Linkage replication of the MYP12 locus in common myopia.

PURPOSE: Myopia is a common disorder with a large public health impact. Although 12 myopia loci have been reported and heterogeneity for high myopia loci have been demonstrated, replication of high-myopia loci with a common myopia phenotype has not been successful. This study reports the successful replication of MYP12 in three large, multigenerational families with autosomal dominant (AD) common myopia (spherical equivalent [SphE]

Vision-related quality of life comparison for emmetropes, myopes after refractive surgery, and myopes wearing spectacles or contact lenses.

PURPOSE: To compare the vision-related quality of life among emmetropes, myopes who had refractive surgery, and myopes who wore spectacles and/or contact lenses. METHODS: This cross-sectional study assessed vision-related quality of life using the Vision Quality of Life Index. Participants were age 18 years or older with a presenting visual acuity of 20/40 or better and no other ocular pathology. Responses were compared among three groups: emmetropes (spherical equivalent [SE] < 0.50 to > -0.50 diopters [D]), myopes (SE < or = -0.50 D) who wore spectacles and/or contact lenses, and myopes who had refractive surgery. RESULTS: The study population included 64 emmetropes, 66 myopes who wore spectacles and/or contact lenses, and 65 myopes who had refractive surgery. No significant differences were found between the refractive surgery and emmetropic groups. In contrast, the spectacle and/or contact lens group had significantly increased odds of having concerns about injuring themselves (odds ratio = 11.5, 95% confidence interval [CI] 2.3, 57.1), difficulties coping with demands in life (odds ratio = 23.6, 95% CI 23.8, 198.1), difficulties fulfilling roles (odds ratio = 5.6, 95% CI 1.4, 22.1), and less confidence joining in everyday activities (odds ratio = 30.6, 95% CI 3.2, 292.3) compared to emmetropes. CONCLUSIONS: Myopia corrected with spectacles or contact lenses had a negative impact on some areas of vision-related quality of life. However, individuals with myopia who had refractive surgery enjoyed the same vision-related quality of life as those with emmetropia. The potential improvement in vision-related quality of life should be considered when recommending treatment for myopia.

Long term vision outcomes of conventional treatment of strabismic and anisometropic functional amblyopia.

PURPOSE: To investigate the long-term vision outcomes of amblyopia treatment in "successfully" compared with "unsuccessfully" treated patients. METHODS: Forty-two participants (n=42, mean age 14.8 years, range 10-25 years) were enrolled in the study. Individuals with strabismic or mixed (strabismic and anisometropic) amblyopia were examined at a mean of 6.6 years (range 1-18 years) after cessation of amblyopia treatment. Participants were classified as being "successfully" treated (Group 1) if visual acuity of 6/7.5 or better was achieved at cessation of treatment, or "unsuccessfully" treated (Group 2) if visual acuity of 6/9 or less was achieved at cessation of treatment. Visual acuity was analyzed by calculating an interocular score or difference in visual acuity between the amblyopic and non amblyopic normal (control) eye. RESULTS: A deterioration of visual acuity occurred in 62% of the participants in both Groups 1 and 2. The mean deterioration of visual acuity over time for either group was less than one LogMAR chart line and was not "statistically significant" by convention (F [1,39]=3.361, p=0.074). The outcomes achieved at cessation of treatment did not "statistically significantly" affect the mean deterioration that occurred over time (F [1,49]=0.031, p=0.860). CONCLUSION: Visual acuity was relatively stable over a mean followup period of 6.6 years. The treatment outcome and the success of amblyopia treatment were found to be irrelevant to long term stability of visual acuity. These findings suggest that amblyopia treatment mostly results in a lasting improvement in visual acuity, and that both unsuccessfully and successfully treated individuals maintain their visual acuity improvement achieved during treatment.

Heritability of refractive error and ocular biometrics: the Genes in Myopia (GEM) twin study.

PURPOSE: A classic twin study was undertaken to assess the contribution of genes and environment to the development of refractive errors and ocular biometrics in a twin population. METHODS: A total of 1224 twins (345 monozygotic [MZ] and 267 dizygotic [DZ] twin pairs) aged between 18 and 88 years were examined. All twins completed a questionnaire consisting of a medical history, education, and zygosity. Objective refraction was measured in all twins, and biometric measurements were obtained using partial coherence interferometry. RESULTS: Intrapair correlations for spherical equivalent and ocular biometrics were significantly higher in the MZ than in the DZ twin pairs (P < 0.05), when refraction was considered as a continuous variable. A significant gender difference in the variation of spherical equivalent and ocular biometrics was found (P < 0.05). A genetic model specifying an additive, dominant, and unique environmental factor that was sex limited was the best fit for all measured variables. Heritability of spherical equivalents of 88% and 75% were found in the men and women, respectively, whereas, that of axial length was 94% and 92%, respectively. Additive genetic effects accounted for a greater proportion of the variance in spherical equivalent, whereas the variance in ocular biometrics, particularly axial length was explained mostly by dominant genetic effects. CONCLUSIONS: Genetic factors, both additive and dominant, play a significant role in refractive error (myopia and hypermetropia) as well as in ocular biometrics, particularly axial length. The sex limitation ADE model (additive genetic, nonadditive genetic, and environmental components) provided the best-fit genetic model for all parameters.

Refractive errors in twin studies.

It is estimated that 1.6 billion people worldwide have myopia, a refractive error, and this number is expected to increase to approximately 2.5 billion by the year 2020. It is now well established that both the environment and genetics play a role in the development of myopia. However, the exact contribution of each of these components to myopia development has yet to be completely determined. Twin studies (classical twin model) are commonly used to determine the weighting of genetic and environmental components in disease. Over the last century, twin studies have investigated the heritability of refractive errors in different sample populations and have collectively supported a genetic basis to refractive errors. However, different sample populations and methods of data collection have produced a wide range of heritability estimates ranging from .5 to .9. This article will review those twin studies that have investigated refractive error, particularly myopia, as well as biometric measures linked to refractive error, to compare heritability estimates and methodology designs.

Mirror-image congenital esotropia in monozygotic twins.

Monozygotic twins had mirror-image congenital esotropia and discordant refractive errors. One had right congenital esotropia surgically corrected during childhood, and the other had left congenital esotropia surgically corrected at 3 and 6 years old.

Methodology and recruitment of probands and their families for the Genes in Myopia (GEM) Study.

PURPOSE: Myopia is considered to be a complex disease involving both environmental and genetic factors. The Genes in Myopia (GEM) Study aims to recruit probands with myopia and their family members to allow genetic analysis of myopia to be undertaken. The purpose of this paper is to describe the methodology and recruitment of probands and families for the GEM Study. METHODS: In a sample-based prospective study, 2,095 probands with myopia of -0.50 DS or worse and a positive family history of myopia were contacted via the Melbourne Excimer Laser Group (MELG) database. Probands and family members recruited into the study undertook a detailed assessment including questionnaire, best-corrected visual acuity, objective and subjective refraction, axial length, anterior chamber depth, keratometry readings, slit-lamp examination, height, weight and head circumference measurements, and blood sample collection for DNA analysis. RESULTS: 280 probands with myopia have been recruited into the GEM Study. Probands had a mean age of 49.33 yrs. (SD +/- 11.64) with the average age of myopia onset being 12.58 years (SD +/- 6.71). The average spherical-component refractive error was: right eye -5.13 DS (SD +/- 3.06) and left eye -5.14 DS (SD +/- 3.16). Probands with extreme myopia (-10 DS or worse) showed the highest study participation rate of 56%, when compared to high (-5 DS < -10 DS) (20%), moderate (-3 DS < - 5 DS) (18%) and low myopia (-0.5 DS < -3 DS) (10%). A total of 279 out of 505 (55%) additional family members recruited were also found to be myopic. CONCLUSIONS: The GEM study has used a targeted approach to identify an Australian cohort with a diverse spread of myopia, ranging from low to extreme. Recruitment of probands via the use of an excimer laser practice has proved to be an efficient and economic means of identifying probands with a family history of myopia. In addition, the participation rate in the study appears to vary reflecting a proband's perception of disease severity.

Evaluation of accuracy in proband-reported family history and its determinants: the Genes in Myopia family study.

PURPOSE: Proband-reported family histories are widely used in epidemiological and genetic studies. The accuracy of these reports may have significant effects on the intended outcome, particularly in genetic studies. This study aims to determine the accuracy of proband-reported family history of myopia and to assess whether demographic or clinical factors are predictive of an accurate history. METHODS: In 2004 to 2005, the study recruited 120 myopic probands (< or = -0.50 D spherical equivalent in both eyes) aged 18 to 72 years and 358 nuclear family members residing within Victoria, Australia as part of the Genes in Myopia (GEM) family study. Data collection used an examiner-administered questionnaire with an ocular examination. Proband-reported family history of myopia was evaluated for agreement with ophthalmic examination results of family members. RESULTS: The statistical measures of accuracy used in this report were sensitivity, specificity, positive predictive value, and negative predictive value. Sensitivity varied from 85 to 98%, specificity from 84 to 96%, positive predictive value from 83 to 97%, and negative predictive value from 84 to 97%. Following multivariate analysis, an evaluation of demographic and clinical factors indicated that the highest predictive accuracy was obtained from proband reporting of their children [odds ratio (OR), 0.38; 95% confidence interval (CI), 0.15 to 0.94] whereas the most inaccurate reporting of a proband was when there was less-severe maternal myopia (per 0.50 D less myopic) (OR, 1.23; 95% CI, 1.06 to 1.43) or for increase in total education of the proband (per 1 year increase) (OR, 1.22; 95% CI, 1.04 to 1.42). CONCLUSIONS: Several variables influence the accuracy of obtaining a family history of myopia. A questionnaire-based approach alone will introduce some error into the study and this should be taken into account when designing and undertaking family-based epidemiological or genetic studies of myopia.

Heritability and shared environment estimates for myopia and associated ocular biometric traits: the Genes in Myopia (GEM) family study.

To examine the familial correlations, heritability (h(2)) and common environmental components (c(2)) of myopia and ocular biometric traits (all treated as continuous outcomes) in families collected through the Genes in Myopia (GEM) family study in Australia. A total of 132 pedigrees (723 participants) were recruited for this study. All individuals completed a risk factor questionnaire and underwent a detailed eye examination including spherical equivalent (SphE) and ocular biometric measurements of axial length (AL), anterior chamber depth (ACD) and corneal curvature (CC). Familial correlations were calculated and h(2) and c(2) were estimated using a variance component model that assumes a multivariate t distribution within each pedigree. Two definitions of common environments (c(2)) were considered: nuclear family (current) shared environment (Model 1) and sib-ship (childhood) shared environment (Model 2). Population ascertainment adjustment was performed using the Blue Mountains eye study dataset. The trends observed for familial correlations suggested that SphE is influenced by both environmental and genetic factors whereas AL, ACD and CC are predominantly genetically determined. This was largely confirmed by variance components modelling. Heritability estimates (adjusted for age, sex and years of education) from the best fitting ACE model (Model 2, childhood shared environment) were 0.50 +/- 0.05 for SphE, 0.73 +/- 0.04 for AL, 0.78 +/- 0.04 for ACD and 0.16 +/- 0.06 for CC. Childhood environmental effects were significant with c(2) estimated to be 0.33 +/- 0.04 for SphE, 0.06 +/- 0.03 for AL, 0.22 +/- 0.04 for ACD and 0.10 +/- 0.05 for CC. Age was associated with SphE, total years of education was associated with AL and sex was associated with all traits studied. We used a novel and conservative approach to account for and estimate common environmental effects by specifying either nuclear family or sib-ship environment when estimating heritability estimates and showed that all traits examined (SphE, AL, ACD and CC) are heritable, thus reflecting a genetic component. These traits therefore all represent candidates for quantitative trait linkage analyses.

Concordant bilateral Duane's Retraction Syndrome (type 1) in female monozygotic twins.

We report a single case study of concordant bilateral Duane's Retraction Syndrome (DRS) (type 1) in female monozygotic (MZ) twins aged 47 years. The twin pair were recruited through the Australian Twin Registry as part of a twin study on myopia. This twin pair were full term and had a similar birth weight: 2.27 kg and 1.81 kg in twin 1 and twin 2, respectively. There was no report of any other childhood medical conditions in either twin. Both twins had an equal amount of restriction in right and left abduction. Narrowing of the palpebral fissures and globe retraction in right and left adduction was also observed in both twins. To our knowledge this is the first case to report concordant bilateral DRS (type 1) in female MZ twins. The concordance for the presence of DRS and associated clinical signs observed in this MZ twin pair supports a genetic origin to DRS.

Marked discordance for myopia in female monozygotic twins.

Female monozygotic twins aged 54 years discordant for myopia are reported. One twin presented with bilateral high myopia (right eye = -6.00/+0.50 x 5 degrees , left eye = -6.00/+0.50 x 45 degrees ) and her identical twin had no significant refractive error (right eye = -0.50/plano, left eye = -0.50/+0.75 x 40 degrees ). An explanation for the striking refractive discordance seen in this case report is yet to be determined.