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Review
. 2019 Jun 26;8(3):49.
doi: 10.1167/tvst.8.3.49. eCollection 2019 May.

Sleep-Wake Disturbance Related to Ocular Disease: A Systematic Review of Phase-Shifting Pharmaceutical Therapies

Colm D Andrews  1   2 , Russell G Foster  3 , Iona Alexander  1 , Sridhar Vasudevan  4 , Susan M Downes  1 , Carl Heneghan  5 , Annette Plüddemann  5
Affiliations
Review

Sleep-Wake Disturbance Related to Ocular Disease: A Systematic Review of Phase-Shifting Pharmaceutical Therapies

Colm D Andrews et al. Transl Vis Sci Technol. .

Abstract

Purpose: Light input, via the eyes, is essential for regulating circadian rhythms. Eye diseases can cause disruption of vital biological rhythms. Of totally blind people, 87% report sleep problems. There are no UK guidelines for visual disturbance-related circadian rhythm disruption. Our objective was to systematically review the literature to determine the effectiveness of pharmacological agents on the sleep quality of patients with sleep disturbance related to ocular disease.

Methods: We searched CENTRAL, MEDLINE, EMBASE, PsycINFO, and CINAHL alongside protocol registries and citation searches. We assessed the risk of bias using the Cochrane Risk of Bias Assessment Tool and assessed the strength of overall evidence using GRADE criteria.

Results: Four studies (n=116) met the inclusion criteria. Low-quality evidence showed that melatonin can cause entrainment (1 study), increases in total sleep time (all 3 studies), and reduction in sleep latency (1 study). Low-to-moderate quality evidence showed tasimelteon causes a significant improvement in entrainment, midpoint of sleep timing, lower-quartile of night-time sleep, and upper-quartile of daytime sleep.

Conclusions: Results should be treated with caution as the melatonin studies had risks of bias due to inadequate reporting of randomization and masking procedures. The tasimelteon trial had a risk of reporting bias due to changing the outcomes after enrolling participants. Despite the paucity of trials, melatonin and tasimelteon may cause entrainment and improve subjective sleep measures with limited side effects.

Translational relevance: Given the relative cost melatonin may be a viable choice for treatment of circadian rhythm sleep disorders in the blind and warrants further research.

Keywords: circadian rhythm; melatonin; sleep.

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Figures

Figure
Figure
Risk of bias summary: review author's judgments about methodologic quality for each included study.
See this image and copyright information in PMC

References

    1. Leger D, Guilleminault C, Defrance R, Domont A, Paillard M. Prevalence of sleep/wake disorders in persons with blindness. Clin Sci. 1999;97:193–199. - PubMed
    1. Roth T. Insomnia: definition, prevalence, etiology, and consequences. J Clin Sleep Med. 2007;3(5 Suppl):S7–S10. - PMC - PubMed
    1. Lockley SW, Arendt J, Skene DJ. Visual impairment and circadian rhythm disorders. Dialogues Clin Neurosci. 2007;9:301–314. - PMC - PubMed
    1. Buxton OM, Cain SW, O'Connor SP, et al. Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Sci Transl Med. 2012;4:129ra43 - PMC - PubMed
    1. Masri S, Kinouchi K, Sassone-Corsi P. Circadian clocks, epigenetics, and cancer. Curr Opin Oncol. 2015;27:50–56. - PMC - PubMed