Optical coherence tomography in adult adrenoleukodystrophy: a cross-sectional and longitudinal study

Abstract

Background Adrenoleukodystrophy (ALD) encompasses different neurological phenotypes, ranging from the most severe cerebral forms (C-ALD) to the less severe adrenomyeloneuropathy (AMN). As visual system can be varyingly involved, we aimed at exploring whether optical coherence tomography (OCT) may detect retinal abnormalities and their longitudinal changes in adult ALD patients. Methods In this cross-sectional and longitudinal study, we measured the thicknesses of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell complex (mGCC), and segmented inner and outer macula at baseline and their changes over time in 11 symptomatic adult ALD males and 10 age-and sex-matched healthy controls. Statistical analyses were performed for the patients as complete group, and splitting them into two subgroups, one (C-ALD) with and the other (AMN) without cerebral parieto-occipital white matter (WM) lesions. Results In the complete ALD group and in the C-ALD subgroup, the average pRNFL, mGCC, and inner macula were significantly thinner than in controls (p ≤ 0.01), whereas in the AMN subgroup, they were constantly, though non-significantly, thinner. Significant outer macula thinning was also observed (p < 0.01). In the complete ALD group, follow-up assessment (mean 26.8 months, range 8-48) showed mildly progressive thinning of inferior pRNFL, average mGCC, and inner macula. Conclusions In adult ALD patients, OCT can reveal retinal abnormalities which are prominent in the more compromised patients, namely those with parieto-occipital WM lesions. The inferior pRNFL, average mGCC and inner macula thicknesses might be sensitive-to-change OCT parameters, but their utility and consistency for short-term longitudinal studies deserve further investigations.

Optical coherence tomography to measure the progression of myelopathy in adrenoleukodystrophy

“…Our findings support the hypothesis that neurodegeneration of the spinal cord is reflected in the retina, and are in line with several other studies that have showed neuroretinal thinning in neurodegenerative and neuro‐inflammatory disorders, including a recent paper describing OCT in patients with ALD 11‐14 . However, similar to those studies, we cannot prove that the same pathological process (a dying‐back axonopathy) is occurring in both the spinal cord and retina.…”

“…Our findings support the hypothesis that neurodegeneration of the spinal cord is reflected in the retina, and are in line with several other studies that have showed neuroretinal thinning in neurodegenerative and neuro-inflammatory disorders, including a recent paper describing OCT in patients with ALD. [11][12][13][14] However, similar to those studies, we cannot prove that the same pathological process (a dying-back axonopathy) is occurring in both the spinal cord and retina. Although it seems unlikely that there is a second, unrelated cause for the retinal neurodegeneration in patients with ALD, only a pathological study in which both spinal cord and retinal nerve fibers are examined could definitively resolve this issue.…”

“…Moreover, this neuroretinal thinning correlated with disease severity 10 . The more recent study of Bianchi‐Marzoli et al showed similar results, which were not significant probably due to the smaller number of patients with myelopathy in this cohort 11 . These studies suggest that neurodegeneration of the spinal cord in ALD is reflected in the retina, a concept that has already been illustrated in a number of other neurodegenerative diseases 12‐14 .…”

“…10 The more recent study of Bianchi-Marzoli et al showed similar results, which were not significant probably due to the smaller number of patients with myelopathy in this cohort. 11 These studies suggest that neurodegeneration of the spinal cord in ALD is reflected in the retina, a concept that has already been illustrated in a number of other neurodegenerative diseases. [12][13][14] As OCT is a fast, noninvasive and reproducible technique, retinal neurodegeneration may be valuable as a new surrogate outcome measure in ALD.…”

Optical coherence tomography in neurodegenerative disorders

“…However, the visual system may be involved and neurodegeneration of the spinal cord in ALD has been correlated with pRNFL thickness 78 . In a cross-sectional and longitudinal study on 11 symptomatic adult ALD males, Bianchi-Marzoli et al 79 showed that OCT can reveal retinal abnormalities in the most disabled patients, particularly in the inferior pRNFL and inner macula.…”