A window to the mind: Developing adaptive optics to understand changes in visual behaviour with eye disorders

Seeing involves a complex set of processes that allow us to extract information from the physical world. As you read this, an image of the text is formed by the optical elements of your eye and this image is sensed by the light-sensitive cells that tile your retina. Neurons in your retina and brain process this sensory input, ultimately allowing you to extract meaning from the text. This happens in a fraction of second between jump-like movements of your eyes that shift your gaze across the text. Even during the periods when we think our eyes are still, they continually make microscopic movements that are fundamental to seeing anything at all.

Disruption to the sensory input, such as by retinal degeneration or refractive errors, places a fundamental limit on the information available to the visual system. Visual disorders significantly impact on an individual's health, wellbeing and quality of life. Visual impairments in childhood can affect school performance, and in the elderly they can severely restrict everyday activities and affect independence. Visual disorders have their effect at many levels, from changes in the eye, to deficits in visual and cognitive processing, and alterations to the efficient movement of the eyes. Visual disorders are best tackled with a cross-disciplinary approach, working across these levels.

Adaptive optics is a powerful technique originally developed for astronomy that has revolutionised the study of the eye, allowing human vision to be characterised with extraordinary precision. By correcting for optical distortions, which are present in every eye, adaptive optics allows imaging of individual cells in the living human eye and provides exciting new capabilities for tracking the tiniest of eye movements with unprecedented accuracy. By manipulating the optical distortions of the eye, adaptive optics also allows investigation of the impact of refractive errors on sight. I will take an interdisciplinary approach, developing adaptive optics techniques in combination with precise experiments in human vision to understand how the visual system processes information and how this is disrupted by visual impairments. I will address these fundamental questions through targeted investigation of two leading causes of visual impairment:

1. Age-related macular degeneration affects around 600,000 people in the UK, severely affecting sight by causing loss of central vision - imagine the difficulty of having a blind spot follow wherever you look. Being incurable, treatments aim to preserve remaining sight and so early detection is crucial. I will investigate the relationship between degeneration in the retina, eye movements and visual function. This will inform interventions, such as visual aids and eye movement training, to make the best use of patients' remaining sight. The high precision of adaptive optics will allow me to make very sensitive measures of alterations to eye movements. I will look for characteristic changes that could be screened for, leading to very early detection of disease.

2. Refractive errors (e.g. myopia and astigmatism) affect around 1 in 7 children in the UK. Even in the healthy eye, there are more complex high-order optical distortions that are not correctable with spectacles. Optical distortions impair visual acuity - such as the ability to identify letters on a chart - but can cause further problems in more cognitively demanding tasks, such as reading. Our society makes heavy use of text to convey important information. My research will use adaptive optics to investigate how optical distortions impact on reading, for example by impairing recognition or disrupting eye movements. This will enable better accessibility to information, through improved visual aids or eye guidance training, or through designing fonts for educational materials that are more robust to refractive errors.

The elderly
Visual impairments have a profound impact on the elderly, making everyday tasks difficult. Age-related macular degeneration is the leading cause of visual impairment in the developed world and affects around 600,000 people in the UK. It causes a loss of the centre of the field of vision, severely limiting mobility and activities such as reading and recognising faces. Being incurable, early detection is crucial for preserving sight. Current detection relies on self-reporting of changes in vision, which may not be noticeable in early onset and has been shown to miss a large proportion of degenerative changes. My research will look for sensitive, objective measures of the onset of AMD through changes in eye movements. In the long term this will allow earlier detection and therefore earlier treatment. In the short to medium term, my research will inform interventions for making the most patients' remaining sight, allowing them to maintain independence and quality of life.

Children
Reading skills are important for children's educational attainment and long-term job prospects. Refractive errors affect around 1 in 7 children in the UK and evidence suggests the affect children's literacy (Bruce et al, 2019. BMJ Open, 6, e010434). Refractive errors are difficult to detect in children and while the NHS recommends testing children's eyesight in their first year of school, there is nothing to ensure that the results are acted upon. My research will link refractive errors to impairment in cognitive tasks such as reading. This will highlight the importance of visual screening early in childhood and the adherence to visual correction. During and beyond the fellowship, I will engage with children, parents and educators through outreach and public engagement activities to maximise the impact of my research. I will engage with the UK Vision Strategy and connect with policy makers such as Public Health England so that, in the medium and long term, visual screening recommendations can be informed by my research. Models of how refractive errors affect processes in reading can inform the development of educational and literacy materials, such that the typeface and layout are robust to visual impairment, making them more accessible.

Industry and Clinic
Adaptive optics is a powerful tool for eye and vision research, yet there are few systems worldwide and most are custom-made instruments in dedicated research laboratories. Adaptive optics allows retinal changes to be detected much earlier and over much shorter timescales. With new developments, such as optogenetics and gene therapy, the need for cell-specific biomarkers for eye disease will be increasingly important. In the short term, collaboration between adaptive optics labs will lead to accelerated development of these techniques. In the medium term, the development of commercially available research instruments will open this technology to those at the forefront of research into sight loss and its treatment. In the longer term this will lead to a clinical tool for early disease detection, closer treatment monitoring and potentially accelerate clinical trials so that treatments are approved faster and at lower cost. The worldwide market for ophthalmology products is £33 billion, including diagnostic instrumentation (£2 billion) and eye care (£10 billion). My research and collaborative network will position the UK to develop this technology for commercial deployment.