Title: Investigation of axial length variation and myopia in health and disease
Funder: The Academy of Medical Sciences

Abstract: Myopia is a growing health concern with a rising prevalence internationally. The majority of myopia develops following excessive axial elongation in childhood, with the scleral remodelling and eye growth often predating refractive error development. The aim of this study is to examine the role of environmental factors, genetics and myopia endophenotypes in excessive elongation beyond that required of normal emmetropisation. Two unique, powerful datasets will be utilised - one of the largest and mostly phenotyped and genotyped twin registries in the world (TwinsUK, n>11000), and the largest molecularly characterised cohort of inherited retinal dystrophies (Moorfields Eye Hospital, n>3000l). Axial lengths will be measured from TwinsUK participants and inherited retinal diseases patients using optical biometry. Using specialised analyses in risk factor modelling, twin modelling and statistical genetics, we will explore novel and known genetic and environmental factors for axial myopia, with a particular focus on the role of errors of light signalling given that time outdoors and light has been shown epidemiologically to be an over-riding protective factor in myopia. Ocular biometry on the twin registry will also be examined in conjunction with other, already collated state of the art ophthalmic imaging (OCT and retinal photography, n=3850), to increase our understanding of the interplay between axial myopia, myopia endophenotypes and risk of sight loss from myopia. In the future I will use the optical biometer sourced with this grant to measure axial length in planned high myopia and myopia treatment clinics with which I am involved.

Lay abstract: Myopia, or short-sightedness, typically occurs as a result of elongation of the eyeball during childhood, with the consequential effect of a focused image forming in front of the retina and the need for optical correction to achieve clear vision. When there is significant myopia and/or elongation of the eyeball, there is an additional risk of sight-loss through associated problems such as degeneration of the central tissue of the retina (called the macula). We will explore to what extent our environment and our genes control the growth of the eyeball using a large twin dataset with already collected extensive information on health and lifestyle - twins provide a powerful opportunity to disentangle these relative effects. Next we will examine what role genes that cause diseases where light cannot be picked up by the retina play in your risk of myopia, given that myopia often develops when a child has a reduced exposure to light. Finally we will start to investigate how a longer eyeball associates with your risk of sight loss from myopia by looking at a range of specialised ophthalmic images on the twins. Ultimately we hope this research will help is to better understand and treat triggers of excessive eye growth in childhood leading to myopia - reducing associated sight loss in the future.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: EYE