Elise Ciner

Genomewide Linkage Scan for Myopia Susceptibility Loci among Ashkenazi Jewish Families Shows Evidence of Linkage on Chromosome 22q12

Mild/moderate (common) myopia is a very common disorder, with both genetic and environmental influences. The environmental factors are related to near work and can be measured. There are no known genetic loci for common myopia. Our goal is to find evidence for a myopia susceptibility gene causing common myopia. Cycloplegic and manifest refraction were performed on 44 large American families of Ashkenazi Jewish descent, each with at least two affected siblings. Individuals with at least -1.00 diopter or lower in each meridian of both eyes were classified as myopic. Microsatellite genotyping with 387 markers was performed by the Center for Inherited Disease Research. Linkage analyses were conducted with parametric and nonparametric methods by use of 12 different penetrance models. The family-based association test was used for an association scan. A maximum multipoint parametric heterogeneity LOD (HLOD) score of 3.54 was observed at marker D22S685, and nonparametric linkage analyses gave consistent results, with a P value of.0002 at this marker. The parametric multipoint HLOD scores exceeded 3.0 for a 4-cM interval, and significant evidence of genetic heterogeneity was observed. This genomewide scan is the first step toward identifying a gene on chromosome 22 with an influence on common myopia. At present, we are following up our linkage results on chromosome 22 with a dense map of >1,500 single-nucleotide-polymorphism markers for fine mapping and association analyses. Identification of a susceptibility locus in this region may eventually lead to a better understanding of gene-environment interactions in the causation of this complex trait.

A Survey of Vision Screening Policy of Preschool Children in the United States

A state-by-state survey regarding preschool vision screening guidelines, policies, and procedures was conducted. Currently 34 states provide vision screening guidelines and 15 states require vision screening of at least some of their preschool-aged children. The Department of Public Health administers the programs in 26 states, the Department of Education in 13. A wide range of professional and lay personnel conduct preschool vision screenings, and nurses participate in the screening process in 22 states. Visual acuity is assessed in 30 states, eye alignment in 24 states, refractive error in eight states, and color vision in 10 states. A combination of screening tests is recommended in 24 states. Currently, 45 states do not require screening of all preschool children. Thus, although laws, guidelines, and recommendations exist in most states, many preschool-age children do not have access to vision screening programs.

The Effectiveness of Irlen Filters for Improving Reading Performance: A Pilot Study

The objectives of this pilot study were to investigate the effectiveness of Irlen filters for improving comfort and reading performance and to determine whether traditional optometric intervention would be effective in relieving the symptoms commonly reported by people seeking help through the use of Irlen filters. Thirty subjects were included in the study: 12 males and 18 females. The ages of the subjects ranged from 9 to 51 (mean = 23.6). They were randomly placed in either an Irlen filter treatment group (n = 11), a vision therapy treatment group (n = 11), or a control group (n = 8). Pre- and posttesting on all subjects included a vision evaluation, reading and intelligence testing, the Irlen scotopic sensitivity screening test, and a symptom questionnaire. Results revealed that subjects in both treatment groups were more comfortable after treatment, although only the vision therapy group showed improvement in vision functioning. The subjects in the Irlen filter group did not show any significant gains in reading rate, word recognition in context, or comprehension.

Vision screening of preschool children: evaluating the past, looking toward the future.

Vision problems of preschool children are detectable with a comprehensive eye examination; however, it is estimated that only 14% of children below the age of 6 years receive an eye examination. Screening is advocated as a cost-effective alternative to identify children in need of further vision care. Thirty-four states recommend or require vision screening of preschool children. Although laws and guidelines exist, only 21 % of preschool children are actually screened for vision problems. There is little agreement concerning the best screening methods, and no validated, highly effective model for screening vision of preschool children. Newer screening tests have been designed specifically for preschool populations, and can be administered by lay screeners. Many have not been validated. Several are recommended by states or organizations without convincing scientific evidence of their effectiveness. This paper summarizes current laws and guidelines for preschool vision screening in the United States, reviews advantages and disadvantages of several test procedures, and provides recommendations for developing future preschool vision screening programs.

Risk Factors for Amblyopia in the Vision in Preschoolers Study

OBJECTIVE To evaluate risk factors for unilateral amblyopia and for bilateral amblyopia in the Vision in Preschoolers (VIP) study. DESIGN Multicenter, cross-sectional study. PARTICIPANTS Three- to 5-year-old Head Start preschoolers from 5 clinical centers, overrepresenting children with vision disorders. METHODS All children underwent comprehensive eye examinations, including threshold visual acuity (VA), cover testing, and cycloplegic retinoscopy, performed by VIP-certified optometrists and ophthalmologists who were experienced in providing care to children. Monocular threshold VA was tested using a single-surround HOTV letter protocol without correction, and retested with full cycloplegic correction when retest criteria were met. Unilateral amblyopia was defined as an interocular difference in best-corrected VA of 2 lines or more. Bilateral amblyopia was defined as best-corrected VA in each eye worse than 20/50 for 3-year-olds and worse than 20/40 for 4- to 5-year-olds. MAIN OUTCOME MEASURES Risk of amblyopia was summarized by the odds ratios and their 95% confidence intervals estimated from logistic regression models. RESULTS In this enriched sample of Head Start children (n = 3869), 296 children (7.7%) had unilateral amblyopia, and 144 children (3.7%) had bilateral amblyopia. Presence of strabismus (P<0.0001) and greater magnitude of significant refractive errors (myopia, hyperopia, astigmatism, and anisometropia; P<0.00001 for each) were associated independently with an increased risk of unilateral amblyopia. Presence of strabismus, hyperopia of 2.0 diopters (D) or more, astigmatism of 1.0 D or more, or anisometropia of 0.5 D or more were present in 91% of children with unilateral amblyopia. Greater magnitude of astigmatism (P<0.0001) and bilateral hyperopia (P<0.0001) were associated independently with increased risk of bilateral amblyopia. Bilateral hyperopia of 3.0 D or more or astigmatism of 1.0 D or more were present in 76% of children with bilateral amblyopia. CONCLUSIONS Strabismus and significant refractive errors were risk factors for unilateral amblyopia. Bilateral astigmatism and bilateral hyperopia were risk factors for bilateral amblyopia. Despite differences in selection of the study population, these results validated the findings from the Multi-Ethnic Pediatric Eye Disease Study and Baltimore Pediatric Eye Disease Study.

Genomewide Scan of Ocular Refraction in African-American Families Shows Significant Linkage to Chromosome 7p15

Refractive development is influenced by environmental and genetic factors. Genetic studies have identified several regions of linkage to ocular refraction, but none have been carried out in African‐derived populations. We performed quantitative trait locus linkage analyses in African‐American (AA) families to identify genomic regions responsible for refraction. We recruited 493 AA individuals in 96 families to participate in the Myopia Family Study. Genotyping of 387 microsatellite markers was performed on 398 participants. The mean refraction among genotyped individuals was −2.87 D (SD=3.58) and myopia of at least 1 D was present in 267 (68%) participants. Multipoint, regression‐based, linkage analyses were carried out on a logarithmic transformation of ocular refraction using the statistical package MERLIN‐REGRESS. Empirical significance levels were determined via 4,898 whole‐genome gene‐dropping simulations. Linkage analyses were repeated after clustering families into two subgroups based on admixture proportions as determined by the software package STRUCTURE. Genomewide significant linkage was seen at 47 cM on chromosome 7 (logarithm of the odds ratio (LOD)=5.87, P=0.00005). In addition, three regions on chromosomes 2p, 3p and 10p showed suggestive evidence of linkage (LOD>2, P<0.005) for ocular refraction. We mapped the first quantitative trait locus for ocular refraction in an AA population to chr.7p15. Two previous studies in European‐derived families reported some evidence of linkage to a nearby region, suggesting that this region may contain polymorphisms that mediate refraction across populations. The genomic region under our linkage peak spans ∼17 Mb and contains ∼170 genes. Further refinement of this region will be pursued in future studies. Genet. Epidemiol. 2008. Published 2008 Wiley‐Liss, Inc.

Candidate high myopia loci on chromosomes 18p and 12q do not play a major role in susceptibility to common myopia

BackgroundTo determine whether previously reported loci predisposing to nonsyndromic high myopia show linkage to common myopia in pedigrees from two ethnic groups: Ashkenazi Jewish and Amish. We hypothesized that these high myopia loci might exhibit allelic heterogeneity and be responsible for moderate /mild or common myopia.MethodsCycloplegic and manifest refraction were performed on 38 Jewish and 40 Amish families. Individuals with at least -1.00 D in each meridian of both eyes were classified as myopic. Genomic DNA was genotyped with 12 markers on chromosomes 12q21-23 and 18p11.3. Parametric and nonparametric linkage analyses were conducted to determine whether susceptibility alleles at these loci are important in families with less severe, clinical forms of myopia.ResultsThere was no strong evidence of linkage of common myopia to these candidate regions: all two-point and multipoint heterogeneity LOD scores were < 1.0 and non-parametric linkage p-values were > 0.01. However, one Amish family showed slight evidence of linkage (LOD>1.0) on 12q; another 3 Amish families each gave LOD >1.0 on 18p; and 3 Jewish families each gave LOD >1.0 on 12q.ConclusionsSignificant evidence of linkage (LOD> 3) of myopia was not found on chromosome 18p or 12q loci in these families. These results suggest that these loci do not play a major role in the causation of common myopia in our families studied.

Prevalence of Vision Disorders by Racial and Ethnic Group among Children Participating in Head Start

OBJECTIVE To compare the prevalence of amblyopia, strabismus, and significant refractive error among African-American, American Indian, Asian, Hispanic, and non-Hispanic white preschoolers in the Vision In Preschoolers study. DESIGN Multicenter, cross-sectional study. PARTICIPANTS Three- to 5-year old preschoolers (n=4040) in Head Start from 5 geographically disparate areas of the United States. METHODS All children who failed the mandatory Head Start screening and a sample of those who passed were enrolled. Study-certified pediatric optometrists and ophthalmologists performed comprehensive eye examinations including monocular distance visual acuity (VA), cover testing, and cycloplegic retinoscopy. Examination results were used to classify vision disorders, including amblyopia, strabismus, significant refractive errors, and unexplained reduced VA. Sampling weights were used to calculate prevalence rates, confidence intervals, and statistical tests for differences. MAIN OUTCOME MEASURES Prevalence rates in each racial/ethnic group. RESULTS Overall, 86.5% of children invited to participate were examined, including 2072 African-American, 343 American Indian (323 from Oklahoma), 145 Asian, 796 Hispanic, and 481 non-Hispanic white children. The prevalence of any vision disorder was 21.4% and was similar across groups (P=0.40), ranging from 17.9% (American Indian) to 23.3% (Hispanic). Prevalence of amblyopia was similar among all groups (P=0.07), ranging from 3.0% (Asian) to 5.4% (non-Hispanic white). Prevalence of strabismus also was similar (P=0.12), ranging from 1.0% (Asian) to 4.6% (non-Hispanic white). Prevalence of hyperopia >3.25 diopter (D) varied (P=0.007), with the lowest rate in Asians (5.5%) and highest in non-Hispanic whites (11.9%). Prevalence of anisometropia varied (P=0.009), with the lowest rate in Asians (2.7%) and highest in Hispanics (7.1%). Myopia >2.00 D was relatively uncommon (<2.0%) in all groups with the lowest rate in American Indians (0.2%) and highest rate in Asians (1.9%). Prevalence of astigmatism >1.50 D varied (P=0.01), with the lowest rate among American Indians (4.3%) and highest among Hispanics (11.1%). CONCLUSIONS Among Head Start preschool children, the prevalence of amblyopia and strabismus was similar among 5 racial/ethnic groups. Prevalence of significant refractive errors, specifically hyperopia, astigmatism, and anisometropia, varied by group, with the highest rate of hyperopia in non-Hispanic whites, and the highest rates of astigmatism and anisometropia in Hispanics.

Stereoacuity development : 6 months to 5 years. A new tool for testing and screening

A new tool to measure changes in random dot stereoacuity development from 6 months to 5 years of age was developed and tested. Either a forced choice or operant preferential looking (PL) paradigm with a happy face target was successfully used to test 136 children. Results indicate that stereoacuity measurements continue to develop through the first years of life. Although children below 24 months of age can be expected to have stereo thresholds in the range of 300 sec arc, there is a transition at approximately 24 months of age after which stereoacuity approaches adult levels. The sensitivity of this test in detecting binocular vision problems was 80%. These results provide guidelines for the assessment of stereoacuity in young children and also provide a new tool for the early detection of binocular vision anomalies.

Stereoacuity Development in Young Children

An operant preferential looking (OPL) test with random dot stereo targets was used to gather developmental data on stereoacuity thresholds in 180 children between 18 and 65 months of age. Results indicated a steady improvement in stereoacuity with age from 250 sec arc in the youngest children tested to 60 sec arc in the oldest group of children. The greatest improvement in stereoacuity occurs at 30 months of age where mean values improve from 225 to 125 sec arc. This large change in stereo threshold appears to be attributable to the significantly higher variability in responses in the children under 30 months of age vs. the lower variability in responses in children over 30 months of age. The overall steady improvements in stereoacuity appear to be a result of the developmental changes in the variability of responses rather than actual neurophysiological changes within the visual system.