Ophthalmology Lay Summaries


Sun exposure may help prevent against short-sightedness

Keywords: eye health, myopia, young adult, sun exposure

What is already known about this subject:

  • Myopia (‘short-sightedness’) is a major health issue worldwide, and its prevalence is increasing.
  • Myopia can be treated with glasses, contacts or refractive surgery, but there is currently no way to prevent it.
  • Time spent outside may help to protect against myopia, although more study is needed to confirm this. Measuring sun damage to the conjunctiva of the eye may be a useful way to objectively measure and quantify time spent outdoors.

What this Raine study adds:

  • Eye examination data and measures of eye damage collected from Raine participants at 21 years of age revealed a strong relationship between time spent outside and myopia, with participants who had more sun damage to their eyes also being less likely to have myopia.
  • Sun damage to the eyes was a useful marker of sun exposure and was highly correlated with participant recall of the amount of time they spent outdoors.
  • Sun exposure to the eyes may be a useful, low-risk way to prevent short-sightedness.

McKnight CM, Sherwin JC, Yazar S, Forward H, Tan AX, Hewitt AW, et al. Myopia in Young Adults Is Inversely Related to an Objective Marker of Ocular Sun Exposure: The Western Australian Raine Cohort Study. Am J Ophthalmol. 2014. [publink]

Identification of new susceptibility genes for glaucoma

Keywords: genetic predisposition to disease, glaucoma, eye disease, intraocular pressure

What is already known about this subject:

  • Glaucoma is the world’s leading cause of blindness.
  • Reducing pressure inside the eye (‘intraocular pressure’) is currently the only way to prevent or treat glaucoma.
  • Both glaucoma and intraocular pressure are highly genetically inherited and share some genetic risk factors. Having a close relative with glaucoma increases an individual’s risk of also having glaucoma ten-fold.
  • While some of the genes for intraocular pressure and glaucoma have been identified, most of the genes influencing intraocular pressure are still unknown.


What this Raine study adds:

  • Genome-wide analysis of DNA data from over 35,000 participants of Asian and European descent (including Raine participants), together with eye examination data identified 7 gene variants associated with intraocular pressure, 4 of which have not previously been described.
  • Three of these gene variants were also found to be associated with glaucoma.
  • Understanding the genes involved in determining intraocular pressure will help in understanding why some people are susceptible to glaucoma and may help in the development of new treatments.

Hysi, P. G., et al. (2014). “Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma.” Nature Genetics 46(10): 1126-1130. [publink]

Sun damage to the eyes of young adults corresponds with pterygium and time spent outdoors

Keywords: eyes, conjunctiva, pterygium, sunlight

What is already known about this subject:

  • Pterygium is a common eye condition that affects people who spend a lot of time outdoors and may be useful as a marker of sun damage to the eyes.
  • A specially developed method of photographing the eyes under ultraviolet light may also be a useful measure of sun damage and is increasingly being shown to be a useful marker of sun exposure and time spent outdoors.
  • There is currently no information describing the number and distribution of young Australian adults with measurable sun damage to their eyes.

What this Raine study adds:

  • Comprehensive eye examination data and information on sun exposure and sun protection behaviour from Raine participants at 20 years of age revealed that 1 in 50 males and 1 in 330 females had pterygium.
  • Measuring the amount of sun damage in photographs taken under ultraviolet light showed that the amount of damage was associated with amount of time spent outdoors, and more damage was seen in participants who had pterygium.
  • Using the techniques above may help to accurately describe the extent of sun damage in the eyes of young Australians in order to help develop appropriate preventative strategies.

McKnight, C. M., et al. (2014). “Pterygium and conjunctival ultraviolet autofluorescence in young Australian adults: the Raine study.” Clin Experiment Ophthalmol. [publink]

Identification of new genes contributing to glaucoma

Keywords: glaucoma, vision loss, genetic inheritance, eye

What is already known about this subject:

  • Glaucoma is the most common cause of non-reversible blindness worldwide.
  • Degeneration of the optic nerve is an important part of the disease process in glaucoma.
  • While some genes contributing to the development of glaucoma have been identified, there are still more to be discovered.

What this Raine study adds:

  • DNA data from nearly 30,000 individuals of European and Asian descent (including Raine participants) identified 10 new genes involved in the optic nerve degeneration that occurs in glaucoma.
  • Together, these newly identified genes more than double the risk of glaucoma.
  • This study has more than doubled the known number of genes contributing to the disease process of glaucoma, and will help in the understanding of the mechanisms underlying this disease.

Springelkamp, H., et al. (2014). “Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process.” Nat Commun 5(4883). [publink]

Eye imperfections are common in healthy young adults and are associated with short-sightedness

Keywords: vision, eye tests, young adult, short-sightedness

What is already known about this subject:

  • The unique properties of an individual’s eye determines the quality of their vision.
  • ‘Monochromatic aberrations’ (so called because of the methods used to detect them) are the result of irregular surfaces (or imperfections) within the eye, which act to reduce the quality of the image produced by the eye.
  • While it is thought that having more monochromatic aberrations leads to poorer vision, a direct relationship has never been clearly demonstrated.

What this Raine study adds:

  • Eye examination data from Raine participants at 20 years of age revealed that a relatively high number of participants had monochromatic aberrations in their eyes.
  • Higher levels of monochromatic aberrations could be present in eyes with good vision.
  • Higher levels of monochromatic aberrations were associated with increased severity of myopia (short-sightedness).
  • This research suggests that monochromatic aberrations and vision problems such as myopia may have a common underlying cause.

Yazar, S., et al. (2014). “Comparison of monochromatic aberrations in young adults with different visual acuity and refractive errors.” Journal of Cataract and Refractive Surgery 40(3): 441-449. [publink]

Multiple prenatal ultrasounds pose no risk to eye development

Keywords: eye development, fetal ultrasound, safety, vision

What is already known about this subject:

  • Fetal ultrasounds have greatly improved prenatal care by allowing developmental problems to be identified early.
  • Ultrasounds are generally thought to be safe, but it is not known if multiple prenatal ultrasounds have an impact on eye development.

What this Raine study adds:

  • Prenatal ultrasound data and physical measurements at birth, together with comprehensive eye examinations in Raine participants at 20 years of age showed no detrimental effect of multiple ultrasound scans on eye health.
  • There is no evidence that repeated fetal ultrasound scanning causes eye problems.

Forward, H., Yazar, S., Hewitt, A. W., Khan, J., Mountain, J. A., Pesudovs, K., … Newnham, J. P. (2014). Multiple prenatal ultrasound scans and ocular development: 20-year follow-up of a randomized controlled trial. Ultrasound in Obstetrics & Gynecology, 44(2), 166-70. doi:10.1002/uog.13399. [publink]

Low vitamin D levels increase the risk of short-sightedness

Keywords: myopia, sun exposure, vitamin D, young adults

What is already known about this subject:

  • Myopia (‘short-sightedness’) is becoming increasingly common in Australia and worldwide.
  • Vitamin D deficiency, usually due to insufficient sun exposure, is also becoming increasingly common.
  • Spending more time outdoors decreases the risk of myopia, though it is not yet known if this is due to increased vitamin D levels.

What this Raine study adds:

  • Vitamin D levels in blood samples and eye examination data from Raine participants at 20 years of age found that young adults with myopia had lower vitamin D levels.
  • Vitamin D deficiency was also associated with a higher risk of myopia.
  • Further research is warranted to investigate whether vitamin D is able to directly influence eye health or if it is a marker for eye sun exposure.

Yazar, S., Hewitt, A. W., Black, L. J., McKnight, C. M., Mountain, J. A., Sherwin, J. C., … Mackey, D. A. (2014). Myopia is associated with lower vitamin D status in young adults. Investigative Ophthalmology & Visual Science, 55(7), 4552-9. doi:10.1167/iovs.14-14589. [publink]


First-born children are at increased risk of short-sightedness

Keywords: birth order, myopia, risk factors, refractive error

What is already known about this subject:

  • Blurred vision due to myopia (‘short-sightedness’) often develops around school age.
  • Environmental factors are important in the development of myopia; including time spent reading/writing (increased risk) and time spent outside (decreased risk).
  • Recent research suggests that pregnancy and birth-related factors may also contribute to vision development and risk of myopia. Birth order has been investigated as a possible contributor, but its relationship with myopia is still unclear.

What this Raine study adds:

  • Myopia and birth order data from participants in four international studies (including Raine) aged 13-22 years of age showed that being first-born (or an only child) was associated with a small increase in risk of myopia.
  • The increase in risk of myopia in first-born individuals was not related to any established risk factors, including time spent outdoors or time spent reading.
  • Understanding the relationship between birth order and myopia may shed light on the biological processes that occur in the development of short-sightedness.

Guggenheim, J. A., McMahon, G., Northstone, K., Mandel, Y., Kaiserman, I., Stone, R. A., … Williams, C. (2013). Birth order and myopia. Ophthalmic Epidemiology, 20(6), 375-84. doi:10.3109/09286586.2013.848457. [publink]

The PDGFRA gene is not related to astigmatism in an Australian population

Keywords: vision, astigmatism, ancestry, genetic predisposition

What is already known about this subject:

  • Light bends as it enters the eye, and this mostly occurs as the light passes into the eye through the film of tears covering its surface. Astigmatism is a type of poor vision that occurs when the surface of the eye is an irregular shape, causing the light that enters the eye to bend inappropriately.
  • Around 35% of Australians have astigmatism, and genetic inheritance may be a contributing factor.
  • Variations in the PDGFRA gene have recently been found to be associated with an increased risk of astigmatism in people of Asian descent. It is not known if this gene is also related to astigmatism in an Australian Caucasian population.

What this Raine study adds:

  • DNA from blood samples and the results of eye examinations performed in Raine participants at 20 years of age, together with data from two other Australian populations found no risk of astigmatism associated with the PDGFRA gene in Australians with Northern European ancestry.
  • More research is needed in order to develop new corrective or therapeutic strategies based on the genetic causes of astigmatism.

Yazar, Seyhan, Aniket Mishra, Wei Ang, Lisa S Kearns, Jenny A Mountain, Craig Pennell, Grant W Montgomery, et al. 2013. “Interrogation of the Platelet-Derived Growth Factor Receptor Alpha Locus and Corneal Astigmatism in Australians of Northern European Ancestry: Results of a Genome-Wide Association Study.” Molecular Vision 19 (November 2012) (January): 1238-46.  [publink]

Differentiating between males and females using hand shape

Keywords: biological markers, anatomy, sex characteristics, genetics, environmental influences

What is already known about this subject:

  • Twin studies are a valuable research tool used to differentiate between the effects of ‘nature’ (genetics) versus ‘nurture’ (environment) on human behaviour and physical characteristics.
  • In the past, studies looking at genetic and environmental influences on physical characteristics have been limited to size-related features because of the difficulty in quantifying the more abstract notion of shape. New techniques have recently been developed, however, that have opened up a new field in characterising shape-related differences between individuals.
  • Very few twin studies have looked at genetic influences on shape-related aspects of human anatomy. This study was designed to demonstrate how useful and applicable these techniques can be, and to see if such measurements are capable of differentiating between the physical characteristics of males and females.

What this Raine study adds:

  • Images of the hands of a subset of Raine participants were digitised and converted into a comprehensive set of measures of hand shape.
  • Hand shape was a more effective way to distinguish between males and females than traditional measures of finger length.
  • New techniques allowing researchers to use shape-based comparisons will be of great benefit to twin studies and understanding the influence of nature versus nurture on human physical characteristics.

Sanfilippo, Paul G, Alex W Hewitt, Jenny A Mountain, and David A Mackey. 2013. “A Geometric Morphometric Assessment of Hand Shape and Comparison to the 2D:4D Digit Ratio as a Marker of Sexual Dimorphism.” Twin Research and Human Genetics : The Official Journal of the International Society for Twin Studies 16 (2) (April): 590-600. doi:10.1017/thg.2013.5. [publink]

Identification of nine new gene variants controlling eye length

Keywords: genetic inheritance, eye, genetic predisposition to disease, refractive error, vision

What is already known about this subject:

  • In the normal eye, light is focused (‘refracted’) onto the surface of the retina, giving a clear image. Refractive error occurs when the eye does not focus light properly, causing blurred vision.
  • The distance between the front and back of the eye (‘axial length’) is easily measured and is strongly genetically inherited. Longer axial length is a major cause of shortsightedness and blurred vision at distance.
  • Understanding the biological processes within the eye that lead to alterations in axial length and the resulting vision problems relies on identifying the genes involved.

What this Raine study adds:

  • A genome-wide association study in over 20,000 individuals of European and Asian descent (including Raine participants) identified 8 new gene variants for axial length and confirmed one previously reported.
  • The identified gene variants fell into two groups: one group of genes also influenced refractive error and the other group were found to control eye size without affecting refractive error.
  • Understanding the genetic basis for the dimensions of the eye may lead to the development of prevention and treatment strategies.

Cheng, C.-Y., Schache, M., Ikram, M. K., Young, T. L., Guggenheim, J. A, Vitart, V., … Baird, P. N. (2013). Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error. American Journal of Human Genetics, 93(2), 264-77. doi:10.1016/j.ajhg.2013.06.016. [publink]

Genes controlling corneal thickness are associated with risk of eye disease

Keywords: genetic inheritance, eye health, cornea, genome-wide association study, glaucoma, keratoconus

What is already known about this subject:

  • Thinning of the cornea (the clear, dome-shaped covering of the eye) is an important cause of keratoconus and is associated with glaucoma; eye conditions that can lead to severe vision impairment and blindness.
  • Corneal thickness is strongly genetically inherited, and mutations in genes controlling corneal thickness have been identified in some rare eye disorders. It is thought that genes controlling corneal thickness may also be important in more common eye diseases, but these genes have not yet been identified.

What this Raine study adds:

  • Genome-wide association studies performed on DNA samples from over 20,000 individuals of Asian and European ancestry (including Raine participants) with and without eye disease demonstrated that genes associated with corneal thickness are also associated with eye disease risk.
  • The genetic pathways regulating corneal thickness are similar in Asian and European populations.
  • Part of the genetic predisposition to glaucoma and keratoconus comes from genes controlling corneal thickness.
  • Understanding the genetic basis of these diseases will help to identify the biological pathways by which they occur.

Lu, Y., Vitart, V., Burdon, K. P., Khor, C. C., Bykhovskaya, Y., Mirshahi, A., … Wong, T. Y. (2013). Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nature Genetics, 45(2), 155-63. doi:10.1038/ng.2506. [publink]

New genes identified in myopia

Keywords: genetics, ancestry, vision problems, risk factors

What is already known about this subject:

  • Vision problems due to refractive error occur when the light that enters the eye is not focused properly.
  • Refractive error is the most common eye disorder worldwide and a major cause of blindness. Myopia (‘short-sightedness’) is the most common form of refractive error and affects over 30% of people from Western populations and 80% of Asians.
  • Some of the genes contributing to refractive error have been identified, but their contribution to the overall problem is small and more genes remain to be discovered. Large-scale genetic studies may help identify more genes that are important in causing refractive error.

What this Raine study adds:

  • Analysis of genetic profiles from DNA collected in blood samples and data from comprehensive eye assessments in over 45,000 individuals (including Raine participants) identified 24 new gene variants associated with refractive error.
  • Many, but not all, of the gene variants increasing the risk of refractive error in people of European descent also increased the risk in people of Asian descent.
  • Individuals with the ‘worst’ combination of genes had a 10-fold increased risk of myopia.
  • Understanding how genes associated with refractive error influence eye development may lead to new treatments for this common yet important visual condition.

Verhoeven, Virginie J M, Pirro G Hysi, Robert Wojciechowski, Qiao Fan, Jeremy A Guggenheim, René Höhn, Stuart MacGregor, et al. 2013. “Genome-Wide Meta-Analyses of Multiancestry Cohorts Identify Multiple New Susceptibility Loci for Refractive Error and Myopia.” Nature Genetics 45 (3) (March): 314-8. doi:10.1038/ng.2554. [publink]

Eye disease is rare in young adults: a baseline for future studies

Keywords: cohort studies, eye diseases, genetics, vision, young adults

What is already known about this subject:

  • Vision problems are a common and important contributor to poor quality of life.
  • The provision of effective eye health services relies not only upon the detection and treatment of eye disease, but on understanding eye health in the general population.
  • Studies investigating eye health have mostly focused on older adults or children, and there is little information available about eye health in young adults, even though preventative strategies would be most useful around this age.

What this Raine study adds:

  • Comprehensive eye assessments performed in Raine participants at 20 years of age revealed moderate to high short-sightedness to be the most common eye condition (5.5%), with other eye diseases occurring only rarely.
  • A large body of normal data describing eye health was collected, and will provide comparison data for other population studies as well as being a baseline for future follow-up studies in the Raine cohort, particularly as the participants age and eye diseases become more common.
  • Understanding the prevalence of and risks associated with eye disease in this age group is essential in providing appropriate health services for disease treatment and prevention.

Yazar, Seyhan, Hannah Forward, Charlotte M McKnight, Alex Tan, Alla Soloshenko, Sandra K Oates, Wei Ang, et al. 2013. “Raine Eye Health Study: Design, Methodology and Baseline Prevalence of Ophthalmic Disease in a Birth-Cohort Study of Young Adults.” Ophthalmic Genetics 34 (4) (December): 199-208. doi:10.3109/13816810.2012.755632. [publink]


Identification of the gene for megalocornea

Keywords: eye development, eye health, corneal disease, genetic inheritance

What is already known about this subject:

  • Megalocornea occurs when the front of the eye does not develop properly. People with megalocornea have abnormally large corneas (the clear layer on the surface of the eye) and are at increased risk of other eye diseases, including glaucoma, cataracts and loss of vision.
  • 90% of megalocornea is genetically inherited. Even though it has long been known that the gene for megalocornea lies on the X chromosome, the gene itself remains unidentified.

What this Raine study adds:

  • DNA samples and detailed eye examination data, together with cognitive testing and brain scans in individuals with and without megalocornea and their families (including Raine participants) found that megalocornea was caused by mutations in the Chordin-like 1 gene.
  • The Chordin-like 1 gene was also found to be important in the development of the cornea and other areas of the eye.
  • The megalocornea gene mutation also caused some brain abnormalities, but these were not associated with any loss of brain function.

Webb, T. R., Matarin, M., Gardner, J. C., Kelberman, D., Hassan, H., Ang, W., … Hardcastle, A. J. (2012). X-linked megalocornea caused by mutations in CHRDL1 identifies an essential role for ventroptin in anterior segment development. American Journal of Human Genetics, 90, 247-259. doi:10.1016/j.ajhg.2011.12.019. [publink]

The TGF4 gene is not associated with the normal range of thickness of the corneal endothelial cell layer in the eye

Keywords: genetic inheritance, cornea, eye health

What is already known about this subject:

  • Fuchs endothelial dystrophy is an eye condition that affects the cornea (the clear front surface of the eye) and causes progressive visual impairment.
  • The corneal endothelial cells are a thin layer of cells that line the back of the cornea and control the amount of fluid in the cornea. In Fuchs endothelial dystrophy, the endothelial cells die, causing fluid to build up within the cornea and causing vision problems.
  • Mutations in the TCF4 gene have recently been shown to increase the risk of Fuchs endothelial dystrophy, but it is not yet known if this gene is also involved in normal corneal endothelial function.

What this Raine study adds:

  • Using the DNA and eye examination data from 20-21 year old Raine participants, researchers found no association between variations in the TGF4 gene and the thickness of the corneal endothelial layer.
  • Individuals carrying the TGF4 gene mutation were identified and will be followed for early signs of eye disease.

Mackey, D. A., Warrington, N. M., Hewitt, A. W., Oates, S. K., Yazar, S., Soloshenko, A., … Pennell, C. E. (2012). Role of the TCF4 Gene Intronic Variant in Normal Variation of Corneal Endothelium. Cornea. doi:10.1097/ICO.0b013e318226155f. [publink]

Genetic variation contributes to differences in corneal curvature

Keywords: vision, cornea, genetic variation, genome-wide association study

What is already known about this subject:

  • The first step in vision is the bending (‘refraction’) of light as it enters the eye. The amount that the light bends depends on the shape and curvature of the cornea located at the front of the eye.
  • Blurred vision and other vision problems occur when the curvature or shape of the cornea is abnormal.
  • It is known that corneal curvature is strongly genetically inherited, but little is known about the specific genes involved. Gene variants contributing to corneal curvature in Singaporean Asians have been identified, but it is not known if these are relevant in Australians.

What this Raine study adds:

  • DNA and eye assessment data from three Australian population cohorts (including Raine) showed that variation in the PDGFRA gene underlies differences in corneal curvature between Australians of Northern European descent.
  • Only one of the two genes identified in Singaporean Asians was found to contribute to corneal curvature in Australians.
  • Some evidence was also found to suggest that another gene (TRIM29) may also be important in determining corneal curvature, but this needs further testing.
  • Understanding the genetic basis of corneal curvature will improve our understanding of how vision disorders occur.

Mishra, A., et al. (2012). “Genetic variants near PDGFRA are associated with corneal curvature in Australians.” Investigative Ophthalmology and Visual Science 53(11): 7131-7136. [publink]