Associations between unilateral amblyopia in childhood and cardiometabolic disorders in adult life:a cross-sectional and longitudinal analysis of the UK Biobank

Background: Amblyopia is a common neurodevelopmental condition and leading cause of childhood visual impairment. Given the known association between neurodevelopmental impairment and cardiometabolic dysfunction in later life, we investigated whether children with amblyopia have increased risk of cardiometabolic disorders in adult life. Methods: This was a cross-sectional and longitudinal analysis of 126,399 United Kingdom Biobank cohort participants who underwent ocular examination. A subset of 67,321 of these received retinal imaging. Data analysis was conducted between November 1st 2021 and October 15th 2022. Our primary objective was to investigate the association between amblyopia and a number of components of metabolic syndrome and individual cardiometabolic diseases. Childhood amblyopia, dichotomised as resolved or persisting by adulthood, cardiometabolic disease and mortality were defined using ophthalmic assessment, self-reported, hospital admissions and death records. Morphological features of the optic nerve and retinal vasculature and sublayers were extracted from retinal photography and optical coherence tomography. Associations between amblyopia and cardiometabolic disorders as well as retinal markers were investigated in multivariable-adjusted regression models. Findings: Individuals with persisting amblyopia (n = 2647) were more likely to be obese (adjusted odds ratio (95% confidence interval): 1.16 (1.05; 1.28)), hypertensive (1.25 (1.13; 1.38)) and diabetic (1.29 (1.04; 1.59)) than individuals without amblyopia (controls, (n = 18,481)). Amblyopia was also associated with an increased risk of myocardial infarction (adjusted hazard ratio: 1.38 (1.11; 1.72)) and death (1.36 (1.15; 1.60)). On retinal imaging, amblyopic eyes had significantly increased venular caliber (0.29 units (0.21; 0.36)), increased tortuosity (0.11 units (0.03; 0.19)), but lower fractal dimension (−0.23 units (−0.30; −0.16)) and thinner ganglion cell-inner plexiform layer (mGC-IPL, −2.85 microns (−3.47; −2.22)). Unaffected fellow eyes of individuals with amblyopia also had significantly lower retinal fractal dimension (−0.08 units (−0.15; −0.01)) and thinner mGC-IPL (−1.14 microns (−1.74; −0.54)). Amblyopic eyes with a persisting visual deficit had smaller optic nerve disc height (−0.17 units (−0.25; −0.08)) and width (−0.13 units (−0.21; −0.04)) compared to control eyes. Interpretation: Although further research is needed to understand the basis of the observed associations, healthcare professionals should be cognisant of greater cardiometabolic dysfunction in adults who had childhood amblyopia. Differences in retinal features in both the amblyopic eye and the unaffected non-amblyopic suggest generalised versus local processes. Funding: Medical Research Council (MR/T000953/1) and the National Institute for Health and Care Research.</p

Impact of CKD on Female Reproductive Hormones

IntroductionIncreasing numbers of women with chronic kidney disease (CKD) are using assisted reproductive technology (ART) to conceive, though the mechanisms by which CKD reduces fertility remain unclear.MethodsThis study investigated the impact of CKD on female reproductive hormones through an observational cohort study of 100 women with CKD and 57 healthy controls recruited from 4 hospital sites. Clinical data and serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone, estradiol, progesterone, anti-Mullerian hormone (AMH), and β–human chorionic gonadotrophin (β-HCG) were measured during the early menstrual cycle or at convenience for amenorrheic participants. Fertility ultrasounds were also performed, and ethical approval was obtained with participant consent.ResultsCompared with healthy controls, patients with CKD had a higher proportion of non-White ethnicity (49.0% vs. 31.8%, P &lt; 0.03), with 22% having undergone renal transplantation. There was no significant difference in age or body mass index (BMI) between the groups. Women with CKD had higher LH levels (5.9 vs. 4.4 IU/l, P &lt; 0.01), which correlated with declining estimated glomerular filtration rate (eGFR) (P &lt; 0.001). AMH levels (13.6 vs. 21.4 pmol/l, P = 0.008) and antral follicle count (AFC) (12.5 vs. 18, P = 0.009) were lower in the CKD group, decreasing with declining eGFR but not after adjusting for age and BMI. Prolactin levels increased with declining eGFR, whereas other hormones showed no significant differences. The AMH-to-AFC ratio did not differ between CKD and controls.ConclusionThis largest prospective study to date on fertility hormonal profiles in CKD underscores the need for longitudinal research to guide informed, timely fertility decisions for women with<p/

Data saves lives: optimising routinely collected clinical data for rare disease research

Necessity driven organisational change in the post-pandemic landscape has seen health care providers adopting innovations to manage and process health data. These include the use of ‘real-world’ datasets of routinely collected clinical information, enabling data-driven delivery. Rare disease risks being ‘left-behind’ unless our clinical and research communities engage with the challenges and opportunities afforded by the burgeoning field of health data informatics. We address the challenges to the meaningful use and reuse of rare disease data, and, through a series of recommendations around workforce education, harmonisation of taxonomy, and ensuring an inclusive health data environment, we highlight the role that those who manage rare disease must play in addressing them

Early life factors for myopia in the British Twins Early Development Study

Purpose Myopia is an increasingly prevalent condition globally. A greater understanding of contemporaneous, early life factors associated with myopia risk is urgently required, particularly in younger onset myopia as this correlates with higher severity and increased complications in adult life. Methods Analysis of a subset of the longitudinal, UK-based Twins Early Development Study (n=1991) recruited at birth between 1994 and 1996. Subjective refraction was obtained from the twin’s optometrists; mean age 16.3 years (SD 1.7). Myopia was defined as mean spherical equivalent ≤−0.75 dioptres. A life course epidemiology approach was used to appropriately weight candidate myopia risk factors during critical periods of eye growth. Adjusted ORs for myopia were estimated using multivariable logistic regression models at each life stage, together with variance explained (r2) and area under the receiver operator characteristic curve (AUROC) statistic of predictive models. Results Factors significantly associated with myopia included level of maternal education (OR 1.33, 95%  CI 1.11 to 1.59), fertility treatment (OR 0.63, 95%  CI 0.43 to 0.92), summer birth (OR 1.93, 95%  CI 1.28 to 2.90) and hours spent playing computer games (OR 1.03, 95%  CI 1.01 to 1.06). The total variance explained by this model was 4.4 % (p&lt;0.001) and the AUROC was 0.68 (95% CI 0.64 to 0.72). Consistent associations were observed with socioeconomic status, educational attainment, reading enjoyment and cognitive variables, particularly verbal cognition, at multiple points over the life course. Conclusions This study identifies known and novel associations with myopia during childhood development; associated factors identified in early life reflect sociological and lifestyle trends such as rates of maternal education, fertility treatment, early schooling and computer games

Identification of a candidate gene for astigmatism

PURPOSE. Astigmatism is a common refractive error that reduces vision, where the curvature and refractive power of the cornea in one meridian are less than those of the perpendicular axis. It is a complex trait likely to be influenced by both genetic and environmental factors. Twin studies of astigmatism have found approximately 60% of phenotypic variance is explained by genetic factors. This study aimed to identify susceptibility loci for astigmatism

Testing the impact of trait prevalence priors in Bayesian-based genetic prediction modeling of human appearance traits

The prediction of appearance traits by use of solely genetic information has become an established approach and a number of statistical prediction models have already been developed for this purpose. However, given limited knowledge on appearance genetics, currently available models are incomplete and do not include all causal genetic variants as predictors. Therefore such prediction models may benefit from the inclusion of additional information that acts as a proxy for this unknown genetic background. Use of priors, possibly informed by trait category prevalence values in biogeographic ancestry groups, in a Bayesian framework may thus improve the prediction accuracy of previously predicted externally visible characteristics, but has not been investigated as of yet. In this study, we assessed the impact of using trait prevalence-informed priors on the prediction performance in Bayesian models for eye, hair and skin color as well as hair structure and freckles in comparison to the respective prior-free models. Those prior-free models were either similarly defined either very close to the already established ones by using a reduced predictive marker set. However, these differences in the number of the predictive markers should not affect significantly our main outcomes. We observed that such priors often had a strong effect on the prediction performance, but to varying degrees between different traits and also different trait categories, with some categories barely showing an effect. While we found potential for improving the prediction accuracy of many of the appearance trait categories tested by using priors, our analyses also showed that misspecification of those prior values often severely diminished the accuracy compared to the respective prior-free approach. This emphasizes the importance of accurate specification of prevalence-informed priors in Bayesian prediction modeling of appearance traits. However, the existing literature knowledge on spatial prevalence is sparse for most appearance traits, including those investigated here. Due to the limitations in appearance trait prevalence knowledge, our results render the use of trait prevalence-informed priors in DNA-based appearance trait prediction currently infeasible.</p

Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.

Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 × 10-5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10-8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size

Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article

Changes in quality of life shortly after routine cataract surgery

Objective A pilot study to explore use of a generic patient-reported outcome measure to assess patient-perceived improvements in quality of life within 2-4 weeks of routine cataract surgery, and to explore differences after first or second eye surgery. Secondary analysis explored effects of gender and ethnicity. Design Prospective observational study. Participants Consecutive patients attending a weekly nurse-led postoperative clinic. Methods The Glasgow Benefit Inventory (GBI), a validated, post-interventional questionnaire (not specific to one particular medical or surgical intervention), was administered. Mean scores were calculated. Scores were compared when patients were grouped by first or second eye, and by gender or ethnicity (unpaired t test). Scores potentially range from +100 (maximum benefit) to -100 (maximum detriment). Results The GBI was administered 113 times to 109 patients (4 patients were seen following both first and second eye surgery). Mean overall score was +22.8 (median +19.4; SD 19.7; 95% CI +19.2 to +26.4). Mean (SD) sub-scores were +30.5 (25.3), +17.8 (26.7) and -3.1 (19.9) for general, social support and physical health sub-domains respectively. Total benefit scores were not significantly different for first or second eye surgery, or across gender (p&gt;0.3). Scores for patients of African (including African Caribbean) ethnicity were significantly higher than those obtained from European patients (p=0.002). Conclusions Patients reported significant improvements in quality of life even a few weeks after cataract surgery, as assessed by the GBI. Second eye surgery appeared to confer similar benefit to first eye surgery. The significant difference in scores between ethnic groups invites further investigatio