The Effect of Refractive Error and Light Exposure on Red and Blue Light-Driven Pupil Responses

Time outdoors is protective against myopia onset, but does not have an effect on myopia progression. Stimulation of the retina by light causes release of dopamine by a retinal circuit including intrinsically photosensitive retinal ganglion cells (ipRGCs), dopaminergic amacrine cells, and photoreceptors. The aim of the current study is to investigate the relationship between ipRGC-mediated pupil dynamics, refractive error, and time outdoors. Twenty-five healthy adult subjects wore visible light and UV sensitive badges for one week to monitor their light exposure and time outdoors. Pupil testing included 3 test sequences of flickering light (0.1 Hz) in the following order: 1) alternating red and blue light flashes (2 min duration); 2) red-only flashes (1 min); 3) and blue-only flashes (1 min). Subjects completed an activity and dietary survey, and blood and saliva samples were collected. There was a significant correlation between refractive error (SEQ, D) and the difference in the mean pupil responses to blue light in the third (blue-only) versus the first (alt blue) test (r=0.42, p=0.037), but not for the difference in the responses to the red light in the second (red-only) versus the first (alt red) test. For this measure of the change in the pupil responses to blue light, an interaction existed between refractive error, and the amount of light exposure over the previous 3 and 5 days. In addition, the decay constants for the pupil re-dilation rates in the blue-only trial correlated to refractive error (r=0.44, p=0.028). Findings of the present study indicated that pupil responses to blue light changed more in non-myopes, relative to myopes, over the course of the three tests used in this protocol. A hypothesis for an underlying mechanism is that the light exposure during the first two tests stimulated retinal dopamine release that affected ipRGC light responses, and this neuromodulatory pathway may be deficient in myopes. Consistent with this hypothesis, prior light exposure over the preceding 3 to 5 days caused pupil re-dilation rates evoked by the blue-only stimulus to be slower, indicative of enhanced ipRGC contribution, in non-myopes but not myopes. More longitudinal research with children is necessary to further investigate the possible role of this dopaminergic retinal circuit in ocular growth and refractive development.