The study, “Optical coherence tomography shows neuroretinal thinning in myelopathy of adrenoleukodystrophy,” was published in the Journal of Neurology.
ALD is a rare neurodegenerative disorder caused by mutations in the ABCD1 gene, which is located on the X chromosome. It is characterized by the accumulation of fatty molecules, called very long-chain fatty acids, which can destroy myelin — the fatty substance that protects nerve cells — and induce neuron degeneration.
In people with ALD, progressive myelopathy — a condition in which neurons from the spinal cord are progressively destroyed due to spinal cord compression or injury — is the main cause of physical disability and the most common manifestation of the disease.
“Measuring the severity and progression of myelopathy in ALD, however, is problematic. Neurological examination and current clinical outcome measures are subject to a high intra- and interrater variability. Moreover, disease progression is very slow, occurring over years or even decades,” the researchers wrote.
Previous studies in other neurodegenerative disorders, including Parkinson’s, Alzheimer’s, multiple sclerosis, and amyotrophic lateral sclerosis, have shown that neurodegeneration also takes place in the retina of the eyes, leading to thinning of some of its layers.
“As axonal degeneration is the pathological hallmark of myelopathy in ALD, thinning of [nerve cell layers in the retina] could reflect spinal cord damage and, therefore, serve as a surrogate outcome measure for myelopathy in ALD,” the investigators wrote.
To investigate this possibility, researchers from the University of Amsterdam in the Netherlands and collaborators used a technique called optical coherence tomography (OCT) — a non-invasive imaging test that uses light to take pictures of the retina — to measure the thickness of the different layers of the retina.
Their main goal was to see if neurodegeneration in the retina of people with ALD could be associated with myelopathy, and if OCT could be used as a surrogate measure of disease progression in future trials with ALD patients.
The study enrolled a total of 62 people with ALD (29 men and 33 women), and 70 individuals of the same age and sex who did not have the disease (control group).
OCT was used on all study participants to measure and compare the thickness of three different nerve layers of the retina — the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), and the peripapillary retinal nerve fiber layer (pRNFL).
The researchers used correlation analyses to evaluate possible relationships between OCT measurements and clinical parameters of myelopathy severity.
Findings revealed that in men with ALD, the RNFL was significantly thinner, compared to those who did not have the disease; while in women with ALD, the pRNFL was significantly thinner compared to controls. No significant differences in the thickness of the GCL were found between those with ALD and the controls.
After dividing those who had ALD into two groups — those with symptoms and those without — and comparing their OCT measurements with the controls, the investigators found that there were statistically significant differences in the thickness of the RNFL in men, and in the pRNFL in both men and women.
In both cases, these differences were significant when comparing symptomatic patients with the controls, and also when comparing those who did not have symptoms with those who did.
Statistical analyses found a moderate correlation between the thickness of the retina and myelopathy severity in men with ALD, but not in women.
Overall, the results “show that the myelopathy of ALD is associated with neuroretinal thinning on OCT. While clinical neurological assessments are subject to high inter- and intrarater variability, OCT has excellent test-retest reliability. Moreover, it is a fast and safe assessment that can largely be done automatically,” the researchers wrote.
“Therefore, OCT may be used to monitor disease progression and serve as a surrogate outcome measure for clinical trials in ALD,” the team suggested.
According to the researchers, further long-term studies are being conducted in this patient cohort to validate the findings.