Pupillary responses to the glare illusion in normal pressure hydrocephalus: insights into network dysfunction and neurodegenerative comorbidities.

BACKGROUND: The glare illusion, in which a central area appears self-luminous due to surrounding luminance gradients, induces pupillary constriction, suggesting involvement of higher-order visual processing beyond the brainstem-mediated light reflex. However, its neural underpinnings remain unclear. This study investigated pupillary responses to glare and control stimuli in patients with normal pressure hydrocephalus (NPH), characterized by predominant white matter pathology, and healthy controls. We also examined whether pupillary responses might be influenced by potential comorbid neurodegenerative conditions. METHODS: Pupillary responses were recorded using pupillometry while participants viewed luminance-matched glare and control stimuli. Pupillary constriction amplitude was evaluated for each condition and compared between conditions. Subgroup analyses were performed according to dopamine transporter (DAT) uptake status. RESULTS: Patients with NPH showed generally attenuated stimulus-evoked pupillary constriction amplitude compared with healthy controls. However, in the overall NPH group, pupillary constriction in response to glare stimuli remained greater than that to control stimuli. This condition-dependent difference was consistently observed for constriction amplitude, but not for constriction velocity. In subgroup analyses, patients with reduced DAT uptake showed no clear difference between conditions, whereas those with preserved DAT uptake retained greater constriction to glare stimuli. CONCLUSIONS: Pupillary constriction may provide a potential physiological marker of higher-order visual processing. The overall attenuation of pupillary responsiveness in NPH is consistent with altered large-scale network regulation associated with white matter pathology. Given the small sample size, the absence of a condition-dependent difference in patients with reduced DAT uptake should be interpreted with caution and warrants further investigation.