A deeper understanding of glaucoma

The biggest known risk factors are ageing and higher pressure in the eye, with all currently licenced treatments working by lowering this pressure. But not everyone responds to treatment, and not everyone’s glaucoma progresses at the same rate. Why is this?

Findings from Moorfields Eye Hospital and UCL are bringing us closer to the answer, identifying new indicators that can show us who is likely to still have vision loss despite treatment. This study was conducted building on previous work funded by Fight for Sight.

The findings are likely to have an impact on how we monitor – and potentially treat – patients with glaucoma in the future. But first let’s break down the research.

Glaucoma: the basics

Glaucoma encompasses a group of eye conditions which are characterised by damage to the optic nerve. This is the nerve that connects the eye to the brain, enabling you to see. Specifically, people with glaucoma have damage to nerve cells called ‘retinal ganglion cells’.

Current treatments reduce the level of pressure in the eye, which in turn reduces damage to these retinal ganglion cells. Sight loss from glaucoma is irreversible – current treatments cannot reverse damage that’s already happened, they can only prevent further loss of vision. But in some patients, treatment can’t even prevent further damage, and until now we’ve not been able to predict who this might be.

Fight for Sight’s small-scale grant: planting the seeds for future knowledge

These nerve cells which are damaged in glaucoma (retinal ganglion cells) use a lot of energy. Because of this, researchers thought that what’s known as the ‘mitochondria’ - the parts of our cells that generate energy – could be dysfunctional in glaucoma, with this lack of energy causing the nerve cells to die. It may be helpful to think of the mitochondria as the cell’s ‘batteries’.

Back in 2016, Fight for Sight awarded Gerassimos Lascaratos, now Associate Professor in Opthalmology at King’s College London, our New Lecturers award for his project in glaucoma.

His team had previously found that some people with healthy mitochondria were seen to be resistant to developing glaucoma despite high eye pressure. So he applied to Fight for Sight for a small grant to explore the idea that the function of the mitochondria could predict who will be most at risk of vision loss in glaucoma. How well our mitochondria work is also considered to be a good measure of ageing, the biggest risk factor for developing glaucoma.

Using knowledge which included findings from this small-scale research, a team at Moorfields Eye Hospital and UCL under Professor Ted Garway-Heath conducted the recently published study on indicators that can predict glaucoma progression despite treatment.

New predictors of vision loss?

The team found two indicators (also known as ‘biomarkers’) linked to the function of the mitochondria. Firstly, patients with vision loss despite treatment had poorer mitochondrial function in white blood cells. They also had lower levels of a molecule called nicotinamide adenine dinucleotide (NAD), which is important for the function of the mitochondria. NAD is made from vitamin B3 in the diet.

These indicators were most prominent in those with glaucoma who had eye pressure levels in a normal range, as well as being associated with vision impairment and blindness despite treatment. 


What do these findings mean?


To start with, these findings mean we have an idea of who may not respond to treatment, because these indicators can be identified via a blood test before treatment even starts. These people can then be monitored more closely or treated more intensively. Essentially, it will identify early on which patients need the most attention.

But we hope the impact of these findings won’t stop there. 
Right now, what we know is that these indicators are associated with poor response to current treatments which reduce pressure. But building on this knowledge might also lead us to more appropriate treatments for those who are less likely to respond to treatments which lower pressure.

For example, if there is evidence that poor functioning of the mitochondria or low NAD levels cause glaucoma, then this could pave the way to new treatment avenues targeting specific mitochondrial pathways. 

What’s next?

Based on the findings that mitochondrial function and NAD levels are lower in people who don’t respond to treatment, the team led by Professor Ted Garway-Heath and Mr Gerassimos Lascaratos are now conducting a clinical trial investigating whether we can slow glaucoma progression with high levels of vitamin B3 supplements.

If successful in multiple clinical trials, this could be the first glaucoma treatment not to lower pressure in the eye, offering another option for those who don’t respond to current treatments.