Eyeworld

SUMMER 2024 | EYEWORLD | 67 G Contact Aboobakar: Inas_Aboobakar @MEEI.HARVARD.EDU Greenwood: michael.greenwood @vancethompsonvision.com Relevant disclosures Aboobakar: None Greenwood: None and whether they warrant close follow-up, Dr. Aboobakar continued. "One day we may be able to offer these patients targeted gene therapies," she said. For adult onset glaucomas, such as primary open angle glaucoma, angle closure, and exfoli- ation glaucoma, there are many genes associat- ed with disease risk. To assess their cumulative impact, PRSs are calculated, which provide information on an individual's glaucoma risk relative to the general population. It may also help identify disease subtypes based on genetic markers, and we can then use this information to provide patients with personalized disease monitoring and therapy, Dr. Aboobakar said. Dr. Greenwood also said that once the genes and downstream effects are identified, targeted therapies that disrupt downstream effects could be developed and prescribed. Dr. Greenwood said his hope is to have genetic testing identify risk very reliably and, if glaucoma develops, assist him in determining the best treatment regimen for the patient going forward. "My dream is [a test that's] easily done in the office as a point-of care test; then it allows for personalized medicine," he said. "The only other thing I would add is a lot of times people hear genetic testing and they think it's scary. There are a lot of unknowns. Once you get your can of worms open, what does all this mean?" Dr. Greenwood said, explaining that education and counseling will remain important. sion as well as earlier initiation and escalation of treatment. "It's also possible to calculate pathway- based PRSs for specific glaucoma-associated genes to assess their clinical impact," Dr. Aboo- bakar said, sharing information about a study in which a mitochondrial PRS was investigated. This PRS consisted of variants in two POAG-as- sociated genes that directly influence levels of nicotinamide adenine dinucleotide phosphate in the mitochondria. Dr. Aboobakar said what's interesting was nicotinamide, which is being in- vestigated as a neuroprotective agent in glauco- ma, also directly influences this pathway. Their group found that among glaucoma cases in the NEIGHBOR consortium dataset, those with the highest percentile of mitochondrial PRS had higher mean IOP as well as much higher preva- lence of paracentral field defects. This suggests that primary open angle glaucoma that's driven by mitochondrial genetic risk may represent a distinct disease type with specific clinical features, and it could also be more responsive to nicotinamide treatment. Dr. Greenwood said that the overall utility of current genetic testing for glaucoma at the moment is limited. "People don't use it on a regular basis, even if it is easily accessible. The information is a little limited," he said. Wish list Dr. Greenwood said that genetic testing is "on the cusp of taking that next step where it goes from something available but not very useful to something that could be quite useful." "As we start to learn more about glaucoma and can identify what genes cause glaucoma and what are risk factors, it becomes more specific of a test, and it becomes a little more useful," he said. The goal of genetic testing, Dr. Aboobakar said, is one day to be able to collect a blood sample from a patient and run a gene panel to identify which genetic variants that they carry. For early onset forms of glaucoma, such as con- genital glaucoma and juvenile open angle glau- coma, this would allow physicians to identify the causal gene mutation for their disease. With that information you can screen first-degree relatives to see if they also carry this mutation Source: iStock.com/Shutter2U

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