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OBJECTIVE Pituitary tumours that compress the optic chiasm are associated with long-term alterations in sleep-wake rhythm. This may result from damage to intrinsically photosensitive retinal ganglion cells (ipRGCs) projecting from the retina to the hypothalamic suprachiasmatic nucleus via the optic chiasm to ensure photoentrainment (i.e., synchronisation to the 24-hour solar cycle through light). To test this hypothesis, we compared the post-illumination pupil response (PIPR), a direct indicator of ipRGC function, between hypopituitarism patients with and without a history of optic chiasm compression. DESIGN Observational study, comparing two predefined groups. METHODS We studied 49 patients with adequately substituted hypopituitarism: 25 patients with previous optic chiasm compression causing visual disturbances (CC+ group) and 24 patients without (CC- group). The PIPR was assessed by chromatic pupillometry and expressed as the relative change between baseline and post-blue-light stimulus pupil diameter. Objective and subjective sleep parameters were obtained using polysomnography, actigraphy and questionnaires. RESULTS Post-blue-light stimulus pupillary constriction was less sustained in CC+ patients compared with CC- patients, resulting in a significantly smaller extended PIPR (mean difference 8.1%, 95% CI 2.2-13.9%, P = 0.008, Cohen's d = 0.78). Sleep-wake timing was consistently later in CC+ patients, without differences in sleep duration, efficiency or other rest-activity rhythm features. Subjective sleep did not differ between groups. CONCLUSION Previous optic chiasm compression due to a pituitary tumour in patients with hypopituitarism is associated with an attenuated PIPR and delayed sleep timing. Together these data suggest that ipRGC function and consequently photoentrainment of the central biological clock is impaired in patients with a history of optic chiasm compression.