Melatonin as a potential biomarker in diabetic retinopathy
Bibliographic record
Abstract
Background: Diabetic retinopathy (DR) is a major complication of diabetes mellitus (DM). Melatonin protects against inflammation and oxidative stress. This review focuses on the literature comparing melatonin levels in patients with and without DR. Methods: A thorough search of the PubMed/MEDLINE, Web of Science, and Embase databases was performed for articles published until April 2025. The inclusion criteria were studies reporting melatonin levels in patients with DR and control groups; studies involving human participants of any age, gender, or ethnicity; and investigations documented in scholarly publications. The exclusion criteria were as follows: animal studies; review articles; case reports; editorials; and conference abstracts; studies not available in English or lacking an English translation; and studies focusing on interventions altering melatonin levels rather than comparing levels between patients with DR and controls. Furthermore, we manually checked the reference lists of the included papers to identify any earlier series that were not initially found in our core search. The Newcastle-Ottawa Scale was used to evaluate study quality. Results: Eight studies with 1004 participants published from 2011 to 2022 were included. The mean age of participants ranged from 39.9 to 72 years. Three studies assessed urinary melatonin excretion, three examined blood melatonin concentrations, one evaluated melatonin concentration in the aqueous humor, and one measured salivary melatonin levels. All samples were collected at night, except for three studies. All studies utilized enzyme-linked immunosorbent assay to measure melatonin concentration, except for the one study, which employed high-performance liquid chromatography. Numerous studies have indicated that patients with DM exhibit reduced melatonin levels relative to healthy controls, and that individuals with DR show lower levels than those without DR. Patients with proliferative DR exhibit reduced nocturnal urinary excretion of 6-sulfatoxymelatonin. Melatonin levels in the aqueous humor were elevated in patients with proliferative DR. Melatonin levels were negatively correlated with both the duration of DM and glycated hemoglobin levels. Conclusions: The findings of this review suggest that patients with DM, particularly those with DR, exhibit altered melatonin production. Reduced systemic melatonin levels may correlate with increased risk and severity of DR. However, the majority of included studies had a case-control design, which hinders the ability to draw causal conclusions regarding the association between melatonin levels and DR. Moreover, confounding factors, including age, duration of DM, medication use, and lifestyle characteristics of participants, were not uniformly considered, and the limited sample sizes restrict the applicability of the results. Future investigations should emphasize longitudinal studies to clarify the temporal dynamics between melatonin levels and DR progression Additional investigations are required to clarify the function of melatonin in the pathogenesis of DR and its viability as a therapeutic target.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.006 | 0.004 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".