Is genotyping the answer to improving glaucoma management?

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genotyping in glaucoma management

This article was originally written by Mr Anthony Khawaja for The Ophthalmologist.

Although glaucoma can cause irreversible, irreparable damage to vision, treatment can slow or halt disease progression, so early detection is important. Unfortunately, our current screening tests – if applied to a general population – don’t work well enough; as a result, population screening for glaucoma is not currently recommended in some countries, including the UK and the US.

Using people’s genetic codes to identify a subset of the population that will benefit from screening may be the solution to this problem. In the last decade, there has been huge progress in discovering many of the genetic variants that contribute to glaucoma risk. It was back in 2018 when we first realized that the great number of risk variants we had discovered could be considered collectively to predict – with surprising accuracy – whether someone would end up developing glaucoma. This approach of combining thousands of risk variants into a single number, a polygenic risk score, has become popular across many common diseases, including glaucoma.

Instead of having to screen whole populations, genotyping enables targeted screening for those at a higher risk for glaucoma. Our current screening tests will perform much better when applied to a subset of the population with a higher prevalence of undetected glaucoma. In other words, there will be far fewer false positive referrals to secondary care if our current screening tests are applied to this enriched subset of the population.

A separate challenge in glaucoma care comes after diagnosis. At present, we cannot accurately predict which of our patients are at the highest risk of progressing and losing vision. If we could better predict this, we could ensure our limited healthcare resources are used optimally, focusing on the highest risk patients, but also saving costs, unnecessary treatment, and follow-up for those at lower risk.

It remains unclear whether the genetic variants which increase the risk of developing glaucoma also increase the risk of vision loss among patients with glaucoma. Instead of comparing people with glaucoma to people without glaucoma in the general population, we need more longitudinal genetic studies amongst cohorts of glaucoma patients, identifying the genetic variants that lead to worse disease.