A genome-wide analysis of 340 318 participants identifies four novel loci associated with the age of first spectacle wear.

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.

Impact of Persisting Amblyopia on Socioeconomic, Health, and Well-Being Outcomes in Adult Life: Findings From the UK Biobank.

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.

An Age- and Stage-Appropriate Patient-Reported Outcome Measure of Vision-Related Quality of Life of Children and Young People with Visual Impairment.

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_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_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.

A commonly occurring genetic variant within the NPLOC4-TSPAN10-PDE6G gene cluster is associated with the risk of strabismus.

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.

Vulnerabilities in diabetic eye screening for children and young people in England.

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.

Cross-cultural validation of the Functional Vision Questionnaire for Children and Young People (FVQ_CYP) with visual impairment in the Dutch population: challenges and opportunities.

BACKGROUND: To assess cross-cultural validity between Dutch and English versions of the FVQ_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_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_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_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_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.

Whole-population vision screening in children aged 4-5 years to detect amblyopia.

Amblyopia is a neurodevelopmental disorder that affects at least 2% of most populations and can lead to permanently reduced vision if not detected and treated within a specific period in childhood. Whole-population screening of children younger than 5 years is applied in many countries. The substantial diversity in existing programmes reflects their heterogeneous implementation in the absence of the complete evidence base that is now a pre-requisite for instituting screening. The functional importance of amblyopia at an individual level is unclear as data are scarce, but in view of the high prevalence the population-level effect might be notable. Screening of all children aged 4-5 years (eg, at school entry) confers most benefit and addresses inequity in access to timely treatment. Screening at younger ages is associated with increased risk of false-positive results, and at older ages with poor outcomes for children with moderate to severe amblyopia. We suggest that the real-life adverse effects of amblyopia should be characterised and screening and diagnosis should be standardised.

Ophthalmic epidemiology in Europe: the "European Eye Epidemiology" (E3) consortium.

The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.

Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium.

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.

Study of Optimal Perimetric Testing In Children (OPTIC): Normative Visual Field Values in Children.

PURPOSE: We sought to define normative visual field (VF) values for children using common clinical test protocols for kinetic and static perimetry. DESIGN: Prospective, observational study. SUBJECTS: We recruited 154 children aged 5 to 15 years without any ophthalmic condition that would affect the VF (controls) from pediatric clinics at Moorfields Eye Hospital. METHODS: Children performed perimetric assessments in a randomized order using Goldmann and Octopus kinetic perimetry, and Humphrey static perimetry (Swedish Interactive Thresholding Algorithm [SITA] 24-2 FAST), in a single sitting, using standardized clinical protocols, with assessment by a single examiner. Unreliable results (assessed qualitatively) were excluded from the normative data analysis. Linear, piecewise, and quantile mixed-effects regression models were used. We developed a method to display age-specific normative isopters graphically on a VF plot to aid interpretation. MAIN OUTCOME MEASURES: Summary measures and graphical plots describing normative VF data for 3 common perimetric tests. RESULTS: Visual field area increased with age on testing with Goldmann isopters III4e, I4e, and I2e (linear regression; P < 0.001) and for Octopus isopters III4e and I4e (linear regression; P < 0.005). Visual field development occurs predominately in the inferotemporal field. Humphrey mean deviation (MD) showed an increase of 0.3 decibels (dB; 95% CI, 0.21-0.40) MD per year up to 12 years of age, when adult MD values were reached and thereafter maintained. CONCLUSIONS: Visual field size and sensitivity increase with age in patterns that are specific to the perimetric approach used. These developmental changes should be accounted for when interpreting perimetric test results in children, particularly when monitoring change over time.

Evaluating the Quantity and Quality of Health Economic Literature in Blinding Childhood Disorders: A Systematic Literature Review.

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.

Socioeconomic and demographic patterning of family uptake of a paediatric electronic patient portal innovation.

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.

Imaging-based detection of anterior chamber inflammation: a comparative diagnostic accuracy study.

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.

Establishing the Normative Data Set Necessary for Imaging-Based Childhood Uveitis Surveillance: A Cross-Sectional Study.

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.

Quality assessment of anterior segment OCT images: Development and validation of quality criteria.

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.

Determinants of non-attendance at face-to-face and telemedicine ophthalmic consultations.

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.

Periodontitis and Outer Retinal Thickness: a Cross-Sectional Analysis of the United Kingdom Biobank Cohort.

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.

Development of the functional vision questionnaire for children and young people with visual impairment: the FVQ_CYP.

OBJECTIVE: To develop a novel age-appropriate measure of functional vision (FV) for self-reporting by visually impaired (VI) children and young people. DESIGN: Questionnaire development. PARTICIPANTS: A representative patient sample of VI children and young people aged 10 to 15 years, visual acuity of the logarithm of the minimum angle of resolution (logMAR) worse than 0.48, and a school-based (nonrandom) expert group sample of VI students aged 12 to 17 years. METHODS: A total of 32 qualitative semistructured interviews supplemented by narrative feedback from 15 eligible VI children and young people were used to generate draft instrument items. Seventeen VI students were consulted individually on item relevance and comprehensibility, instrument instructions, format, and administration methods. The resulting draft instrument was piloted with 101 VI children and young people comprising a nationally representative sample, drawn from 21 hospitals in the United Kingdom. Initial item reduction was informed by presence of missing data and individual item response pattern. Exploratory factor analysis (FA) and parallel analysis (PA), and Rasch analysis (RA) were applied to test the instrument's psychometric properties. MAIN OUTCOME MEASURES: Psychometric indices and validity assessment of the Functional Vision Questionnaire for Children and Young People (FVQ_CYP). RESULTS: A total of 712 qualitative statements became a 56-item draft scale, capturing the level of difficulty in performing vision-dependent activities. After piloting, items were removed iteratively as follows: 11 for high percentage of missing data, 4 for skewness, and 1 for inadequate item infit and outfit values in RA, 3 having shown differential item functioning across age groups and 1 across gender in RA. The remaining 36 items showed item fit values within acceptable limits, good measurement precision and targeting, and ordered response categories. The reduced scale has a clear unidimensional structure, with all items having a high factor loading on the single factor in FA and PA. The summary scores correlated significantly with visual acuity. CONCLUSIONS: We have developed a novel, psychometrically robust self-report questionnaire for children and young people-the FVQ_CYP-that captures the functional impact of visual disability from their perspective. The 36-item, 4-point unidimensional scale has potential as a complementary adjunct to objective clinical assessments in routine pediatric ophthalmology practice and in research.

Temporal trends in the epidemiology of childhood severe visual impairment and blindness in the UK.

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.