Prevalence and causes of functional low vision in school-age children: results from standardized population surveys in Asia, Africa, and Latin America.

PURPOSE: Data on the prevalence and causes of functional low vision (FLV) in adults and children are lacking but are important for planning low-vision services. This study was conducted to determine the prevalence and causes of FLV among children recruited in eight population-based prevalence surveys of visual impairment and refractive error from six countries (India [2 locations]; China [2 locations]; Malaysia, Chile, Nepal, and South Africa). METHODS: Using the same protocol, 4082 to 6527 children aged 5 (or 7) to 15 years were examined at each site. Uncorrected and presenting visual acuities were successfully measured with retroilluminated logMAR tumbling-E charts in 3997 to 5949 children; cycloplegic autorefraction was performed and best corrected acuities assessed. All children were examined by an ophthalmologist and a cause of visual loss assigned to eyes with uncorrected acuity < or =6/12. The prevalence of FLV was determined overall and by site; associations with gender, age, parental education and urban/rural location were assessed with logistic regression. RESULTS: The prevalence of FLV ranged from 0.65 to 2.75 in 1000 children, with wide confidence intervals. The overall prevalence was 1.52 in 1000 children (95% CI 1.16-1.95). FLV was significantly associated with age (odds ratio [OR] 1.13 for each year, P = 0.01), and parental education was protective (OR 0.75 for each of five levels of education, P = 0.017). Retinal lesions and amblyopia were the commonest causes. CONCLUSIONS: More studies are needed to determine the prevalence and causes of FLV in children so that services can be planned that promote independence, improve quality of life, and increase access to education

Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia

Rare variant analyses across multiethnic cohorts identify novel genes for refractive error

Peer reviewe

APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans

Myopia is the most common vision disorder and the leading cause of visual impairment worldwide. However, gene variants identified to date explain less than 10% of the variance in refractive error, leaving the majority of heritability unexplained (“missing heritability”). Previously, we reported that expression of APLP2 was strongly associated with myopia in a primate model. Here, we found that low-frequency variants near the 5’-end of APLP2 were associated with refractive error in a prospective UK birth cohort (n = 3,819 children; top SNP rs188663068, p = 5.0 × 10&lt;sup&gt;−4&lt;/sup&gt;) and a CREAM consortium panel (n = 45,756 adults; top SNP rs7127037, p = 6.6 × 10&lt;sup&gt;−3&lt;/sup&gt;). These variants showed evidence of differential effect on childhood longitudinal refractive error trajectories depending on time spent reading (gene x time spent reading x age interaction, p = 4.0 × 10&lt;sup&gt;−3&lt;/sup&gt;). Furthermore, Aplp2 knockout mice developed high degrees of hyperopia (+11.5 ± 2.2 D, p &lt; 1.0 × 10&lt;sup&gt;−4&lt;/sup&gt;) compared to both heterozygous (-0.8 ± 2.0 D, p &lt; 1.0 × 10&lt;sup&gt;−4&lt;/sup&gt;) and wild-type (+0.3 ± 2.2 D, p &lt; 1.0 × 10&lt;sup&gt;−4&lt;/sup&gt;) littermates and exhibited a dose-dependent reduction in susceptibility to environmentally induced myopia (F(2, 33) = 191.0, p &lt; 1.0 × 10&lt;sup&gt;−4&lt;/sup&gt;). This phenotype was associated with reduced contrast sensitivity (F(12, 120) = 3.6, p = 1.5 × 10&lt;sup&gt;−4&lt;/sup&gt;) and changes in the electrophysiological properties of retinal amacrine cells, which expressed Aplp2. This work identifies APLP2 as one of the “missing” myopia genes, demonstrating the importance of a low-frequency gene variant in the development of human myopia. It also demonstrates an important role for APLP2 in refractive development in mice and humans, suggesting a high level of evolutionary conservation of the signaling pathways underlying refractive eye development.</p

Determining Possible Shared Genetic Architecture Between Myopia and Primary Open-Angle Glaucoma

PURPOSE: To determine genetic correlations between common myopia and primary open-angle glaucoma (POAG). // METHODS: We tested the association of myopia polygenic risk scores (PRSs) with POAG and POAG endophenotypes using two studies: the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) study comprising 798 POAG cases with 1992 controls, and the Rotterdam Study (RS), a population-based study with 11,097 participants, in which intraocular pressure (IOP) and optic disc parameter measurements were catalogued. PRSs were derived from genome-wide association study meta-analyses conducted by the Consortium for Refractive Error and Myopia (CREAM) and 23andMe. In total, 12 PRSs were constructed and tested. Further, we explored the genetic correlation between myopia, POAG, and POAG endophenotypes by using the linkage disequilibrium score regression (LDSC) method. // RESULTS: We did not find significant evidence for an association between PRS of myopia with POAG (P = 0.81), IOP (P = 0.07), vertical cup-disc ratio (P = 0.42), or cup area (P = 0.25). We observed a nominal association with retinal nerve fiber layer (P = 7.7 × 10-3) and a significant association between PRS for myopia and disc area (P = 1.59 × 10-9). Using the LDSC method, we found a genetic correlation only between myopia and disc area (genetic correlation [RhoG] = -0.12, P = 1.8 × 10-3), supporting the findings of the PRS approach. // CONCLUSIONS: Using two complementary approaches we found no evidence to support a genetic overlap between myopia and POAG; our results suggest that the comorbidity of these diseases is not influenced by common variants. The association between myopia and optic disc size is well known and validates this methodology

Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia

Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (area under the curve (AUC) = 0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes that participate in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may enable the prediction of refractive error and the development of personalized myopia prevention strategies in the future.</p

Femtosecond laser-assisted cataract surgeries reported to the European Registry of Quality Outcomes for Cataract and Refractive Surgery : baseline characteristics, surgical procedure, and outcomes

Purpose To describe a large cohort of femtosecond laser-assisted cataract surgeries in terms of baseline characteristics and the related outcomes. Setting Eighteen cataract surgery clinics in 9 European countries and Australia. Design Prospective multicenter case series. Methods Data on consecutive eyes having femtosecond laser-assisted cataract surgery in the participating clinics were entered in the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO). A trained registry manager in each clinic was responsible for valid reporting to the EUREQUO. Demographics, preoperative corrected distance visual acuity (CDVA), risk factors, type of surgery, type of intraocular lens, visual outcomes, refractive outcomes, and complications were reported. Results Complete data were available for 3379 cases. The mean age was 64.4 years ± 10.9 (SD) and 57.8% (95% confidence interval [CI], 56.1-59.5) of the patients were women. A surgical complication was reported in 2.9% of all cases (95% CI, 2.4-3.5). The mean postoperative CDVA was 0.04 ± 0.15. logarithm of the minimum angle of resolution. A biometry prediction error (spherical equivalent) was within ±0.5 diopter in 71.8% (95% CI, 70.3-73.3) of all surgeries. Postoperative complications were reported in 3.3% (95% CI, 2.7-4.0). Patients with good preoperative CDVA had the best visual and refractive outcomes; patients with poor preoperative visual acuity had poorer outcomes. Conclusions The visual and refractive outcomes of femtosecond laser-assisted cataract surgery were favorable compared with manual phacoemulsification. The outcomes were highly influenced by the preoperative visual acuity, but all preoperative CDVA groups had acceptable outcomes

A multiethnic genome-wide analysis of 19,420 individuals identifies novel loci associated with axial length and shared genetic influences with refractive error and myopia

Introduction: Long axial length (AL) is a risk factor for myopia. Although family studies indicate that AL has an important genetic component with heritability estimates up to 0.94, there have been few reports of AL-associated loci.Methods: Here, we conducted a multiethnic genome-wide association study (GWAS) of AL in 19,420 adults of European, Latino, Asian, and African ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, with replication in a subset of the Consortium for Refractive Error and Myopia (CREAM) cohorts of European or Asian ancestry. We further examined the effect of the identified loci on the mean spherical equivalent (MSE) within the GERA cohort. We also performed genome-wide genetic correlation analyses to quantify the genetic overlap between AL and MSE or myopia risk in the GERA European ancestry sample.Results: Our multiethnic GWA analysis of AL identified a total of 16 genomic loci, of which 5 are novel. We found that all AL-associated loci were significantly associated with MSE after Bonferroni correction. We also found that AL was genetically correlated with MSE (rg = −0.83; SE, 0.04; p = 1.95 × 10−89) and myopia (rg = 0.80; SE, 0.05; p = 2.84 × 10−55). Finally, we estimated the array heritability for AL in the GERA European ancestry sample using LD score regression, and found an overall heritability estimate of 0.37 (s.e. = 0.04).Discussion: In this large and multiethnic study, we identified novel loci, associated with AL at a genome-wide significance level, increasing substantially our understanding of the etiology of AL variation. Our results also demonstrate an association between AL-associated loci and MSE and a shared genetic basis between AL and myopia risk

Strategies to address inequity of uncorrected refractive error in the Western Pacific: A modified Delphi process.

PURPOSE: Uncorrected refractive error is the leading cause of vision impairment globally; however, little attention has been given to equity and access to services. This study aimed to identify and prioritise: (1) strategies to address inequity of access to refractive error services and (2) population groups to target with these strategies in five sub-regions within the Western Pacific. METHODS: We invited eye care professionals to complete a two-round online prioritisation process. In round 1, panellists nominated population groups least able to access refractive error services, and strategies to improve access. Responses were summarised and presented in round 2, where panellists ranked the groups (by extent of difficulty and size) and strategies (in terms of reach, acceptability, sustainability, feasibility and equity). Groups and strategies were scored according to their rank within each sub-region. RESULTS: Seventy five people from 17 countries completed both rounds (55% women). Regional differences were evident. Indigenous peoples were a priority group for improving access in Australasia and Southeast Asia, while East Asia identified refugees and Oceania identified rural/remote people. Across the five sub-regions, reducing out-of-pocket costs was a commonly prioritised strategy for refraction and spectacles. Australasia prioritised improving cultural safety, East Asia prioritised strengthening school eye health programmes and Oceania and Southeast Asia prioritised outreach to rural areas. CONCLUSION: These results provide policy-makers, researchers and funders with a starting point for context-specific actions to improve access to refractive error services, particularly among underserved population groups who may be left behind in existing private sector-dominated models of care

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

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.</p