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Table 2 Characteristics of studies included in meta-analysis

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

Reference; country

Tear sample collection method

Method of quantification

Participants in the Control group

Participants in the Diabetes group

Participants in the Complications group

Reported biomarkers

Number of participants

Sex

Age (years) Presented as mean ± SD or range or median (IQR)

Number of participants

Sex

Age (years) Presented as mean ± SD or range or median (IQR)

Complication; number of participants

Sex

Age (years) Presented as mean ± SD or range or median (IQR)

Mei et al [37]; China

Capillary collection strip

Electrochemical platform; ELISA

5

-

-

-

-

-

DR: 5

-

-

VEGF

Sorkhabi et al [41]; Iran

Capillary tube

ELISA

20

8 M and 12 F

46.05+13

20

12 M and 8 F

47.75+5.6

NPDR: 25; PDR: 25

NPDR: 13 M and 12 F; PDR: 10 M and 15 F

NPDR: 52.04+8.7; PDR: 52.92+10.1

TNF-α, IL-8 and IL-1RA

Liu et al [42]; China

Glass capillary tube

ELISA; mulitplex cytokine analysis

15

8 M and 7 F

59+2.42

15

8 M and 7 F

61.27+1.95

DR: 15

7 M and 8 F

61.07±2.16

IL-1β, IL-1RA, IL-6, IL-8, IL-10, VEGF and MCP-1

Azhan et al [43]; Malaysia

Schirmer strip

ELISA

33

19 M and 14 F

69.6+7.5

-

-

-

NPDR: 32

18 M and 14 F

67.3+7.0

VEGF

Ang et al [52]; USA

Schirmer strip

Human immunoassay kit

-

-

-

30

17 M and 13 F

64.6+8.8

NPDR: 28; PDR: 30

NPDR: 11 M and 17 F; PDR: 16 M and 14 F

NPDR: 58.5+8.2; PDR: 52.3+9.6

VEGF

Kim et al [44]; South Korea

Capillary tube

Multiplex immunobead assay; magnetic luminex screening assay

30

15 M and 15 F

67.5 (60–72)

30

7 M and 23 F

70 (63–74)

-

-

-

MCP-1, IL-6, IL-8, and VEGF

Manchikanti et al [38]; India

10 μl micropipette tip attached to a plastic pipette

ELISA

21

19 M and 2 F

51.33±10.683

-

-

-

NPDR: 10; PDR: 11

19 M and 2 F

54.59±11.58

TNF-α and IL-1β

Amorim et al [26]; Portugal

Schirmer I test

BCA protein assay kit; LC-MS/MS; multiplex analysis

12

3 M and 9 F

54±11

13

7 M and 6 F

59±11

NPDR: 25; PDR: 16

NPDR: 18 M and 7 F; PDR: 13 M and 3 F

NPDR: 65±9; PDR: 66±6

IL-1β and IL-6

Byambajav et al [39]; UK

Glass capillary micropipette

Magnetic bead panel

17

6 M and 11 F

52+16

41

25 M and 16 F

62+21

DED: 47

29 M and 18 F

64+16

IL-6, TNF-α, VEGF, IL-1β, IL-1RA, and IL-8

Zhou et al [45]; China

Glass capillary tube

Immune bead–based array

22

10 M and 12 F

57.32±9.66

-

-

-

DR: 48

29 M and 19 F

59.15 ± 9.51

TNF-α and IL-6

Liu et al [40]; China

Glass capillary micropipette

Multiplex bead analysis

29

5 M and 24 F

62.4±7.5

24

7 M and 17 F

63.5±10.1

DED: 32

14 M and 18 F

61.8±9.8

TNF-α and IL-1β

Hashemi et al [46]; Iran

Schirmer's standard strip

ELISA

30

15 M and 15 F

56.90±8

30

16 M and 14 F

58.8±7.74

DR: 30

14 M and 16 F

62.2±7.0

VEGF

Machalińska et al [47]; Poland

Schirmer's standard strip

Multiplex fluorescent bead-based immunoassays, High sensitivity cytokine assay

52

25 M and 27 F

63+12

-

-

-

DR: 52

35 M and 17 F

65+11.5

TNF- α, VEGF, IL-1β, IL-6, and IL-8

Sheikhrezaee et al [28]; Iran

Schirmer's standard strip

ELISA

30

15 M and 15 F

56.9±8

30

16 M and 14 F

58.8±7.8

DR: 30

14 M and 16 F

62.2±7

VEGF

Costagliola et al [27]; Italy

Schirmer's standard strip

ELISA

16

8 M and 8 F

53 (47-58)

-

-

-

NPDR: 16; PDR: 16

NPDR: 9 M and 7 F; PDR: 10M and 6 F

NPDR: 54 (49-67); PDR: 59 (52-73)

TNF-α

Amil-Bangsa et al [48]; Malaysia

Glass capillary tube

ELISA

-

-

-

15

8 M and 7 F

58.3±4.8

Mild NPDR: 15; moderate NPDR: 15; severe NPDR: 15

Mild: 6 M and 9 F, moderate: 9 M and 6 F; severe 12 M and 3 F

Mild: 57.0±4.8; moderate: 58.9±4.7; severe: 57.5±4.8

TNF-α

Stolwijk et al [49]; Netherlands

Glass capillary tube

Bradford's assay, HPLC, SDS-PAGE

26

-

39.7+11.5

25

-

33.4+12.1

DR: 29

-

46.3+10.4

LTF and LZM

Zou et al [50]; China

Schirmer I test

TMT Labeling, HPLC, LC-MS

5

2 M and 3 F

54.80±6.06

-

-

-

DED: 10

4 M and 6 F

55.50±4.79

LTF and LZM

Yu et al [51]; China

Glass microcapillary tube

Lowry method, SDS-PAGE

67

32 M and 35 F

-

-

-

-

NPDR: 70; PDR: 63

NPDR: 36 M and 34 F; PDR: 31 M and 35 F

-

LTF and LZM

Total participants: 1413

430

273

710

 
  1. Characteristics of 19 studies included in the meta-analysis
  2. BCA bicinchoninic acid, DED dry eye disease, DR diabetic retinopathy, ELISA enzyme-linked immunosorbent assay, EV extracellular vesicle, F female, HPLC high-performance liquid chromatography, IL-1β interleukin-1 beta, IL-1RA interleukin-1 receptor antagonist, IL-6 interleukin-6, IL-8 interleukin-8, LC-MS/MS liquid chromatography-mass spectrometry/mass spectrometry, LTF lactoferrin, LZM lysozyme, M male, MCP-1 monocyte chemoattractant protein-1, NPDR non-proliferative diabetic retinopathy, PDR proliferative diabetic retinopathy, SDS-PAGE sodium dodecyl-polyacrylamide gel electrophoresis, TBUT tear break up time, TMT tandem mass tag, TNF-α tumor necrosis factor-alpha, VEGF vascular endothelial growth factor