Pam Garoufalis

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.

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.

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 probands perception of disease severity.

Testing Protocol and Recruitment in the Genes in Myopia Twin Study

Purpose: The genes in myopia twin study were established to assess the relative genetic contribution of spherical equivalent using a classical twin model. This manuscript will provide a detailed outline of the methodological design, twin recruitment, and the prevalence of myopia in the genes in myopia twin study. Methods: All Victorian-based twins registered with the Australian Twin Registry aged 18 years or older were invited to participate genes in myopia twin study. Each subject underwent a general questionnaire, comprehensive eye examination, and a blood sample was collected. Myopia was defined as worse than or equal to −0.50 diopters sphere (in at least one eye). Results: A total of 627 twin pairs out of 4,158 twin pairs consented to participate in the genes in myopia twin study. A total of 345 monozygotic and 267 dizygotic twin pairs aged between 18 and 86 years were examined. The response rate for monozygotic twins (19.8%) was almost double that of dizygotic twins (11.7%). The overall prevalence of myopia was 29.7% for all twins. Conclusions: The genes in myopia twin study is the first Australian-based twin study to assess refraction in an adult twin population and the largest of its kind in the world. The comprehensive testing protocol used in the in the genes in myopia twin study has provided an extensive twin database for genetic analysis. Participation rate was found to vary according to zygosity, gender, and age.

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 × 5°, left eye = −6.00/+0.50 × 45°) and her identical twin had no significant refractive error (right eye = −0.50/plano, left eye = −0.50/+0.75 × 40°). An explanation for the striking refractive discordance seen in this case report is yet to be determined.

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 (≤−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.

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.