Retinal atrophy as possible biomarker for amyotrophic lateral sclerosis and Kennedy disease

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The retina is considered an anatomical projection of the central nervous system with the same embryological origins. Unmyelinated axons of retinal ganglion cells form the retinal nerve fiber layer (RNFL) which extends like the optic nerve and connects to the lateral geniculate nucleus (LGN) in the thalamus, which serves as the first relay center of the visual pathway.

The presence of retinal pathology is closely linked to cognitive deficits in patients with Alzheimer's disease (AD), the deposition of amyloid-β plaques leading to retinal thickening. Specifically, peripapillary thinning of the retinal nerve fiber layer is the most common finding in many neurological conditions such as multiple sclerosis, stroke, neuromyelitis optica, dementia with Lewy bodies, Parkinson's, and Alzheimer's disease. Contradictory results are described in amyotrophic lateral sclerosis.

Even though some biomarkers have been validated and incorporated into new clinical diagnostic criteria, most have suboptimal test accuracy and are either very expensive, such as detecting Aβ and Tau deposits in the brain by positron emission tomography (PET), or quite invasive such as as a measure of tau protein and Aβ peptide levels in cerebrospinal fluid analysis. These retinal changes are clinically measurable using existing non-invasive techniques and can be used for the early diagnosis of neurodegenerative disorders.

Optical coherence tomography (OCT) is a relatively inexpensive, harmless, and rapid technique that allows objective retinal measurements and quantification in vivo. OCT is commonly used in ophthalmology to assess retinal integrity through high-resolution cross-sectional scans of retinal layers such as RNFL and CGL at different locations such as the macula or papilla. It is also an interesting tool for neurological research.

A new study sheds light on the pathological significance and clinical value of retinal atrophy in patients with amyotrophic lateral sclerosis and Kennedy disease (spinal and bulbar muscular atrophy).

Authors from Padua, Italy recruited thirty-five patients with amyotrophic lateral sclerosis, thirty-seven with Kennedy disease, and forty-nine age-matched healthy controls were included in a longitudinal study of a year. Spectrum-domain optical coherence tomography was performed at the study entry and after 12 months.

Peripapillary retinal nerve fiber layer thickness was significantly thinner in amyotrophic lateral sclerosis and Kennedy disease compared to healthy controls. The peripapillary retinal nerve fiber layer was thinner in Kennedy disease compared to amyotrophic lateral sclerosis, but the difference was not statistically significant. In Kennedy's disease, pRNFL atrophy was significantly correlated with both disease severity and duration, whereas no significant correlation was found in amyotrophic lateral sclerosis.

During follow-up, the thickness of the peripapillary retinal nerve fiber layer remained stable in Kennedy disease whereas it decreased significantly in amyotrophic lateral sclerosis. : The authors conclude that retinal atrophy in amyotrophic lateral sclerosis and Kennedy disease. However, the study has no statistical value because the sample is much too small, and we know that the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) and the functional assessment of bulbar spinal muscular atrophy (SBMA-FRS) are not reliable markers of disease progression. In fact, the use of tools to turn over, to clear the bronchi, or respiratory assistance leads to an improvement in this type of measurement, without the progression of the disease being changed.

So as usual, while the authors obviously did a lot of work, we do not know much more after this study than before reading it.

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