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.

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.

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.

Role of ethnicity and socioeconomic status (SES) in the presentation of retinoblastoma: findings from the UK.

BACKGROUND: The relationship between the ethnic background or socioeconomic status (SES) and late retinoblastoma (Rb) presentation in the UK is unclear. We aimed to investigate if such correlations exist in a cohort of non-familial Rb cases. METHODS: A cross-sectional study based at the two centres providing Rb care in the UK. Included were non-familial Rb cases that presented from January 2006 to December 2011. Epidemiological and clinical data were retrieved from medical charts, as well as patients' postcodes used to obtain the Index of Multiple Deprivation (IMD) score. A postal questionnaire was sent to participants' parents to collect further, person-level, information on languages spoken and household socioeconomic position. Statistical correlations to advanced Rb at presentation as well as to treatment by enucleation and need for adjuvant chemotherapy were investigated. RESULTS: The cohort included 189 cases, 98 (51.8%) of which were males. The median age at diagnosis was 16 months (IQR 8-34 months). Of the study patients, 153 (81%) presented with advanced Rb; 78 (41%) with group D and 75 (40%) with group E Rb. A total of 134 (72%) patients were treated with enucleation. South Asian ethnicity and being in the most deprived IMD quintile were associated with a higher likelihood of presentation with advanced disease, but these estimates did not reach statistical significance. Older age at presentation was associated with enucleation and bilateral disease with adjuvant chemotherapy. CONCLUSIONS: In this national UK study of patients with non-familial Rb, there was no evidence of an association of ethnicity or SES and the risk of presenting with advanced disease. These findings may reflect equality in access of healthcare in the UK.

Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia.

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

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.

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.

Study of Optimal Perimetric Testing in Children (OPTIC): evaluation of kinetic approaches in childhood neuro-ophthalmic disease.

AIMS: We compared feasibility, quality and outcomes of visual field (VF) testing in children with neuro-ophthalmic disease between the discontinued 'gold-standard' Goldmann and Octopus perimeters. METHODS: Children with neuro-ophthalmic disease, attending Great Ormond Street Hospital, London, were assessed using standardised protocols by one examiner in a single sitting, using Goldmann and Octopus kinetic perimetry. Outputs were classified to compare severity of loss and defect type. Test quality was assessed using both qualitative and quantitative methods. RESULTS: Thirty children (40% female) aged 5-15 years participated. Goldmann perimetry was completed in full by 90.0% vs 72.4% for Octopus. Inability to plot the blind spot was the most common reason for not completing testing. Over 75% completed a test in ≤20 min. Duration was similar between perimeters (paired t-test, mean difference: 0.48min (-1.2, 2.2), p=0.559). The lowest quality tests were for Octopus perimetry in children <8 years, without significant differences between perimeters in older children (McNemar's test, χ2=1.0, p=0.317). There was broad agreement between Goldmann and Octopus outputs (good quality, n=21, Bland-Altman, mean difference for isopters I4e (-514.3 deg2 (-817.4, -211.2), p=0.814), I2e (-575.5 deg2 (-900.1, -250.9), p=0.450) and blind spot (20.8 deg2 (5.7, 35.8), p=0.451)). However, VF severity grades and defect type matched in only 57% and 69% of tests, respectively. Octopus perimetry underestimated severe VF defects. CONCLUSIONS: Informative perimetry is feasible in children ≥8 years with neuro-ophthalmic conditions, with either Goldmann or Octopus perimeters. However, meaningful differences exist between the two approaches with implications for consistency in longitudinal assessments.

5-year outcomes after primary intraocular lens implantation in children aged 2 years or younger with congenital or infantile cataract: findings from the IoLunder2 prospective inception cohort study.

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

Impact of varying the definition of myopia on estimates of prevalence and associations with risk factors: time for an approach that serves research, practice and policy.

BACKGROUND: Refractive error is an increasing global public health concern that requires robust and reliable research to identify modifiable risk factors and provide accurate estimates of population burden. We investigated the impact of reclassification of individuals when using different threshold values of spherical equivalent (SE) to define myopia, on estimates of frequency, distribution and associations with risk factors, to inform current international initiatives to standardise definitions. METHODS: A random sample of 1985 individuals from the 1958 British birth cohort, at age 44, had autorefraction and self-reported on educational attainment and social class.Refraction status assigned in three different models using SE: (A) moderate to high myopia -3 diopters (D) or more extreme (≤-3.00D), (B) hypermetropia +1.00D or more extreme (≥+1.00D) and (C) mild myopia using three different thresholds: -1.00D, -0.75D or -0.50D, hence reciprocal changes in definition of emmetropia. RESULTS: Frequency estimates and associations with risk factors altered significantly as the threshold value for myopia moved towards SE 0.0D: prevalence of mild myopia increased from 28% to 47%, the association with highest educational attainment attenuated and with higher social class strengthened, with changes in risk ratios of approximately 20%. CONCLUSION: Even small changes in the threshold definition of myopia (±0.25D) can significantly affect the conclusions of epidemiological studies, creating both false-positive and false-negative associations for specific risk factors. An international classification for refractive error, empirically evidenced and cognisant of the question(s) being addressed and the population(s) being studied, is needed to serve better translational research, practice and policy.

Comparison of Quality and Output of Different Optimal Perimetric Testing Approaches in Children With Glaucoma.

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

Prevalence of diabetic retinopathy in children and young people living with diabetes: protocol for a systematic review.

INTRODUCTION: The frequency of diabetes mellitus in childhood is increasing. Thus, more children and young people are at risk of developing diabetic retinopathy and diabetes related visual impairment. However, there is no consensus on optimal screening strategies for the paediatric population reflecting the lack of clarity about the current burden of disease in this group. We aim to estimate the prevalence of diabetic retinopathy in children and young people living with types 1 or 2 diabetes, and to investigate potential sources of heterogeneity in this figure so as to inform screening strategies for this population. METHODS AND ANALYSIS: PubMed and EMBASE will be searched from 1995 to 2016 using the OvidSP platform with no language restriction. Additionally, manual review of the references lists of included articles will be conducted. Two investigators will independently screen titles and abstracts for potential eligibility. Studies which report prevalence of diabetic retinopathy among general populations of children and young people with types 1 or 2 diabetes will be included. Pooled prevalence estimates of diabetic retinopathy reported in studies with sample size greater than 200 participants will be calculated by the random effect model. Forest plots will be used to summarise individual and pooled estimates of the prevalence. Heterogeneity between studies will be assessed using the I2 statistic and explored through meta-regressions and subgroup analyses if the necessary data are available. ETHICS AND DISSEMINATION: Ethics approval is not required as this is a review of anonymised published data. We will report the findings of this systematic review in a peer-reviewed journal, and share it with the relevant professionals including health authorities through our Diabetic Eye disease in Childhood Study collaborative network. CLINICAL TRAIL REGISTRATION: PROSPERO (CRD42017067178).

Trends in Visual Health Inequalities in Childhood Through Associations of Visual Function With Sex and Social Position Across 3 UK Birth Cohorts.

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

Study of Optimal Perimetric Testing In Children (OPTIC): development and feasibility of the kinetic perimetry reliability measure (KPRM).

INTRODUCTION: Interpretation of perimetric findings, particularly in children, relies on accurate assessment of test reliability, yet no objective measures of reliability exist for kinetic perimetry. We developed the kinetic perimetry reliability measure (KPRM), a quantitative measure of perimetric test reproducibility/reliability and report here its feasibility and association with subjective assessment of reliability. METHODS: Children aged 5-15 years, without an ophthalmic condition that affects the visual field, were recruited from Moorfields Eye Hospital and underwent Goldmann perimetry as part of a wider research programme on perimetry in children. Subjects were tested with two isopters and the blind spot was plotted, followed by a KPRM. Test reliability was also scored qualitatively using our examiner-based assessment of reliability (EBAR) scoring system, which standardises the conventional clinical approach to assessing test quality. The relationship between KPRM and EBAR was examined to explore the use of KPRM in assessing reliability of kinetic fields. RESULTS: A total of 103 children (median age 8.9 years; IQR: 7.1 to 11.8 years) underwent Goldmann perimetry with KPRM and EBAR scoring. A KPRM was achieved by all children. KPRM values increased with reducing test quality (Kruskal-Wallis, p=0.005), indicating greater test-retest variability, and reduced with age (linear regression, p=0.015). One of 103 children (0.97%) demonstrated discordance between EBAR and KPRM. CONCLUSION: KPRM and EBAR are distinct but complementary approaches. Though scores show excellent agreement, KPRM is able to quantify within-test variability, providing data not captured by subjective assessment. Thus, we suggest combining KPRM with EBAR to aid interpretation of kinetic perimetry test reliability in children.

Do visually impaired children and their parents agree on the child's vision-related quality of life and functional vision?

AIMS: To investigate agreement between children with visual impairment (VI) and their parents on their ratings of the child's vision-related quality of life (VQoL) and functional vision (FV) using two novel self-report patient-reported outcome measures developed for this population. METHODS: 99 children aged 10-15 years (mean age=12.2, SD=1.9) with VI (best corrected acuity (logarithm of the minimum angle of resolution) 0.50 or worse in better eye) and their parents participated in a national postal survey, completing the child and proxy versions of our novel instruments assessing VQoL and FV of children with VI-the vision-related quality of life instrument for children and young people (VQoL_CYP) and the functional vision questionnaire for children and young people (FVQ_CYP), respectively. Parent-child agreement was investigated using the Bland-Altman (BA) method. Variation across key sociodemographic and clinical characteristics was examined using the Intraclass Correlation Coefficient. RESULTS: Average parental ratings of their child's VQoL and FV were significantly lower than the children's own ratings, but the range of disagreement was wide, with parents both overestimating and underestimating their child's VQoL (mean score difference=5.7, BA limits of agreement (LOA): lower -22.10 (CI 95% -24.61 to 19.59) and upper 33.50 (CI 95% 30.99 to 36.01)), but more consistently underestimating the child's FV (mean score difference=-11.8, BA LOA: lower -39.60 (CI 95% -42.12 to 37.08) and upper 16 (CI 95% 13.48 to 18.52)). There was variation in agreement by some child characteristics, including vision level, time of onset and course of VI progression. CONCLUSIONS: Visually impaired children and their parents perceive the broader impact of living with VI very differently. There is value in routine capture of information independently from children and their parents for comprehensively gauging the impact of childhood VI and tailoring appropriate interventions.

Visual Function, Social Position, and Health and Life Chances: The UK Biobank Study.

IMPORTANCE: The adverse impact of visual impairment and blindness and correlations with socioeconomic position are known. Understanding of the effect of the substantially more common near-normal vision (mild impairment) and associations with social position as well as health and life chances is limited. OBJECTIVE: To investigate the association of visual health (across the full acuity spectrum) with social determinants of general health and the association between visual health and health and social outcomes. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional epidemiologic study was conducted using UK Biobank data from 6 regional centers in England and Wales. A total of 112 314 volunteers (aged 40-73 years) were assessed in June 2009 and July 2010. Data analysis was performed from May 20, 2013, to November 19, 2014. MAIN OUTCOMES AND MEASURES: Habitual (correction if prescribed) distance visual acuity was used to assign participants to 1 of 8 categories from bilateral normal visual acuity (logMAR, 0.2 or better; Snellen equivalent, 6/9.5 or better) to visual impairment or blindness (logMAR, 0.5 or worse; Snellen equivalent, 6/19 or worse) using World Health Organization and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision taxonomy. Relationships between vision, key social determinants and health and social outcomes (including the main factors that define an individual's life-the social, economic, educational, and employment opportunities and outcomes experienced by individuals during their life course) were examined using multivariable regression. RESULTS: Of the of 112 314 participants, 61 169 were female (54.5%); mean (SD) age was 56.8 (8.1) years. A total of 759 (0.7%) of the participants had visual impairment or blindness, and an additional 25 678 (22.9%) had reduced vision in 1 or both eyes. Key markers of social position were independently associated with vision in a gradient across acuity categories; in a gradient of increasing severity, all-cause impaired visual function was associated with adverse social outcomes and impaired general and mental health. These factors, including having no educational qualifications (risk ratio [RR], 1.86 [95% CI, 1.69-2.04]), having a higher deprivation score (RR, 1.08 [95% CI, 1.07-1.09]), and being in a minority ethnic group (eg, Asian) (RR, 2.05 [95% CI, 1.83-2.30]), were independently associated with being in the midrange vision category (at legal threshold for driving). This level of vision was associated with an increased risk of being unemployed (RR, 1.55 [95% CI, 1.31-1.84]), having a lower-status job (RR, 1.24 [95% CI, 1.09-1.41]), living alone (RR, 1.24 [95% CI, 1.10-1.39]), and having mental health problems (RR, 1.12 [95% CI, 1.04-1.20]). CONCLUSIONS AND RELEVANCE: Impaired vision in adults is common, and even near-normal vision, potentially unrecognized without assessment, has a tangible influence on quality of life. Because inequalities in visual health by social position mirror other health domains, inclusion of vision in generic initiatives addressing health inequalities could address the existing significant burden of underrecognized and/or latent visual disability. Longitudinal investigations are needed to elucidate pathophysiologic pathways and target modifiable mechanisms.

Accuracy and Utility of Self-report of Refractive Error.

IMPORTANCE: Large-scale generic studies offer detailed information on potential risk factors for refractive error across the life course, but ophthalmic examination in such cases to determine the refractive error phenotype is challenging and costly. Thus, refractive status is commonly assigned using questionnaires. In a population survey, often only a few condition-specific self-reported questions can be included, so the questions used must be effective in ruling in those who have the trait of interest and ruling out those who do not. OBJECTIVE: To determine the accuracy of identification of refractive status using self-reported age at and/or reason for first use of glasses or contact lenses (optical correction). DESIGN, SETTING, AND PARTICIPANTS: The UK Biobank study, a cross-sectional epidemiologic study, included 117 278 participants aged 40 to 69 years in 6 regional centers in England and Wales. Data for the present study were assessed from June 2009 to July 2010. Patients underwent autorefraction measurement. Spherical equivalent in the more extreme eye was used to categorize myopia (-1.00 diopter [D] or more extreme) and hypermetropia (+1.00 D or more extreme). MAIN OUTCOMES AND MEASURES: Sensitivity and specificity of the reason for optical correction were assessed using autorefraction as the gold standard. Receiver operating characteristic curves assessed the accuracy of self-reported age at first use of optical correction and incremental improvement with addition of the reason. RESULTS: Of the 95 240 participants who reported using optical correction (55.6% female; mean [SD] age, 57.7 [7.5] years), 92 121 (96.7%) provided their age at first use and 93 156 (97.8%) provided the reason. For myopia, sensitivity of the reason for optical correction was 89.1% (95% CI, 88.7%-89.4%), specificity was 83.7% (95% CI, 83.4%-84.0%), and positive and negative predictive values were 72.7% (95% CI, 72.2%-73.1%) and 94.0% (95% CI, 93.8%-94.2%), respectively. The area under the curve was 0.829 (95% CI, 0.826-0.831) and improved to 0.928 (95% CI, 0.926-0.930) with combined information. By contrast, self-report of the reason for optical correction of hypermetropia had low sensitivity (38.1%; 95% CI, 37.6%-38.6%), and the area under the curve with combined information was 0.713 (95% CI, 0.709-0.716). CONCLUSIONS AND RELEVANCE: In combination, self-report of the reason for and age at first use of optical correction are accurate in identifying myopia. These findings indicate an agreed set of questions could be implemented effectively in large-scale generic population-based studies to increase opportunities for integrated research on refractive error leading to development of novel prevention or treatment strategies.

Measuring the Quality of Life of Visually Impaired Children: First Stage Psychometric Evaluation of the Novel VQoL_CYP Instrument.

PURPOSE: To report piloting and initial validation of the VQoL_CYP, a novel age-appropriate vision-related quality of life (VQoL) instrument for self-reporting by children with visual impairment (VI). METHODS: Participants were a random patient sample of children with VI aged 10-15 years. 69 patients, drawn from patient databases at Great Ormond Street Hospital and Moorfields Eye Hospital, United Kingdom, participated in piloting of the draft 47-item VQoL instrument, which enabled preliminary item reduction. Subsequent administration of the instrument, alongside functional vision (FV) and generic health-related quality of life (HRQoL) self-report measures, to 101 children with VI comprising a nationally representative sample enabled further item reduction and evaluation of psychometric properties using Rasch analysis. Construct validity was assessed through Pearson correlation coefficients. RESULTS: Item reduction through piloting (8 items removed for skewness and individual item response pattern) and validation (1 item removed for skewness and 3 for misfit in Rasch) produced a 35-item scale, with fit values within acceptable limits, no notable differential item functioning, good measurement precision, ordered response categories and acceptable targeting in Rasch. The VQoL_CYP showed good construct validity, correlating strongly with HRQoL scores, moderately with FV scores but not with acuity. CONCLUSIONS: Robust child-appropriate self-report VQoL measures for children with VI are necessary for understanding the broader impacts of living with a visual disability, distinguishing these from limited functioning per se. Future planned use in larger patient samples will allow further psychometric development of the VQoL_CYP as an adjunct to objective outcomes assessment.