Genomics and Glaucoma

Personalized medicine, precision medicine, individualized or stratified care… All these phrases essentially mean the same thing – that we treat each patient as an individual with the most beneficial approach rather than applying the same standards of care to the whole population.

In the move towards personalized medicine, genomics is going to be a significant driver. Our genetic code can help predict the risks of bad outcomes, as well as potential risks of side effects from certain treatments, and chances of responding positively to others (including varying doses). Genetic code screening for specific variants is inexpensive (~$60), and will most likely become the standard in predicting and diagnosing many diseases, as long as we know exactly what we should look for.

Glaucoma is a very complex condition, with hundreds of risk factors working together, and various thresholds within each factor; nevertheless, it is also vitally important to detect disease at an early stage, to prevent irreversible vision loss. And so, huge sample sizes are needed to develop a deeper understanding of the genetics of this disorder.

In the past year or so, we have made real advances towards developing a comprehensive view of the genetics of glaucoma, using big studies, such as the UK Biobank (see page XX). We are now in the process of figuring out how useful the genetic information really is – and which aspects of it are important. We have found, for example, that if you take the strongest genetic variants for glaucoma and eye pressure, and you add it to the OHTS study risk calculator (1), it strongly improves prediction ability, more so than other variables, such as age or cup-to-disc ratio.

My paper, published last year, identified over 130 genetic variants that predict higher IOP, and which can determine glaucoma risk (2). What does that mean? Right now, using genetic markers measured at birth, and taking a person’s sex into consideration, we can predict the likelihood of developing glaucoma with 76 percent accuracy. In turn, this information can help us decide which parts of the population are at a higher risk and, therefore, may benefit from a personalized screening program. Population-wide screening for glaucoma is not recommended, as there the false positive rate is too high; personalized screening for high-risk individuals would be a big step towards preventing sight loss as a result of disease progression.

As genotyping is now affordable, I can see a future where every person who comes into contact with a healthcare system will go through this process. One challenge associated with genomics is the need to ensure that any system ultimately developed should be accessible and useful for ophthalmologists and centers around the world. To date, most genomic research has been conducted on people from European backgrounds, so any benefits derived from available data – and potentially the most appropriate treatments – will be applicable only to people from those backgrounds.

A pertinent ethical question arises: should we develop a potentially more successful way of practicing medicine even though it can only be offered to people from one ethnic background at first? It seems clear that more work needs to be done to replicate prior research for other ethnic groups – and to develop a framework that leaves no group of patients disadvantaged.