Ameenat Lola Solebo

Risks and outcomes associated with primary intraocular lens implantation in children under 2 years of age: the IoLunder2 cohort study

Background/aims To investigate outcomes following cataract surgery with and without primary intraocular lens (IoL) implantation in children under 2 years of age with congenital or infantile cataract. Method Prospective population based cohort study undertaken through the British Isles Congenital Cataract Interest Group, with systematic data collection on children undergoing surgery in UK and Ireland between January 2009 and December 2010. ORs for the association between IoL implantation and visual acuity, postoperative glaucoma and reoperation at 1 year after surgery were estimated using multivariable regression analysis to control for potential confounders. Results Of 221 children, 56/131 with bilateral and 48/90 with unilateral cataract underwent primary IoL implantation. IoL implantation was independently associated with better visual outcome in bilateral (OR 4.6, 95% CI 1.6 to 13.1, p=0.004) but not unilateral disease. IoL use increased the odds of reoperation requiring repeat general anaesthetic (bilateral OR 5.5, p<0.01; unilateral OR 16.7, p<0.01). IoL implantation did not reduce the odds of postoperative glaucoma. Conclusions The use of IoLs in cataract surgery in young children should be critically reassessed, particularly used in settings/communities where close, long-term follow-up is challenging. The absence of visual benefit and the lack of a previously postulated protective effect against postoperative glaucoma serve to question the value of IoLs in unilateral disease. The potential association between IoL use and better early visual outcomes in bilateral disease needs to be balanced against the risk of reoperation and exposure to additional general anaesthetics during a key period of neurodevelopment.

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.

Epidemiology of blindness in children

An estimated 14 million of the world’s children are blind. A blind child is more likely to live in socioeconomic deprivation, to be more frequently hospitalised during childhood and to die in childhood than a child not living with blindness. This update of a previous review on childhood visual impairment focuses on emerging therapies for children with severe visual disability (severe visual impairment and blindness or SVI/BL). For children in higher income countries, cerebral visual impairment and optic nerve anomalies remain the most common causes of SVI/BL, while retinopathy of prematurity (ROP) and cataract are now the most common avoidable causes. The constellation of causes of childhood blindness in lower income settings is shifting from infective and nutritional corneal opacities and congenital anomalies to more resemble the patterns seen in higher income settings. Improvements in maternal and neonatal health and investment in and maintenance of national ophthalmic care infrastructure are the key to reducing the burden of avoidable blindness. New therapeutic targets are emerging for childhood visual disorders, although the safety and efficacy of novel therapies for diseases such as ROP or retinal dystrophies are not yet clear. Population-based epidemiological research, particularly on cerebral visual impairment and optic nerve hypoplasia, is needed in order to improve understanding of risk factors and to inform and support the development of novel therapies for disorders currently considered ‘untreatable’.

Accuracy of routine data on paediatric cataract in the UK compared to active surveillance: lessons from the IOLu2 study

Background/aims As part of the UK and Ireland study of primary IOL implantation in children under 2, active surveillance has been undertaken to identify children aged <2 years undergoing surgery for cataract. Ascertainment through active surveillance has been compared to the routine NHS capture of episodes of surgery, in order to identify any weaknesses in routine data collection. Methods NHS information centre data on the number of children undergoing lens extraction in the first two years of life were compared to the number of cases reported through active surveillance. Results In 2009 and 2010 in the United Kingdom, 483 episodes of lens extraction in children aged <2 years with lens-related disease were reported to NHS databases, compared to 490 cases of lens extraction for congenital / infantile cataract ascertained by the BCCIG through active surveillance. There was also disparity in the coding of procedures. Conclusions There is evidence of incomplete and inaccurate reporting to NHS information centres of cataract surgery in children aged <2 years. If the accuracy of the coding could be improved then the Hospital Activity Statistics offer a reasonable approach to monitoring trends in the NHS. Nevertheless, active surveillance clinical networks remain a more robust method of case ascertainment for research.

Screening for diabetic retinopathy in children and young people in the UK: potential gaps in ascertainment of those at risk

Guidelines in the UK recommend that children and young people living with Type 1 and Type 2 diabetes undergo annual screening for diabetic retinopathy from the age of 12 years [1]. This is currently delivered though a large number of regional diabetic eye screening programmes that are responsible for identifying eligible children and young people, and inviting them to a screening appointment (Fig. 1). In 2014/2015, the National Paediatric Diabetes Audit, based on secondary (hospital-based) care data for over 27 600 children, revealed that only 64% of eligible children and young people in England had been recorded as having undergone diabetic retinopathy screening during the last audit year; of whom, 13% were reported to have at least background diabetic retinopathy [2]. One potential cause of low screening coverage is incomplete ascertainment of the eligible population. There has been no systematic investigation of how this population is identified in diabetic eye screening programmes in England. Through multidisciplinary collaborative clinical research network–the Diabetic Eye disease in Childhood Study (DECS) group–we are undertaking a multifaceted research programme to address the current paucity of information about the frequency and natural history of childhood diabetic eye disease, to inform service planning including diabetic eye screening. From this programme, we report here a survey (both postal and electronic approaches) of the 70 English diabetic eye screening programmes conducted between October 2015 and February 2016. In the absence of a centralized register, contact details of programme leads were identified manually through multiple sources, and at least two reminders were sent to non-responding diabetic eye screening programmes. Questionnaires were received from 42 programmes (response rate, 60%). All programmes used primary care (family practitioner) registration systems to compile their screening lists. Eighteen programmes (43%) also drew on information from hospital diabetes clinics (secondary care) as a complementary source. Less than one-third of programmes (n = 13) actively searched for eligible patients not registered with a family practitioner, a group classified as hard to reach by the diabetic eye screening programmes. 52% of programmes (n = 22) included patients with ‘syndromatic’/secondary diabetes such as Wolfram Syndrome. In 19% (n = 8) of programmes, screening lists were generated entirely manually, for example, using referral letters from family practitioners, and in 24% (n = 10) combined manual and electronic methods were used.

Improving outcomes in congenital cataract

Lens regeneration after cataract surgery in infants is a clinical phenomenon with which paediatric ophthalmologists battle. Lin et al.1 reported a novel surgical technique that aimed to convert this postoperative complication into an alternative therapy for children aged under 24 months. However, the early outcomes reported in the experimental group fall short of outcomes achievable through conventional treatment in this population. As the authors offer no comment or explanation for this discrepancy, this new approach cannot be considered effective or safe for affected children. There is a Reply to this Comment by Liu, Y. et al. Nature 556, https://dx.doi.org/10.1038/nature26150 (2018). Regeneration of residual lens cells following surgical removal of congenital cataract can result in re-opacification, which needs to be treated by further intraocular surgery, necessitating repeated general anaesthetics during a sensitive period of neurodevelopment. The adaptation of this regenerative process by Lin et al.1, in which a novel surgical method of cataract removal preserves endogenous lens cells, enabling functional lens regeneration, may eventually lead to the development of treatments for degenerative disease. However, issues relating to adult cataract (an age-related degenerative process) and congenital and infantile cataract are conflated in their report. Cataract is virtually universal in older age, making cataract surgery one of the most common surgical procedures, with enviably excellent visual outcomes. By contrast, infantile cataract is uncommon, affecting 3–15 per 10,000 children worldwide and, by definition, present from birth or early infancy2. We now understand that mutations within the genes responsible for the production or orchestration of the lens epithelial progenitor/stem cells (LECs) are responsible for the majority of bilateral congenital or infantile cataract, even in cases where there is no family history3. Thus the treatment approach adapted by Lin et al.1, which relies on regeneration of lens stem cells without addressing the persisting underlying genetic defect, cannot be definitive. Children treated using this technique may require further surgery but Lin et al. do not acknowledge this in the article. The rationale for the trial reported by Lin et al.1 is the need to address adverse outcomes associated with the use of artificial intraocular lenses, which are implanted in some children to replace the focusing power of the removed cataractous lens4. However, surgery with intraocular lens implantation was not the ‘control’ standard approach evaluated within the report. Equivalence in vision outcomes between their intervention and control groups was reported, but these should also have been assessed against the extant benchmark. Outcomes in infantile cataract have improved substantially over the past few decades, largely owing to the application of basic neuroscientific understanding of sensitive and critical periods in visual neurodevelopment. Cataractrelated childhood visual impairment is largely due to bilateral stimulus deprivation amblyopia: the failure to restore a normal trajectory of visual neuro development during a brief and finite window of opportunity. This critical window closes at some point during the first six months of life. Thus, younger age at surgery is the strongest predictor of better visual outcome and, in cataract present from birth, the window for intervention is conventionally considered to be the first six to eight weeks of life. Hence whole-population newborn screening programmes exist in many countries to ensure early diagnosis of congenital cataract and prompt referral for specialist treatment. In settings where such programmes do not yet exist, late diagnosis and treatment, resulting in irreversible amblyopia, drives poor visual outcomes. We have previously, on behalf of the British Isles Congenital Cataract Interest Group, reported outcomes within a contemporaneous, nationally representative cohort of children undergoing surgery in the British Isles for congenital and infantile cataract in the first two years of life (IoLunder2 study)4. These outcomes are comparable to those found in other contemporary reports5 and are more than twofold better than those reported by Lin et al. in either their experimental or control groups. Indeed, the mean acuity achieved in their trial is the threshold for legal definition of blindness, an outcome that would lead most ophthalmologists, and probably most parents, to question the value of this new proposed intervention. Effective treatment for congenital cataract requires, alongside surgery, post-operative management of the loss of refractive (focusing) power through removal of the natural lens. Failure to appropriately manage this results in dense amblyopia. As the method described in Lin et al. involves an 8-month post-operative period of lens regeneration with consequent partially obscured and poorly focused vision, the inevitable resultant amblyopia may explain the poor visual outcomes. The authors offer no other explanation, and do not describe how the rapidly changing and highly defocused refractive state (moving through 18 diopter units of refractive error in 8 months) was managed. Had the report adhered to the international reporting standard of CONSORT6 it might be have been possible to assess the quality (internal validity) and generalizability (external validity) of the trial. For example, it is necessary to know: whether the control and intervention groups were equivalent with respect to baseline clinical characteristics (particularly age at surgery); how randomization was undertaken; the power calculation and the primary outcome and secondary outcomes on which this was based; how clustering by surgeon was addressed; and how clustering and correlation of outcome data were addressed in the analysis, given that both eyes of each subject were treated and analysed. The authors have described their study as a phase 1 trial, but the aim of such an investigation is to assess adverse outcomes of treatment, such as uncorrected high or irregular refractive outcome, which will drive the visual system towards amblyopia and resultant visual impairment. As the paper stands, it is not possible to agree with its principal conclusion that it provides evidence supporting the superiority of the novel treatment. A tempered report, clearly articulating the limitations of the approach with respect to outcome and permanency of effect, would have avoided giving the false impression that the new approach can be expected to supercede current treatment practices. A.L.S. and J.R. are supported by the National Institute for Health Research (NIHR) Biomedical Research Centres at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, and at the UCL Institute of Child Health/Great Ormond Street Hospital for children. A.L.S. is supported by fellowships from the Ulverscroft Vision Research Group and the Academy of Medical Sciences.

Epidemiology of Congenital Cataract

Congenital and infantile cataract is responsible for a fifth of the world’s blind children despite its treatable nature. It is thus an important cause of avoidable childhood visual disability. International variance in the frequency of the disorder reflect the global patterns of the overall health and survival of children as well as the socio-economic developmental status of and health infrastructure within the regions in question. Epidemiological research underpins the management of congenital cataract informing practice at both population level, e.g. screening and service planning, and child level, e.g. prognostication and clinical decision making. As the majority of cases are due to as yet undetermined causes, secondary prevention approaches (surgical and optical rehabilitation), and epidemiological investigation and assessment of these approaches, are key to reducing the burden of childhood cataract blindness.

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).

Methods of ascertainment of children and young people living with diabetes mellitus: a mapping exercise of National Health Service diabetic eye screening programmes

Abstract 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.

Risks and outcomes associated with primary intraocular lens implantation in children under 2 years old with congenital and infantile cataract: the UK and Ireland IoLunder2 cohort study

Abstract Background Public health initiatives to prevent childhood blindness have emphasised the importance of effective intervention for congenital cataract. Primary intraocular lens implantation, an important recent management innovation, has been rapidly adopted despite the absence of robust supporting evidence. The IoLunder2 study aimed to provide much needed insights into visual and adverse outcomes after surgery with and without primary intraocular lens implantation in children aged under 2 years. Methods Active surveillance case identification of cataract surgery and systematic data collection were undertaken through the British Congenital Cataract Interest Group (comprising 173 ophthalmologists who manage affected children in the UK and Ireland), which identified more children undergoing surgery for cataract than were reported to the National Health Service statutory databases. Multivariable regression analysis was used to estimate associations of intraocular lens use with visual outcome (assessed with standard hospital-specific but harmonised protocols) and incidence of adverse events at 1 year after surgery, with adjustment for all relevant confounding factors (eg, ocular comorbidity or age at surgery), which were agreed a priori on the basis of previous research or biological plausibility. All reported odds ratios (ORs) are fully adjusted. Findings Of 221 children, 56 of 131 with bilateral cataract and 48 of 90 with unilateral cataract had primary intraocular lens implantation. Implantation was independently associated with better visual outcome in bilateral (OR 5·4, 95% CI 1·09–26·4, p=0·04) but not unilateral disease, and with increased odds of reoperation (bilateral OR 5·5, 95% CI 2·3–13·2, p=0·002; unilateral 16·7, 4·1–68·9, p=0·009). Intraocular lens use did not reduce the odds of postoperative glaucoma, the key sight-threatening complication, after surgery in bilateral or unilateral cataract. Interpretation Use of intraocular lenses in young children, particularly in settings where follow-up is limited, should be critically reassessed. The absence of visual benefit and the lack of a previously postulated protective effect against postoperative glaucoma question the value of intraocular lens implantation in unilateral disease. The association between intraocular lens implantation and better early visual outcomes in bilateral disease needs to be balanced against the risk of reoperation and exposure to general anaesthetics during a key neurodevelopmental period. Funding Ulverscroft Vision Research Group, Great Ormond Street Hospital/UCL Institute of Child Health National Institute for Health Research Biomedical Research Centre, and Moorfields Eye Hospital NHS Foundation Trust/UCL Institute of Ophthalmology National Institute for Health Research Biomedical Research Centre.