The role of melatonin and circadian rhythms in the pathogenesis of diabetic retinopathy: A systematic review

Aims: This review investigates literature on systemic melatonin levels and circadian timing in diabetic retinopathy (DR), examining their associations with DR. Methods: Our search was conducted in March 14, 2024, and included the databases Medline, Web of Science, Scopus, ProQuest Health, Latin American and Caribbean Health Sciences Literature (LILACS), Cochrane, International Standard Randomised Controlled Trial Number (ISRCTN) registry, and International Clinical Trials Registry Platform (ICTRP). Results: Our review analysed twelve articles measuring melatonin concentration in saliva, blood serum, urine, or aqueous humour. Studies measuring melatonin levels in saliva found no significant differences in the average nocturnal or daytime melatonin levels between type 2 diabetes (T2D) patients with and without DR. The studies comparing serum melatonin levels in patients with different stages of DR and controls showed inconsistent results. Only two studies measured the endogenous onset of melatonin secretion, known as dim light melatonin onset (DLMO), a highly accurate biomarker for circadian regulation. These studies showed that only 33% and 57% of patients with DR had detectable DLMO in saliva and serum, respectively. All studies evaluating overnight melatonin production using urinary aMT6s (urinary 6-sulfaoxymelatonin) levels found that DR was associated with lower nocturnal melatonin production. Conclusions: Our review results showed evidence of reduced nocturnal melatoin production in DR with no significant changes in melatonin circadian timing.