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Circulating microRNAs as biomarkers for diabetic retinopathy stage identification: A DTA systematic review and meta-analysis

Authors: Miriam Martínez-Santos; María Ybarra; Maria E. Pires; Chiara Ceresoni; Elías Martínez-López; Javier Sancho-Pelluz; Maria Oltra; +1 Authors

Circulating microRNAs as biomarkers for diabetic retinopathy stage identification: A DTA systematic review and meta-analysis

Abstract

Purpose To evaluate the diagnostic accuracy of circulating miRNAs in distinguishing between different diabetic retinopathy (DR) stages in type 2 diabetes mellitus (T2DM). Methods We conducted a systematic review and meta-analysis in accordance with PRISMA-DTA and Cochrane guidelines. The protocol was not registeres and no external funding was received. A comprehensive search was performed in PubMed, CENTRAL, Scopus, Web of Science, ScienceDirect, and ClinicalTrials (up to January 2025) to identify diagnostic test accuracy studies on circulating miRNAs for DR. Eligible studies included three predefined comparisons: healthy controls versus DR (CTL vs DR), T2DM without DR versus DR (T2DM vs DR), and non-proliferative versus proliferative DR (NPDR vs PDR). DR diagnosis was confirmed using fundus fluorescein angiography and/or fundus examination. Two reviewers independently conducted study selection, data extraction, and risk of bias assessment with QUADAS-2; certainty of evidence was assessed using GRADE. Data were synthesized using a bivariate random-effects meta-analysis, with subgroup analyses, meta-regression, and sensitivity analyses to explore heterogeneity. Data were synthesized via a bivariate random-effects meta-analysis, with subgroup analyses, meta-regression, and sensitivity tests to explore heterogeneity. Results Sixteen studies (1849 participants; 21 miRNAs) were included. For CTL vs DR (7 studies), pooled sensitivity was 77% (70–82) and specificity 84% (77–89), AUC 0.86 (0.82–0.89). For T2DM vs DR (9 studies), sensitivity was 81% (75–86) and specificity 80% (71–87), AUC 0.88 (0.84–0.91). For NPDR vs PDR (12 studies), sensitivity was 84% (79–87) and specificity 82% (76–88), AUC 0.90 (0.87–0.93). Heterogeneity arose chiefly from sample matrix, normalization strategies and inter-study expression trends. Patient selection posed the greatest bias risk. Conclusions Circulating miRNAs exhibit promising diagnostic accuracy for differentiating among various stages of DR. However, future large, prospective studies in diverse populations and standardized pre-analytical protocols are required to confirm and translate these findings.

Country
Spain
Keywords

Diabetic Retinopathy, Systematic reviews, Metaanalysis, Publication ethics, Diagnostic medicine, MicroRNAs, Diabetes Mellitus, Type 2, Diabetic retinopathy, 32 Ciencias Médicas, miRNAs, Humans, Systematic Reviews as Topic/methods, diagnostic medicine, Circulating MicroRNA, Biomarkers, metaanalysis, Research Article

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    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    2
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
2
Top 10%
Average
Average
Green
gold