Researchers from the United Kingdom have developed a diagnostic technique capable of detecting the earliest hallmark of glaucoma: apoptosis of individual retinal ganglion cells (RGCs).
The technique is called DARC, which stands for detection of apoptosing retinal cells. It is performed simply with a single intravitreal injection of fluorescent labeled annexin V, after which the apoptotic cells appear as bright white spots on in vivo retinal images due to the binding of the dye to an RGC outer lipid membrane.
Schematic of the DARC technology. After injection of fluorescent annexin V, apoptotic cells are identified by the binding of annexin to phosphatidylserine on the outer memebrane of retinal ganglion cells.
"Detecting glaucoma early is vital as symptoms are not always obvious. Although detection has been improving, most patients have lost a third of vision by the time they are diagnosed,” said lead researcher professor Francesca Cordeiro from University College of London (UCL) Institute of Ophthalmology. “Now, for the first time, we have been able to show individual cell death and detect the earliest signs of glaucoma.”
Cordeiro and her team tested the dye (ANX776) in 8 healthy subjects and 8 patients with glaucomatous neurodegeneration. Their phase 1 findings were published last month in BRAIN.
They demonstrated that single ANX776-labeled cells could be seen in a dose-dependent pattern (P<0.001) up to 6 hours after injection. The number of dying RGCs (or DARC count) was more than 2-fold higher in glaucoma patients compared with healthy controls, and it was significantly greater in patients who later showed increasing rates of disease progression, based on optic disc, retinal nerve fiber layer or visual field parameters (P=0.045).
Additionally, the DARC count significantly correlated with decreased central corneal thickness (R= −0.68, P=0.006) and increased cup-to-disc ratios (R=0.47, P =0.038) in both glaucoma patients and older patients.
ANX776 was found to be safe and with no serious adverse events. The dye has a short half-life of 10 to 36 minutes.
Researchers hope that eventually it may be possible for opticians to perform the tests, enabling even earlier detection of the disease.
“While we cannot cure the disease, our test means treatment can start before symptoms begin. In the future, the test could also be used to diagnose other neurodegenerative diseases," Cordeiro said.