Research progress on the detection of tear markers and application in fundus diseases_Chinese Journal of Ocular Fundus Diseases

Authors：

Zhang Kaiyan ¹ ,  Ding Huan ² , Ye Wenfang ² , Zhang Shuyuan ²

1. Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou 570311, China;
2. Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou 570311, China;

Corresponding?author：

Ding Huan, Email: ping_guo_183@126.com

Keywords：

Tear fluid; Biomarkers; Fundus diseases; Review

DOI：

10.3760/cma.j.cn511434-20250612-00265

Video：

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Abstract Full text Figures/Tables Video References Cited by

Tear fluid, as an important ocular surface fluid, can effectively reflect both ocular and systemic metabolic states through its compositional changes, making it an ideal source for discovering disease biomarkers. Current tear collection methods mainly include the Schirmer strip test and microcapillary collection, while detection technologies encompass enzyme-linked immunosorbent assay, protein chip technology, mass spectrometry, Olink targeted proteomics, and bead-based multiplex assays. Studies have shown that various biomarkers in tear fluid, such as proteins, cytokines, and chemokines that are closely associated with the pathophysiological processes of fundus diseases including diabetic retinopathy, retinal vein occlusion, age-related macular degeneration, retinopathy of prematurity, and uveitis, demonstrating potential as indicators for early diagnosis, disease assessment, and therapeutic monitoring. As a non-invasive and convenient detection tool, tear analysis shows broad application prospects in the diagnosis and treatment of fundus diseases. However, further optimization of collection and detection techniques, along with large-scale clinical studies to validate the clinical utility of tear biomarkers, is still needed to promote their standardization and widespread adoption in clinical practice.

Citation： Zhang Kaiyan, Ding Huan, Ye Wenfang, Zhang Shuyuan. Research progress on the detection of tear markers and application in fundus diseases. Chinese Journal of Ocular Fundus Diseases, 2026, 42(3): 259-264. doi: 10.3760/cma.j.cn511434-20250612-00265 Copy

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1.
2.
3.
4. Altman J, Jones G, Ahmed S, et al. Tear film microRNAs as potential biomarkers: a review[J/OL]. Int J Mol Sci, 2023, 24(4): 3694[2023-02-12]. https://pubmed.ncbi.nlm.nih.gov/36835108/. DOI: 10.3390/ijms24043694.
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14. Waszczykowska A, Go? R, Waszczykowska E, et al. The role of angiogenesis factors in the formation of vascular changes in scleroderma by assessment of the concentrations of VEGF and sVEGFR2 in blood serum and tear fluid[J/OL]. Mediators Inflamm, 2020, 2020: 7649480[2020-01-24]. https://pubmed.ncbi.nlm.nih.gov/32410862/. DOI: 10.1155/2020/7649480.
15. Chen Y, Meng Y, Tan M, et al. Changes in expression of inflammatory cytokines and ocular indicators in pre-diabetic patients with cataract[J/OL]. BMC Ophthalmol, 2025, 25(1): 119[2025-03-10]. https://pubmed.ncbi.nlm.nih.gov/40065310/. DOI: 10.1186/s12886-025-03892-5.
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26.
27. Antman G, Ritzer L, Galor A, et al. The relationship between dry eye disease and human microbiota: a review of the science[J/OL]. Exp Eye Res, 2024, 245: 109951[2024-06-03]. https://pubmed.ncbi.nlm.nih.gov/38838972/. DOI: 10.1016/j.exer.2024.109951.
28.
29. Bao J, Zhang P, Wu B, et al. Gp130 promotes inflammation via the STAT3/JAK2 pathway in allergic conjunctivitis[J/OL]. Invest Ophthalmol Vis Sci, 2023, 64(4): 5[2023-04-03]. https://pubmed.ncbi.nlm.nih.gov/37022703/. DOI: 10.1167/iovs.64.4.5.
30.
31. Zhou Y, Ma B, Liu Q, et al. Transmembrane protein CMTM6 alleviates ocular inflammatory response and improves corneal epithelial barrier function in experimental dry eye[J/OL]. Invest Ophthalmol Vis Sci, 2024, 65(1): 4[2024-01-02]. https://pubmed.ncbi.nlm.nih.gov/38165704/. DOI: 10.1167/iovs.65.1.4.
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45.
46. Amorim M, Martins B, Caramelo F, et al. Putative biomarkers in tears for diabetic retinopathy diagnosis[J/OL]. Front Med (Lausanne), 2022, 9: 873483[2022-05-25]. https://pubmed.ncbi.nlm.nih.gov/35692536/. DOI: 10.3389/fmed.2022.873483.
47. Costagliola C, Romano V, De Tollis M, et al. TNF-alpha levels in tears: a novel biomarker to assess the degree of diabetic retinopathy[J/OL]. Mediators Inflamm, 2013, 2013: 629529[2013-10-23]. https://pubmed.ncbi.nlm.nih.gov/24259948/. DOI: 10.1155/2013/629529.
48.
49. Machalińska A, Kuligowska A, Ziontkowska-Wrza?ek A, et al. The severity of diabetic retinopathy corresponds with corneal nerve alterations and ocular discomfort of the patient[J/OL]. Int J Mol Sci, 2024, 25(11): 6072[2024-05-31]. https://pubmed.ncbi.nlm.nih.gov/38892258/. DOI: 10.3390/ijms25116072.
50. Cao N, Feng L, Xu W, et al. Tear glucose is associated with the presence and severity of diabetic retinopathy[J/OL]. Int J Retina Vitreous, 2025, 11(1): 13[2025-02-06]. https://pubmed.ncbi.nlm.nih.gov/39915852/. DOI: 10.1186/s40942-025-00636-x.
51.
52. Stepanov A, Usharova SA, Malsagova KA, et al. Tear proteome revealed association of S100A family proteins and mesothelin with thrombosis in elderly patients with retinal vein occlusion[J/OL]. Int J Mol Sci, 2022, 23(23): 14653[2022-11-24]. https://pubmed.ncbi.nlm.nih.gov/36498980/. DOI: 10.3390/ijms232314653.
53.
54.
55.
56.
57.
58.
59.
60. Shahidatul-Adha M, Zunaina E, Aini-Amalina MN. Evaluation of vascular endothelial growth factor (VEGF) level in the tears and serum of age-related macular degeneration patients[J/OL]. Sci Rep, 2022, 12(1): 4423[2022-03-15]. https://pubmed.ncbi.nlm.nih.gov/35292705/. DOI: 10.1038/s41598-022-08492-7.
61.
62. Sabri K, Ells AL, Lee EY, et al. Retinopathy of prematurity: a global perspective and recent developments[J/OL]. Pediatrics, 2022, 150(3): e2021053924[2022-09-01]. https://pubmed.ncbi.nlm.nih.gov/35948728/. DOI: 10.1542/peds.2021-053924.
63. Magnani JE, Omar M, Mercy P, et al. Quantitative analysis of tear angiogenic factors in retinopathy of prematurity: a pilot biomarker study[J/OL]. J AAPOS, 2023, 27(1): e1-e6[2022-12-26]. https://pubmed.ncbi.nlm.nih.gov/36581150/. DOI: 10.1016/j.jaapos.2022.10.007.
64. Murugeswari P, Vinekar A, Prakalapakorn SG, et al. Correlation between tear levels of vascular endothelial growth factor and vitamin D at retinopathy of prematurity stages in preterm infants[J/OL]. Sci Rep, 2023, 13(1): 16175[2023-09-27]. https://pubmed.ncbi.nlm.nih.gov/37759071/. DOI: 10.1038/s41598-023-43338-w.
65.
66.
67. Wu D, Fan Z, Hu Y, et al. Identifying potential tear biomarkers in premature infants with retinopathy of prematurity based on proteome and transcriptome analysis[J/OL]. Graefe's Arch Clin Exp Ophthalmol, 2025, 2025: E1(2025-06-12)[2025-05-09]. https://pubmed.ncbi.nlm.nih.gov/40343554/. DOI: 10.1007/s00417-025-06838-1. [published online ahead of print].
68.
69. Carre?o E, Portero A, Herreras JM, et al. Cytokine and chemokine tear levels in patients with uveitis[J/OL]. Acta Ophthalmol, 2017, 95(5): e405-e414[2016-11-22]. https://pubmed.ncbi.nlm.nih.gov/27873479/. DOI: 10.1111/aos.13292.

Chinese Journal of Ocular Fundus Diseases

Research progress on the detection of tear markers and application in fundus diseases

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