Glaucoma affects an estimated 300,000 Australians but half of them don’t know it. Early detection is considered vital to prevent irreversible vision loss and blindness.
With the global eyecare sector’s focus on World Glaucoma Week between 6–12 March, Insight takes a closer look at advances in glaucoma research in Australia, particularly innovations in testing and diagnostic technologies.
Recognising the limitations of current glaucoma screening techniques, including timeliness and cost effectiveness, researchers have seized on the opportunity to target these shortcomings to design low-cost tests that deliver rapid results.
Not only can their new screening and diagnostic tools detect glaucoma sooner, they could potentially one day form part of national screening programs and alleviate the direct and indirect costs of glaucoma to the Australian healthcare system, projected to hit $784 million by 2025.
This month Insight speaks with three researchers, all non-eyecare professionals but experts in their chosen fields, about their work to develop all new imaging devices – and even a blood test – to pick up high-risk individuals before irreversible vision loss sets in.
Fluorescent hyperspectral imaging
Physicist and biomedical engineer Professor Ewa Goldys has collaborated with a team of clinicians, including ophthalmologists, to develop a novel imaging technology for early detection and monitoring.
Goldys is deputy director of the ARC Centre of Excellence for Nanoscale Biophotonics at UNSW that develops novel tools for biomedical diagnostics.
The centre’s research has now extended into the ophthalmic industry where she is working with a team of clinicians – including Clinical Associate Professor Andrew White at Westmead Hospital, Professor Robert Casson, Head of Ophthalmology and Visual Sciences at the University of Adelaide, and UNSW Scientia Fellow Dr Nicole Carnt – to develop a bespoke camera that will help ophthalmologists measure the oxidative stress of cells and tissues in the retina.
“Ophthalmology is an area of clinical medicine producing extensive images of the eye – even mobile phone cameras today are equipped with amazing image capability. At the same time, science is developing better technical analysis of images. We’re building on that particular junction in time to provide deeper image analysis,” Goldys says.
In 2021, she was awarded Glaucoma Australia (GA)’s ‘Quinlivan’ Research Grant to support her research in fluorescent imaging technology to detect glaucoma.
Goldys’ imaging innovation obtains information about the health status of the retina and the optic nerve, providing the opportunity for early disease detection and the ability to commence treatment before irreversible blindness sets in.
“Neurons die, which is irreversible. We need to know when do neurons start to be in trouble?,” she says. “When there is progressive loss of vision, it is clearly too late. We need to address vision loss earlier. This represents an unmet need.”
Refurbishing current technology that is user-friendly and non-invasive, Goldys and her team are photographing the eye, then splitting the image into different colour segments.
“Our lab is full of bespoke imaging systems. We are currently refurbishing and re-engineering a fundus camera for trials with a small Australian company called Quantitative Pty Ltd,” she says.
“It’s like shining sunlight through a prism. Once separated into individual colours, light provides nuanced information. We’re interpreting colours and shapes of cells, by a method that links colour to specific molecules, which are central to metabolism.
“Cells need energy to survive. At a cellular level, neurodegeneration is a symptom of cells losing energy supply.”
As part of their pre-clinical research, Goldys and her team are currently testing metabolism in cells that are affected, and are interfering with cells by exposing them to oxidative stress.
“We have proven oxidative stress is inducing colour change in cells. Our study on this was published in peer-reviewed journal Redox Biology, which is not an ophthalmology journal,” Goldys says, adding she is aware of the debate in ophthalmology about countering oxidative stress by supplementing with antioxidants.
Their proof-of-concept study demonstrated that an imbalance of unstable molecular species called ‘free radicals’ will change the colour of cells – and a new imaging technique could allow clinicians to detect and decode this colour without needing to take samples from the body.
“In our study of cell cultures and tissues in the lab, we found that colour is like a thermometer for oxidative stress,” Goldys says.
With the support of the ‘Quinlivan’ Research Grant for the next two years, Goldys hopes to have finished pre-clinical trials within one year.
Genetic testing for degenerative eye disease
Dr Georgie Hollitt from Flinders University College of Medicine and Public Health, and Flinders Medical Centre, is leading a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration.
Known as the Genetic Risk Assessment of Degenerative Eye Disease (GRADE) study, Hollitt is building on the work from previous work including a long-running international collaboration between Flinders University and the QIMR Berghofer Medical Research Institute, and other research partners around the world, to identify genetic risk factors for glaucoma.
Working alongside Professor Jamie Craig and Associate Professor Owen Siggs, both from Flinders University, Hollitt is part of a team of Australian researchers who have identified 107 genes that increase the risk of glaucoma, and developed a genetic test using thousands of common genetic variants to detect people at risk of going blind from the condition. Their ultimate aim is to be able to offer blood or saliva tests to people when they turn 50 (regardless of family history) so they can find out if they are at risk, and then act to prevent vision loss.
“Glaucoma and age-related macular degeneration (AMD) are the two most common causes of irreversible vision loss among elderly people worldwide. This is because both diseases are asymptomatic in the early stages, there are no clear screening recommendations for either condition, and broad community screening is not currently cost-effective,” Hollitt says.
“This is problematic as current glaucoma treatment options are highly effective at slowing or preventing disease progression, while AMD treatments for early-stage disease are currently undergoing clinical trials. For these reasons, identifying cost-effective screening methods to facilitate early diagnosis and timely intervention is important. This can be achieved with polygenic risk score (PRS) testing.”
Flinders University is conducting a prospective clinical trial which aims to clinically validate the PRS tests for both glaucoma and AMD.
The study is inviting 1,000 individuals aged over 50 years from the general population in South Australia to have their PRS calculated for both conditions.
“The scores will be used to categorise participants as being in either the highest 10%, lowest 10% or within the middle 80% of risk within the study population, based on our previous work in Nature Genetics,” Hollitt says.
The previous study she is referring to characterised optic nerve photographs of 67,040 UK Biobank participants and used a multitrait genetic model to identify risk loci for glaucoma.
“A portion of individuals from each group will then undergo a thorough eye examination to compare the rate of glaucoma or AMD diagnostic classification across the risk spectrum of the PRS, with an expectation to see a higher rate of glaucoma and AMD diagnosis in the high-risk groups of the PRS compared to the average or low risk groups,” Hollitt says.
“The tests, performed on a blood or saliva sample, have the potential to identify high-risk individuals before irreversible vision loss occurs, and also have the potential to allow glaucoma and AMD screening to reach a broad population. With more data supporting the clinical validity of this testing, PRS may soon become part of routine clinical care.”
Hollitt says the application of PRS testing would not be possible without assessing the attitudes of healthcare professionals towards it.
To that end, Flinders University is also conducting a questionnaire-based study assessing this in the context of glaucoma.
“Healthcare professionals, including ophthalmologists, optometrists and orthoptists, will be at the forefront of the delivery of personalised medicine so it will be important to demonstrate acceptability of PRS testing from these groups before it is implemented into clinical practice,” Hollitt explains.
“This confidential online survey will inform training and resources for healthcare workers who may be involved in offering the test, referring or counselling patients as well as interpreting results from the test.”
(For more information regarding GRADE and the questionnaire, contact Dr Georgie Hollitt at firstname.lastname@example.org).
In addition to the GRADE study, the same team has expanded on the Targeting at Risk Relatives of Glaucoma patients for Early Diagnosis and Treatment (TARRGET) study after preliminary results were reported last year.
This family-based study, a partnership between Glaucoma Australia, Flinders University, the University of Western Australia/Lions Eye Institute, the University of Tasmania, Sydney Eye Hospital and WA Department of Health, provides personalised risk information to family members of a person with glaucoma and encourages them to have a glaucoma screening appointment.
The first phase of TARRGET approached immediate family members of people with advanced glaucoma and has recently expanded to include family members of people with non-advanced disease.
To date, more than 3,500 people with glaucoma have been sent forms requesting mailing information for their family. From this, more than 2,000 family members have been sent personalised risk information and 785 family members have completed an eye check and provided information back to the study regarding their glaucoma status.
Based on current return rates, the study expects to receive contact details for approximately another 2,000 family members who will, over the coming 12 months, also receive personalised information regarding their risk of developing glaucoma based on the type and severity of glaucoma in their affected family member.
Feedback from family members to date indicates that more than 50% of those contacted have glaucoma or show suspicious early signs of glaucoma requiring monitoring (glaucoma suspects). These are family members of people with advanced disease, and in the future the study will continue to include data from family members of those with non-advanced glaucoma. The study encourages family members to talk to each other about glaucoma and reminds participants that eye health checks must be a regular and ongoing commitment to prevent vision loss.
Computerised glaucoma screening test
Dr Dinesh Kumar and other inventors of a new rapid screening test for glaucoma that could help advance early detection of the disease are planning clinical trials starting sometime this year.
Developed by a research team of engineers and ophthalmologists led by RMIT University in Melbourne, the test uses infrared sensors to monitor eye movement and can produce accurate results within seconds.
While current glaucoma screening techniques are based on measuring the patient’s visual field, this new technique developed at RMIT estimates the damage to the nerves and is therefore more direct, its developer says. As opposed to the current method of diagnosing glaucoma, which requires a 20-minute visual field test, the new test takes 10 seconds to show if there is a risk of glaucoma, which could lend itself to being a central component in a national screening program.
Lead researcher Dr Dinesh Kumar, Professor and leader of Biosignals, School of Engineering at RMIT University, says early detection, diagnosis and treatment could help prevent blindness, so making screening faster and more accessible is critical.
“This research will allow a non-contact, easy-to-use and low-cost test that can be performed routinely at general clinics,” he says.
“It could also promote a community-wide screening program, reaching people who might not otherwise seek treatment until it’s too late.”
Speaking about the novelty of the new diagnostic test, Kumar highlights how it differs from current methods.
“The current method of detecting glaucoma is based on a retinal functionality test and is a measure of secondary symptoms,” he explains.
“Our method estimates the effect of the partial alteration of the optical nerve conduction by measuring the changes to the reflexive adaptation to ambient light conditions and is measuring a primary symptom of the disease.”
The pioneering technology differentiates between glaucoma and healthy eyes by analysing changes in pupil diameter and pupillary hippus.
Kumar says his team’s technical brief involved engineering a solution to overcome the disadvantages inherent in current measuring techniques.
“In glaucoma patients, the optic nerve is partially compromised due to excessive intraocular pressure. We have measured the complexity of the pupil reflexivity during steady state ambient light conditions. Reduction in the complexity is an indication that the optic nerve pathway is partially blocked or damaged,” Kumar says.
“While this can be achieved using different techniques such as delay in the response to a stimuli, the difficulty in such is that it requires accurate control of the ambient light conditions. The other disadvantage of using stimuli-based approach is that it would measure the delay, which may not be evident when the nerve is partially compromised.”
He continues: “We have overcome the above limitations by measuring the natural reflex of the pupil in normal light conditions. We have measured the continually changing pupil diameter and measured the signal properties. Not only is this quick, and does not require a special-purpose room, it also does not require the patient to voluntarily participate and can be observed using an infrared camera located at about 0.5 meters from the patient’s face. Being a more direct measure of the change, this has the potential for detecting the disease even before there are any vision symptoms, though this has not yet been tested.”
In the study conducted by Kumar and RMIT colleagues Dr Quoc Cuong Ngo, Susmit Bhowmik and Marc Sarossy, pupils were measured 60 times per second using a low-cost commercial eye tracker.
The study’s corresponding paper, ‘Pupillary complexity for the screening of glaucoma’, was published in IEEE Access and credits Essendon Eye Clinic and Laser Centre for assisting with the study.
Under ambient light conditions, patients looked at a computer screen while custom software measured and analysed specific changes in their pupil size. The software then compared the results against existing samples of glaucoma and healthy eyes to determine the risk of glaucoma.
Co-author Dr Quoc Cuong Ngo says the new technology was faster and better than any similar AI-based approach.
“Our software can measure how the pupil adjusts to ambient light and capture minuscule changes in the shape and size of the pupil,” he says.
“Existing AI glaucoma tests require the patient to be perfectly still for up to 10 minutes. Our tech does the job in 10 seconds, without compromising on accuracy.”
The team is now looking to adapt the technology to work with smartphone cameras instead of the eye tracker used in the study and investigate its suitability to detect the disease even without visual field symptoms. With further research, the software could also be extended to detect other neurological conditions.
Kumar is hopeful the test could be available to the Australian market by the end of 2023. For more information about a commercial partnership or the clinical trial, email email@example.com.