Worldwide 20,000–40,000 children with congenital or childhood cataract are born every year with varying degrees and patterns of lens opacification with a broad aetiology. In most cases of bilateral cataract, a causative genetic mutation can be identified, with autosomal dominant inheritance being most common in 44% of cases. Variants in genes involve lens-specific proteins or those that regulate eye development, thus giving rise to other associated ocular abnormalities. Approximately 15% of cases have systemic features, hence paediatric input is essential to minimise comorbidities and support overall development of children at high risk of visual impairment. In some metabolic conditions, congenital cataract may be the presenting sign, and therefore prompt diagnosis is important where there is an available treatment. Multidisciplinary management of children is essential, including ophthalmic surgeons, orthoptists, paediatricians, geneticists and genetic counsellors, and should extend beyond the medical team to include school and local paediatric visual support services. Early surgery and close follow up in ophthalmology is important to optimise visual potential and prevent amblyopia. Routine genetic testing is essential for the complete clinical management of patients, with next-generation sequencing of 115 genes shown to expedite molecular diagnosis, streamline care pathways and inform genetic counselling and reproductive options for the future. Lay title Childhood cataract: how to manage patients Lay abstract Cataract is a clouding of the lens in the eye. Cataract occurring in children has many different causes, which may include infections passed from mother to child during pregnancy, trauma, medications and exposure to radiation. In most cases of cataract occurring in both eyes, a genetic cause can be found which may be inherited from parents or occur sporadically in the developing baby itself while in the womb. Cataracts may occur on their own, with other eye conditions or be present with other disorders in the body as part of a syndrome. Genetic testing is important for all children with cataract as it can provide valuable information about cause, inheritance and risk to further children and signpost any other features of the disease in the rest of the body, permitting the assembly of the correct multidisciplinary care team. Genetic testing currently involves screening for mutations in 115 genes already known to cause cataract and has been shown to expedite diagnosis and help better manage children. Genetic counselling services can support families in understanding their diagnosis and inform future family planning. In order to optimise vision, early surgery for cataract in children is important. This is because the brain is still developing and an unobstructed pathway for light to reach the back of the eye is required for normal visual development. Any obstruction (such as cataract) if left untreated may lead to permanent sight impairment or blindness, even if it is removed later. A multidisciplinary team involved in the care of a child with cataract should include ophthalmic surgeons, orthoptists, paediatricians, geneticists and genetic counsellors, and should extend beyond the medical team to include school and local child visual support services. They will help to diagnose and manage systemic conditions, optimise vision potential and help patients and their families access best supportive care.

Two national surveys of vision impairment and blindness were undertaken in The Gambia in 1986 and 1996. These provided data for the inception of The Gambia’s National Eye Health Programme (NEHP) within the Ministry of Health and Social Welfare. There have been important developments in the eye health services provided by the NEHP in the last 20 years. At the same time, the population has also undergone major demographic changes that may have led to substantial changes in the burden of eye disease. We conducted a National Eye Health Survey of vision impairment, blindness and its comorbidities in adults in The Gambia in 2019. We examined a nationally representative population-based sample of adults 35 years and above to permit direct comparison with the data available from the previous surveys. Alongside a comprehensive vision and eye examination, the survey provides nationally representative data on important comorbidities in this population: diabetes, hypertension, obesity, hearing impairment, disability and mental health. Secondly, it estimates access to assistive technologies and eye health services. Thirdly, it is powered to allow a five-year follow up cohort study to measure the incidence and progression of eye disease.

Two national surveys of vision impairment and blindness were undertaken in The Gambia in 1986 and 1996. These provided data for the inception of The Gambia’s National Eye Health Programme (NEHP) within the Ministry of Health and Social Welfare. There have been important developments in the eye health services provided by the NEHP in the last 20 years. At the same time, the population has also undergone major demographic changes that may have led to substantial changes in the burden of eye disease. We conducted a National Eye Health Survey of vision impairment, blindness and its comorbidities in adults in The Gambia in 2019. We examined a nationally representative population-based sample of adults 35 years and above to permit direct comparison with the data available from the previous surveys. Alongside a comprehensive vision and eye examination, the survey provides nationally representative data on important comorbidities in this population: diabetes, hypertension, obesity, hearing impairment, disability and mental health. Secondly, it estimates access to assistive technologies and eye health services. Thirdly, it is powered to allow a five-year follow up cohort study to measure the incidence and progression of eye disease.

EPHA2 is a transmembrane tyrosine kinase receptor that, when disrupted, causes congenital and age-related cataracts. Cat-Map reports 22 pathogenic EPHA2 variants associated with congenital cataracts, variable microcornea, and lenticonus, but no previous association with microphthalmia (small, underdeveloped eye, ≥2 standard deviations below normal axial length). Microphthalmia arises from ocular maldevelopment with >90 monogenic causes, and can include a complex ocular phenotype. In this paper, we report two pathogenic EPHA2 variants in unrelated families presenting with bilateral microphthalmia and congenital cataracts. Whole genome sequencing through the 100,000 Genomes Project and cataract-related targeted gene panel testing identified autosomal dominant heterozygous mutations segregating with the disease: (i) missense c.1751C>T, p.(Pro584Leu) and (ii) splice site c.2826-9G>A. To functionally validate pathogenicity, morpholino knockdown of epha2a/epha2b in zebrafish resulted in significantly reduced eye size ± cataract formation. Misexpression of N-cadherin and retained fibre cell nuclei were observed in the developing lens of the epha2b knockdown morphant fish by 3 days post-fertilisation, which indicated a putative mechanism for microphthalmia pathogenesis through disruption of cadherin-mediated adherens junctions, preventing lens maturation and the critical signals stimulating eye growth. This study demonstrates a novel association of EPHA2 with microphthalmia, suggesting further analysis of pathogenic variants in unsolved microphthalmia cohorts may increase molecular diagnostic rates.

Few estimates are available of the need for assistive devices (ADs) in African settings. This study aimed to estimate population-level need for glasses and hearing aids in The Gambia based on (1) clinical impairment assessment, and (2) self-reported AD awareness, and explore the relationship between the two methods. The Gambia 2019 National Eye Health Survey is a nationally representative population-based sample of 9188 adults aged 35+ years. Participants underwent standardised clinical vision assessments including the need for glasses (distance and near). Approximately 25% of the sample underwent clinical assessment of hearing and hearing aid need. Data were also collected on self-reported awareness, need and access barriers to vision and hearing ADs. Overall, 5.6% of the study population needed distance glasses (95% CI 5.0–6.3), 45.9% (95% CI 44.2–47.5) needed near glasses and 25.5% (95% CI 22.2–29.2) needed hearing aids. Coverage for each AD was very low (<4%). The agreement between self-report and clinical impairment assessment for AD need was poor. In conclusion, there is high prevalence and very low coverage for distance glasses, near glasses and hearing aids in The Gambia. Self-report measures alone will not provide an accurate estimate of AD need.

Childhood cataract affects 2.5–3.5 per 10,000 children in the UK, with a genetic mutation identified in 50–90% of bilateral cases. However, cataracts can also manifest in adolescence and early adulthood in isolation, as part of a complex ocular phenotype or with systemic features making accurate diagnosis more challenging. We investigate our real-world experience through a retrospective review of consecutive bilateral cataract patients (0–25 years) presenting to the ocular genetics service at Moorfields Eye Hospital between 2017 and 2020. Fifty-four patients from 44 unrelated families were identified, with a median age of 13.5 years (range 1 to 68 years) and a median age at diagnosis of 43.9 months IQR (1.7–140.3 months); 40.7% were female and 46.3% were Caucasian. Overall, 37 patients from 27 families (61.4%) were genetically solved (50%) or likely solved (additional 11.4%), with 26 disease-causing variants (8 were novel) in 21 genes; the most common were crystallin genes, in 8 (29.6%) families, with half occurring in the CRYBB2 gene. There was no significant difference in the molecular diagnostic rates between sporadic and familial inheritance (P = 0.287). Associated clinical diagnoses were retinal dystrophies in five (18.5%) and aniridia in three (11.1%) families. Bilateral cataracts were the presenting feature in 27.3% (6/22) of either complex or syndromic cases, and isolated cataract patients were 11.5 years younger (rank-sum Z = 3.668, P = 0.0002). Prompt genetic investigation with comprehensive panel testing can aid with diagnosis and optimise management of cataract patients.

Introduction The aim of this study was to ascertain the incidence of thyroid cancer for patients categorised as Thy3, 3a or 3f across four tertiary thyroid multidisciplinary centres in the UK. Material and methods This is a retrospective case series examining patients who presented with a thyroid nodule and diagnosed as Thy3, 3a or 3f according to the Royal College of Pathologists modified British Thyroid Association and Royal College of Physicians Thy system. Results In total, 395 patients were included in this study. Of these, 136 turned out to have benign thyroid disease and 24 had micropapillary thyroid carcinomas. The overall rate of thyroid malignancy was 28.8%. For each subcategory, the rate of malignancy was Thy3 24.7.7%, Thy3a 30.4% and Thy3f 29.2. However, the incidence of thyroid malignancy varied considerably between the four centres (Thy 3f 18-54%). Discussion The diagnosis of thyroid cancer is evolving but detection for malignancy for indeterminate nodules remains below 50% for most centres around the world. In 2014, the British Thyroid Association subdivided the original Thy3 category into Thy3a and Thy3f and recommended a more conservative approach to management for Thy3a nodules. Despite this, only two centres yielded a higher conversion rate of malignancy in the new higher graded Thy3f group compared with Thy3a. Conclusion It is debateable whether the new 'Thy3' subcategories are more useful than the original. Local thyroid malignancy rates may also be more useful than national averages to inform treatment decisions.

No abstract