Thinning of Eye’s Retina May Be Useful Marker of FA Progression

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by Steve Bryson PhD |

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Reduced thickness of the peripapillary retinal nerve fiber layer (RNFL) in the eye’s retina is associated with worse disease severity in people with Friedreich’s ataxia (FA), an Irish study concluded.

Follow-up measurements showed a thinning in this layer was linked to worsening disease severity, suggesting that regular eye assessments may become a “quantifiable biomarker for the evaluation of disease progression in [FA], the scientists noted.

The study, “Longitudinal Assessment Using Optical Coherence Tomography in Patients with Friedreich’s Ataxia,” was published in the journal Tomography.

FA is genetic condition marked by a deficiency in the frataxin protein, which is required for the normal function of mitochondria, which are the powerhouses of cells. The lack of frataxin disrupts energy production and takes a toll on tissues with high energy requirements, such as muscles and nerves.

While visual symptoms are not always reported in FA, patients frequently experience ocular manifestations, including trouble with fixating gaze and involuntary eye movement.

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In line with this, patients often exhibit a thinning in certain retinal layers, namely in the RNFL, which essentially indicates lower nerve cell levels in these regions of the retina. The retina is the back part of the eye that contains the cells that sense light and the nerve cells that transmit signals from the eyes to the brain.

RNFL thickness also has been shown to correlate with neurological function and disability, but whether the thickness of this layer changes with disease severity over time is still unclear.

Now, a team of scientists at the Tallaght University Hospital, in Dublin, measured this retinal layer in 48 FA patients, all of Irish descent, and compared the findings with those of 48 age- and sex-matched healthy controls.

“This is the first Irish study investigating retinal involvement in individuals with Friedreich’s ataxia,” the team wrote.

Among the patients, 22 had a history of FA in their family. The mean age at symptom onset was 13.8 years and patients had been living with the disease for a mean of 19.5 years. At the time of first assessment, patients were on average 33.4 years.

All FA individuals showed various degrees of ataxia, with the majority (75%) needing a wheelchair, from occasional use to all the time. Disease of the heart muscle (cardiomyopathy) was diagnosed in 21 FA patients, while 10 had diabetes, six hearing loss, and 18 scoliosis — a sideways curvature of the spine, which is common in FA.

The mean visual acuity of those with FA was significantly lower than in the control group. Also, two-thirds of patients experienced abnormal eye movements, including rapid eye movements known as square wave jerks, and nystagmus — the involuntary side-to-side, up and down motion of the eyes.

The thickness of retinal layers was measured by optical coherence tomography (OCT), a noninvasive imaging technology used to record high-resolution cross-sectional images of the retina. Researchers measured the overall average RNFL thickness as well as the four areas, or quadrants, of the RNFL. These quadrants are called the superior, nasal, inferior, and temporal.

OCT analysis revealed a significant reduction in the overall average RNFL thickness in patients compared with controls. The RNFL was thinner in all quadrants except for the temporal area. Other retinal layers, namely the macula and fovea, also were thinner in patients than in controls.

A statistical analysis then found a significant relationship between thinner RNFL in all sectors but the nasal, and worse disease severity, as assessed by the Scale for the Assessment and Rating of Ataxia (SARA), in which higher scores indicate worse ataxia.

A total of 20 FA patients repeated OCT scans over a mean follow-up of 28.4 months, or slightly longer than two years. Over time, there was a significant reduction in the overall RNFL thickness and most RNFL quadrants. Significant thinning also occurred in the macula and fovea, regions in the retina that focus the light for clear vision.

At follow-up, progression of disability was documented in 19 of these 20 individuals, whose mean SARA score increased from 18.9 at the study start to 21.9 at follow-up. Here, worse disease severity was associated with a greater decline in RNFL thickness.

“Our results confirm significant RNFL and macular thinning even in patients without clinically apparent visual impairment and highlight the usefulness of OCT in detecting these changes as the disease progresses,” the researchers wrote.

“Furthermore, the longitudinal data showing significant progression rates of retinal damage detectable through OCT support the usefulness of this cost-effective technique as an objective tool in future therapeutic trials,” they added.