Increasing the molecular diagnosis rates of primary congenital glaucoma 

Primary congenital glaucoma (PCG) is the most common form of glaucoma in babies and small children, typically diagnosed before the age of three. 

‘Primary’ indicates that the condition doesn’t arise from another illness or condition (like an eye tumour), and ​‘congenital’ means it is present at birth.

PCG is associated with a defect in the development of the trabecular meshwork and the anterior chamber angle, which are involved in the drainage system of aqueous humour, the clear fluid inside the front part of the eye. This defect obstructs the normal flow of fluid, creating more resistance and increasing pressure within the eye.

Whilst rare, PCG is a serious eye condition that can lead to loss of vision if left untreated due to the increased pressure that can damage the fibres that make up the optic nerve.

We know that PCG is caused by changes in our genetic code, known as mutations. Only a small number of these glaucoma mutations (around 10) can be used to diagnose someone with PCG if they are offered genetic screening. 

However, genetic testing associated with childhood glaucoma can be inconsistent or inconclusive, meaning that the majority of people do not know the underlying cause of their condition. 

Nicola will identify novel PCG mutations by analysing data from the 100,000 Genomes Project.

The 100,000 Genomes Project was established to offer patients affected by rare diseases or cancer the opportunity to screen their entire genetic code (their genome) to determine their diagnosis and develop personalised treatments. 

As part of this, 77 families affected by PCG were recruited, with 42 families coming from Moorfields Eye Hospital, of which only eight (19%) received a genetic result through screening the known glaucoma genes. The genome data from each unsolved family is now available for further investigation. 

Nicola will be working with families with PCG from Moorfields Eye Hospital who have yet to receive a genetic diagnosis for their PCG.

She will use publicly available scientific data on the genes involved in forming and maintaining the trabecular meshwork and the anterior chamber angle of the eye to create a list of potential disease genes to screen the unsolved PCG families.

If Nicola identifies mutations in two or more unrelated families, this will be enough evidence to say that a novel glaucoma gene has been discovered.

This project has the potential to help more families understand the cause of their glaucoma and enable them to have access to the genetic counselling and family planning options that they need.

New glaucoma genes discovered could be adopted onto the NHS genetic testing panels for PCG, thus supporting increased and early diagnosis and allowing future work to investigate the severity of PCG caused by different genetic mutations.

Improving our wider understanding of how PCG develops according to a person’s genes will also lay the foundations for developing personalised treatments to help prevent or slow down sight loss.