Retinal neurovascular alterations are associated with optic radiation microstructure in adrenomyeloneuropathy: A susceptibility separation MRI study

Abstract Adrenomyeloneuropathy (AMN), the predominant adult‐onset phenotype of X‐linked adrenoleukodystrophy, lacks practical in vivo markers for characterizing central white matter involvement and its relationship to visual pathway abnormalities. We investigated 104 individuals across the clinical spectrum using a multimodal framework combining susceptibility separation MRI to quantify the myelin‐associated diamagnetic susceptibility metric (χ_dia), diffusion tractography, optical coherence tomography and angiography (OCT/OCTA), visual evoked potentials (VEP), and plasma lipid profiling. AMN patients showed widespread white matter microstructural abnormalities, accompanied by retinal structural and microvascular alterations. Visual conduction was also impaired, with prolonged P100 latency in AMN patients compared with healthy controls. Selected retinal neurovascular measures were associated with optic radiation microstructural metrics after correction for multiple comparisons, with the strongest associations observed for fractional anisotropy (FA). Longer P100 latency was likewise associated with lower optic radiation FA, providing functional evidence of visual pathway involvement complementary to retinal imaging. Associations involving χ_dia were more limited than those involving FA. These cross‐sectional findings demonstrate concurrent retinal neurovascular, visual conduction, and central white matter abnormalities in AMN and support further longitudinal evaluation of retinal imaging and visual electrophysiology as accessible complements to brain MRI for assessing disease‐related changes.