Glaucoma genetics - unlocking better patient care
4 March 2022
Moorfields Eye Charity is proud to have supported Dr Anthony Khawaja as he continues to establish himself as a leader in eye health with a focus on innovating glaucoma care.
Dr Anthony Khawaja is associate professor at the UCL Institute of Ophthalmology and consultant ophthalmic surgeon at Moorfields.
A particular area of focus for his research team is investigating the genetic and environmental epidemiology of glaucoma.
Anthony’s ultimate aim is to combine extensive genetics data and artificial intelligence (AI) to develop prediction models that can enable efficient population screening of glaucoma, and more personalised care of glaucoma patients in the clinic.
A national consultation of patients, carers, relatives and eye health professionals (the James Lind Alliance Priority Setting Partnership for glaucoma) identified “What causes glaucoma?” as a top research question.
We were previously unable to explain to patients with primary open angle glaucoma why their intraocular pressure was raised. We are now able to explain that, at least in part, their raised IOP and glaucoma is due to the collective effect of over 100 parts of their genetic code and that these variants influence the structures that drain aqueous from within the eye.
Dr Anthony Khawaja (programmatic report 2021)
We continue to support Anthony’s exciting work including a Springboard Award which aims to develop adoptable tools that will enable earlier detection and more effective glaucoma management.
Research highlights and outcomes to date
The genetic architecture underlying glaucoma
Anthony led studies of large genetic databases including over 100,000 European participants of UK Biobank.
This work identified genes associated primary open angle glaucoma (POAG) and intraocular pressure (IOP), a risk factor for glaucoma.
The genetic variants the team identified were able to predict POAG cases in independent studies with 75% accuracy.
Predicting and modelling glaucoma progression
In collaboration with Google Health Genomics, the team used deep learning AI algorithms to learn and predict key changes to the optic nerve in glaucoma from images of the retina at the back of the eye.
These algorithms were then applied to 80,000 retinal photos combined with the largest genetic study to date.
This allowed the researchers to link the observed changes caused by glaucoma to underlying genetic variations and model the development of the condition.
Modifiable risk factors for glaucoma
Working with a multidisciplinary team, of nutritionists, statistical geneticists, epidemiologists and clinicians the team are investigating other possible risk factors for glaucoma, such as diet, exercise and medications.
So far, they looked into the association of caffeine intake which yielded very interesting results. Caffeine intake may increase eye pressure and risk of glaucoma, but only in people who are genetically predisposed to glaucoma.
Impact and looking to the future
The results from Anthony and his team’s work represent a huge leap forward in the understanding of contributing factors in POAG pathogenesis.
Despite the very complex nature of POAG, the statistical power afforded by multiparticipant study enabled detection of over 100 important genetic determinants.
These genetic variants underpin a substantial proportion of IOP variability and vision loss secondary to higher IOP.
Targeted population screening to prevent sight loss
Delayed presentation is the major risk factor for developing sight loss from glaucoma. Earlier diagnosis of people at risk is key to preventing sight loss.
Excitingly, the team showed that the genetic variants they identified had a potential to predict POAG cases with 75% accuracy.
This means, even before any ophthalmic examination, these genetic markers can identify people within a population that are at risk of glaucoma.
Targeting these high-risk people may improve the effectiveness of current glaucoma screening tests, reduce the number of false positives, enable earlier diagnosis and treatment, and prevent irreversible vision loss.
Personalised glaucoma therapy choices
Measuring the genetic variants that the team identified may help us predict how glaucoma patients would respond to different treatments and choose the optimal therapeutic intervention.
New treatments for glaucoma
All the novel genes and pathways the team identified as regulating IOP are potential targets for new glaucoma treatments.
Reflecting on some of Anthony’s key achievements since 2017:
- 65 publications, including high impact publications in the prestigious academic journal Nature Genetics
- featured in the Ophthalmologist 2020 Power List, which names the most influential figures in the field of eye care and research
- shared his research at many conferences and presented as invited lecturer internationally
- led patient focus group examining the attitudes towards genetic testing for glaucoma care
- shared his research and campaigned raising awareness of glaucoma through numerous national radio interviews and media interest and coverage, including New York Times, Guardian, Telegraph, The Times