DARC test illuminates glaucoma progression

A test dubbed DARC can detect glaucoma progression 18 months earlier than the current gold standard method, according to results from a UCL-sponsored clinical trial.

A patient's retina showing hyperfluorescent signals - each white spot is a single 'sick' retinal nerve cell. Imagery supported by DARC technology used in the Phase II clinical trial (Image: UCL/Western Eye Hospital)

The technology, supported by an artificial intelligence (AI) algorithm, could help accelerate clinical trials and eventually be used in a wider range of detection and diagnostics. The Wellcome-funded study is published in Expert Review of Molecular Diagnostics.

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"We have developed a quick, automated and highly sensitive way to identify which people with glaucoma are at risk of rapid progression to blindness," said lead researcher Professor Francesca Cordeiro, UCL Institute of Ophthalmology, Imperial College London, and Western Eye Hospital Imperial College Healthcare NHS Trust.

Glaucoma is caused by the death of cells in the retina and is the leading global cause of irreversible blindness.

According to UCL, the DARC (Detection of Apoptosing Retinal Cells) test involves injecting into the bloodstream a fluorescent dye that attaches to retinal cells, and illuminates those that are in the process of apoptosis, which is describe as a form of programmed cell death. The damaged cells appear bright white when viewed in eye examinations.

Evaluating eye diseases can be problematic because specialists often disagree when viewing the same scans, so the researchers have incorporated an AI algorithm into their method.

In the Phase II clinical trial of DARC, the AI was used to assess 60 of the study participants composed of 20 people with glaucoma and 40 control subjects. The AI was initially trained by analysing the retinal scans - after injection of the dye - of the healthy control subjects. The AI was then tested on the glaucoma patients.

Those taking part in the AI study were followed up 18 months after the main trial period to see whether their eye health had deteriorated.

The researchers were able to accurately predict progressive glaucomatous damage 18 months before that seen with the current gold standard OCT retinal imaging technology, as every patient with a DARC count over a certain threshold was found to have progressive glaucoma at follow-up.

"These results are very promising as they show DARC could be used as a biomarker when combined with the AI-aided algorithm," said Professor Cordeiro. "What is really exciting, and actually unusual when looking at biological markers, is that there was a clear DARC count threshold above which all glaucoma eyes went on to progress.”

First author Dr Eduardo Normando, Imperial College London and Western Eye Hospital Imperial College Healthcare NHS Trust, said: "After further research in longitudinal studies, we hope that our test could have widespread clinical applications for glaucoma and other conditions."

The team is also applying the DARC test to rapidly detect cell damage caused by conditions other than glaucoma, such as other neurodegenerative conditions that involve the loss of nerve cells, including age-related macular degeneration, multiple sclerosis, and dementia.

The AI-supported technology has recently been approved by the UK's Medicines and Healthcare products Regulatory Agency and the USA's Food and Drug Administration as an exploratory endpoint for testing a new glaucoma drug in a clinical trial.

The researchers are also assessing the DARC test in people with lung disease, and hope that by the end of this year, the test may help to assess people with breathing difficulties from Covid-19. DARC is being commercialised by Novai.