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.

Trends in the long-term impact of childhood visual impairment on health and social outcomes in the UK: a cross-cohort study across three decades of disability-related legislation and policy implementation.

BACKGROUND: Childhood vision impairment (VI) can adversely impact health and social outcomes and limit life chances. We investigated whether its adverse impacts into adult life changed during a period in which legislation, policy and services to address inequalities relating to disability were implemented. METHODS: Cross-cohort study comprising 14 247 participants from the 1946, 1958 and 1970 British birth cohorts (BC). Participants dichotomized as VI at age 15/16 (distance visual acuity was 6/12 or worse in the better-seeing eye) or normally sighted. Associations of childhood VI with health, well-being, socioeconomic and social participation outcomes in mid-adult life were investigated using regression models adjusted for participants' early life socioeconomic markers and sex. Change in adjusted odds ratios of >10% in the same direction in successive cohorts, or a > 20% difference between 1970BC and one older cohort were considered meaningful. RESULTS: Trends over time in impacts of childhood onset VI into mid-adult life were complex. This included worsening of odds of poorer physical health (odds ratio 1.47; 95% confidence interval 1.02-2.14), living in unsatisfactory (1.54; 1.03-2.29) or overcrowded (2.34; 1.26-4.06) households, being unemployed (2.19; 1.19-3.97) and not gaining additional educational qualifications during mid-adult life (1.61; 1.08-2.47). By contrast the odds of not participating in some social activities (e.g. seeing friends) improved over time. Associations with other outcomes were unchanged. CONCLUSIONS: Many adverse impacts of childhood VI do not appear ameliorated over time by legislation, policies and provision that would have been expected to reduce inequalities. Moreover, some were increased. Childhood VI continues to cast a life-long shadow.

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.

Visual Axis Opacity after Intraocular Lens Implantation in Children in the First 2 Years of Life: Findings from the IoLunder2 Cohort Study.

PURPOSE: Appropriate correction of aphakia is key to good outcomes. There may be clinical settings where and populations in whom accessing or managing aphakic contact lenses is challenging. Strategies to target the increased risk of visual axis opacity (VAO) after primary intraocular lens (IOL) implantation in infancy are necessary. We describe the predictors of VAO after primary IOL implantation for unilateral or bilateral congenital or infantile cataract in children younger than 2 years of age. DESIGN: Population-based (United Kingdom and Ireland), prospective, inception cohort study undertaken through a national clinical network. PARTICIPANTS: A total of 105 children (57 with bilateral cataract, 48 with unilateral cataract, total 162 eyes) undergoing primary IOL implantation in the first 2 years of life between January 2009 and December 2010. METHODS: Observational longitudinal study with multilevel, multivariable modeling to investigate associations between outcome of interest and child- and treatment-specific factors, including age, axial length, socioeconomic status, IOL model, and postoperative steroid use. MAIN OUTCOME MEASURES: Postoperative proliferative or inflammatory visual axis opacity (VAO) requiring surgical correction. RESULTS: Visual axis opacity occurred in 67 eyes (45%), typically within the first postoperative year. Use of a 3-piece IOL model (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.09-0.99, P = 0.03) and increasing age at surgery (OR, 0.97, 95% CI, 0.95-0.99, P = 0.02) were each independently protective against the development of proliferative VAO. Inflammatory VAO was independently associated with socioeconomic deprivation (OR, 5.39; 95% CI, 1.46-19.89; P = 0.01). CONCLUSIONS: Visual axis opacification is common after IOL implantation in early childhood. The findings of this prospective cohort study suggest that the use of 3-piece IOL models may reduce the risk of pseudophakic VAO in children younger than 2 years of age.

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.

Tests for detecting strabismus in children aged 1 to 6 years in the community.

BACKGROUND: Strabismus (misalignment of the eyes) is a risk factor for impaired visual development both of visual acuity and of stereopsis. Detection of strabismus in the community by non-expert examiners may be performed using a number of different index tests that include direct measures of misalignment (corneal or fundus reflex tests), or indirect measures such as stereopsis and visual acuity. The reference test to detect strabismus by trained professionals is the cover‒uncover test. OBJECTIVES: To assess and compare the accuracy of tests, alone or in combination, for detection of strabismus in children aged 1 to 6 years, in a community setting by non-expert screeners or primary care professionals to inform healthcare commissioners setting up childhood screening programmes.Secondary objectives were to investigate sources of heterogeneity of diagnostic accuracy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12) (which contains the Cochrane Eyes and Vision Trials Register) in the Cochrane Library, the Health Technology Assessment Database (HTAD) in the Cochrane Library (2016, Issue 4), MEDLINE Ovid (1946 to 5 January 2017), Embase Ovid (1947 to 5 January 2017), CINAHL (January 1937 to 5 January 2017), Web of Science Conference Proceedings Citation Index-Science (CPCI-S) (January 1990 to 5 January 2017), BIOSIS Previews (January 1969 to 5 January 2017), MEDION (to 18 August 2014), the Aggressive Research Intelligence Facility database (ARIF) (to 5 January 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 5 January 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 5 January 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 5 January 2017. We did not use any date or language restrictions in the electronic searches for trials. In addition, orthoptic journals and conference proceedings without electronic listings were searched. SELECTION CRITERIA: All prospective or retrospective population-based test accuracy studies of consecutive participants were included. Studies compared a single or combination of index tests with the reference test. Only those studies with sufficient data for analysis were included specifically to calculate sensitivity and specificity and determine diagnostic accuracy.Participants were aged 1 to 6 years. Studies reporting participants outside this range were included if subgroup data were available.Permitted settings included population-based vision screening programmes or opportunistic screening programmes, such as those performed in schools. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. In brief, two review authors independently assessed titles and abstracts for eligibility and extracted the data, with a third senior author resolving any disagreement. We analysed data primarily for specificity and sensitivity. MAIN RESULTS: One study from a total of 1236 papers, abstracts and trials was eligible for inclusion with a total number of participants of 335 of which 271 completed both the screening test and the gold standard test. The screening test using an automated photoscreener had a sensitivity of 0.46 (95% confidence interval (CI) 0.19 to 0.75) and specificity of 0.97 (CI 0.94 to 0.99). The overall number affected by strabismus was low at 13 (4.8%). AUTHORS' CONCLUSIONS: There is very limited data in the literature to ascertain the accuracy of tests for detecting strabismus in the community as performed by non-expert screeners. A large prospective study to compare methods would be required to determine which tests have the greatest accuracy.

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.

Increasing Prevalence of Myopia in Europe and the Impact of Education.

PURPOSE: To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. DESIGN: Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E(3)) Consortium. PARTICIPANTS: The E(3) Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. METHODS: Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤-0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. MAIN OUTCOME MEASURES: Variation in age-specific myopia prevalence for differing years of birth and educational level. RESULTS: There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5), and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio-2.43 (CI, 1.26-4.17) and 2.62 (CI, 1.31-5.00), respectively-whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21-6.57). CONCLUSIONS: Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia.

Prevalence of refractive error in Europe: the European Eye Epidemiology (E(3)) Consortium.

To estimate the prevalence of refractive error in adults across Europe. Refractive data (mean spherical equivalent) collected between 1990 and 2013 from fifteen population-based cohort and cross-sectional studies of the European Eye Epidemiology (E(3)) Consortium were combined in a random effects meta-analysis stratified by 5-year age intervals and gender. Participants were excluded if they were identified as having had cataract surgery, retinal detachment, refractive surgery or other factors that might influence refraction. Estimates of refractive error prevalence were obtained including the following classifications: myopia ≤-0.75 diopters (D), high myopia ≤-6D, hyperopia ≥1D and astigmatism ≥1D. Meta-analysis of refractive error was performed for 61,946 individuals from fifteen studies with median age ranging from 44 to 81 and minimal ethnic variation (98 % European ancestry). The age-standardised prevalences (using the 2010 European Standard Population, limited to those ≥25 and <90 years old) were: myopia 30.6 % [95 % confidence interval (CI) 30.4-30.9], high myopia 2.7 % (95 % CI 2.69-2.73), hyperopia 25.2 % (95 % CI 25.0-25.4) and astigmatism 23.9 % (95 % CI 23.7-24.1). Age-specific estimates revealed a high prevalence of myopia in younger participants [47.2 % (CI 41.8-52.5) in 25-29 years-olds]. Refractive error affects just over a half of European adults. The greatest burden of refractive error is due to myopia, with high prevalence rates in young adults. Using the 2010 European population estimates, we estimate there are 227.2 million people with myopia across Europe.

Associations between unilateral amblyopia in childhood and cardiometabolic disorders in adult life: a cross-sectional and longitudinal analysis of the UK Biobank.

Background: Amblyopia is a common neurodevelopmental condition and leading cause of childhood visual impairment. Given the known association between neurodevelopmental impairment and cardiometabolic dysfunction in later life, we investigated whether children with amblyopia have increased risk of cardiometabolic disorders in adult life. Methods: This was a cross-sectional and longitudinal analysis of 126,399 United Kingdom Biobank cohort participants who underwent ocular examination. A subset of 67,321 of these received retinal imaging. Data analysis was conducted between November 1st 2021 and October 15th 2022. Our primary objective was to investigate the association between amblyopia and a number of components of metabolic syndrome and individual cardiometabolic diseases. Childhood amblyopia, dichotomised as resolved or persisting by adulthood, cardiometabolic disease and mortality were defined using ophthalmic assessment, self-reported, hospital admissions and death records. Morphological features of the optic nerve and retinal vasculature and sublayers were extracted from retinal photography and optical coherence tomography. Associations between amblyopia and cardiometabolic disorders as well as retinal markers were investigated in multivariable-adjusted regression models. Findings: Individuals with persisting amblyopia (n = 2647) were more likely to be obese (adjusted odds ratio (95% confidence interval): 1.16 (1.05; 1.28)), hypertensive (1.25 (1.13; 1.38)) and diabetic (1.29 (1.04; 1.59)) than individuals without amblyopia (controls, (n = 18,481)). Amblyopia was also associated with an increased risk of myocardial infarction (adjusted hazard ratio: 1.38 (1.11; 1.72)) and death (1.36 (1.15; 1.60)). On retinal imaging, amblyopic eyes had significantly increased venular caliber (0.29 units (0.21; 0.36)), increased tortuosity (0.11 units (0.03; 0.19)), but lower fractal dimension (-0.23 units (-0.30; -0.16)) and thinner ganglion cell-inner plexiform layer (mGC-IPL, -2.85 microns (-3.47; -2.22)). Unaffected fellow eyes of individuals with amblyopia also had significantly lower retinal fractal dimension (-0.08 units (-0.15; -0.01)) and thinner mGC-IPL (-1.14 microns (-1.74; -0.54)). Amblyopic eyes with a persisting visual deficit had smaller optic nerve disc height (-0.17 units (-0.25; -0.08)) and width (-0.13 units (-0.21; -0.04)) compared to control eyes. Interpretation: Although further research is needed to understand the basis of the observed associations, healthcare professionals should be cognisant of greater cardiometabolic dysfunction in adults who had childhood amblyopia. Differences in retinal features in both the amblyopic eye and the unaffected non-amblyopic suggest generalised versus local processes. Funding: Medical Research Council (MR/T000953/1) and the National Institute for Health and Care Research.

Show don't tell: assessing the impact of co-developed patient information videos in paediatric uveitis.

BACKGROUND/OBJECTIVES: There is a paucity of online educational content targeting children and young people with uveitis. We evaluated the impact of a co-designed patient education video on subjective and objective understanding of childhood uveitis. SUBJECTS/METHODS: Co-designed patient education media were produced in collaboration with the Childhood Uveitis Studies steering group and the Great Ormond Street Hospital Generation R Young People's Advisory Group and narrated by children. Patients managed within the Uveitis service at GOSH were invited to take part in a pre-post survey, undertaken immediately prior to and following viewing of a patient education video. RESULTS: Forty-three patients participated. These were stratified according to age, duration of disease, and treatment type for analysis. Self-rated knowledge improved across all groups (p = 0.001), particularly in those with a new diagnosis of uveitis (Z = -8.124, p < 0.001). Objective knowledge scores improved across all questions, especially in younger children, those with new disease, and those on steroid only treatment (Z = -3.847, p < 0.001, Z = -3.975, p < 0.001, Z = -3.448, p < 0.001; respectively). Most participants reported the videos to be easy to understand and with the right amount of information. All stated that they learned something new. CONCLUSIONS: Patient understanding of disease and treatment is crucial to achieving the best possible outcomes for this chronic, relapsing remitting and potentially blinding disorder. Our findings data shows the potential value of co-designed patient information videos, specifically in our study benefitting younger patients and those recently diagnosed. We suggest that other clinical teams could collaborate fruitfully with patient groups to develop similar videos to target possible misinformation and potentially improve patient outcomes.

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.