Changes in eye blood vessels may serve as biomarkers in Fabry: Study

But more data needed to set grading system for varying disease stages

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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The image of a human eye is captured in the lens of a giant telescope as a person looks at the stars.

Changes in the blood vessels within the eyes of people with Fabry disease may act as reliable, noninvasive biomarkers for disease activity, a new study suggests.

But, its researchers say, future studies need to collect data over time to establish a grading system for vascular changes during various stages of Fabry.

“We hypothesize that significant changes … occur in later stages of the disease and therefore measuring [them] has great potential to be used as a retinal biomarker,” the team wrote.

The eye study, “Correlation of retinal vascular characteristics with laboratory and ocular findings in Fabry disease: exploring ocular diagnostic biomarkers,” was published in the Orphanet Journal of Rare Diseases.

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Assessing eye blood vessels of Fabry patients vs. healthy individuals

In Fabry disease, mutations in the GLA gene lead to a deficiency in alpha-galactosidase A, known as Gal A, an enzyme responsible for breaking down fatty molecules called globotriaosylceramides — Gb3 and lyso-Gb3. As a result, these molecules form deposits in small blood vessels and most tissues in the body, causing damage.

The most commonly reported eye manifestation in Fabry is cornea verticillata, or deposits in the cornea, the transparent layer on the eye surface, that form a faint golden-brown circle-like pattern. Other eye-related symptoms include cataracts, or cloudy lenses, abnormal twisting or widening of blood vessels, and microaneurysms, which are localized bulges in the walls of blood vessels.

Based on these features, researchers in Germany wondered whether changes in the small blood vessels within the eyes of Fabry patients might serve as biomarkers for disease activity and progression.

“Early diagnosis, evaluation of progression and management of [Fabry disease] could be improved by identifying more biomarkers that reflect activity and progression of the disease,” they wrote.

To that end, the team assessed both eyes of 38 Fabry patients — comprising 13 men and 25 women — and 24 healthy people who served as controls, of whom 11 were men and 13 were women. Altogether, that made for 76 patient eyes and 48 control eyes.

The scientists used noninvasive optical coherence tomography angiography, or OCTA, a medical imaging technique. It uses light waves to visualize blood vessels in various parts of the body, without the need for injections or invasive procedures.

Early diagnosis, evaluation of progression and management of [Fabry disease] could be improved by identifying more biomarkers that reflect activity and progression of the disease.

Cornea verticillata was seen in 55% of the 76 patient eyes examined, alongside abnormally twisted blood vessels, known as vascular tortuosity, in 26% of eyes.

The blood vessel area density, or VAD — the proportion of vessel area over the total area measured — was assessed in the three layers of the retina, which is the light-sensing area at the back of the eye. These layers are the superficial (top) vascular plexus, or SVP, the intermediate (middle) capillary plexus, or ICP, and the deep (bottom) capillary plexus, or DCP.

OCTA measurements showed the mean vessel area density was significantly higher in all three retinal layers in patients, and around all circular sections within all layers, compared with controls. There was no relationship between age and blood vessel densities, except for a weak correlation between older age and fewer blood vessels in the middle layer (ICP).

A significantly higher vessel area density was found in all three retinal layers in patients with cornea verticillata than in those without. Still, patients with and without cornea verticillata had significantly higher vessel density than did controls.

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Changes in eyes found to affect all layers of retina at back of eye

When looking at the eyes of patients with and without cornea verticillata, the area at the center of the eye that lacks blood vessels — called the foveal avascular zone — was significantly larger in the top retinal layer (SVP) in patients without cornea verticillata and in controls.

Blood test data showed a significantly higher proportion of patients with cornea verticillata had elevated lyso-Gb3 than those without (90% vs. 23%). No significant differences were found in the proportion of patients with and without cornea verticillata regarding GLA enzyme activity.

More patients with twisted blood vessels in the retina had elevated lyso-Gb3 than did those without (80% vs. 50%). Fabry patients with low GLA enzyme activity had a larger foveal avascular zone within the retina’s middle layer (ICP).

Lastly, patients with higher blood levels of lyso-Gb3 had higher vessel area density in the retina’s bottom layer (DCP) compared with patients with normal lyso-Gb3 concentration.

“Our findings suggest that the vascular remodeling in [Fabry disease] affects all retinal vascular layers,” the researchers concluded, noting that “the deeper layers seem to be more susceptible to vascular damage earlier in the course of the disease when compared to superior [top] vascular layers.”

The researchers suggested that “increased plasma concentration of lysoGb3 and increase in VAD in deep vascular layers could be reliable biomarkers of activity of the disease.” In addition, “cornea verticillata could be used as a predictive biomarker for VAD changes and disease progression.”