Intrinsically Photosensitive Retinal Ganglion Cell Activity Is Associated with Decreased Sleep Quality in Patients with Glaucoma

Purpose To use the pupillary light reflex and polysomnography to evaluate the function of intrinsically photosensitive retinal ganglion cells (ipRGCs) and to correlate this function with structural damage in glaucoma. Design Cross-sectional study. Participants A study was conducted on both eyes of 45 participants (32 patients with glaucoma and 13 healthy subjects). Methods For the pupillary reflex evaluation, patients were tested in the dark using a Ganzfeld system (RETIport; Roland Consult, Brandenburg, Germany); pupil diameter was measured with an eye tracker system. To preferentially stimulate ipRGCs, we used a 1-second 470-nm flash with a luminance of 250 cd/m 2 . To stimulate different retinal photoreceptors, we used a 1-second 640-nm flash with a luminance of 250 cd/m 2 . All of the subjects underwent polysomnography. Subjects underwent standard automated perimetry and optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec Inc, Dublin, CA). Main Outcome Measures Correlations between ipRGC activity, as measured by the pupillary light reflex, and polysomnography parameters, and correlations between retinal nerve fiber layer (RNFL) thickness and the pupillary light reflex and polysomnography parameters. Results The mean patient ages in the healthy and glaucoma groups were 56.8±7.8 years and 61.5±11.6 years, respectively ( P  = 0.174). Patients with glaucoma had significantly lower average total sleep time, sleep efficiency, and minimum oxyhemoglobin saturation compared with the healthy subjects ( P   = 0.008, P  = 0.002, and P  = 0.028, respectively). Patients with glaucoma had significantly higher arousal durations after falling asleep and more periodic limb movements ( P  = 0.002 and P  = 0.045, respectively). There was an inverse correlation between the rapid eye movement latency and the peak of the pupillary response to the blue flash ( P  = 0.004). The total arousals were inversely correlated with the sustained blue flash response ( P  = 0.029). The RNFL thickness was associated with the peak and sustained responses to the blue flash ( P P  = 0.023). Conclusions This study demonstrated that decreased ipRGC function caused by glaucoma affected pupillary response and sleep quality.