful for counseling patients but only 65% (n = 81) reported it was "easy" to obtain them. Factors independently associated with higher screening uptake were a higher proportion of patients referred from primary care (OR = 1.005; 95%CI = 1.004-1.007 per 1% of increase), absence of "out-of-catchment area" patients (OR = 1.13; 95%CI = 1.04-1.22), and easy access to eye screening results (OR = 1.45; 95%CI = 1.34-1.56)., Conclusions: There is limited direct communication between the services involved in diabetic eye care for CYP in England. This risks reducing the effectiveness of diabetic retinopathy screening. Similar vulnerabilities are likely to exist in other countries where retinopathy screening for CYP has been "bolted on" to provision for adults., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: We compared feasibility, quality and outcomes of visual field (VF) testing in children with neuro-ophthalmic disease between the discontinued 'gold-standard' Goldmann and Octopus perimeters., Methods: Children with neuro-ophthalmic disease, attending Great Ormond Street Hospital, London, were assessed using standardised protocols by one examiner in a single sitting, using Goldmann and Octopus kinetic perimetry. Outputs were classified to compare severity of loss and defect type. Test quality was assessed using both qualitative and quantitative methods., Results: Thirty children (40% female) aged 5-15 years participated. Goldmann perimetry was completed in full by 90.0% vs 72.4% for Octopus. Inability to plot the blind spot was the most common reason for not completing testing. Over 75% completed a test in ≤20 min. Duration was similar between perimeters (paired t-test, mean difference: 0.48min (-1.2, 2.2), p=0.559). The lowest quality tests were for Octopus perimetry in children <8 years, without significant differences between perimeters in older children (McNemar's test, χ 2 =1.0, p=0.317). There was broad agreement between Goldmann and Octopus outputs (good quality, n=21, Bland-Altman, mean difference for isopters I4e (-514.3 deg 2 (-817.4, -211.2), p=0.814), I2e (-575.5 deg 2 (-900.1, -250.9), p=0.450) and blind spot (20.8 deg 2 (5.7, 35.8), p=0.451)). However, VF severity grades and defect type matched in only 57% and 69% of tests, respectively. Octopus perimetry underestimated severe VF defects., Conclusions: Informative perimetry is feasible in children ≥8 years with neuro-ophthalmic conditions, with either Goldmann or Octopus perimeters. However, meaningful differences exist between the two approaches with implications for consistency in longitudinal assessments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Strabismus refers to an abnormal alignment of the eyes leading to the loss of central binocular vision. Concomitant strabismus occurs when the angle of deviation is constant in all positions of gaze and often manifests in early childhood when it is considered to be a neurodevelopmental disorder of the visual system. As such, it is inherited as a complex genetic trait, affecting 2-4% of the population. A genome-wide association study (GWAS) for self-reported strabismus (1345 cases and 65,349 controls from UK Biobank) revealed a single genome-wide significant locus on chromosome 17q25. Approximately 20 variants across the NPLOC4-TSPAN10-PDE6G gene cluster and in almost perfect linkage disequilibrium (LD) were most strongly associated (lead variant: rs75078292, OR = 1.26, p = 2.24E-08). A recessive model provided a better fit to the data than an additive model. Association with strabismus was independent of refractive error, and the degree of association with strabismus was minimally attenuated after adjustment for amblyopia. The association with strabismus was replicated in an independent cohort of clinician-diagnosed children aged 7 years old (116 cases and 5084 controls; OR = 1.85, p = 0.009). The associated variants included 2 strong candidate causal variants predicted to have functional effects: rs6420484, which substitutes tyrosine for a conserved cysteine (C177Y) in the TSPAN10 gene, and a 4-bp deletion variant, rs397693108, predicted to cause a frameshift in TSPAN10. The population-attributable risk for the locus was approximately 8.4%, indicating an important role in conferring susceptibility to strabismus.

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

Background: International initiatives to prevent childhood blindness have highlighted the importance of early, effective intervention for congenital and infantile cataract. In the UK, intraocular lens implantation has been widely adopted by surgeons to treat these conditions. However, evidence about the benefits and risks of this technique in different age groups is limited. The IoLunder2 study assessed outcomes following primary intraocular lens implantation in children aged 2 years and younger with congenital or infantile cataract., Methods: The IoLunder2 study was a prospective observational cohort study done at 31 sites in the UK and Ireland. Eligible children were aged 2 years or younger who had cataract surgery concurrently with intraocular lens implantation or conventional treatment (aphakic correction with contact lenses or glasses) after cataract surgery between Jan 1, 2009, and Dec 31, 2010. Children with significant ocular comorbidity precluding lens implantation, defined by the presence of complex persistent fetal vasculature, other ocular structural anomalies, severe microcornea (horizontal corneal diameter <9·5 mm), or severe microphthalmos (axial length <16 mm), were excluded from the analysis of the key outcomes. Postoperative visual rehabilitation was assessed at 1, 3, and 5 years after surgery with a 4m logarithm of the minimum angle of resolution (logMAR) notation test. Best corrected visual outcome (acuity) overall was assessed 5 years after surgery for children with bilateral and unilateral cataract. We also used multivariable logistic and linear regression to model the association between intraocular lens implantation and outcomes of interest (vision, glaucoma, and visual axis opacity)., Findings: A total of 256 eligible children were recruited; two had incomplete data and were excluded. 158 of the 254 included children (102 [65%] with bilateral cataract and 56 [35%] with unilateral cataract) had no significant ocular morbidity and were analysed for the key outcomes. Primary intraocular lens implantation was done in 88 (56%) of 158 children (50 children with bilateral cataract and 38 children with unilateral cataract). 70 (44%) of 158 children had conventional treatment (52 with bilateral cataract and 18 with unilateral cataract). Overall median visual acuity at 5 years was 0·34 logMAR (IQR 0·20-0·54) for children with bilateral cataract and 0·70 logMAR (IQR 0·3-1·3) in the operated eye for children with unilateral cataract. Primary intraocular lens implantation was not associated with better visual outcome than conventional treatment in children with bilateral cataract (adjusted coefficient -0·1, 95% CI -0·5 to 0·3, p=0·48) or unilateral cataract (adjusted coefficient -0·3, -0·6 to 0·2, p=0·36), or reduced incidence of postoperative glaucoma in children with bilateral cataract (adjusted odds ratio [OR] 0·5, 0·10 to 1·80, p=0·28), but was associated with a five times higher risk of reoperation for visual axis opacity requiring general anaesthesia in children with bilateral cataract (adjusted OR 5·94, 95% CI 2·14-16·47, p=0·001) and a 20 times higher risk in children with unilateral cataract (20·15, 3·01-134·00, p=0·001)., Interpretation: The findings of this cohort study indicate that intraocular lens implantation does not confer better vision or protection against postoperative glaucoma, and conversely increases the risk of requiring early reoperation in children younger than 2 years with bilateral or unilateral cataract. The routine use of intraocular lens implantation in this age group cannot be recommended., Funding: National Institute for Health Research, Ulverscroft Foundation, and the Academy of Medical Sciences., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Refractive error is an increasing global public health concern that requires robust and reliable research to identify modifiable risk factors and provide accurate estimates of population burden. We investigated the impact of reclassification of individuals when using different threshold values of spherical equivalent (SE) to define myopia, on estimates of frequency, distribution and associations with risk factors, to inform current international initiatives to standardise definitions., Methods: A random sample of 1985 individuals from the 1958 British birth cohort, at age 44, had autorefraction and self-reported on educational attainment and social class.Refraction status assigned in three different models using SE: (A) moderate to high myopia -3 diopters (D) or more extreme (≤-3.00D), (B) hypermetropia +1.00D or more extreme (≥+1.00D) and (C) mild myopia using three different thresholds: -1.00D, -0.75D or -0.50D, hence reciprocal changes in definition of emmetropia., Results: Frequency estimates and associations with risk factors altered significantly as the threshold value for myopia moved towards SE 0.0D: prevalence of mild myopia increased from 28% to 47%, the association with highest educational attainment attenuated and with higher social class strengthened, with changes in risk ratios of approximately 20%., Conclusion: Even small changes in the threshold definition of myopia (±0.25D) can significantly affect the conclusions of epidemiological studies, creating both false-positive and false-negative associations for specific risk factors. An international classification for refractive error, empirically evidenced and cognisant of the question(s) being addressed and the population(s) being studied, is needed to serve better translational research, practice and policy., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.

Importance: There is limited evidence to support the development of guidance for visual field testing in children with glaucoma., Objective: To compare different static and combined static/kinetic perimetry approaches in children with glaucoma., Design, Setting, and Participants: Cross-sectional, observational study recruiting children prospectively between May 2013 and June 2015 at 2 tertiary specialist pediatric ophthalmology centers in London, England (Moorfields Eye Hospital and Great Ormond Street Hospital). The study included 65 children aged 5 to 15 years with glaucoma (108 affected eyes)., Main Outcomes and Measures: A comparison of test quality and outcomes for static and combined static/kinetic techniques, with respect to ability to quantify glaucomatous loss. Children performed perimetric assessments using Humphrey static (Swedish Interactive Thresholding Algorithm 24-2 FAST) and Octopus combined static tendency-oriented perimetry/kinetic perimetry (isopter V4e, III4e, or I4e) in a single sitting, using standardized clinical protocols, administered by a single examiner. Information was collected about test duration, completion, and quality (using automated reliability indices and our qualitative Examiner-Based Assessment of Reliability score). Perimetry outputs were scored using the Aulhorn and Karmeyer classification. One affected eye in 19 participants was retested with Swedish Interactive Thresholding Algorithm 24-2 FAST and 24-2 standard algorithms., Results: Sixty-five children (33 girls [50.8%]), with a median age of 12 years (interquartile range, 9-14 years), were tested. Test quality (Examiner-Based Assessment of Reliability score) improved with increasing age for both Humphrey and Octopus strategies and were equivalent in children older than 10 years (McNemar test, χ2 = 0.33; P = .56), but better-quality tests with Humphrey perimetry were achieved in younger children (McNemar test, χ2 = 4.0; P = .05). Octopus and Humphrey static MD values worse than or equal to -6 dB showed disagreement (Bland-Altman, mean difference, -0.70; limit of agreement, -7.74 to 6.35) but were comparable when greater than this threshold (mean difference, -0.03; limit of agreement, -2.33 to 2.27). Visual field classification scores for static perimetry tests showed substantial agreement (linearly weighted κ, 0.79; 95% CI, 0.65-0.93), although 25 of 80 (31%) were graded with a more severe defect for Octopus static perimetry. Of the 7 severe cases of visual field loss (grade 5), 5 had lower kinetic than static classification scores., Conclusions and Relevance: A simple static perimetry approach potentially yields high-quality results in children younger than 10 years. For children older than 10 years, without penalizing quality, the addition of kinetic perimetry enabled measurement of far-peripheral sensitivity, which is particularly useful in children with severe visual field restriction.

Introduction: The frequency of diabetes mellitus in childhood is increasing. Thus, more children and young people are at risk of developing diabetic retinopathy and diabetes related visual impairment. However, there is no consensus on optimal screening strategies for the paediatric population reflecting the lack of clarity about the current burden of disease in this group. We aim to estimate the prevalence of diabetic retinopathy in children and young people living with types 1 or 2 diabetes, and to investigate potential sources of heterogeneity in this figure so as to inform screening strategies for this population., Methods and Analysis: PubMed and EMBASE will be searched from 1995 to 2016 using the OvidSP platform with no language restriction. Additionally, manual review of the references lists of included articles will be conducted. Two investigators will independently screen titles and abstracts for potential eligibility. Studies which report prevalence of diabetic retinopathy among general populations of children and young people with types 1 or 2 diabetes will be included. Pooled prevalence estimates of diabetic retinopathy reported in studies with sample size greater than 200 participants will be calculated by the random effect model. Forest plots will be used to summarise individual and pooled estimates of the prevalence. Heterogeneity between studies will be assessed using the I 2 statistic and explored through meta-regressions and subgroup analyses if the necessary data are available., Ethics and Dissemination: Ethics approval is not required as this is a review of anonymised published data. We will report the findings of this systematic review in a peer-reviewed journal, and share it with the relevant professionals including health authorities through our Diabetic Eye disease in Childhood Study collaborative network., Clinical Trail Registration: PROSPERO (CRD42017067178)., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Importance: Despite the existing country-specific strategies tackling social inequalities in visual health in adults, little is known about trends in visual function in childhood and its association with social position., Objective: To investigate the distribution of childhood visual function in the United Kingdom and associations with early-life social position between 1961 and 1986, a period of significant social change., Design, Setting, and Participants: Longitudinal cohort study using harmonized data sets from the British 1946, 1958, and 1970 national birth cohorts. In total, 14 283 cohort members with complete data on visual acuity at age 15 or 16 years, measured in 1961, 1974, and 1986, respectively, for each cohort, and social position were assessed., Main Outcomes and Measures: Using habitual distance visual acuity (with correction if prescribed), participants were assigned to a visual function category ranging from bilateral normal to visual impairment/severe visual impairment/blindness (International Statistical Classification of Diseases, Tenth Revision, Clinical Modification). Distribution of visual function over time and associations with social position (risk ratios [RRs] and 95% confidence intervals) were analyzed., Results: Complete data were available for 3152 participants (aged 15 years; 53% boys [n = 1660]) in the 1946 Medical Research Council National Survey of Health and Development, 6683 participants (aged 16 years; 51% boys [n = 3420]) in the 1958 National Child Development Study, and 4448 participants (aged 16 years; 48% boys [n = 2156]) in the 1970 British Birth Cohort Study. The proportion of children with bilateral normal vision decreased by 1.3% (95% CI, -5.1% to 2.7%) in 1974 and 1.7% (95% CI, -5.9% to 2.7%) in 1986. The risk of overall impaired vision increased by 1.20 times (95% CI, 1.01-1.43) and the risk of visual impairment/severe visual impairment/blindness by 1.75 times (95% CI, 1.03-2.98) during this period. Girls were consistently at increased risk of all vision impairment categories. Higher social position at birth and in childhood was associated with reduced risk of visual impairment/severe visual impairment/blindness (RR, 0.58; 95% CI, 0.20-1.68) and unilateral impairment (RR, 0.89; 95% CI, 0.72-1.11), respectively., Conclusions and Relevance: Our study provides evidence of temporal decline in childhood visual function between 1961 and 1986. Despite the limited power of the analysis owing to the small sample size of those with impaired vision, we found an emergence of a contribution of sociodemographic status to the cohort effect that may be the antecedent of the current picture of childhood blindness. Equally, early-life social position may also have contributed to the current social patterning in visual function in older adults in the United Kingdom. These findings highlight the potential value of targeting children in national ophthalmic public policies tackling inequalities.