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A global problem requiring more research measuring outcomes that matter to children and their parents

The investigation of the genetic basis of refractive error and myopia entered a new stage with the introduction of genome-wide association studies (GWAS). Multiple GWAS on many ethnic groups have been published over the years, providing new insight into the genetic architecture and pathophysiology of refractive error. This is a review of the GWAS published to date, the main lessons learned, and future possible directions of genetic studies of myopia and refractive error.

Children are a priority in “Vision 2020”, the World Health Organization's recently launched global initiative for the prevention of avoidable visual impairment by the year 2020.1Successful implementation in the United Kingdom will depend to a greater extent on improvements in secondary and tertiary preventive strategies, to treat and rehabilitate affected children, than on the currently limited primary preventive approaches to the major paediatric eye diseases. Early detection is important to the successful management of children with ophthalmic disorders. In recognition of this, over the past few decades in the UK diverse activities have been implemented to promote early detection of specific ophthalmic conditions in children as well as to monitor their visual development. These comprise physical examinations by various health professionals and effectively form a continuum of screening and surveillance whose purpose and value is best considered in terms of sequential gain. Although now well established, these practices have arisen haphazardly and few have been subject to rigorous evaluation of their benefits. Indeed the scientific basis of some has been seriously questioned.2 In the UK they are undertaken within the broader context of a national programme of child health surveillance.3 Changes in this, such as the increased emphasis on health promotion,3 increasing responsibilities of general practitioners,4 and reconsideration of the roles of health visitors and school nurses,5 consequently have implications for ophthalmological screening and surveillance. The Children's Sub-Group of the National Screening Committee (NSC) of the UK has recently reviewed screening for ophthalmic disorders and visual deficits in children for the first time. The NSC categorised existing activities into five separate screening programmes for retinopathy of prematurity (ROP) in preterm/low birthweight infants; congenital cataract and other ocular anomalies in newborn and young infants; amblyopia and impaired vision in preschool age children; impaired vision, …

Established in Britain in the 19th century, the sight impairment register has been the sole means of routinely monitoring the frequency and causes of visual impairment in children to plan services and prioritise research.1 Although not a prerequisite, certification and consequent registration is often the catalyst for statutory assessment of special educational needs. It is also often the portal for accessing social services.2 Certification remains voluntary in the UK, by contrast with similar registers elsewhere. However, considerable effort has recently been directed to addressing previous concerns about incomplete reporting of information and underascertainment of eligible individuals.1 2 We have previously reported incidence and causes of severe visual impairment (SVI) or blindness (BL) and associated mortality3 in a nationally representative group of children with SVI/BL in the UK. We now report on the BL certification status of these children 1 year after diagnosis. Active surveillance was undertaken, simultaneously but independently, through the British Ophthalmological4 and British Paediatric5 Surveillance Units, whose reporting bases comprise all consultant ophthalmologists and paediatricians, respectively, in the UK. Every month for 1 year (2000), clinicians reported all children aged

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Shotton K, Powell C, Voros G, Hatt Sr. Interventions for unilateral refractive amblyopia. Cochrane Database of Systematic Reviews 2008, Issue 4, Art. No.: CD005137. DOI: 10.1002/14651858.CD005137.pub2. Further information for this Cochrane review is available in this issue of EBCH in the accompanying EBCH Summary. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration

Globally, the prevalence of blindness among children is estimated to be approximately one tenth of that in adults, at around 0.7 per 1000.1-3 However, blindness in childhood has far reaching implications for the affected child and family, and throughout life profoundly influences educational, employment, personal, and social prospects.4 Thus, the control of childhood blindness has been identified as a priority of the World Health Organisation’s (WHO) global initiative for the elimination of avoidable blindness by the year 2020.5 Measures of disease frequency alone, however, afford a limited understanding of the public health significance of childhood blindness. The global financial cost of blindness with an onset during childhood, in terms of loss of earning capacity (per capita GNP), is greater than the cost of adult blindness and has recently been estimated to be between US$6000 million and $27 000 million.6 Most of this is accounted for by children living in high income countries, where the prevalence is less, but life expectancy and earning capacity greater, than in low income countries. These financial costs alone, however, provide only one perspective of the public health burden of blindness. Improved understanding and quantification require the application of indicators which measure the impact of blindness in terms of morbidity (years of disability suffered) as well as mortality (years of life lost through premature blindness associated death). Such indicators are useful in identifying those in the population in greatest need and for setting priorities in provision of health services. They are also important in the assessment of effectiveness of interventions and …

Summary Background In the 1940s and 1950s retinopathy of prematurity (ROP) was the single commonest cause of blindness in children in many industrialised countries; it now accounts for only 6–18% of blindness registrations. It is not known what proportion of blindness is due to ROP in countries that do not have blindness registers. Information on blindness in children in these countries can be obtained by examining children in schools for the blind. Methods Between 1991 and 1996, 4121 children in 23 countries with a visual acuity in the better eye of less than 6/60 were examined with a standard method. Findings The proportion of severe visual impairment or blindness due to ROP ranged from 0% in most African countries to 38·6% in Cuba. Interpretation These data suggest that ROP is becoming a major cause of potentially preventable blindness among children in middle-income countries that have introduced neonatal intensive-care services for preterm and low-birthweight babies.

The causes of visual loss in 1411 children attending schools for the blind in different geographical areas in India are described. Ninety-three percent (1318) of the children were severely visually impaired (SVI) or blind (i.e. corrected acuity in the better eye of20/200 [6/60]). In 60% of SVI/blind children vision loss was attributable to factors operating in the prenatal period, in 47% the prenatal factors were known and definite, and in 13% prenatal factors were the most probable causes. Hereditary retinal dystrophies and albinism were seen in 19% of SVI/blind children and 23% had congenital ocular anomalies. There were variations in the relative importance of different causes by state. The observed pattern of causes of visual loss is intermediate between those seen in industrialised countries and in the poorest developing countries. This suggests that strategies to combat childhood blindness in India need to address concurrently both preventable and treatable causes. The need for aetiological studies, particularly on anophthalmos and microphthalmos, is highlighted.A cross-sectional study of 1411 children 3-15 years of age attending schools for the blind in 9 states of India in 1993 investigated the causes of visual impairment. 113 of these children (8%) were severely visually impaired and 1205 (85%) were blind. Severe visual impairment or blindness was hereditary in 23% of cases, attributable to intrauterine factors in 2%, related to perinatal factors in 1%, acquired postnatally in 28%, and of undetermined etiology in 46%. The most common mode of inheritance in hereditary cases was autosomal recessive (52%). Retinal dystrophies and albinism together accounted for 84% of hereditary disorders. Vitamin A deficiency was implicated in 19% of cases. If children with congenital anomalies were combined with those in whom definite hereditary or intrauterine factors were identified, 47% of all cases of severe visual impairment and blindness in this study were attributable to prenatal factors. This rate increases to 60% if undetermined cases presumed to involve prenatal factors are included. The 4 major causes of visual impairment and blindness were vitamin A deficiency, congenital ocular anomalies, inherited retinal dystrophies, and cataract. There were variations in the relative importance of these causes by state. The observed pattern of causes of visual loss is intermediate between those seen in developed countries and the poorest developing countries. Strategies to combat childhood blindness in India should address both preventable and treatable causes. Of particular importance in India, given the high proportion of autosomal recessive disorders, is education about the risks involved in consanguineous marriages.

Cataract is the most important cause of treatable childhood blindness. There are an estimated 200,000 children blind from cataract worldwide; 20,000 to 40,000 children with developmental bilateral cataract are born each year. Rubella is still an important cause of preventable disease in many countries. In the developing world, there is a need to improve early case detection and referral services and to establish centers with expertise in the assessment, surgical treatment, and long-term management of the child with cataract.

Congenital colour vision defects (CVD) are common, inherited (most commonly X linked), non-progressive, and untreatable disorders.1 2 Screening children for these disorders is established practice in the United Kingdom, primarily so that those affected can be advised about occupational preclusions.2 Population based work on the broader impact of colour vision defects is, however, limited. We investigated the association between CVD and education and unintentional injury in the 1958 British birth cohort.3 4 Despite attrition, people remaining were representative of the original sample, including with respect to colour vision status. The latter was assessed in 12 534 children aged 11 years using the Ishihara test,1 with CVD being the inability to identify all 24 plates. Corrected distance acuity was measured with Snellen charts. We analysed educational, perceptual, and motor skills tests done at 7, 11, and 16 years3 4 together with highest educational qualification by 33 (none, below O level or equivalent, O level or equivalent, A level or equivalent, or higher). We converted education test scores …

There is evidence from developed countries that genetic disease is the major cause of childhood blindness. Little data are available from most developing and newly industrialised countries concerning the relative importance of hereditary diseases as a cause of childhood blindness. Children in schools for the blind in 13 countries of Africa, Latin America and Asia were examined between 1990 and 1994 using a standardised method The anatomical site of abnormality and underlying aetiology were analysed for children with a corrected acuity in the better eye of less than 6/60 (severe visual impairment and blindness, svi/BL). In these countries II-39% of svi/BL was attributed to genetic disease. Genetic diseases were responsible for a higher proportion of childhood visual loss in countries with higher levels of socio-economic development. An autosomal recessive mode of inheritance was reported in 22-52% of children with genetic disease. Retinal dystrophies were the commonest form of genetic eye disease (49-80%) in all countries apart from Thailand and the Philippines where cataract was the commonest (43.9%). The role of consanguinity, and opportunities for further research are discussed.

It is estimated that at least 200,000 children in India have severe visual impairment or blindness and approximately 15,000 are in schools for the blind. Although this represents a small percentage of the estimated 5 million blind in India, it is significant in terms of 'blind-years'. Strategies to combat childhood blindness require accurate data on the causes to allocate resources to appropriate preventive and curative services. Since socio-economic factors vary in different areas of this industrializing country data should be representative of the country as a whole. This is the first multi-state study to be undertaken in India using the Record for Children with Blindness and Low Vision from the World Health Organization/PBL Programme. A total of 1411 children in 22 schools from nine states in different geographical zones were examined by an ophthalmologist and optometrist. Of these, 1318 children were severely visually impaired or blind (SVI/BL). The major causes of SVI/BL in this study were: (1) corneal staphyloma, scar and phthisis bulbi (mainly attributable to vitamin A deficiency) in 26.4%; (2) microphthalmos, anophthalmos and coloboma in 20.7%; (3) retinal dystrophies and albinism in 19.3%; and (4) cataract, uncorrected aphakia and amblyopia in 12.3%. This mixed pattern of causes lies in an intermediate position between the patterns seen in developing countries and those seen in industrialised countries. The causes identified indicate the importance both of preventive public health strategies and of specialist paediatric ophthalmic and optical services in the management of childhood blindness in India.

Purpose To identify heritable genetic factors altering susceptibility to refractive error in the general population. Methods This was a genetic association study of refractive error investigating genetic polymorphisms in regions previously reported through linkage. Two study panels were drawn from the British 1958 Birth Cohort, composed of 2211 persons 44 years of age at the time of visit. Two main outcomes were considered: refractive error as a continuous outcome (spherical equivalent) and myopia as a diagnosis (defined as spherical equivalent equal to or worse than-1.00 diopter). Genotyping was initially performed in 1188 subjects from the outer tertiles of the population distribution, using customized arrays of single nucleotide polymorphisms (SNPs) saturating regions of previously reported highly significant linkage. In a second stage, SNPs most significantly associated were validated in 1023 more persons. Findings were investigated further through human fetal expression studies. Results Polymorphisms within the SERPINI2 gene were associated with refractive error in two different European subgroups from the 1958 British Birth Cohort (meta-analysis P = 7.4E-05 for rs9810473). Association was also significant for myopia (best association: OR = 0.80; 95% CI, 0.69-0.93; P = 0.003 for rs10936538). Expression profiling of SERPINI2 revealed that the gene is expressed in the retina and in other eye and CNS tissues. Conclusions The novel association of SERPINI2 with refractive error and myopia is suggestive of a possible link between physiological pathways controlling eye growth and development and those controlling glucose metabolism. The findings indicate that SERPINI2 is a promising candidate for further investigations of the genetic susceptibility to myopia.

PURPOSE. Childhood-onset hereditary retinal disorders comprise a group of visually disabling conditions with variable onset and progression of visual impairment. Their impact on the health-related quality of life (HRQoL) of affected individuals, as well as the broader impact on their families has not been investigated previously.METHODS. In a cross-sectional study, a generic age-appropriate instrument, the PedsQL, was used to assess self-reported HRQoL in a subsample of a representative group of children with hereditary retinal disorders and their siblings as well as parental (proxy) assessment of HRQoL of their affected children. In addition, parents reported the broader impact and effect on functioning of the family using the PedsQL Family Impact Module.RESULTS. Affected children (n = 44) reported worse HRQoL than their unaffected siblings (n = 34) and notably, also worse scores than those reported by children with various serious chronic systemic disorders. On average, parents assessed their child's HRQoL to be worse than that self-reported by the child. There was an overall adverse impact on the family and its functioning, although siblings did not report impaired HRQoL themselves.CONCLUSIONS. This study demonstrates the significant impact, on both affected children and their families, of living with an untreatable, often progressive, and sometimes blinding ophthalmic disorder. It highlights the importance of support for affected individuals and their families, which may be targeted through use of generic or vision-related quality-of-life instruments for children as the latter become more widely available. Assessment of HRQoL would also be an important outcome measure in clinical trials of novel therapies for hereditary retinal disorders. (Invest Ophthalmol Vis Sci. 2011;52:7981-7986) DOI:10.1167/iovs.11-7890

PURPOSE. Anophthalmos, microphthalmos, and typical coloboma (AMC) form an interrelated spectrum of congenital eye anomalies that can cause significant visual loss and cosmetic disfigurement in children. This prospective study of children born in the United Kingdom was undertaken to determine the incidence of AMC diagnosed by ophthalmologists and to explore sociodemographic risks.METHODS. Recruitment was achieved though an established active surveillance system of U.K. ophthalmologists supported by a new research network of interested specialists, the Surveillance of Eye Anomalies (SEA-UK) Special Interest Group. It started October 1, 2006, and continued over 18 months.RESULTS. One hundred thirty-five children were newly diagnosed with AMC. Typical colobomatous defects were the commonest phenotype, and anophthalmos was rare (n = 7). Both eyes were affected in 55.5% of the children. The cumulative incidence of AMC by age 16 years was 11.9 per 100,000 (95% CI, 10.9-15.4). Of the children examined, 41.5% had not seen an ophthalmologist by 3 months of age. The incidence in Scotland was nearly double that in England and Wales. The children of Pakistani ethnicity had a 3.7 (95% CI, 1.9-7.5) times higher risk of AMC than did white children. There was some evidence to suggest a higher incidence in the more socioeconomically deprived. The sibling risk ratio was 210 (95% CI, 25-722).CONCLUSIONS. This is the first prospective study of AMC, and it establishes the frequency across the United Kingdom. Comparisons with data quoted in the literature are difficult because study methodologies differ, but the frequency appears to be lower than that quoted for other developed countries. There are geographic and ethnic variations in incidence that warrant further investigation. (Invest Ophthalmol Vis Sci. 2011; 52: 558-564) DOI:10.1167/iovs.10-5263

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.

Background Strabismus is a common disorder of largely unknown cause reported to occur more frequently in children with neurodevelopmental conditions and in children born prematurely or of low birth weight. Population-based investigation of other potential early-life influences has been limited. Objective To investigate the prevalence of and the early-life risk factors associated with childhood strabismus. Design Cross-sectional analytical study of a nationally representative sample of children participating in the Millennium Cohort Study. Setting United Kingdom. Participants A population-based sample of 14 980 children aged 3 years. Main Outcome Measures Parental report of “isolated” strabismus and “neurodevelopmental” strabismus (ie, in the context of neurologic disorders), considered separately. Results Three hundred forty-three children had strabismus (of whom 20 [5.8%] had neurodevelopmental/neurologic disorders), giving a total weighted prevalence of 2.1% (95% confidence interval, 1.8%-2.4%). In multivariable analysis, the risk of isolated strabismus was reduced in children of nonwhite maternal ethnicity and was increased in those born after an assisted or cesarean delivery and in those who were of low birth weight and preterm (in particular, late preterm). An increased risk of neurodevelopmental strabismus was independently associated with maternal smoking into later pregnancy, maternal illnesses in pregnancy, and decreasing birth weight for gestational age and sex. Socioeconomic status was associated with isolated (inverse relationship) and neurodevelopmental (U-shaped relationship) strabismus. Conclusions Several early-life social and biological factors are associated with strabismus, with differences in patterns between isolated and neurodevelopmental forms. Further collaborative research could explore this hypothesis to identify modifiable risk factors.

Purpose To report the incidence of and factors associated with postoperative open-angle glaucoma in a nationally representative group of children undergoing surgery for congenital or infantile cataract. Design Noncomparative interventional cohort study. Participants All children in the United Kingdom who were newly diagnosed with congenital or infantile cataract in a 12-month period in 1995 and 1996 (the British Congenital/Infantile Cataract Study) were eligible for this study. One hundred sixty-five children with congenital or infantile cataract underwent cataract surgery. Methods All the children were traced through their managing ophthalmologists. Standardized outcome data were collected at least 6 years after diagnosis. For children undergoing cataract extraction, Cox regression analysis was performed to determine incidence of postoperative open-angle glaucoma and the effect of key factors considered, a priori, potentially to be associated with it (i.e., age at detection and surgery, type of cataract surgery, primary intraocular lens implantation, severe postoperative uveitis, and microphthalmia). Main Outcome Measures Development of open-angle glaucoma after cataract surgery. Results Postoperative glaucoma developed in 27 of 275 eyes of 165 children who underwent cataract surgery. The overall annual incidence of postoperative glaucoma was 5.25 per 100 cataract operations. The median time to development of postoperative glaucoma was 1.34 years (range, 0.39 months–6.73 years). Younger age at detection of cataract was the only factor independently associated with the development of glaucoma when all other factors of interest (which were all statistically associated with age at detection) were accounted for. A 10-fold increase in the age at detection (for example, 30 days compared with 3 days) was associated with a 64% decrease in the hazard ratio (95% confidence interval, 41%–79%; P Conclusions Median time to development of postoperative open-angle glaucoma in the present study was lower than that reported previously, emphasizing the need for vigilance from the early postoperative period. Earlier detection of cataract was the only significant factor associated with the development of glaucoma after surgery for congenital cataract.

EDITOR—We recognise that people with colour vision defects can experience difficulties in everyday life. These vary according to the nature and severity of the condition as well as the personal circumstances of the affected person and the ability to develop adaptive strategies, as illustrated by Wiegersma and Sellars and on bmj.com.1 Several criteria have to be …

EDITOR—The description in 1941 by an Australian ophthalmologist of congenital cataract occurring after rubella in pregnancy was one of the first clearly demonstrated risk factors for congenital anomalies in humans.1 Several of the major ophthalmic long term effects of prenatal rubella infection, such as cataract, microphthalmos, and retinopathy, are recognisable at birth or in early infancy.2 Their diagnosis in children is recognised to be important in identifying the population at …

Editor—We strongly support Johnson’s recommendation for a standard minimum dataset for follow up studies,1 which includes information on visual function. There are very limited data available on the incidence of severe visual impairment and blindness among children in the UK. Estimates have often been based on the national registers of partial sight and blindness. However, these have documented limitations in …

What should be done in Britain about existing and proposed programmes to screen preschool children for the related conditions of amblyopia, refractive error, and strabismus? Those who have visited this debate before may not be surprised that the recently published systematic review on preschool vision screening from the NHS Centre for Reviews and Dissemination identified serious deficiencies in the research evidence which informs current policy.1 However, the conclusions that “Providers currently offering screening programmes should consider discontinuing them” and, “From an ethical point of view, it is appropriate to continue to screen only in the context of a controlled trial of treatment” will undoubtedly prove more controversial. The available research evidence has been interpreted differently in similar reviews from North America,2 3where it has been concluded that preschool vision screening should continue. Why have reviewers reached different conclusions from essentially the same data? By integrating existing information in an unbiased manner, systematic reviews should provide data for …

Background The aim of diabetic eye screening is to reduce preventable visual loss by identifying and treating sight-threatening diabetic retinopathy. The National Institute for Health and Care Excellence recommends that annual screening for diabetic retinopathy should start at 12 years of age. However, the National Paediatric Diabetes Audit reported that in 2013–14 only 52% of eligible children and young people underwent screening in England. Complete ascertainment of children and young people living with diabetes is essential for effective screening. This study aimed to investigate how eligible children and young people are identified in the 70 English diabetic eye screening programmes. Methods In the absence of a centralised or comprehensive list, the contact details of clinical leads or programme managers were manually identified through multiple sources including National Health Service Trust websites. A postal and electronic survey of the 70 English diabetic eye screening programmes was conducted between Oct 1, 2015, and Feb 29, 2016. Findings Of the 42 replying programmes (response rate 60%), 18 (43%) used both hospital diabetes clinics and general practice registration systems to compile screening lists. In eight programmes (19%), the lists were generated entirely manually (eg, referral letters from general practitioners). The frequency of list update was variable, ranging from daily to 6 monthly. 13 programmes (31%) actively searched for diabetic patients not registered with a general practitioner, and 22 (52%) included patients with diabetes other than type 1 or 2 diabetes mellitus. Information about attendance at hospital eye services after referral was available to 39 (93%) units. All screening programmes used data management software. Interpretation Existing methods of identification of children and young people eligible for diabetic eye screening are highly heterogeneous across England, thereby risking incomplete ascertainment of this population. In the context of the continuing Diabetic Eye Disease in Childhood Study, we are doing further work to assess the level of ascertainment of children and young people, and to better understand the natural history of diabetic retinopathy in this population, including incidence of sight-threatening diabetic retinopathy across the English diabetic eye screening programmes. This currently unavailable information is needed to inform ophthalmic services and screening strategies. Funding Ulverscroft Foundation, National Institute for Health Research Biomedical Research Centre at University College London Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, and Diabetes Research & Wellness Foundation. The funding organisations had no role in the design or conduct of this research.