PURPOSE. Melanopsin expressing intrinsically photosensitive retinal ganglion cells (ipRGC) input to multiple brain regions including those for pupil control, circadian rhythms, sleep and mood regulation. Here we measured ipRGC function and its relationship to sleep quality and depression in patients with advanced AMD. METHODS. The melanopsin-mediated post-illumination pupil response (PIPR) was measured in 53 patients with advanced AMD (age 78.8 +/- 8.8 years) and in 20 healthy controls (age 72.5 +/- 3.3 years). Sleep quality and efficiency was assessed using the Pittsburgh Sleep Quality Index (PSQI). Risk of depression was determined using the Center for Epidemiologic Studies Depression questionnaire. RESULTS. The group with AMD showed significantly reduced pupil constrictions (P = 0.039); PIPR amplitudes (P = 0.003); global sleep scores (P = 0.01); and higher levels of depression (P < 0.001) than the control group. There was a significant correlation between the PIPR amplitude and global sleep score in the AMD group (P = 0.01). The amplitude of PIPR significantly correlated with sleep efficiency (P = 0.008; regression, P = 0.01, R-2 = 0.13), but not sleep quality (P = 0.23) in the AMD group. There was no correlation between PIPR and depression scores. CONCLUSIONS. Intrinsically photosensitive RGC dysfunction in advanced AMD contributes to the observed reduction in sleep efficiency. The correlation between the melanopsin-mediated PIPR and sleep may indicate reduced photic input to the suprachiasmatic nucleus and ventrolateral preoptic area due to ipRGC dysfunction in AMD.