Eye Abnormalities May Serve as Early Biomarkers for hATTR Amyloidosis

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by Vanda Pinto PhD |

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Changes in the function of the retina, in combination with nerve damage in the cornea, can be used as early biomarkers of hereditary transthyretin (hATTR) amyloidosis, also known as familial amyloid polyneuropathy (FAP), a study reports.

Researchers suggest that a complete eye exam could be useful to detect problems in the retina (region at the back of the eye that enables vision) and the cornea (the eye’s clear protective outer layer) before patients develop symptoms.

The case series study, “Ocular Involvement in Hereditary Transthyretin Amyloidosis A Case Series Describing Novel Potential Biomarkers,” was published in the journal Genes.

In hATTR amyloidosis, a protein called transthyretin clumps and accumulates in different tissues and organs, impairing their function. These protein aggregates, also known as amyloid deposits, can also build up in fluids surrounding different portions of the eye, causing eye problems and vision impairments.

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However, only a few studies have examined hATTR amyloidosis patients before reaching the clinical stage of eye disease, according to the study’s researchers. In addition, no research on how eye function is affected in hATTR amyloidosis has been performed until now.

In the new study, scientists from Italy set out to identify potential biomarkers in hATTR amyloidosis patients by assessing abnormalities in the corneal nerves, as well as structural and functional alterations in the retina.

Nine patients, between 51 and 87 years old, with a confirmed diagnosis of hATTR amyloidosis by genetic testing associated with signs or symptoms of the disease were enrolled between March and July 2019 at the outpatient eye clinic Fondazione Policlinico Universitario A. Gemelli-IRCCS, in Rome.

The researchers used optical coherence tomography, an imaging test that uses light to take pictures of the retina. They also used electroretinography (ERG) to evaluate the electrical responses of several cell types in the retina, including light-sensitive photoreceptors (rods and cones), inner retinal cells (bipolar and amacrine cells), and ganglion cells.

Corneal nerve fibers were visualized using corneal confocal microscopy (CCM), a non-invasive clinical technique that is used to detect alterations in the cornea and early nerve damage.

The case series included six men and three women. Eight had active disease and one was an unaffected carrier. The age at diagnosis was between 48 and 81 years. Mean disease duration was 35.42 months (nearly three years).

Best corrected visual acuity, a measure of visual acuity, was maintained in all patients, except in one.

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However, ERG findings revealed a series of abnormalities in retinal cell responses found in the eyes of the patients. Specifically, investigators found that mixed rod-cone and cone ERG b-wave amplitudes were reduced and that b-wave responses triggered by light were significantly delayed in the eyes of patients when compared to normal reference values.

Additionally, photopic negative response (PhNR) amplitude, a measure of ganglion cell function, was significantly reduced in patients, while PhNR latency was significantly increased.

Vitreous opacities or floaters and structural abnormalities of the retina were observed in 13 out of the 18 patient eyes analyzed. Results also revealed that corneal nerves in the patients’ eyes were thinner, shorter, more fragmented, and less dense than expected.

“The main findings of the study are the alterations of retinal function, even in the presence of minimal or absent structural retinal damage, in association with corneal nerves abnormalities, in patients with a confirmed diagnosis of primary hATTR amyloidosis and no visual impairment,” the authors wrote.

The researchers also noted that CCM and ERG are both quick, easy, and non-invasive exams that may potentially be useful screening tests for hATTR amyloidosis.

“Our data suggest that a complete ophthalmological examination is useful in hATTR patients to detect a subclinical ocular involvement,” they wrote.