Jesse Lin

Variants of N-acetyltransferase NAT1 and a case-control study of colorectal adenomas.

N-acetyltransferase NAT1, together with enzymes CYP1A2 and NAT2, helps convert heterocyclic amines to mutagens. Epidemiologic studies of the association of variants of these enzymes with colorectal cancer may provide indirect support for a heterocyclic amine mechanism. We used single strand conformation polymorphism and heteroduplex analysis to screen fro mutations in the NAT1 coding region in a case-control study (n = 932) of colorectal adenomas, which are precursors to cancer. Thirteen different single-base mutations were found: C97T, C190T, T402C, G445A-G459A-T640G ( a combination of three mutations), C559T, G560A, A613G, A752T, T777C, G781A, and A787G. Function of novel mutations was tested by bacterial production of enzymes and measurements of Km, Vmax, and stability. However, on 24-control individuals and 18 cases carried an inactivating NAT1 mutation. When combined with our data on the NAT2 acetylation polymorphism, we saw no evidence for an association between N-acetyltransferases and prevalence of adenomas. Larger sample sizes are required for further evaluation.

Risk Factors Associated with Childhood Strabismus: The Multi-Ethnic Pediatric Eye Disease and Baltimore Pediatric Eye Disease Studies

OBJECTIVE To investigate risk factors associated with esotropia or exotropia in infants and young children. DESIGN Population-based cross-sectional prevalence study. PARTICIPANTS Population-based samples of 9970 children 6 to 72 months of age from California and Maryland. METHODS Participants were preschool African-American, Hispanic, and non-Hispanic white children participating in the Multi-Ethnic Pediatric Eye Disease Study and the Baltimore Eye Disease Study. Data were obtained by parental interview and ocular examination. Odd ratios and 95% confidence intervals were calculated to evaluate the association of demographic, behavioral, and clinical risk factors with esotropia and exotropia. MAIN OUTCOME MEASURES Odds ratios (ORs) for various risk factors associated with esotropia or exotropia diagnosis based on cover testing. RESULTS In multivariate logistic regression analysis, esotropia was associated independently with prematurity, maternal smoking during pregnancy, older preschool age (48-72 months), anisometropia, and hyperopia. There was a severity-dependent association of hyperopia with the prevalence of esotropia, with ORs increasing from 6.4 for 2.00 diopters (D) to less than 3.00 D of hyperopia, to 122.0 for 5.00 D or more of hyperopia. Exotropia was associated with prematurity, maternal smoking during pregnancy, family history of strabismus, female sex, astigmatism (OR, 2.5 for 1.50 to <2.50 D of astigmatism, and 5.9 for ≥2.5 D of astigmatism), and anisoastigmatism in the J0 component (OR, ≥2 for J0 anisoastigmatism of ≥0.25 D). CONCLUSIONS Prematurity and maternal smoking during pregnancy are associated with a higher risk of having esotropia and exotropia. Refractive error is associated in a severity-dependent manner to the prevalence of esotropia and exotropia. Because refractive error is correctable, these risk associations should be considered when developing guidelines for the screening and management of refractive error in infants and young children. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Prevalence of Myopia, Hyperopia, and Astigmatism in Non-Hispanic White and Asian Children: Multi-Ethnic Pediatric Eye Disease Study

PURPOSE To determine the age-, gender-, and ethnicity-specific prevalence of myopia, hyperopia, and astigmatism in non-Hispanic white (NHW) and Asian preschool children. DESIGN Population-based, cross-sectional study. PARTICIPANTS A population-based sample of 1501 NHW children and 1507 Asian children aged 6-72 months from Los Angeles County and Riverside County, California. METHODS Eligible children underwent an in-home and in-clinic interview and a comprehensive eye examination including cycloplegic autorefraction from 100 census tracts. MAIN OUTCOME MEASURES The proportion of children with myopia (spherical equivalent [SE] ≤-1.00 diopter [D]), hyperopia (SE ≥ +2.00 D) and cylindrical refractive error ≥1.50 D in the worse eye. The astigmatism type was defined as with-the-rule (WTR; +cylinder axis 90°±15°) and against-the-rule (ATR; + cylinder axis 180°±15°); all other orientations were considered oblique (OBL). RESULTS The prevalence of myopia, hyperopia, and astigmatism in NHW children was 1.20% (95% confidence interval [CI], 0.76%-1.89%), 25.65% (95% CI, 23.5%-27.9%), and 6.33% (95% CI, 5.21%-7.68%), respectively. The prevalence of WTR, ATR, and OBL astigmatism in NHW children was 4.33%, 1.00%, and 1.00%, respectively. Prevalence was lower with older age groups for astigmatism (P = 0.0002), but not for myopia (P = 0.82) or hyperopia (P = 0.31). In Asian children, the prevalence of myopia, hyperopia, and astigmatism was 3.98% (95% CI, 3.11%-5.09%), 13.47% (95% CI, 11.8%-15.3%), and 8.29% (95% CI, 7.01%-9.80%), respectively. The prevalence of WTR, ATR, and OBL astigmatism was 6.50%, 0.80%, and 1.00% respectively. The prevalence of hyperopia was higher in girls than boys (P = 0.0002), but no differences were found for myopia and astigmatism. CONCLUSIONS Hyperopia was the most common refractive error in both Asian and NHW children. However, compared with NHW children, myopia was relatively more prevalent, and hyperopia less prevalent, among Asian children. The prevalence of astigmatism was greatest in infants, and WTR astigmatism predominated at all ages. Myopia showed relatively stable prevalence across age groups, whereas hyperopia prevalence decreased after infancy and then increased again in older age groups; however, longitudinal studies are needed to evaluate refractive changes over time in individual children. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Risk Factors for Hyperopia and Myopia in Preschool Children: The Multi-Ethnic Pediatric Eye Disease and Baltimore Pediatric Eye Disease Studies

PURPOSE To describe the risk factors associated with hyperopia and myopia among children 6 to 72 months of age. DESIGN Population-based cross-sectional study. PARTICIPANTS Population-based samples of 9970 children 6 to 72 months of age from Los Angeles County, California, and Baltimore, Maryland. METHODS Participants were preschool African-American, Hispanic, and non-Hispanic white children (n = 9770) from Los Angeles, California, and Baltimore, Maryland. Parental questionnaires and a comprehensive eye examination were administered. Demographic, behavioral, and clinical risk factors associated with hyperopia (≥2.00 diopters [D]) and myopia (≤-1.00 D) were determined. MAIN OUTCOME MEASURES Odds ratios (ORs) for risk factors associated with myopia and hyperopia. RESULTS Compared with non-Hispanic whites, African-American (OR, 6.0) and Hispanic (OR, 3.2) children were more likely to be myopic. Children 6 to 35 months of age were more likely to be myopic compared with those 60 to 72 months of age (OR, ≥1.7). Compared with African-American children, non-Hispanic white (OR, 1.63) and Hispanic (OR, 1.49) children were more likely to be hyperopic. Children whose parents had health insurance (OR, 1.5) and those with a history of maternal smoking during pregnancy (OR, 1.4) were more likely to have hyperopia. Astigmatism of 1.5 D or more at any axis was associated with myopia (OR, 4.37) and hyperopia (OR, 1.43). CONCLUSIONS Children in specific racial or ethnic groups and age groups are at higher risk of having myopia and hyperopia. Cessation of maternal smoking during pregnancy may reduce the risk of hyperopia in these children. Given that both myopia and hyperopia are risk factors for the development of amblyopia and strabismus, these risk factors should be considered when developing guidelines for screening and intervention in preschool children. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Risk Factors for Decreased Visual Acuity in Preschool Children: The Multi-Ethnic Pediatric Eye Disease and Baltimore Pediatric Eye Disease Studies

OBJECTIVE To investigate risk factors associated with unilateral or bilateral decreased visual acuity (VA) in preschool children. DESIGN Population-based, cross-sectional prevalence study. PARTICIPANTS Population-based samples of 6504 children ages 30 to 72 months from California and Maryland. METHODS Participants were preschool African-American, Hispanic, and non-Hispanic white children from Los Angeles, California, and Baltimore, Maryland. Data were obtained by a parental interview and a detailed ocular examination. Logistic regression models were used to evaluate the independent associations between demographic, behavioral, and clinical risk factors with unilateral and bilateral decreased VA. MAIN OUTCOME MEASURES Odds ratios (ORs) for various risk factors associated with interocular difference (IOD) in VA of ≥2 lines with ≤20/32 in the worse eye, or bilateral decreased VA <20/40 or <20/50 if <48 months of age. RESULTS In multivariate logistic regression analysis, 2-line IOD with a VA of ≤20/32 was independently associated with Hispanic ethnicity (OR, 2.05), esotropia (OR, 8.98), spherical equivalent (SE) anisometropia (ORs ranging between 1.5 and 39.7 for SE anisometropia ranging between 0.50 to <1.00 diopters [D] and ≥2.00 D), and aniso-astigmatism in J0 or J45 (ORs ranging between 1.4 and ≥5.3 for J0 or J45 differences ranging between 0.25 to <0.50 D and ≥1.00 D). Bilateral decreased VA was independently associated with lack of health insurance (OR, 2.9), lower primary caregiver education (OR, 1.7), astigmatism (OR, 2.3 and 17.6 for astigmatism 1.00 to <2.00 D and ≥2.00 D), and SE hyperopia ≥4.00 D (OR, 10.8). CONCLUSIONS Anisometropia and esotropia are risk factors for IOD in VA. Astigmatism and high hyperopia are risk factors for bilateral decreased VA. Guidelines for the screening and management of decreased VA in preschool children should be considered in light of these risk associations. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Prevalence of Astigmatism in 6- to 72-Month-Old African American and Hispanic Children: The Multi-Ethnic Pediatric Eye Disease Study

PURPOSE To determine the age-, gender-, and ethnicity-specific prevalence of astigmatism in African American and Hispanic children aged 6 to 72 months. DESIGN Population-based, cross-sectional study. PARTICIPANTS The Multi-Ethnic Pediatric Eye Disease Study is a population-based evaluation of the prevalence of vision disorders in children ages 6 to 72 months in Los Angeles County, California. Seventy-seven percent of eligible children completed a comprehensive eye examination. This report provides the results from 2994 African American and 3030 Hispanic children. METHODS Eligible children in 44 census tracts were identified during an in-home interview and scheduled for a comprehensive eye examination and in-clinic interview. Cycloplegic autorefraction was used to determine refractive error. MAIN OUTCOME MEASURES The proportion of children with astigmatism defined as cylindrical refractive error ≥ 1.50 diopters (D) in the worse eye. The astigmatism type was defined as with-the-rule (WTR) (+ cylinder axis 90 ± 15 degrees) and against-the-rule (ATR) (+ cylinder axis 180 ± 15 degrees); all other orientations were considered oblique (OBL). The prevalence of astigmatism and its types were also determined for worse eye cylindrical refractive error ≥ 3.00 D. RESULTS Prevalence of astigmatism ≥ 1.50 D was higher in Hispanic children compared with African American children (16.8% vs. 12.7%, respectively; P<0.0001). Hispanic children also showed a higher prevalence of astigmatism ≥ 3.00 D than African American children (2.9% vs. 1.0% respectively; P<0.0001). The prevalence of astigmatism ≥ 1.50 D showed a significant decreasing trend with age (P<0.0001). The prevalence of WTR, ATR, and OBL astigmatism ≥ 1.50 D was 13.9%, 0.6%, and 2.2%, respectively, in Hispanic children, and 7.8%, 2.2%, and 2.7%, respectively, in African American children. CONCLUSIONS We observed ethnicity-related differences in astigmatism prevalence in preschool children. The age-related decrease in astigmatism prevalence in preschool children likely reflects emmetropization.

Fixation Preference and Visual Acuity Testing in a Population-based Cohort of Preschool Children with Amblyopia Risk Factors

PURPOSE To compare the clinical assessment of fixation preference (FP) to visual acuity (VA) in a population-based sample of preschool children with amblyopia risk factors. DESIGN Evaluation of diagnostic test in a population-based study. PARTICIPANTS 243 children with anisometropia and/or strabismus, aged 30 to 72 months, living in Los Angeles County, CA [corrected] METHODS Before measuring VA, FP testing was performed at near and usually without correction, using the binocular fixation pattern in children with strabismus >10 prism diopters (Delta), or the induced tropia test for children with strabismus <or=10Delta or without strabismus. We determined the sensitivity and specificity of FP testing for predicting unilateral amblyopia, defined by optotype VA, among children with amblyopia risk factors. MAIN OUTCOME MEASURE Grade of FP. RESULTS Sensitivity of FP testing for amblyopia among children with anisometropia was 20% (9/44) and specificity was 94% (102/109). Among strabismic children, sensitivity was 69% (9/13; worse in children 30-47 than 48-72 months old) and specificity was 79% (70/89), with similar findings for esotropia and exotropia. CONCLUSION The ability of FP testing to correctly identify amblyopia in preschool children with amblyopia risk factors is poor. Clinicians should be wary of using FP as a surrogate measure of interocular difference in VA in young children. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any materials discussed in this article.

Risk Factors for Astigmatism in Preschool Children: The Multi-Ethnic Pediatric Eye Disease and Baltimore Pediatric Eye Disease Studies

OBJECTIVE To evaluate risk factors for astigmatism in a population-based sample of preschool children. DESIGN Population-based cross-sectional study. PARTICIPANTS Population-based samples of 9970 children ages 6 to 72 months from Los Angeles County, California, and Baltimore, Maryland. METHODS A cross-sectional study of children participating in the Multiethnic Pediatric Eye Disease Study and the Baltimore Eye Disease Study was completed. Data were obtained by clinical examination or by in-person interview. Odds ratios and 95% confidence intervals (CI) were calculated to evaluate potential associations between clinical, behavioral, or demographic factors and astigmatism. MAIN OUTCOME MEASURES Odds ratios (ORs) for various risk factors associated with astigmatism. RESULTS Participants with myopia (≤-1.0 diopters) were 4.6 times as likely to have astigmatism (95% CI, 3.56-5.96) than those without refractive error, whereas participants with hyperopia (≥+2.00 diopters) were 1.6 times as likely (95% CI, 1.39-1.94). Children 6 to <12 months of age were approximately 3 times as likely to have astigmatism than children 5 to 6 years of age (95% CI, 2.28-3.73). Both Hispanic (OR, 2.38) and African-American (OR, 1.47) children were as likely to have astigmatism than non-Hispanic white children. Furthermore, children whose mothers smoked during pregnancy were 1.46 times (95% CI, 1.14-1.87) as likely to have astigmatism than children whose mothers did not smoke. CONCLUSIONS In addition to infancy, Hispanic and African-American race/ethnicity and correctable/modifiable risk factors such as myopia, hyperopia, and maternal smoking during pregnancy are associated with a higher risk of having astigmatism. Although the prevalence of smoking during pregnancy is typically low, this association may suggest etiologic pathways for future investigation. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Prevalence and causes of visual impairment in Asian and non-Hispanic white preschool children: Multi-ethnic Pediatric Eye Disease Study.

PURPOSE To determine the prevalence and causes of decreased visual acuity (VA). DESIGN Population-based cross-sectional study. PARTICIPANTS Multi-ethnic sample of children 30 to 72 months of age identified in Los Angeles. METHODS All eligible children underwent a comprehensive ophthalmic evaluation including monocular VA testing, cover testing, cycloplegic autorefraction, fundus evaluation, and VA retesting with refractive correction. Decreased VA was defined as presenting or best-measured VA worse than 20/50 in children 30 to 47 months of age and worse than 20/40 for children 48 months of age and older. The prevalence and causes of decreased VA were determined, for both presenting and best-measured VA, in the better-seeing and the worse-seeing eyes. MAIN OUTCOME MEASURES Prevalence and causes of decreased vision. RESULTS Presenting VA was assessed in 1840 children and best-measured VA was assessed in 1886 children. Presenting VA was decreased in the worse eye of 4.2% of Asian children and of 3.6% of non-Hispanic white (NHW) children. Close to one-fourth of these cases had no identifiable cause, and 81% of these resolved on retesting. Decreased presenting VA in the worse eye with an identifiable ophthalmic cause was present in 3.4% of Asian children and in 2.6% of NHW children. Decreased presenting VA attributable to simple refractive error (myopia ≥ 0.5 diopters [D]; hyperopia ≥ 3.0 D; astigmatism ≥ 2.0 D or ≥ 1.5 D for children older than 36 months) was present in the worse eye of 2.3% of Asian children and of 1.4% of NHW children and in the better eye of 0.5% of Asian children and of 0.3% of NHW children. Decreased best-measured VA attributable to a cause was present in the worse eye of 1.2% of both Asian children and NHW children and in the better eye of 0.2% of Asian and of 0.3% of NHW children. Amblyopia related to refractive error was the most common cause, and was 10 times as common as ocular disease. Severe visual impairment was rare. CONCLUSIONS Seventy percent of all decreased VA in Asian and NHW preschool children and more than 90% of decreased VA with an identifiable cause is related to refractive error--either uncorrected refractive error or amblyopia resulting from refractive error. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Color Vision Deficiency in Preschool Children: The Multi-Ethnic Pediatric Eye Disease Study

PURPOSE To determine the sex- and ethnicity-specific prevalence of color vision deficiency (CVD) in black, Asian, Hispanic, and non-Hispanic white preschool children. DESIGN Population-based, cross-sectional study. PARTICIPANTS The Multi-Ethnic Pediatric Eye Disease Study is a population-based evaluation of the prevalence of vision disorders in children in Southern California. A total of 5960 subjects 30 to 72 months of age were recruited for the study, of whom 4177 were able to complete color vision testing (1265 black, 812 Asian, 1280 Hispanic, and 820 non-Hispanic white). METHODS Color vision testing was performed using Color Vision Testing Made Easy color plates (Home Vision Care, Gulf Breeze, FL), and diagnostic confirmatory testing was performed using the Waggoner HRR Diagnostic Test color plates (Home Vision Care). MAIN OUTCOME MEASURES Testability of color vision in preschool children between 30 and 72 months of age and prevalence of CVD stratified by age, sex, and ethnicity. RESULTS Testability was 17% in children younger than 37 months of age, increasing to 57% in children 37 to 48 months of age, 89% in children 49 to 60 months of age, and 98% in children 61 to 72 months of age. The prevalence of CVD among boys was 1.4% for black, 3.1% for Asian, 2.6% for Hispanic, and 5.6% for non-Hispanic white children; the prevalence in girls was 0.0% to 0.5% for all ethnicities. The ethnic difference in CVD was statistically significant between black and non-Hispanic white children (P = 0.0003) and between Hispanic and non-Hispanic white children (P = 0.02). In boys, most CVD cases were either deutan (51%) or protan (34%); 32% were classified as mild, 15% as moderate, and 41% as severe. CONCLUSIONS Testability for CVD in preschool children is high by 4 years of age. The prevalence of CVD in preschool boys varies by ethnicity, with the highest prevalence in non-Hispanic white and lowest in black children.