Thinner nerve layer in retina, tied to vision loss, prevalent in FA patients

Children to adults show 'significantly thinner' layer, a possibly congenital defect

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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People with Friedreich’s ataxia (FA), regardless of age, have a thinner layer of nerve cells in the eye’s retina compared with unaffected individuals, a study involving almost 200 patients found.

Such thinning, which correlated with neurological disease severity and vision loss, continued to increase over time. Researchers believe retinal thinning arises from early developmental deficits in patients and worsens with neurodegeneration as the disease progresses.

“The present findings suggest a need for more extensive longitudinal studies with adults and children with [FA] and reveal an unmet need for vision-directed drug development including small molecules or gene therapy to treat vision loss,” the scientists wrote.

The study, “Retinal hypoplasia and degeneration result in vision loss in Friedreich ataxia,” was published in the Annals of Clinical and Translational Neurology.

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‘Pathologically thin retinas early’ in Friedreich’s ataxia, affecting vision

In addition to the neuromuscular symptoms of FA, optic neuropathy, or damage to the optic nerve that connects the eyes and the brain, affects patients.

Progressive vision loss can be common in FA, leading to blindness for some. However, the biological underpinnings of such loss are not well defined, the researchers, mostly with Children’s Hospital of Philadelphia and the University of Pennsylvania, wrote.

Their study looked into changes in the thickness of the eye’s retinal nerve fiber layer (RNFL) among FA patients and evaluated whether such changes contribute to vision loss.

The retina is the back layer of the eyeball containing cells that are sensitive to light. Their activation triggers nerve impulses in the RNFL that are carried to the brain via the optic nerve, enabling vision.

A loss, or thinning, of nerves in this layer can be visualized and measured using a technique called optical coherence tomography (OCT).

OCT scans were performed on 198 FA patients taking part in the ongoing Friedreich’s Ataxia Clinical Outcome Measure Study (FACOMS) study (NCT03090789), evaluating the disease’s natural course, or its natural history. OCT scans from 77 people without FA served as a control group.

Patients were representative of the larger FA population, covering a wide range of ages, the researchers noted.

Results showed that RNFLs were significantly thinner among FA patients than controls, despite most patients retaining high-contrast vision.

Thin retinal nerve fiber layer evident in children as well as adults

Sixty-one pediatric patients, comprising almost one-third of the total FA group, showed RNFL thinning similar to that observed overall.

The finding surprised the researchers, as children with FA are often “minimally affected or even un-affected” in other clinical measures of neurological disease progression.

“The majority of those with [Friedreich’s ataxia] have pathologically thin retinas early in disease (even at presentation) despite having intact high-contrast vision,” the scientists wrote.

This suggests that RNFL thinning to some degree is congenital in FA patients, meaning it results from an underdevelopment of tissues (hypoplasia) and is not simply a product of progressive neurodegeneration.

Still, retinal nerve fiber layers were thinner in patients with a higher disease burden, defined as a longer disease duration and higher number of GAA repeats in the FXN gene, which is “an indication of further degeneration over time,” the researchers wrote.

Male patients had modestly but significantly thinner RNFLs than females, suggesting that sex is another factor influencing retinal degeneration.

OCT measures were able to significantly predict patients’ neurological disease severity, with a thinner RNFL generally linked to more severe neurological disease progression, as assessed by the modified Friedreich’s Ataxia Rating Scale and FA Functional Disease Stage.

Likewise, a thinner retinal nerve fiber layer was predictive of visual acuity deficits. Mathematical models showed that an RNFL thickness at or below 68 micrometers (μm) indicated a significant vision loss.

Potential for vision loss that could start ‘in third decade of life’

Among patients with multiple OCT measurements, RFNL thickness was found to decrease at an annual rate of 1.2 μm in FA patients, which the scientists noted is about double the rate of decline seen in healthy people.

“Assuming a typical age of [disease] onset of approximately 11 years, a person with 700 GAA [repeats] … could expect to start experiencing vision loss in the third decade of life,” the researchers wrote, adding that other factors “uncovered in this study” could influence the rate of progression.

Study findings overall “support the development of a vision-directed treatment for selected patients early in the disease to prevent RNFL loss from reaching the critical threshold,” the team wrote.

Of note, the FACOMS natural history study is recruiting up to 2,000 FA patients, ages 4 to 80, at various U.S. and global sites. Control groups, including disease carriers, may also be welcome.