How Multiple Genes Affect Vision Development and Lead to Rare Vision Disorder

An international team of health researchers has, for the first time, described how genetic defects influence the spectrum of vision development and cause problems in the development of babies’ eyes.

Researchers from the University of Leicester led an international effort made up of 20 expert centers in the largest study of its kind to date, examining genes associated with arrested foveal development.

The fovea is part of the retina at the back of the human eye and is the structure responsible for sharp central vision. Arrested development of the fovea, or foveal hypoplasia, is rare and is often caused by genetic changes. This permanent condition can have serious consequences and can affect the individual’s ability to read, drive, and perform other daily tasks.

There is currently no treatment available for this condition. Most often, during infancy, one of the first visible signs of a foveal problem is “twitching eyes”. This is often seen in the first six months of life. There are large gaps in our knowledge of which genes control foveal development and when in development this occurs.

Now, in a study published in the journal Ophthalmology Combining data from more than 900 cases around the world, the researchers were able to identify the spectrum of genetic changes behind these foveal defects and – importantly – when they occur in the development of the unborn baby.

Dr Helen Kuht is a research orthoptist and Wellcome Trust Postdoctoral Fellow in the Ulverscroft Eye Unit, University of Leicester, and first author of the study. She says:

“This research has really helped solve the puzzle of why some babies with these genetic changes have foveal hypoplasia of varying severity. Allowing us to diagnose, predict future vision and help prioritize genetic testing, further advice and support.”

Dr Mervyn Thomas is an NIHR Clinical Fellow in Ophthalmology and Genomic Medicine at the University of Leicester and University Hospitals of Leicester NHS Trust. He previously pioneered a global standard for grading the severity of foveal hypoplasia called the Leicester Grading System. Dr. Thomas, lead author of this study, added:

“Most previous studies in this area have been limited to one or two centers, making it difficult to draw meaningful conclusions in rare disorders like foveal hypoplasia. With this study, we were able to combine datasets from major collaborating centers around the world.

“We are extremely grateful to all of our collaborators who have come forward to support this effort and to the funders in each country who have made this possible. It has helped to understand how these genes influence foveal development and to what extent foveal development is stopped based on the genetic defect.”

Arrested development of the fovea is detected using a special camera, called optical coherence tomography (OCT), which can scan the back of the eye. The researchers used OCT scans to identify the location of the fovea, a small pit measuring around 2mm in diameter.

These scans were then analyzed to rank the severity of each individual case using the Leicester grading system and compared to genetic markers to identify genes associated with different disease severities.

Identifying these relationships between genetic defects and the degree of arrested foveal development is the first step in constructing possible future treatments for people with foveal hypoplasia.

Leicester established the Foveal Development Investigators Group (FDIG) in 2020, bringing together expertise in foveal development research spanning 11 countries. These include centers in the UK, South Korea, Denmark, the Netherlands, the US, China, France, Australia, Germany, Brazil and India.

Dr. Brian Brooks is a senior researcher at the National Eye Institute in the United States, head of the branch of ophthalmic genetics and visual function, and co-author of this study. He added:

“Dr. Kuht and Dr. Thomas have assembled the world’s largest consortium of researchers interested in the causes of foveal hypoplasia. Their work represents the best cross-sectional data we have on the genetics of this condition to date.”

The study was funded by the UK Medical Research Council, Fight for Sight, Nystagmus Network, Ulverscroft Foundation, Wellcome Trust, Korea Centers for Diseases Control and Prevention, the National Research Foundation of Korea.

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