Evidence map›Paper›PMID 39939938›Full record

SynthesisBMC medicine2025

Tear-fluid-derived biomarkers of ocular complications in diabetes: a systematic review and meta-analysis.

Mya Polkamp, Nhan H T Pham, Wilson K M Wong, Hrishikesh P Hardikar, Pooja S Kunte, Morven A Cameron, Anandwardhan A Hardikar, Mugdha V Joglekar

Abstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Mya Polkamp *Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Building 30, David Pilgrim and Goldsmith Avenue, Campbelltown, NSW, 2560, Australia.
Nhan H T Pham *Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Building 30, David Pilgrim and Goldsmith Avenue, Campbelltown, NSW, 2560, Australia.
Wilson K M Wong *Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Building 30, David Pilgrim and Goldsmith Avenue, Campbelltown, NSW, 2560, Australia.
Hrishikesh P HardikarDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Building 30, David Pilgrim and Goldsmith Avenue, Campbelltown, NSW, 2560, Australia.
Pooja S KunteDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Building 30, David Pilgrim and Goldsmith Avenue, Campbelltown, NSW, 2560, Australia.
Morven A CameronAnatomy and Cell Biology, School of Medicine, Western Sydney University, Building 30, David Pilgrim and Goldsmith Avenue, Campbelltown, NSW, 2560, Australia.
Anandwardhan A HardikarDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Building 30, David Pilgrim and Goldsmith Avenue, Campbelltown, NSW, 2560, Australia. A.Hardikar@westernsydney.edu.au.
Mugdha V JoglekarDiabetes and Islet Biology Group, School of Medicine, Western Sydney University, Building 30, David Pilgrim and Goldsmith Avenue, Campbelltown, NSW, 2560, Australia. m.joglekar@westernsydney.edu.au.

Funding

Juvenile Diabetes Research Foundation International 3-PDF-2023-1324-A-NNational Health and Medical Research Council 2011557Novo Nordisk Fonden,Denmark NNF23SA0087252
6 · The paper itself

Abstract

backgroundEarly identification and management of sight-threatening ocular complications of diabetes using imaging or molecular biomarkers could help prevent vision loss. However, access to specialized infrastructure and expertise is limited, especially in remote areas of the world. Tear-fluid may offer an easier, non-invasive, and localized screenshot of ocular disease. To the best of our knowledge, there is no systematic review and meta-analysis on tear-fluid-based biomarkers for ocular complications in diabetes.

methodsArticles were extracted from PubMed, Embase, Medline, and Web of Science using the MeSH and Emtree terms. The keywords include (diabetes), (diabetic retinopathy), (diabetes mellitus, type 1), (diabetes mellitus, type 2), (insulin-dependent diabetes), (insulin resistant diabetes), (tears), (lacrimal fluid), (biological marker), and (biomarker, marker). Concentrations of tear-fluid biomarkers in individuals with diabetes, diabetic ocular complications, and healthy controls were extracted and standardized mean differences (SMDs) and 95% CIs were calculated. Heterogeneity was assessed using subgroup and leave-one-out sensitivity analyses. Publication and risk of bias were performed using the Egger's test and Cochrane guidelines. The quality of evidence was evaluated using the Newcastle-Ottawa scale.

resultsNine hundred eleven papers were identified, 19 of which met the study criteria and were included in the meta-analysis. Participants (n = 1413) belonged to three groups: healthy controls (Controls), diabetes without any complications (Diabetes), and diabetes with ocular complications (Complications). Actual concentrations were reported for TNF-α, VEGF, IL-1RA, IL-1β, IL-6, IL-8, lactoferrin, lysozyme, and MCP-1 in at least three different studies. Meta-analyses demonstrated that TNF-α concentration was significantly higher in the tear-fluid of Complications group when compared to Controls (SMD = - 1.08, 95% CIs = - 1.78, - 0.38, p = 0.003) or when compared to Diabetes (SMD = - 0.78, 95% CIs = - 1.48, - 0.09, p = 0.03). However, it was not different when Controls were compared to Diabetes (SMD = - 1.00, 95% CIs = - 2.27, 0.28, p = 0.13). VEGF demonstrated a similar trend indicating specificity of tear-fluid TNF-α and VEGF for diabetic ocular complications.

conclusionsAcross all biomolecules meta-analyzed in this study, TNF-α and VEGF were identified as the most important biomarkers that could potentially offer a non-invasive tear-fluid-based assessment of progression to ocular complications in diabetes, especially in rural and remote areas where diabetes-related expertise and infrastructure are limited.

trial registrationPROSPERO (CRD42023441867) https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=441867 .

Indexed as

Diabetes ComplicationsDiabetic RetinopathyEye DiseasesTearsBiomarkersHumansBiomarkersBiomarker discoveryCytokinesDiabetesDiabetic ocular complicationsIsletProteinsRisk stratificationTear-fluidTears

Identifiers

PMID39939938
PMCPMC11823092

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.