Introduction and Objective: Caffeine has neurovascular and anti-oxidative effects that may influence diabetic microvascular injury. Observational evidence on coffee intake and diabetic retinopathy (DR) remains inconsistent. We aimed to synthesize all available human data since 2015 evaluating the association between coffee or caffeine exposure and the prevalence or incidence of DR. Methods: We systematically searched PubMed, Embase, Web of Science, and preprint servers (2015-2025) for human studies reporting quantitative associations between coffee/caffeine intake or biomarkers and DR. Two reviewers extracted data and assessed study quality using the Newcastle-Ottawa Scale. Random-effects meta-analyses were performed separately for self-reported, biomarker-based, and prospective data. Sensitivity and heterogeneity analyses (I², leave-one-out) were conducted. Results: Six studies (n ≈ 12 000 participants) met criteria: two self-report cross-sectional (KNHANES 2022, Spain 2023), one biomarker (NHANES 2025), one prospective cohort (UK Biobank 2023), and two Mendelian-randomization analyses (2024-2025). Pooled self-report data showed lower odds of DR with higher coffee/caffeine intake (OR 0.45, 95% CI 0.28-0.74, I² = 0%). The biomarker study found higher urinary caffeine associated with greater DR odds (OR ≈ 2.0, 95% CI 1.3-3.2), whereas the prospective cohort observed no significant association. MR studies yielded mixed causal estimates. Conclusion: Across recent literature, self-reported higher coffee intake correlates with reduced DR prevalence, but biomarker and cohort findings are inconsistent. Evidence quality is moderate and limited by cross-sectional design and exposure heterogeneity. Further prospective and mechanistic studies are warranted to clarify whether caffeine exerts protective or confounding effects on retinal microvascular disease in diabetes. Disclosure D. Savage-Lobeck: None. D. Mohammed: None. S. Mohammed: None.
Savage-Lobeck et al. (Fri,) studied this question.
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