Genetics & Glaucoma Risk Assessment for a Personalised Approach

SightScore is the brainchild of Jamie Craig, Professor of Ophthalmology at Flinders University, and his team. The polygenic risk score tool emerged in 2021 following decades of painstaking genetic research using genome wide association studies of over 400,000 individuals.¹ Accredited by National Authorities Testing Australia (NATA), the test has been available since November 2023, with interest described by Prof Craig as “very strong”.

For ophthalmologists and optometrists on the front lines of glaucoma care, SightScore offers a valuable new dimension to risk assessment and patient management. By providing an individualised genetic risk profile, it enables more precise and personalised decision making around diagnosis, monitoring, and treatment initiation.

Dr Nathan Kerr, a prominent glaucoma specialist in Melbourne and early adopter of SightScore, described it as a “significant milestone in glaucoma care”.

“We now have a commercially available tool that allows us to provide better care to our patients – and it has been developed right here on our doorstep. I’d put personalised genetic testing right up there with visual fields and optical coherence tomography (OCT) in terms of its impact on how we manage glaucoma,” he told mivision.

As a glaucoma specialist, Dr Kerr said he has found the assessment tool “very easy to integrate into his practice”, and particularly valuable for assessing glaucoma suspects and discussing risk with family members of glaucoma patients.

FROM LAB TO CLINIC

The journey from initial genetic discoveries to a clinically useful test has been a long one – both in terms of developing the technology and getting clinicians and the public onboard with the notion of genetic testing.

Fortunately, Prof Craig was not alone. His cofounding team comprises some of the world’s best in this field: Stuart McGregor, Professor of Statistical Genetics at the Queensland Institute of Medical Research Berghofer Medical Research Institute, an international authority in glaucoma genetic risk prediction; Alex Hewitt, Professor of Ophthalmology at the University of Tasmania and the Centre for Eye Research Australia, and Board Member of the Ophthalmic Research Institute of Australia; Owen Siggs, Snow Fellow and Faculty Member at the Garvan Institute of Medical Research, with over 15 years’ experience in academic genetic research and clinical medicine; and Johnathon Matthews who has extensive management experience in the medical devices industry.

To commercialise the test, they formed Seonix Bio, which is headed by Nick Haan, an experienced leader in the genomic diagnostics industry, who was a co-founder and CEO of BlueGnome, a company acquired by US sequencing giant Illumina in 2012.

Prof Craig explained that when genetics was discussed in years gone by, clinicians’ eyes would “glaze over” as it seemed relevant only to rare familial cases. Now, however, genetics clearly impacts the risk assessment for every glaucoma patient.

HOW SIGHTSCORE WORKS

SightScore works by analysing thousands of genetic variants associated with glaucoma risk, then generating a percentile score that indicates where an individual falls on the spectrum of genetic risk compared with the general population. The test report provides clinicians with key metrics, like the likelihood of glaucoma diagnosis or need for treatment initiation within specific timeframes.

Crucially, the PRS has been extensively validated in real-world clinical settings. Additionally, Prof Craig and his team have undertaken extensive work to scientifically validate the SightScore test in very large clinical trials, using data from Australian glaucoma patients and glaucoma suspects.

At the time of going to print, the PRS was only able to manage and report on the world’s common ethnicities. However, by early 2025 Prof Craig expects that having made “huge leaps” in the past few months, it will be capable of reporting on “a wider range of ethnicities” as well.

ENHANCING CLINICAL DECISION MAKING

In combination with a patient’s medical history, clinical risk factors, and eye examination, the report can be useful to consider:

• The age for a patient’s first glaucoma check,
• How often a patient should be monitored for glaucoma,
• When a patient should be prioritised for investigation by an ophthalmologist,
• The optimal clinical environment for the individual patient,
• Management strategy for a patient with glaucoma, including some treatment decisions, and
• Informing blood relatives (parents, siblings, adult children) about their risk of developing glaucoma.

Both Prof Craig and Dr Kerr insist that SightScore doesn’t replace clinical judgement, but rather enhances it by providing an additional layer of objective data. They agreed that this genetic risk information can be particularly valuable in borderline cases, or when deciding on treatment initiation.

As an example, Prof Craig spoke about a patient with borderline intraocular pressure whose PRS came back in the one percentile. This made him feel confident in not progressing with treatment, despite the pressure.

“There are times when we’re on the fence; when we look at someone and we’re not sure what to do, and if the score comes back in the midrange, you just go, ‘okay, I’m going to follow my instincts on this patient’. But there are other times when I think, ‘if I start a treatment now, that patient’s going to be on that treatment for life, and I’m not sure they really need it’.”

He said the test is also helpful for patients with high scores who are resistant to treatment, as it provides a way to explain why their condition may be more problematic.

USER-FRIENDLY IMPLEMENTATION

A key factor in SightScore’s early success has been its user-friendly implementation process. Dr Kerr described how the company sets up a dashboard accessible from any web browser, with no special software required. The ordering process for SightScore kits is straightforward and integrated seamlessly into the clinical workflow.

Importantly, patients have found the process easy to navigate: Dr Kerr reported that both young and elderly patients have had no issues with registering the kit and sending it off.

“I was pleasantly surprised to find that 100% of my patients who have been given the SightScore kit have followed through and performed the test,” he told mivision. “So even though there is a charge associated with it, patients realise this data is so valuable in helping manage their individual case.”

The non-invasive PRS is performed by collecting a saliva sample, which is mailed to Seonix Bio for processing. DNA is extracted from the sample and analysed for risk, with results made available via a secure clinician portal within four to six weeks. The reports themselves have been designed with both clinicians and patients in mind, with results “expressed in a way that both the clinician without expertise in genetics, and also patients, can clearly understand,” said Dr Kerr.

The layout includes a bell curve to help patients visually understand where their risk lies relative to the general population. Additionally, it includes “very clinically relevant metrics” to help determine the likelihood of a patient’s diagnosis and the likelihood of them needing to start or escalate treatment over a specific number of years.

Prof Craig observed that patients prefer to receive the information in different ways. He emphasised the importance of tailoring the discussion to each patient’s needs and level of anxiety, presenting the feedback in terms appropriate for that individual patient.

“You might have a patient who has already taken on board that they’re going to have treatment, so you can present the data in a way that says, ‘yes, you are on the 90th percentile for risk, but that’s pretty much what I was expecting. You’ve got a couple of family members with glaucoma, and we could see that your intraocular pressure is a little high’. Whereas another patient with the same scores, might say, ‘this is something my brother and sister had, but I don’t believe I have that problem, and I don’t want to take those drops because I read that they can cause darkening of my skin’. This patient may need help in understanding the seriousness of their situation, which could be conveyed with the PRS result.

For each of these scenarios, “it’s a different process, but you can show them the result and say, ‘we need to really look at what this means for you in the future in terms of treatment because we have studies that show that people in your position are much more likely to need these treatments’.”

FUTURE DIRECTIONS

While SightScore is currently focussed on glaucoma risk, both Prof Craig and Dr Kerr see enormous potential for expanding genetic risk assessment in ophthalmology. Prof Craig mentioned exciting unpublished data supporting the use of SightScore to detect the genetic risk of secondary glaucomas like pseudoexfoliation, as well as early data on angle closure glaucoma.

Beyond glaucoma, other potential targets include keratoconus to identify people early in the disease who might require more intensive treatment like cross-linking.

“And we’re working in the space of Fuch’s dystrophy, looking at the endothelium and risk of corneal failure in some situations.”

He said the “other big ones” are macular degeneration, where treatments are quickly evolving (for dry), and secondly, myopia control. “So, we think the space will expand a lot and eventually, you will be able to order multiple risk assessments on the one test,” Prof Craig said.

The team is also working towards integrating genetic risk data with traditional clinical risk factors to create more comprehensive risk calculators. This would allow clinicians to input factors like age, intraocular pressure, corneal thickness, and family history alongside genetic data for a more integrated risk assessment.

Although private health insurers are currently legally unable to use their members’ genetic profiling to inform premiums, Prof Craig believes they will ultimately see value in using profiling to better manage resources.

“I think that health insurers in particular, when they fully understand the implications of these types of tests, will realise there’s a lot of money to be saved because they will be in a position to introduce interventions for disease prevention… it may also be that they can give the resources to people who need them the most, and people who don’t need the resources, they can save on that.

“I would hope that in the future they might actually be interested in funding genetic screening (for their members) if they see an evidence base that provides value.”

GLOBAL EXPANSION

With SightScore already making waves among ophthalmologists in Australia and New Zealand, Seonix Bio is now broadening its local reach into optometry and setting its sights on international markets.

While some optometry practices, including Health Partners in Adelaide and National Pharmacies, have been part of test programs, Prof Craig said ideally, more will come on board because “it would be great in the future if every new referral came (to a glaucoma specialist) with their score already attached”.

He said general practitioners could also be encouraged to offer the test to family members of people being treated for glaucoma. “Often, I see patients with severe glaucoma, and they ask me about their four children, but I don’t have the capacity to go, ‘right, well, I’ll see all four of them next week and we’ll do the test’… in the future they will be doing things like cardiovascular and cancer risk profiling in the primary care setting as well.”

Prof Craig is equally excited about plans for international expansion. “To be now in a position where we can clearly impact every patient we see in terms of their risk, I think that’s a really good place to be. But there’s so much more that we are going to be able to do. We’re launching in the United States, where there is a large patient population and openness to new technologies that could change practice.”

Europe is also on the horizon, with particular interest from western European countries due to genetic similarities with many Australian patients.

A NEW ERA IN GLAUCOMA CARE

As SightScore gains traction in clinical practice, it’s clear that genetic risk assessment is ushering in a new era in glaucoma management. By providing clinicians with unprecedented insight into each patient’s individual risk profile, it enables more targeted, personalised care that has the potential to significantly improve outcomes.

Congratulating Prof Craig and his team, Dr Kerr said the test is changing the way clinicians manage patients, allowing them to identify those at higher risk who need careful monitoring or earlier treatment, while also potentially reducing overtreatment in lowerrisk patients.

Prof Craig emphasised the potential for genetic risk assessment to help prevent severe cases of glaucoma. He noted that some of the worst patients they encounter are those with very severe damage at first meeting, or those who progress rapidly under care. The hope is that with tools like SightScore, they might be able to get ahead of these cases and prevent severe progression.

For ophthalmologists and optometrists on the front lines of glaucoma management, this practical new tool, developed in Australia, offers a powerful new ally in the fight against this sight-threatening disease.

Reference

1. Craig J, Han X, Qassim A., et al., Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression. Nat Genet 2020;52(2):160-66. doi: 10.1038/s41588-019-0556-y.