Eye scan shows nerve damage, inflammation in Fabry patients
Noninvasive IVCM test may be useful in monitoring cornea, study finds
Noninvasive in vivo confocal microscopy (IVCM) detected signs of nerve damage in the cornea — the eye’s transparent outer layer — in people with Fabry disease, who also had higher levels of inflammatory immune cells in the cornea than healthy individuals, a study found.
“IVCM provides parameters that reliably indicate corneal nerve damage and inflammatory activation in patients with [Fabry disease],” the researchers wrote.
The study, “Corneal neuro-immune crosstalk in Fabry disease: An in vivo confocal microscopic study,” was published in the Journal of Neuroimmunology.
Fabry disease is caused by mutations in the GLA gene that reduce the production of the alpha-galactosidase A (alpha-Gal A) enzyme, leading to the accumulation of the molecule globotriaosylceramide (Gb3) in various tissues. This causes progressive organ damage and a wide range of Fabry symptoms.
The disorder is inherited in an X-linked dominant manner, meaning a person has to inherit only one mutated copy of the GLA gene on a single X chromosome for the disease to develop. Males, who only have one X chromosome, tend to have more severe disease than females, who have two X chromosomes, one of which houses a healthy GLA copy.
Study looks at IVCM and corneal cells
Gb3 can accumulate in the densely packed small nerve fibers within the cornea, which convey sensory information about touch, pain, and temperature. Damage to these small nerve fibers — a condition known as corneal small fiber neuropathy — can cause severe eye pain and other serious complications.
IVCM allows for direct visualization of the small nerve fibers in the cornea. It can also detect immune cells, primarily corneal Langerhans cells, which act as local sentinels of the immune system and can promote an inflammatory response upon the detection of tissue damage.
While IVCM has been used to detect Gb3 deposits in the cells of the cornea, studies focusing on corneal nerve changes in Fabry are limited, with no previous studies investigating corneal inflammatory cells.
“In-depth understanding of corneal nerve changes and innovated evaluation of corneal inflammatory status in patients with [Fabry] are urgently needed for the further application of IVCM as a valuable marker of [Fabry],” wrote the research team in China, who applied IVCM to both eyes of 31 Fabry patients (13 females and 18 males), ages 14-64, and those of 25 age- and sex-matched healthy individuals, who served as a control group.
The IVCM results showed that the density and number of nerves within the cornea were significantly lower in Fabry patients than in controls, as was the reflectivity, a measure of how bright nerves appear under IVCM. Fabry patients also had more nerve tortuosity (or abnormally twisted nerve fibers) in the cornea, a sign of nerve damage.
Although corneal sensation was reduced in Fabry patients, there was no statistically significant difference from the controls, meaning the difference could have occurred by chance.
Men and boys with Fabry showed more severe corneal neuropathy than female patients, especially in the length of corneal nerve fibers. Still, more women and girls with the disease had signs of significant corneal neuropathy than female controls, including a decrease in corneal nerve fiber length, density, branch density, and reflectivity, and an increase in nerve tortuosity.
Researchers noted no differences in IVCM parameters among patients with different types of Fabry (classical or late onset) or various degrees of disease severity, as assessed by the Mainz Severity Score Index.
When the team examined the immune cells in the cornea, the density of Langerhans cells was significantly higher in Fabry patients than in controls in the center and edges of the cornea. Leukocytes, or white blood cells, were also higher in the central cornea in patients, but not in the peripheral cornea regions. A higher density of Langerhans cells was found in the central cornea of male patients compared with female patients.
IVCM detected a similar density of Langerhans cells across different degrees of disease severity, and a nonsignificant increase in the central cornea of those with classical Fabry than late-onset Fabry.
“Our study demonstrates that IVCM can provide a spectrum of parameters in monitoring the neuro-immune crosstalk in the cornea in patients with [Fabry],” the researchers wrote. “Our findings strongly encourage further efforts in assessing the progressive peripheral neuropathy and chronic inflammatory response by IVCM in more patients with [Fabry] over a longer follow-up period.”
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