Glaucoma is one of the leading causes of irreversible blindness in the United States. More than 3 million Americans have glaucoma, and by 2050, that number is expected to rise to 6.3 million.
Although there are many types of glaucoma, they can generally be broken down into either juvenile/early onset or adult/later onset forms. These can be further subdivided as open-angle or angle-closure glaucoma based on the anatomy of the anterior chamber angle, the site of fluid drainage from the eye, which can change over time.
Understanding genetic risk factors
The two strongest risk factors for open-angle glaucoma, the most common form of the disease in North America, are advancing age and elevated intraocular pressure. Genetics also play an important role, especially in first-degree blood relatives of patients with glaucoma, who have up to a nine times greater risk of developing the disease. However, although genetics are known to impact glaucoma, our understanding of the extent of that impact is still evolving.
Genetic testing and genomic studies have added to that understanding. In the broad sense, genetic testing is used to assess the risk of diseases caused by changes in a single gene. An individual will have their own unique combination of genes related to glaucoma, a disease influenced by many genetic variants, and that combination may or may not lead to glaucoma.
Although there are a number of ways to study genes, one of the most important techniques being employed is genome-wide association study (GWAS), which involves comparing genomes (the complete set of DNA found in an individual human cell) from groups of people in order to find genetic markers associated with the risk of a certain disease. Recent GWAS have successfully identified over 100 specific genetic locations consistent with risk for various types of open-angle and angle-closure glaucoma (including juvenile-onset, exfoliation glaucoma, normal tension glaucoma, and primary angle-closure glaucoma). Interestingly, these studies found genetic similarities in groups having different ancestries (individuals of European, Japanese, African, and multi-ancestry descent have all been studied).
Looking to the future
As more glaucoma-related genes are discovered, the opportunity to provide more personalized risk assessment and medical care is enhanced. As an example, genetic risk scores are a powerful new approach that combines the effects of hundreds or thousands of genetic variants to predict an individual’s risk of disease, and how that risk compares to others in the general population.
Genetic testing is just becoming available to optometrists and ophthalmologists, and it holds promise for early identification and intervention, potentially reducing the burden of vision loss from glaucoma. In 2024, we are still in the discovery phase and there are no clear recommendations on the widespread use of genetic testing. Ultimately, continued advances in genetic technologies and personalized medicine are paving the way for earlier diagnoses and more effective and targeted treatments. However, further research is needed to fully understand the genetic underpinnings of glaucoma and to inform the development of comprehensive screening and treatment strategies.
