Seeing the brain through the eye. Retinal windows into hallucinations and cognition in Lewy body spectrum

Objectives Visuo-perceptual and visuospatial impairments as well as visual hallucinations are hallmark features of dementia with Lewy bodies (DLB) and its prodromal stage (MCI-LB). Retinal imaging techniques, including Optical Coherence Tomography (OCT) and OCT Angiography (OCTA), offer a promising window into central nervous system. This study aimed to investigate retinal alterations in DLB and MCI-LB using OCT/OCTA to identify potential disease biomarkers and to explore correlations between retinal integrity, cognitive performance, and hallucination severity. Materials Retinal scans were obtained from 14 patients with DLB, 13 with MCI-LB, and 18 healthy controls (HC), who underwent a complete ophthalmological, neurological, and neuropsychological evaluations at Sapienza University Hospital in Rome. Methods Retinal layer thickness, vascular density, and optic nerve head (ONH) parameters were compared across groups using a one-way ANOVA. Pearson’s correlations were computed between retinal measures and clinical/neuropsychological scores. Results Several retinal parameters showed significant differences between groups (p < 0.05). DLB patients exhibited thinning of the retinal pigment epithelium (RPE) and ONH Retinal Nerve Fiber Layer (RNFL), and reduced Choriocapillaris Flow and Peripapillary Density compared to HC. Relative to MCI-LB, DLB also exhibited reduced thickness in RNFL, Ganglion Cell Layer (GCL), Inner Plexifrom Layer (IPL), Inner Retinal Layer (IRL), and macular/parafoveal regions. Unexpectedly, MCI-LB patients showed thicker inner retinal layers than both other groups. Moreover, positive correlations were found between retinal parameters and performance in visuospatial tasks. Notably, retinal parameters, especially IPL, GCL, ONH RNFL, parafoveal thickness, and Ganglion Cell Complex (GCC), also correlated negatively with complex visual hallucinations (CVH) in terms of frequency, duration, and severity. Discussion DLB patients showed a thinning of retinal parameters compared to HC, whereas MCI-LB had thicker inner retinal layers. This finding might reflect an early compensatory mechanism occurring before the retinal degeneration in DLB stage. The association between retinal parameters and visuospatial/visuo-perceptual performance as well as CVH suggests that retinal degeneration may contribute to alterations in perceptual processing. Indeed, inner retinal alterations might contribute to CVH by weakening bottom-up sensory inputs and destabilizing perceptual integration. Conclusions Retinal parameters—particularly IPL, GCL, IRL, ONH RNFL, and RPE—are altered in DLB and MCI-LB and are associated with DLB clinical features. These preliminary findings support a possible role of retinal biomarkers in identifying Lewy body disease even in in early stage.