Neurobiology of disease · 2026
Retinal thinning and dorsal visual stream degeneration in neuronal intranuclear inclusion disease: Multimodal MRI/OCT evidence with network and mediation analyses.
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Yuan Panpan, Liang Xiaofang, Zhou Yi, Tian Yuxi, Tai Hongfei, Pan Hua, Chen Bin, Zhuo Zhizheng, Liu Yaou, Zhang Zaiqiang, Wang Xingao
Аннотация
OBJECTIVE: To determine whether retinal thinning in neuronal intranuclear inclusion disease (NIID) is associated with multilevel abnormalities across the visual system and with clinical severity.
METHODS: Forty patients with NIID and 40 healthy controls underwent optical coherence tomography to measure peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) thickness. Among patients with NIID, 37 underwent structural MRI for quantification of visual-region volumes and 30 underwent resting-state functional MRI for graph-theoretical assessment of visual-network topology. Cognitive function and activities of daily living were evaluated in the NIID cohort. Partial correlation and exploratory mediation analyses were used to examine associations among retinal, neuroimaging, and clinical measures.
RESULTS: Patients with NIID showed diffuse thinning of the RNFL and GCC relative to controls, with mean GCC showing the best discrimination between groups. Thinner retinal measures were associated with poorer cognition, worse daily function, and lower mean cortical thickness. Structural MRI identified volume abnormalities in selected visual-system regions, particularly the lateral geniculate nucleus, early visual cortex, and dorsal/parietal regions, and retinal thickness correlated positively with the volumes of several visual regions. Poorer daily function was associated with a lower clustering coefficient of the visual network. Left V3d, the dorsal part of area V3 in the occipital visual cortex, partially mediated the association between retinal thinning and functional impairment.
CONCLUSIONS: These findings support coordinated retina-brain involvement in NIID across retinal, structural, and network levels, and identify OCT-derived RNFL and GCC thickness as accessible, noninvasive candidate biomarkers of disease severity.
METHODS: Forty patients with NIID and 40 healthy controls underwent optical coherence tomography to measure peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) thickness. Among patients with NIID, 37 underwent structural MRI for quantification of visual-region volumes and 30 underwent resting-state functional MRI for graph-theoretical assessment of visual-network topology. Cognitive function and activities of daily living were evaluated in the NIID cohort. Partial correlation and exploratory mediation analyses were used to examine associations among retinal, neuroimaging, and clinical measures.
RESULTS: Patients with NIID showed diffuse thinning of the RNFL and GCC relative to controls, with mean GCC showing the best discrimination between groups. Thinner retinal measures were associated with poorer cognition, worse daily function, and lower mean cortical thickness. Structural MRI identified volume abnormalities in selected visual-system regions, particularly the lateral geniculate nucleus, early visual cortex, and dorsal/parietal regions, and retinal thickness correlated positively with the volumes of several visual regions. Poorer daily function was associated with a lower clustering coefficient of the visual network. Left V3d, the dorsal part of area V3 in the occipital visual cortex, partially mediated the association between retinal thinning and functional impairment.
CONCLUSIONS: These findings support coordinated retina-brain involvement in NIID across retinal, structural, and network levels, and identify OCT-derived RNFL and GCC thickness as accessible, noninvasive candidate biomarkers of disease severity.