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.

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.

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.

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.

Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.

Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 × 10(-12) for SNP rs634990 in Caucasians, and 9.65 × 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 × 10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.

The improving outcomes in intermittent exotropia study: outcomes at 2 years after diagnosis in an observational cohort.

BACKGROUND: The purpose of this study was to investigate current patterns of management and outcomes of intermittent distance exotropia [X(T)] in the UK. METHODS: This was an observational cohort study which recruited 460 children aged < 12 years with previously untreated X(T). Eligible subjects were enrolled from 26 UK hospital ophthalmology clinics between May 2005 and December 2006. Over a 2-year period of follow-up, clinical data were prospectively recorded at standard intervals from enrolment. Data collected included angle, near stereoacuity, visual acuity, control of X(T) measured with the Newcastle Control Score (NCS), and treatment. The main outcome measures were change in clinical outcomes (angle, stereoacuity, visual acuity and NCS) in treated and untreated X(T), 2 years from enrolment (or, where applicable, 6 months after surgery). Change over time was tested using the chi-square test for categorical, Wilcoxon test for non-parametric and paired-samples t-test for parametric data. RESULTS: At follow-up, data were available for 371 children (81% of the original cohort). Of these: 53% (195) had no treatment; 17% (63) had treatment for reduced visual acuity only (pure refractive error and amblyopia); 13% (50) had non surgical treatment for control (spectacle lenses, occlusion, prisms, exercises) and 17% (63) had surgery. Only 0.5% (2/371) children developed constant exotropia. The surgically treated group was the only group with clinically significant improvements in angle or NCS. However, 8% (5) of those treated surgically required second procedures for overcorrection within 6 months of the initial procedure and at 6-month follow-up 21% (13) were overcorrected. CONCLUSIONS: Many children in the UK with X(T) receive active monitoring only. Deterioration to constant exotropia, with or without treatment, is rare. Surgery appears effective in improving angle of X(T) and NCS, but rates of overcorrection are high.

Temporal trends in frequency, type and severity of myopia and associations with key environmental risk factors in the UK: Findings from the UK Biobank Study.

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.

Study of Optimal Perimetric Testing In Children (OPTIC): developing consensus and setting research priorities for perimetry in the management of children with glaucoma.

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.

Myopia over the lifecourse: prevalence and early life influences in the 1958 British birth cohort.

PURPOSE: To investigate the hypothesis that the excessive growth of the eye in myopia is associated with general growth and thus influenced by early life biological and social factors, and that these associations underlie recent secular trends of increasing prevalence and severity of myopia. DESIGN: Cohort study. PARTICIPANTS: A total of 2487 randomly selected 44-year-old members of the 1958 British birth cohort (27% subsample). METHODS: Diverse and detailed biological, social, and lifestyle data have been collected by following members since birth through a series of clinical examinations or face-to-face interviews carried out by trained examiners. At 44 years, cohort members underwent autorefraction using the Nikon Retinomax 2 (Nikon Corp., Tokyo, Japan) under non-cycloplegic conditions. A lifecourse epidemiologic approach, based on 4 sequential multivariable "life stage" models (preconceptional; prenatal, perinatal, and postnatal; childhood; and adult), was used to examine the influence of early life biological, social and lifestyle factors, growth patterns, and "eye-specific" factors on myopia. MAIN OUTCOME MEASURES: Myopia severity (all, mild/moderate: spherical equivalent -0.75 to -5.99 diopters [D]; severe: ≥-6.00 D extreme vs. emmetropia -0.74 to +0.99 D) and myopia onset (early [<16 years] vs. later). RESULTS: A total of 1214 individuals (49%; 95% confidence interval, 48.8-50.8) were myopic (late onset in 979 [80.6%]). Myopia was positively associated with low birthweight for gestational age, gender, greater maternal age, higher paternal occupational social class, and maternal smoking in early pregnancy. Myopia was independently associated with proxy markers of near work and educational performance, with some differences by onset and severity. In adults, greater height and higher educational attainment and socioeconomic status were associated with myopia. CONCLUSIONS: Trends in the key influences on child health and growth identified as novel putative risk factors in this study are consistent with global trends of increasing myopia: increasing births to older mothers, increasing rates of intrauterine growth retardation and survival of affected children, increasing persistence of smoking in pregnancy, and changing socioeconomic status. Prospects for prevention of myopia would be improved by a paradigm shift in myopia research, with lifecourse and genetic epidemiologic approaches applied in tandem in large unselected populations.

Outcomes of childhood epilepsy at age 33 years: a population-based birth-cohort study.

PURPOSE: There is uncertainty about health and socioeconomic outcomes of children with epilepsy, knowledge of adult outcomes, and factors associated with adverse outcomes are essential to guide prognosis, improve management, and determine appropriate allocation of resources. METHODS: A subgroup of 101 children with epilepsy (onset ≤ age 16 years) were previously identified and reported from the 1958 National Child Development Study (NCDS), a national United Kingdom birth cohort study. In the current study we examine outcomes of this unique childhood epilepsy subgroup at age 33 compared to unaffected NCDS cohort members in mental and general health, education and employment, marriage, and parenthood. Multivariable regression analyses were used to investigate factors (including etiology, cognitive development, parental interest, and childhood anxiety/depression at age 11 years) associated with adverse outcomes. key findings: Sixty-five (66%) were still participating at 33 years. Median follow-up after epilepsy onset was 28 years (range 17-33 years). Thirty participants [46%, 95% confidence interval (CI) 35-58] had epilepsy onset <5 years, 32 (49%, 95% CI 37-61) had "symptomatic" epilepsy, and 33 (51%, 95% CI 39-63) had idiopathic epilepsy. Thirty-one participants (48%) reported being seen by their doctor for epilepsy in the preceding year, 27 (42%) were registered disabled, 39 (60%) had a drivers license, and 42 (65%) thought their epilepsy made it harder to get/keep a paid job. People who had childhood epilepsy had an increased risk of death [standardized mortality rate (SMR) 3.1, 95% CI 1.1-6.1]. Childhood epilepsy was associated with poor general and mental health at 33 years on univariable analyses, but not after adjusting for childhood cognitive development/comorbidities and anxiety over acceptance by peers/adults at age 11. Childhood epilepsy was an independent risk factor for not being married [odds ratio (OR) 0.45, 95% CI 0.05-0.94] or being a parent (OR 0.67, 95% CI 0.42-0.91). People with childhood epilepsy and poor cognitive development compared to those with poor cognitive development without epilepsy had a greater proportion with subsequent poor mental health (56% vs. 24%, difference in proportion 33%, 95% CI 12-50), and a lesser proportion who married (39% vs. 78%, difference in proportion -39%, 95% CI -56 to -19). SIGNIFICANCE: Compared to the unaffected population, children with epilepsy with good cognitive development/without comorbidities have similar adult health, educational, and employment outcomes but have difficulties with establishing and maintaining personal relationships. A combination of having childhood epilepsy plus poor cognitive development is more likely to be associated with adverse outcomes compared to having poor cognitive development without childhood epilepsy. Children with epilepsy have increased risk of death compared to the rest of the population. Pharmacologic management alone is inadequate and long-term psychosocial support is needed.

Epidemiology of visual impairment, sight-threatening or treatment-requiring diabetic eye disease in children and young people in the UK: findings from DECS.

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.

Prevalence of eye disease in early childhood and associated factors: findings from the millennium cohort study.

PURPOSE: To report the prevalence and distribution of eye conditions and visual impairment and associations with early social and biological factors using parental report of diagnosed eye conditions and additional chronic illnesses. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: We included 14 981 children, aged 3 years, participating in the United Kingdom Millennium Cohort Study. METHODS: Data on demographic, socioeconomic, and maternal and child health factors were obtained by maternal report through structured interview and verbatim reports of diagnosed eye problems and additional chronic illnesses were recorded. Multinomial regression analyses were used to calculate risk ratios of the association of eye disease (with or without associated visual impairment), with socioeconomic and early life factors. MAIN OUTCOME MEASURES: Parental report of diagnosed eye conditions and other chronic illnesses. RESULTS: Overall, at 3 years, 5.7% (95% confidence interval, 5.2-6.3%; n = 881) of children had ≥ 1 eye condition with 0.24% (0.15-0.3%; n = 45) reported to have associated visual impairment. In the majority, time of onset was reported to be the first year of life. Eye disorders without report of visual impairment were independently associated with lower socioeconomic status, decreasing birth weight, and prematurity. Visual impairment was more likely in those of low birthweight for gestational age and from an ethnic minority group. Maternal illnesses during pregnancy were associated with eye disease without reported visual impairment, as was white ethnicity. CONCLUSIONS: Good research opportunities exist within the context of population-based general health surveys to use parental report to estimate minimum prevalence, investigate associations of eye disease with a broad range of environmental factors, and as a mechanism for "flagging" individuals with eye disease in a population sample for further study. Our findings regarding the association of parentally reported childhood eye disease with early life factors such as modest degrees of prematurity, ethnicity and maternal ill-health warrant further investigation. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.