Genetic variants may predict glaucoma risk

Researchers identify genetic variants that may predict glaucoma risk

Moorfields Eye Charity is excited to report on a breakthrough study on glaucoma which has been published today in the prestigious journal Nature Genetics, and co-authored by Moorfields consultant eye surgeon Anthony Khawaja.  The study led by scientists from King’s College London, University College London, Massachusetts Eye and Ear and Harvard Medical School has identified 133 genetic variants that could pave the way for a genetic-based screening program to help identify the world’s leading cause of incurable blindness.

Glaucoma is the name given to a group of eye conditions in which the optic nerve is damaged where it leaves the eye.  For the eye to work properly a certain level of pressure is needed for the eye to keep its shape.  However, if the eye pressure gets too high, the optic nerve can be damaged, leading to sight loss.

There are virtually no symptoms of glaucoma in the early stages and no pain is associated with increased eye pressure. Vision loss begins with the loss of peripheral vision, although this may go unnoticed for some time.

A leap forward in understanding

The results of the study represents a major advance in the fight to tackle the degenerative condition which has virtually no symptoms in the early stages and affects 480,000 people in England and millions worldwide.  To better understand the development of glaucoma, the researchers studied 140,000 people drawn from the UK Biobank and EPIC-Norfolk. Elevated pressure in the eye is the most important risk factor for glaucoma and is created by the continual renewal of fluids within the eye.

  • Eye pressure readings were taken which were compared with a DNA analysis of each patient to assess how likely it was that they would develop the condition.

By comparing the pressure test results with a genetic analysis of the many common, small variations in DNA that contribute a tiny amount to overall eye pressure, the team was able to identify 133 genetic variants in the DNA of those who had high pressure readings, and so were at highest risk of developing the condition.

  • The genetic variations were able to predict whether someone might develop glaucoma with 75% accuracy.

Speaking about this publication, Dr Khawaja (consultant eye surgeon at Moorfields Eye Hospital and researcher associated with the NIHR Biomedical Research Centre at Moorfields and UCL Institute of Ophthalmology), said:

With this new knowledge, we are now more able to predict the risk of an individual developing glaucoma.  The predictive genetic markers could be measured as early as birth, even though glaucoma develops later in adulthood.

These results help us to better understand the previously unknown mechanisms that cause this damaging disease. By understanding how glaucoma develops we can, in time, get ahead of the curve of the condition and support both those living with the disease and those who may develop it.

Robert Dufton, chief executive at Moorfields Eye Charity, said:

Providing funding for the development of research career pathways is extremely important to Moorfields Eye Charity.  We are delighted to be supporting Anthony by enabling him to take time to focus on research alongside his clinical activities.  This investment of philanthropic support in pioneering research has the ability to improve diagnosis, treatment and understanding of sight loss.


What are the next steps in this research?

Speaking with Moorfields Eye Charity, Dr Khawaja discussed his own research programmes and the potential research avenues the results of this paper could stimulate.  Stemming from the current study, there are opportunities to carry out replica studies to establish if prediction accuracy can be increased and for biomedical science researchers to delve into molecular basis of these genetic variants.  

Anthony Khawaja
Anthony Khawaja, consultant eye surgeon at Moorfields

Some really interesting avenues he would like to investigate are the potential for personalised medicine and stratifying patients to enhance their treatment and outcome experiences. 

Currently genetic screening is not viable as too many false positives would arise.  However, what might soon be possible is to identify a subgroup of people at higher risk.  Feasibility studies are needed to determine if using these genetic variants could be a viable approach for targeted screening.  Such screening could help identify people at risk of glaucoma early and before their sight is irreversibly affected.  

Another area for investigation is whether response to treatment type can be indicated by the genetic variants.   Understanding this connection could shed light on why some patients respond to certain treatments while others do not.