PURPOSE: The intrinsically photosensitive retinal ganglion cells (ipRGCs) regulate pupil size and circadian rhythms. Stimulation of the ipRGCs using short-wavelength blue light causes a sustained pupil constriction known as the post-illumination pupil response (PIPR). Here we examined the effects of ipRGC stimulation on axial length changes to imposed optical defocus in young adults. MATERIALS AND METHODS: Nearly emmetropic young participants were given either myopic (+3 D, n = 16) or hyperopic (-3 D, n = 17) defocus in their right eye for 2 h. Before and after defocus, a series of axial length measurements for up to 180 s were performed in the right eye using the IOL Master following exposure to 5 s red (625 nm, 3.74 × 10 photons/cm/s) and blue (470 nm, 3.29 × 10 photons/cm/s) stimuli. The pupil measurements were collected from the left eye to track the ipRGC activity. The 6 s and 30 s PIPR, early and late area under the curve (AUC), and time to return to baseline were calculated. RESULTS: The PIPR with blue light was significantly stronger after 2 h of hyperopic defocus as indicated by a lower 6 and 30 s PIPR and a larger early and late AUC (all p<0.05). Short-wavelength ipRGC stimulation also significantly exaggerated the ocular response to hyperopic defocus, causing a significantly greater increase in axial length than that resulting from the hyperopic defocus alone (p = 0.017). Neither wavelength had any effect on axial length with myopic defocus. CONCLUSIONS: These findings suggest an interaction between myopiagenic hyperopic defocus and ipRGC signaling.