Morning Salivary Cortisol and Sleep Quality Among African Americans with Chronic Open Angle Glaucoma (COAG)

Bruce I. Gaynes1, Michael Savitt2, Amy Babiuch3. Department of Ophthalmology, Loyola University Chicago, Maywood, IL.1 Department of

Ophthalmology, Rush University Medical Center, Chicago, IL. 2 Department of Ophthalmology, Cleveland Clinic Foundation, Elyria, OH.3

Purpose•Chronic open angle glaucoma (COAG) is an insidious disease of enigmatic origin associated with elevated intraocular pressure and progressive vision loss. •The disease has a notable racial predilection with African Americans and Hispanics having higher incidence and more recalcitrant course compared to Caucasians. •Of note, African Americans have a comparatively high prevalence of adrenal cortical adenomas/hyperplasia resulting in excessive secretion of cortisol.1

•Even subclinical hypercortisolism is associated with metabolic consequences including reduced insulin sensitivity, hypertension and type 2 diabetes.1 •Prolonged hypercortisolism can promote exaggerated intraocular pressure responses resulting in a particularly recalcitrant form of COAG.• it is posited therefore that African Americans with moderate to severe glaucoma demonstrate abnormal elevation in measures of cortisol as a chronobiotic marker for COAG. •As a chronobiotic, cortisol is associated with sleep quality, thus, it is postulated that loss of sleep quality will be found in concert with abnormalities of cortisol. •Furthermore, COAG may disrupt intrinsically photosensitive retinal ganglion (ipRGCs) cells resulting in breakdown of the normal circadian light-dark cycle further affecting sleep quality. •The purpose then of this study is to test the hypotheses that morning salivary cortisol levels are abnormally elevated among African Americans with COAG and that sleep quality among African Americans with glaucoma is deficient.

MethodsCross-sectional analysis of morning (AM) salivary cortisol in conjunction with evaluation of sleep quality among consecutively enrolled African American individuals over age 40 of either gender with COAG as documented by visual field and/or optic nerve abnormality. Subjects with a history of diabetes mellitus, immune disorders or corticosteroid use in the past 6 weeks prior to study entry were excluded. Subjects were asked to fast after midnight the morning of their test and refrain from brushing their teeth upon arising. Morning salivary cortisol specimens were collected at approximately 9:00 AM and subjected to ELISA based assay conducted in duplicate. Sleep quality was assessed at the time of salivary specimen collection using both the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleep Survey

ResultsFifteen female and 6 male subjects were enrolled for study with an age range from 43-91 years (median age 71). Salivary cortisol levels ranged from 3.94-37.34 ng/mL (median 17.45 ng/mL, Figure 1). A one sample two tailed t test (alpha = 0.05) of morning salivary cortisol levels showed a statistically significant difference between a historical control sample2 (mean 2.80 ng/mL) and the study sample (p < 0.0001, Figure 2). Score on the PSIQ ranged from 2-19 (median 9). Epworth scores ranged from 0-16 (median 5). With α = 0.05, Pearson correlation between levels of AM salivary cortisol and intraocular pressure or age was not significant (p = 0.3985 and 0.3348, respectively). In addition, Spearman rank correlation between AM salivary cortisol and performance of either the PSQI or Epworth survey was found not significant (p = 0.1545 and 0.0970 respectively). No relationship was found between age and score of the PSQI (p = 0.3191). However the relationship between salivary cortisol and score on the PSQI demonstrated a notable inverse trend (Figure 3). Of interest, the 25th percentile score of the PSQI was 5. Assuming PSQI scores over 5 are indicative of poor sleep quality, 75% of the study participants were found to have abnormal sleep measures. Results of the Epworth sleep survey were less robust.

ConclusionsCompared to historical controls, study findings support the hypothesis that African Americans with documented COAG demonstrate abnormal, albeit variable, AM salivary cortisol levels. However, AM salivary cortisol levels correlated poorly with IOP, age and sleep status. Study data support the notion that sleep abnormalities are highly prevalent among African American individuals with COAG regardless of age. Moreover, study findings support previous research suggesting that reduced AM salivary cortisol levels are related to poor sleep quality.3 It is posited that COAG alters the integrity of intrinsically photosensitive retinal ganglion cell (ipRGC) function leading to disruption of the circadian light-dark sleep cycle. It is important to note limitations of the study characterized in particular by the small sample size and confounding effects of present and past use of ocular hypotensive therapies. Further study is necessary to clarify salivary cortisol as a valid clinical biomarker in COAG management and the effect of COAG on ipRGC function.

AcknowledgementsThe authors wish to acknowledge the expert assistance of Dr. Malford Cullum in the design of this project. We would also like to recognize Denise Voskuil-Marre in the collection of the salivary specimens. The gracious support of the Richard A. Perritt Charitable Foundation is noted.

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