A new genetic testing protocol developed in Brisbane could help identify patients at risk of age-related macular degeneration (AMD) decades before symptoms appear, potentially allowing for earlier intervention and lifestyle modifications.
The MacuCheck protocol, developed by Dr Erwin Groeneveld of the Brisbane Eye Clinic in partnership with Genomics for Life laboratory, combines genetic markers with clinical risk factors to provide a comprehensive whole of life risk assessment for AMD progression.
“Between 50 and 70 years of age is really when people should know their risk, because that gives them the timeframe they need to make lifestyle adjustments that will have an impact when they’re between 80 and 100,” Dr Groeneveld explained.
The three-step protocol combines analysis of single nucleotide polymorphisms at two gene loci, with multimodal imaging and clinical review. Results are expressed both as an odds ratio and a predictive metric for advanced vision loss, which is derived from the National Eye Institute’s Casey online AMD risk calculator to project probability scores over different timeframes.
The development of the test came in response to more frequent questioning from relatives and carers
Responding to Relative Concerns
The development of the test came in response to more frequent questioning from relatives and carers of Dr Groeneveld’s AMD patients, who were concerned about their own risk factors. After unsuccessful attempts to access selective genetic testing through commercial laboratories, he partnered with clinical geneticist Professor Michael Gebbutt and the Genomics for Life laboratory to develop targeted probes for the specific markers.
“We’ve used the test on about 20 or 30 patients through the course of the year, just getting a bit of a read on it,” Dr Groeneveld said. “Some patients have come back with odds ratios of 20, some with odds ratios of five. Out of curiosity, we’ve even done some gene testing on patients who have been diagnosed with wet AMD and are being treated with anti-VEGF to confirm cross correlation.”
Identifies for Early Intervention
The test costs AU$195 out of pocket, requires a mouth swab, and takes approximately six to eight weeks for results. While it cannot predict with certainty who will develop AMD, it can help identify those at higher risk who might benefit most from early intervention strategies.
Dr Groeneveld believes it will be particularly valuable for three groups: those aged 50–70 years with a family history of advanced AMD, individuals concerned about age-related loss of independence, and those showing early retinal changes (drusen) in one or both eyes.
“The results can help guide preventative strategies, particularly around lifestyle factors that influence disease progression,” Dr Groeneveld said. “It will also be particularly useful for guiding patients with diseases that we know place them at greater risk of AMD. We know, for example, that atherosclerosis and cholesterol levels play a significant role in AMD risk, suggesting that more aggressive management of these conditions could be beneficial for patients identified as high-risk of AMD.1
Dr Groeneveld spoke of an ageing patient with a family history of AMD who jumped at the chance of the test. “She had a choroidal melanoma in one eye that required enucleation. Her other eye was recovering from cataract surgery. She was extremely anxious because, as a very high-level writer, her vision’s incredibly important to her. And she’s on her own.
“She asked me what her risk for getting macular degeneration was because her mother, who lived to be over 100, had macular degeneration in the last years. I said, ‘look, I can’t see any evidence of drusen at the moment, so I can’t tell you. The only way that we can find out would be with the gene test’.
“And she said, ‘well, how soon can I do that?’”
The test can also provide reassurance to those found to have lower genetic risk factors.
Some Hesitancy
While some organisations have been hesitant about genetic testing for AMD, arguing it doesn’t assist with diagnosis or treatment of advanced disease, Dr Groeneveld maintains that its value lies in prevention and early intervention.
“By the time they’ve got advanced disease, we don’t need the gene testing anymore,” he said. “But if you know that your odds ratios are high, although that’s not going to be a direct correlation that says this person is definitely going to get it, you’ll know the chances are higher.”
The test can also provide reassurance to those found to have lower genetic risk factors. “For people who don’t have a high odds ratio, who don’t have the at-risk genetic polymorphisms, it’s very reassuring for them to know that they don’t have a high risk and that they don’t really need to be concerned that they’re going to lose their visual independence as they get older,” Dr Groeneveld said.
Looking ahead, the genetic information gathered could also prove valuable for future clinical research, particularly in clinical trial design where matching treatment and control groups based on genetic risk factors could provide more meaningful results.
Ophthalmologists and optometrists can contact Genomics for Life directly to request MacuCheck testing kits. The laboratory has developed a CPD program for primary care providers that provides guidance on test result interpretation and how to advise patients.
Visit: genomicsforlife.com.au.
Reference
- Mauschitz MM, Finger RP. Age-related macular degeneration and cardiovascular diseases: Revisiting the common soil theory. Asia Pac J Ophthalmol (Phila). 2022;11(2):94-99. doi: 10.1097/APO.0000000000000496.
