When do myopia genes have their effect? Comparison of genetic risks between children and adults

Previous studies have identified many genetic loci for refractive error and myopia. We aimed to investigate the effect of these loci on ocular biometry as a function of age in children, adolescents, and adults. The study population consisted of three age groups identified from the international CREAM consortium: 5,490 individuals aged 25 years. All participants had undergone standard ophthalmic examination including measurements of axial length (AL) and corneal radius (CR). We examined the lead SNP at all 39 currently known genetic loci for refractive error identified from genome-wide association studies (GWAS), as well as a combined genetic risk score (GRS). The beta coefficient for association between SNP genotype or GRS versus AL/CR was compared across the three age groups, adjusting for age, sex, and principal components. Analyses were Bonferroni-corrected. In the age group <10 years, three loci (GJD2, CHRNG, ZIC2) were associated with AL/CR. In the age group 10–25 years, four loci (BMP2, KCNQ5, A2BP1, CACNA1D) were associated; and in adults 20 loci were associated. Association with GRS increased with age; β = 0.0016 per risk allele (P = 2 × 10–8) in <10 years, 0.0033 (P = 5 × 10–15) in 10- to 25-year-olds, and 0.0048 (P = 1 × 10–72) in adults. Genes with strongest effects (LAMA2, GJD2) had an early effect that increased with age. Our results provide insights on the age span during which myopia genes exert their effect. These insights form the basis for understanding the mechanisms underlying high and pathological myopia

Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error : the CREAM consortium

Peer reviewe

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Abstract: Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia

Three horizontal muscle surgery for large-angle infantile esotropia: Validation of a table of amounts of surgery

PurposeTo validate a table of amounts of three horizontal muscle surgery in patients with large-angle infantile esotropia (60 prism dioptres, PD).MethodsA prospective interventional case series reporting the postoperative alignment of 51 patients (27 male, 24 female) over a 15-year period was conducted. Surgery amounts were according to a published table developed on a previous patient cohort (n=49), using bilateral medial rectus recession with graded unilateral lateral rectus resection. Kaplan-Meier life-table survival curves were formulated for success to orthotropia (±10 PD) after one and subsequent horizontal muscle surgeries for up to 8 years follow-up.ResultsThe median preoperative deviation was 65 PD (range 60-80 PD) and median age at surgery was 11.8 months (range 5.1 months-3.6 years). Surgical success to orthotropia (±10 PD) after one surgery was 100% at 2 months, 95.7% at 6 months, 91.3% at 12 months, 77.8% at 4 years, and 73.6% at 8 years. Postoperative failure requiring further horizontal surgery occurred in 17.6% (residual esotropia 4, consecutive exotropia 5).ConclusionsOur second cohort has reproduced the success rate of the previous cohort (77.8% vs 77.1% at 4 years). If the published table of surgical amounts is used, three horizontal muscle surgery in large-angle infantile esotropia (≥60 PD) appears to have a good long-term success rate, and does not lead to the high rates of either residual esotropia or consecutive exotropia reported by others in the literature

Human error in strabismus surgery: Quantification with a sensitivity analysis

Background- Reoperations are frequently necessary in strabismus surgery. The goal of this study was to analyze human-error related factors that introduce variability in the results of strabismus surgery in a systematic fashion. Methods- We identified the primary factors that influence the outcome of strabismus surgery. For each of the human-error related factors we quantified variation with clinical assessments: measurement of the angle of strabismus, surgical strategy and surgical accuracy. Firstly, six patients were examined by six orthoptists, and accuracy of prism cover tests was assessed. Secondly, a questionnaire with sample cases (10°, 15° and 20° of infantile esotropia) was put to orthoptists, to determine variation in current surgical strategy. Finally, photographs made during surgery were analyzed to assess surgical accuracy. The influence of human-error related factors was related to the influence of inter-patient differences with a mechanical model. The relative contribution of all factors was assessed with a sensitivity analysis, and results were compared to clinical studies. Results- The surgical trajectory of strabismus surgery could be modeled mathematically. Measurement of angle of strabismus, surgical technique, anatomy and physiology were considered. Variations in the human-error related factors were: (1) the latent angle at distant fixation was measured with a 90% confidence interval of 5°, and comprised 20% of the total variance of the postoperative angle, (2) orthoptists decided for bilateral recessions of, respectively, 7.3±1.7 mm (total amount of two recessions), 9.1±1.2 mm and 10.3±1.3 mm, which comprised 15% of the total variance, and (3) surgical accuracy was estimated at ±0.5 mm, which comprised 20% of the total variance. Conclusion- The human error in strabismus surgery could be quantified with a sensitivity analysis. Approximately half of the reoperations in strabismus surgery are caused by inaccuracy in the measurement of the angle of strabismus, variability in surgical strategy and imprecise surgery.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin