Investigation of genetic susceptibility to retinal toxicity in patients taking hydroxychloroquine

Brief Lay background

Hydroxychloroquine (HCQ) is an anti-malarial drug that is also widely used to treat joint and skin conditions. But its long-term use can lead to incurable blindness due to irreversible damage to the retina – the light-sensitive tissue at the back of the eye. This is called HCQ retinopathy.

Around 1 in 10 patients who take the drug for more than five years will develop HCQ retinopathy – with this figure rising to 1 in 5 patients who use it for more than 20 years.

What problem/knowledge gap does it help address

People receiving HCQ are offered regular eye health checks to spot early signs of retinopathy. But this screening programme can only identify retinal damage that has already occurred.

If doctors could predict a patient’s susceptibility to HCQ retinopathy upfront, they could adjust their treatment accordingly – preventing sight loss in people most at risk of developing the condition.

Aim of the project

To identify genetic variations in a person’s DNA that could be used to predict their risk of developing HCQ retinopathy.

Key procedures/objectives

1. Recruit 110 patients with HCQ retinopathy – and 330 people who have used the drug for more than 15 years but with no sign of the condition.
2. Collect relevant information on all participants (including the dose and duration of HCQ, age, sex, ethnicity and other risk factors) – and perform a comprehensive eye test including a detailed scan of the retina to confirm the presence or absence of the condition.
3. Compare genetic data between patients and controls – to look for DNA variations that could be used to predict the risk of HCQ retinopathy.  

Potential impact on people with sight loss

A one-off genetic test that can accurately predict a person’s susceptibility to HCQ retinopathy could lead to personalised treatment – helping to prevent blindness and reduce the burden of unnecessary testing.