Predicting the onset of myopia in children by age, sex, and ethnicity: Results from the CLEERE Study.

SIGNIFICANCE: Clinicians and researchers would benefit from being able to predict the onset of myopia for an individual child. This report provides a model for calculating the probability of myopia onset, year-by-year and cumulatively, based on results from the largest, most ethnically diverse study of myopia onset in the United States. PURPOSE: This study aimed to model the probability of the onset of myopia in previously nonmyopic school-aged children. METHODS: Children aged 6 years to less than 14 years of age at baseline participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study who were nonmyopic and less hyperopic than +3.00 D (spherical equivalent) were followed up for 1 to 7 years through eighth grade. Annual measurements included cycloplegic autorefraction, keratometry, ultrasound axial dimensions, and parental report of children's near work and time spent in outdoor and/or sports activities. The onset of myopia was defined as the first visit with at least -0.75 D of myopia in each principal meridian. The predictive model was built using discrete time survival analysis and evaluated with C statistics. RESULTS: The model of the probability of the onset of myopia included cycloplegic spherical equivalent refractive error, the horizontal/vertical component of astigmatism (J0), age, sex, and race/ethnicity. Onset of myopia was more likely with lower amounts of hyperopia and less positive/more negative values of J0. Younger Asian American females had the highest eventual probability of onset, whereas older White males had the lowest. Model performance increased with older baseline age, with C statistics ranging from 0.83 at 6 years of age to 0.92 at 13 years. CONCLUSIONS: The probability of the onset of myopia can be estimated for children in the major racial/ethnic groups within the United States on a year-by-year and cumulative basis up to age 14 years based on a simple set of refractive error and demographic variables.

Myopia in African Americans Is Significantly Linked to Chromosome 7p15.2-14.2.

Purpose: The purpose of this study was to perform genetic linkage analysis and association analysis on exome genotyping from highly aggregated African American families with nonpathogenic myopia. African Americans are a particularly understudied population with respect to myopia. Methods: One hundred six African American families from the Philadelphia area with a family history of myopia were genotyped using an Illumina ExomePlus array and merged with previous microsatellite data. Myopia was initially measured in mean spherical equivalent (MSE) and converted to a binary phenotype where individuals were identified as affected, unaffected, or unknown. Parametric linkage analysis was performed on both individual variants (single-nucleotide polymorphisms [SNPs] and microsatellites) as well as gene-based markers. Family-based association analysis and transmission disequilibrium test (TDT) analysis modified for rare variants was also performed. Results: Genetic linkage analysis identified 2 genomewide significant variants at 7p15.2 and 7p14.2 (in the intergenic region between MIR148A and NFE2L3 and in the noncoding RNA LOC401324) and 2 genomewide significant genes (CRHR2 and AVL9) both at 7p14.3. No genomewide results were found in the association analyses. Conclusions: This study identified a significant linkage peak in African American families for myopia at 7p15.2 to 7p14.2, the first potential risk locus for myopia in African Americans. Interesting candidate genes are located in the region, including PDE1C, which is highly expressed in the eyes, and known to be involved in retinal development. Further identification of the causal variants at this linkage peak will help elucidate the genetics of myopia in this understudied population.

Long-term longitudinal changes in axial length in the Caucasian myopic and hyperopic population with a phakic intraocular lens.

PURPOSE: To determine the long-term longitudinal axial length changes in myopic and hyperopic adults with an iris-fixated phakic intraocular lens (pIOL). METHODS: The medical records of patients aged ≥18 years with myopia or hyperopia who were treated with pIOL implantation between 1996 and 2011 for refractive correction with a minimum follow-up of 5 years after pIOL implantation were analyzed. The main outcome measure was change in ocular axial length over time. RESULTS: 149 eyes of 149 myopic patients and 27 hyperopic eyes of 27 patients were included in this study. Mean patient age was 37.1 ± 10.4 years (35% male) in the myopic group and 39.4 ± 9.4 years (4% male) in the hyperopic group. The eyes of the myopic patients showed a significant mean increase in axial length of 0.45 ± 0.61 mm after a mean follow-up time of 144 ± 38 months (p < 0.001). In 26 eyes (17%), the axial length had increased by ≥1 mm. The mean annual axial length increase was 0.04 ± 0.06 mm. Axial elongation was associated with a higher degree of myopia (p < 0.001) and younger age (p = 0.02). The eyes of the hyperopic patients showed no change in axial length over time. CONCLUSIONS: Myopic eyes corrected with an iris-fixated pIOL show continuous increase in axial length at an adult age. Although this study is limited to subjects with a pIOL, this is the first time myopization in Caucasian adults has been reported in a large long-term longitudinal study.

Prevalence and risk factors of myopia in Han and Yugur older adults in Gansu, China: a cross-sectional study.

Few studies have investigated the prevalence of myopia in Northwest China. This cross-sectional study aimed to investigate the prevalence and associated factors of myopia and high myopia in adults aged 40-80 years in the Han and Yugur populations living in Gansu Province, Northwest China. A total of 3,845 participants were included. The overall age- and sex-adjusted prevalence of myopia (spherical equivalent (SE) < -0.5 D), high myopia (SE < -6.0 D) and hyperopia (SE > + 0.5 D) were 16.4%, 0.7% and 26.2% in Yugur participants, respectively, and 34.3%, 5.0% and 19.2% in Han participants, respectively. The prevalence of myopia and high myopia in Han participants was significantly higher than that in Yugur participants (both P < 0.001). Yugur population, birth in rural areas, smoking history and outdoor work were found to be negatively associated with myopia. Higher education level and a family history of myopia were found to be positively associated with myopia in the study population. High myopia was negatively associated with Yugur population, aging, birth in rural areas and was positively associated with a family history of myopia. This study provided valuable information regarding the environmental risk factors of myopia and revealed an ethnic disparity in the prevalence of myopia in Gansu Province, Northwest China.

Sleep Duration, Bedtime, and Myopia Progression in a 4-Year Follow-up of Chinese Children: The Anyang Childhood Eye Study.

Purpose: To investigate the relationship between sleep duration and bedtime with myopia progression and axial elongation during a 4-year follow-up in primary school children. Methods: This study included 1887 children (aged 7.09 ± 0.41 years) who had cycloplegic refractions data at baseline and a fourth visit and 2209 children (aged 7.10 ± 0.41 years) for axial length. All children underwent comprehensive ophthalmologic examinations, including cycloplegic refraction and ocular biometry, and standardized questionnaires, including average night-time sleep duration (h/d) and bedtime (time to bed). Myopia was defined as spherical equivalent < -0.5 diopters. Results: At the last follow-up, the mean myopia progression and axial elongation for all children were -1.89 ± 1.28 diopters and 1.22 ± 0.57 mm. After stratifying the sleep duration into tertile groups, myopia progression and axial elongation were slower in children with highest sleep duration tertile (P = 0.04 and P =0.014) in girls but not in boys, compared with the middle sleep duration tertile. However, after adjusting for potential confounders, no significant association was found for sleep duration with myopia progression and axial elongation for the children (P = 0.255 and P = 0.068), and the association with axial elongation was only of borderline significance in girls (P = 0.045). The bedtime was not associated with myopia progression and axial elongation in the regression analyses (P = 0.538; P = 0.801). Conclusions: These results show that there was no significant association between sleep duration and bedtime with myopia progression and axial elongation among children. The findings in girls might be related to the earlier onset of puberty.

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.

Clinical characteristics of congenital lamellar cataract and myopia in a Chinese family.

To investigate the clinical characteristics and the genetic defect in a Chinese family with congenital lamellar cataract with myopia. Three generations of a single family were recruited in the present study. A detailed family history and clinical data were recorded. A total of 100 unrelated ethnically matched controls without family history of congenital cataracts and myopia were also recruited. Genomic DNA was extracted from peripheral blood leukocytes. The sequencing of candidate genes was performed to screen out the disease-causing mutation. The effects of amino acid changes on the structure of proteins were predicted by bioinformatics analysis. Affected individuals presented lamellar lens opacities and myopia. Direct sequencing revealed a heterozygous c. 34 C>T variation in the αA-crystallin protein (CRYAA) gene, which resulted in the replacement of a highly conserved arginine by cystine at codon 12 (p.R12C). This mutation co-segregated with all affected individuals and was not observed in unaffected members or the 100 normal controls. Bioinformatic analysis showed that a highly conserved region was located around Arg12, an increase in local hydrophobicity was shown around the substitution site and the secondary structure of the mutant CRYAA protein has been changed. This is the case of a congenital lamellar cataract phenotype with myopia associated with the mutation of Arg12Cys (p.R12C) in CRYAA. Our finding confirms the high rate of mutations at this dinucleotide. In addition, these results demonstrate a myopia susceptibility locus in this region, which might also be associated with the mutation in CRYAA.

Ethnic disparity in prevalence and associated risk factors of myopia in adolescents.

BACKGROUND/PURPOSE: To examine ethnic disparity in prevalence and associated factors of myopia in adolescents using the Unites States National Health and Nutrition Examination Survey (NHANES) dataset. METHODS: Participants who were aged 12-19 years were included from NHANES (1999-2008). Logistic regression analyses were applied to identify risk factors associated with myopia after stratification by race. RESULTS: A total of 9,960 participants were included in the prevalence analysis, and 6,571 in the risk factor analysis. Other race (excluded Mexican American, other Hispanic, non-Hispanic white, non-Hispanic black) participants had the highest frequency of myopia (42.77%). Multivariate analyses of the whole population suggested that the odds of myopia were significantly lower in participants with household smokers (odds ratio [OR] = 0.79, 95% confidence interval [CI]: 0.66-0.97), and significantly greater in Mexican American race (OR = 1.28, 95% CI: 1.01-1.62), other Hispanic (OR = 1.79, 95% CI: 1.10-2.92) and in participants with senior high school graduate education (OR = 1.79, 95% CI: 1.01-3.18), watched 2 hours of television daily (OR = 1.27, 95% CI: 1.02-1.59), used the computer for 1 hour daily (OR = 1.276, 95% CI: 1.02-1.57). When examined by race/ethnicity, 1 hour of computer use increased the odds of myopia in the non-Hispanic White group, in Mexican Americans a higher family poverty income ratio and 2 hours of television time was associated with myopia, and in the Other Hispanic group, a higher family poverty income ratio was associated with myopia, while males and those with a higher sugar had a lower risk of myopia. CONCLUSION: Risk factors for myopia vary with race/ethnicity.

Early Diagnosis of Keratoconus in Chinese Myopic Eyes by Combining Corvis ST with Pentacam.

Purpose: This study was designed to evaluate and compare the sensitivity and specificity of the Belin/Ambrósio Deviation (BADD), Corneal Biomechanical Index (CBI) and Tomographic and Biomechanical Index (TBI) for the diagnosis of keratoconus in Chinese myopic eyes prior to undergoing corneal refractive surgery.Methods: A total of 125 patients (185 eyes) planned to undergo corneal refractive surgery were selected from the Refractive Center of Beijing Tongren Hospital between December 2017 and December 2018. They were divided into four groups: the normal group, bilateral keratoconus (BK) group, unilateral keratoconus (UK) group, and the forme fruste keratoconus (FFK) group. After determining the BADD, CBI, and TBI for each eye using the Corvis ST combined with Pentacam, the sensitivity and specificity of these three indices in diagnosing keratoconus were analyzed through receiver operating characteristic (ROC) curves.Results: The TBI exhibited the highest diagnostic efficiency in normal vs. UK (area under the ROC curve [AUROC]: 0.992), normal vs. UK+BK (AUROC: 0.988), normal vs. UK+BK* (*stand randomly selecting one eye of each patient in BK group) (AUROC: 0.982), normal vs. UK+BK+FFK (AUROC: 0.965), and normal vs. UK+BK*+FFK (AUROC: 0.953). The CBI demonstrated the highest diagnostic efficiency in normal vs. FFK (AUROC: 0.897). Finally, the BADD showed the highest diagnostic efficiency in normal vs. BK (AUROC: 0.998) and normal vs. BK* (AUROC: 0.996).Conclusion: The BADD, CBI, and TBI performed well in diagnosing keratoconus in Chinese myopic eyes. The CBI showed the highest diagnostic efficiency compared with normal for FFK. In addition, the TBI offered the greatest accuracy in detecting keratoconus and FFK eyes vs. the other parameters.

MRI of posterior eye shape and its associations with myopia and ethnicity.

PURPOSE: To evaluate posterior eye shape variations across a wide refractive error range using brain MRI in a multiethnic cohort. METHODS: Adult subjects in the multiethnic Singapore Epidemiology of Eye Disease study were included. Spherical equivalent (SE) was measured using subjective refraction, and axial length (AL) was measured using optical biometry. MRI was performed using a 3-Tesla whole body scanner with a 32-channel head coil. The radii and asphericity based on fitting of the posterior two-thirds of the eye (240°) were calculated. The refractive error status was categorised as myopic (SE<-0.5 D) or non-myopic (SE≥-0.5 D). RESULTS: A total of 450 adult participants (mean age 64.2±6.5 years old) were included. Less oblate asphericity was associated with more myopic SE, longer AL and with a refractive error categorisation of myopia (p<0.001 for all). Asphericity values were less oblate in myopic compared with non-myopic eyes (p<0.001). Multivariate analysis showed that Chinese subjects had less oblate eyes than Malay and Indian subjects, especially in non-myopic eyes. CONCLUSIONS: A less oblate posterior eye shape was associated with myopic eyes. Chinese eyes have less oblate shapes than Malay and Indian eyes, especially in non-myopic eyes.

The Adaptation and Acceptance of Defocus Incorporated Multiple Segment Lens for Chinese Children.

PURPOSE: We investigated the adaptability and acceptance of a novel spectacle lens design that was recently reported to achieve a significant antimyopia effect. DESIGN: A prospective, cross-over study. METHODS: Twenty children were recruited to wear both Defocus Incorporated Multiple Segments (DIMS) and single vision (SV) lens, with a random assignment of which type of lens was experienced first. For each type of lens, high and low contrast central distant visual acuity (VA) and high contrast mid-peripheral near VA were measured at both 500 lux and 50 lux ambient illuminance after 30 minutes' and a week's wearing of the lens. A self-developed questionnaire was applied to evaluate the visual discomfort at the 1-week visit. All quantitative data were analyzed by paired t test, while qualitative data were analyzed with the χ2 or Wilcoxon signed-rank tests. RESULTS: Central VA was not affected by DIMS lens compared with SV lens in all circumstances (all P > .05). However, the mid-peripheral near VA was found to reduce by approximately 0.06 logarithm of minimal angle of resolution unit in 2 of 4 quadrants (500 lux; P < .05) and in 3 quadrants (50 lux; P < .05) for DIMS lenses. No improvement was detected in the 1-week visit. Mid-peripheral blurred vision was the main visual complaint, which was noticed only once or twice a day. Being aware of the average antimyopic efficacy, 90% of children subjects preferred DIMS lenses. CONCLUSION: Mid-peripheral vision through DIMS lenses was slightly affected compared with SV lenses. Otherwise, DIMS lenses received good tolerance and acceptance by Chinese children.

Comparison of intraocular lens power calculation formulas in Chinese eyes with axial myopia.

PURPOSE: To assess the accuracy of intraocular lens (IOL) power calculation formulas in Chinese eyes with axial lengths (ALs) longer than 26.0 mm. SETTING: Department of Cataract Surgery, Shanxi Eye Hospital, China. DESIGN: Prospective case series. METHODS: This study evaluated (1) two new formulas (Barrett Universal II and Hill-RBF 2.0), (2) three vergence formulas (Haigis, Holladay 1, and SRK/T), and (3) the original and modified Wang-Koch AL adjustment formulas with Holladay 1 and SRK/T. The User Group for Laser Interference Biometry lens constants were used for IOL power calculation. The refractive prediction error was calculated by subtracting the predicted refraction from the actual refraction postoperatively. The mean numerical error (MNE), percentage of eyes with hyperopic outcomes, and mean absolute error (MAE) were determined. RESULTS: The study comprised 136 eyes. The Barrett and Hill-RBF formulas had MNEs close to zero (-0.09 D to 0.03 D), the Haigis, Holladay 1, and SRK/T produced hyperopic MNEs (0.25 to 0.70 D), and the original and modified Wang-Koch AL adjustment formulas induced myopic MNEs (-0.48 to -0.22 D). The original Wang-Koch formulas produced significantly lower percentages of eyes with hyperopic outcomes (15% to 18%) than all other formulas (28% to 91%). There were no significant differences in MAEs between the Barrett, Hill-RBF, Haigis, and original and modified Wang-Koch adjustment with the Holladay 1 (0.32 to 0.41 D). CONCLUSION: The performances of the Barrett and Hill-RBF were comparable in long eyes. The incidence of hyperopic outcome with the Wang-Koch AL adjustment formula was significantly lower than other formulas.

Genome-wide scans of myopia in Pennsylvania Amish families reveal significant linkage to 12q15, 8q21.3 and 5p15.33.

Myopia is one of the most common ocular disorders in the world, yet the genetic etiology of the disease remains poorly understood. Specialized founder populations, such as the Pennsylvania Amish, provide the opportunity to utilize exclusive genomic architecture, like unique haplotypes, to better understand the genetic causes of myopia. We perform genetic linkage analysis on Pennsylvania Amish families that have a strong familial history of myopia to map any potential causal variants and genes for the disease. 293 individuals from 25 extended families were genotyped on the Illumina ExomePlus array and merged with previous microsatellite data. We coded myopia affection as a binary phenotype; myopia was defined as having a mean spherical equivalent (MSE) of less than or equal to - 1 D (diopters). Two-point and multipoint parametric linkage analyses were performed under an autosomal dominant model. When allowing for locus heterogeneity, we identified two novel genome-wide significantly linked variants at 12q15 (heterogeneity LOD, HLOD = 3.77) in PTPRB and at 8q21.3 (HLOD = 3.35) in CNGB3. We identified further three genome-wide significant variants within a single family. These three variants were located in exons of SLC6A18 at 5p15.33 (LODs ranged from 3.51 to 3.37). Multipoint analysis confirmed the significant signal at 5p15.33 with six genome-wide significant variants (LODs ranged from 3.6 to 3.3). Further suggestive evidence of linkage was observed in several other regions of the genome. All three novel linked regions contain strong candidate genes, especially CNGB3 on 8q21.3, which has been shown to affect photoreceptors and cause complete color blindness. Whole genome sequencing on these regions is planned to conclusively elucidate the causal variants.

Exome genotyping and linkage analysis identifies two novel linked regions and replicates two others for myopia in Ashkenazi Jewish families.

BACKGROUND: Myopia is one of most common eye diseases in the world and affects 1 in 4 Americans. It is a complex disease caused by both environmental and genetics effects; the genetics effects are still not well understood. In this study, we performed genetic linkage analyses on Ashkenazi Jewish families with a strong familial history of myopia to elucidate any potential causal genes. METHODS: Sixty-four extended Ashkenazi Jewish families were previously collected from New Jersey. Genotypes from the Illumina ExomePlus array were merged with prior microsatellite linkage data from these families. Additional custom markers were added for candidate regions reported in literature for myopia or refractive error. Myopia was defined as mean spherical equivalent (MSE) of -1D or worse and parametric two-point linkage analyses (using TwoPointLods) and multi-point linkage analyses (using SimWalk2) were performed as well as collapsed haplotype pattern (CHP) analysis in SEQLinkage and association analyses performed with FBAT and rv-TDT. RESULTS: Strongest evidence of linkage was on 1p36(two-point LOD = 4.47) a region previously linked to refractive error (MYP14) but not myopia. Another genome-wide significant locus was found on 8q24.22 with a maximum two-point LOD score of 3.75. CHP analysis also detected the signal on 1p36, localized to the LINC00339 gene with a maximum HLOD of 3.47, as well as genome-wide significant signals on 7q36.1 and 11p15, which overlaps with the MYP7 locus. CONCLUSIONS: We identified 2 novel linkage peaks for myopia on chromosomes 7 and 8 in these Ashkenazi Jewish families and replicated 2 more loci on chromosomes 1 and 11, one previously reported in refractive error but not myopia in these families and the other locus previously reported in the literature. Strong candidate genes have been identified within these linkage peaks in our families. Targeted sequencing in these regions will be necessary to definitively identify causal variants under these linkage peaks.

PEDIATRIC RETINAL DETACHMENT IN AN ASIAN POPULATION WITH HIGH PREVALENCE OF MYOPIA: Clinical Characteristics, Surgical Outcomes, and Prognostic Factors.

PURPOSE: To evaluate the clinical characteristics and surgical outcomes of pediatric retinal detachments (RDs) in an Asian population. METHODS: Retrospective review of 171 eyes of 152 pediatric patients with rhegmatogenous RD over a 20-year period. RESULTS: Myopia was the most common risk factor in our population. At 6 months, primary anatomical success was 60.7%, and overall anatomical success was 86.7%. A total of 46.8% had best-corrected visual acuity of 20/40 or better, and 81.6% had best-corrected visual acuity of 20/200 or better. In primary RDs, high myopia (≤-6D) patients had a lower primary anatomical success compared to patients with moderate myopia (≤-2D) (59.3 vs. 100% P = 0.03). Increasing age and absence of proliferative vitreoretinopathy were associated with anatomical and visual success. Pars plana vitrectomy as the primary procedure was associated with decreased odds of anatomical success. A longer duration of symptoms, cataract, and a larger RD extent were associated with poorer functional outcome. CONCLUSION: Myopia was the commonest risk factor for pediatric RD in our population. Good anatomical and functional outcome can be achieved with surgery. Increasing age at presentation and absence of proliferative vitreoretinopathy was associated with anatomical and functional success. High myopia was associated with poorer anatomical and functional outcome.

Intraocular pressure and myopia progression in Chinese children: the Anyang Childhood Eye Study.

PURPOSE: To explore the relationship between intraocular pressure (IOP) at baseline and myopia progression in Chinese children from the Anyang Childhood Eye Study. DESIGN: Prospective school-based cohort study. METHODS: A total of 1558 grade 7 students completed the entire 2-year study. Ocular biometry, cycloplegic refractions and pneumotonometry were performed. Three years of follow-up have been completed for the children aged 12 years. The refractive groups and the tertiles of IOP were assessed by analysis of variance, to look for differences in mean values of spherical equivalent and IOP, respectively. RESULTS: The children's mean baseline IOP was 15.87±3.42 mm Hg. Mean IOP was significantly higher in girls by 0.57 mm Hg (p=0.024). In the whole sample, there was a mean change in spherical equivalent of -1.05 D over 2 years. The baseline IOP was 15.69 mm Hg in those progressing 1 D or more vs 16.09 mm Hg for those progressing <1 D (p=0.022). In the myopic group, myopes progressing >1 D had mean IOP of 15.94 vs 16.42 mm Hg for those myopes progressing 1 D or less (p=0.024). CONCLUSIONS: In this sample of Chinese children, myopia progression over 2 years was inversely related to IOP, suggesting that IOP had essentially no relationship with myopia progression in school children. The lower IOP in progressing myopic eyes may indicate more compliant sclerae.

Refractive Error in Chinese Preschool Children: The Shanghai Study.

PURPOSE: To examine the prevalence of refractive error and some associated factors in Chinese preschool children. METHODS: The Jinshan District Eye Study was a school-based survey of eye health in a large sample of 4- to 6-year-olds attending kindergartens from May 2013 to December 2013 in Shanghai. Refractive error was measured using an autorefractor under noncycloplegic conditions. Axial length (AL) was measured with an ocular biometry system. In addition, body height and weight were also recorded. RESULTS: A total of 7,166 children successfully completed their refraction measurements. The median (interquartile range) of spherical equivalent (SE) for all the children was +0.25 D (-0.13 D to +0.62 D), and the range was -15.88 to +18.13 D. The mean AL for all the children was 22.35±0.70 mm, and the range was 18.20 to 27.71 mm. The overall prevalence of myopia (-1.00 D or less), hyperopia (+2.00 D or greater), and astigmatism (1.00 D or greater) were 5.9%, 1.0%, and 12.7%, respectively. After multivariate analysis, more myopic SE (or less hyperopic SE) was significantly associated with girls, longer AL, taller, and lighter. CONCLUSION: Shanghai has a high prevalence of refractive error in the world. However, longitudinal studies are needed to evaluate refractive changes over time in individual children and warranted to prevent the development of myopia.

Retinal nerve fiber bundle trajectories in Chinese myopic eyes: Comparison with a Caucasian based mathematical model.

Previously we developed a mathematical model for describing the retinal nerve fiber bundle (RNFB) trajectories in the human retina. The model was based on Caucasian eyes that were not selected regarding refraction. The aim of this study was to determine the characteristics of the RNFB trajectories in Chinese myopic eyes. We collected high quality red free fundus images from 80 eyes of 80 Chinese myopic subjects (median [interquartile range/range] refraction -3.9 [-6.0 to -2.5/-10 to -1] D). We traced all visible RNFBs (n = 1460) and evaluated their trajectories using the previously published mathematical model. In the superior-temporal region, the RNFB trajectories of the Chinese myopic eyes were similar to that of the Caucasian eyes (86% of trajectories within the 95% central range of the Caucasian model). In the inferior-temporal region, the trajectories of the Chinese low to moderate myopic eyes were also similar to that of the Caucasian eyes (85%); trajectories of the high myopic eyes (spherical equivalent beyond -6.00 D) were clearly less curved (75%). Associations between individual deviations from the model and axial length, retinal vessel course, and optic disc anatomy were studied with multiple linear regression analysis. In the superior-temporal region, the trajectories were associated with retinal vessel course (P = 0.008) and optic disc size (P = 0.016). In the inferior-temporal region, there was a significant association with axial length (P < 0.001), retinal vessel course (P = 0.006), and disc torsion (P = 0.009).

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

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

CCDC102B confers risk of low vision and blindness in high myopia.

The incidence of high myopia is increasing worldwide with myopic maculopathy, a complication of myopia, often progressing to blindness. Our two-stage genome-wide association study of myopic maculopathy identifies a susceptibility locus at rs11873439 in an intron of CCDC102B (P = 1.77 × 10-12 and Pcorr = 1.61 × 10-10). In contrast, this SNP is not significantly associated with myopia itself. The association between rs11873439 and myopic maculopathy is further confirmed in 2317 highly myopic patients (P = 2.40 × 10-6 and Pcorr = 1.72 × 10-4). CCDC102B is strongly expressed in the retinal pigment epithelium and choroids, where atrophic changes initially occur in myopic maculopathy. The development of myopic maculopathy thus likely exhibits a unique background apart from the development of myopia itself; elucidation of the roles of CCDC102B in myopic maculopathy development may thus provide insights into preventive methods for blindness in patients with high myopia.