Intrinsically Photosensitive Retinal Ganglion Cell Function, Sleep Efficiency and Depression in Advanced Age-Related Macular Degeneration

Abstract

Citation: Maynard ML, Zele AJ, Kwan AS, Feigl B. Intrinsically photosensitive retinal ganglion cell function, sleep efficiency and depression in advanced age-related macular degeneration. Invest Ophthalmol Vis Sci. 2017;58:990-996. DOI:10.1167/ iovs.16-20659 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 6 8.8 years) and in 20 healthy controls (age 72.5 6 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 ¼ 0.039); PIPR amplitudes (P ¼ 0.003); global sleep scores (P ¼ 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 ¼ 0.01). The amplitude of PIPR significantly correlated with sleep efficiency (P ¼ 0.008; regression, P ¼ 0.01, R 2 ¼ 0.13), but not sleep quality (P ¼ 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.

The association between clinically diagnosed insomnia and age‐related macular degeneration: a population‐based cohort study

“…Reduced nocturnal synthesis of melatonin and sleep disturbance in AMD have been reported in the literature (Rosen et al 2009;Khurana et al 2016;Lv et al 2016;P erez-Canales et al 2016;Maynard et al 2017). Compared with age-and gender-matched controls, Rosen et al (2009) found 40% lower level of urinary 6-sulfatoxymelatonin (aMT6s), major metabolite of melatonin, in patient with AMD.…”

“…Short (<6 hr) and long (>8 hr) sleep duration per night are independently associated with exudative AMD and geographic atrophy, respectively (Khurana et al 2016;P erez-Canales et al 2016). Poor sleep efficiency in patients with advanced AMD was also observed (Maynard et al 2017).…”

The associations of objectively measured sleep duration and sleep disturbances with diabetic retinopathy

“…This could explain why DME was associated with high risk for insomnia but not short sleep duration in our study. mRGC loss and dysfunction have previously been shown in macular disease such as DME and agerelated macular degeneration [26,34]. On the other hand, insomnia might contribute to the development of DME through other mechanisms such as hyperarousals and increased serum cortisol and adrenocorticotrophic hormone levels [33,35,36].…”

Intrinsically photosensitive retinal ganglion cell mediated pupil function is impaired in Parkinson’s disease

“…The reduction in the post-illumination pupil response amplitude (closer to baseline diameter) in the PD group compared to controls indicates that melanopsin-mediated ipRGC inputs to pupil control pathway are impaired, and that this effect size is both large and clinically relevant (difference between medians = 17.49%). Reduced ipRGC function has been associated with impaired sleep in retinal diseases (Gracitelli et al ., 2015, Maynard et al ., 2017) and while there was reduced sleep quality in patients with Parkinson’s disease compared to the control group, this difference was not statistically significant. We acknowledge however that alternative methods of sleep assessment such as polysomnography may be more sensitive than the PSQI in detecting sleep deficits.…”