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Table 1 Characteristics of included study

From: Exploring leukocyte differential count ratio profiles as inflammatory biomarkers in diabetic retinopathy: a systematic review and meta-analysis

No.

Author, Year

Design Study

Age (mean ± SD, years)

Population

Diagnosis of DR

DR groups

Differential Count Ratio Profile

Findings

1

Abdullah, 2021 [15]

case–control

DR 7.36 ± 8.35; no DR 55.24 ± 10.83

India

ICDR severity scales

no DR and DR

NLR

NLR were higher in DR group

2

Akdogan, 2016 [16]

retrospective cohort

59.8 ± 9.2

Turkey

dilated funduscopy

control, DM without DR, DM with DR

NLR and PLR

PLR were higher in DR compared to control. No difference in NLR group

3

Atli, 2022 [17]

cross-sectional

NPDR 61.44 ± 6.25; PDR 60.86 ± 4.70; no DR 56.15 ± 10.03; control 43.10 ± 7.82

Turkey

digital fundus based on ETDRS

control, no DR, NPDR and PDR

NLR and PLR

higher NLR and PLR in PDR group

4

Bhattacharyya, 2021 [18]

cross-sectional

59.89 ± 10.9

India

ICDR severity scale

DM with nephropathy, neuropathy, and retinopathy

NLR

NLR higher in DM with more than one microvascular complication

5

Chittawar, 2017 [19]

cross-sectional

51.12 ± 11.28

India

comprehensive assessment include dilated funduscopy and fundus FA based on ETDRS

DM only

NLR

Higher quartile NLR (2.60–6.28) increase DR incidence

6

Cardoso, 2021 [20]

prospective cohort

60.0 ± 9.6

Brazil

comprehensive assessment includes dilated funduscopy, OCT macula based on ICDR severity scale

microvascular DR and macrovascular complications

NLR, PLR, MLR

no hematological parameter was predictive of any microvascular outcome including retinopathy

7

Ciray, 2015 [21]

cross-sectional

59.7 ± 11.3

Turkey

dilated funduscopy based on ICDR severity scale

NPDR and PDR

NLR

Higher NLR was not associated with DR and severity of DR

8

Dascalu AM, 2023 (a) [11]

retrospective cohort

no DR 66.9 ± 5.76; NPDR 66.4 ± 6.07; PDR 62.0 ± 10.59

Romania

Visual Evoked Potentials

no DR, NPDR, PDR

NLR, PLR

Higher NLR associated with PDR. PLR were not different statistically among groups

9

Dascalu AM, 2023 (b) [10]

retrospective cohort

65.6 ± 8.9

Romania

examination microdots, blot hemorrhage, hard exudates, soft exudates, and new vessel formation

no DR, NPDR, PDR

NLR, PLR, MLR, SII

Higher NLR, MLR, MPV, and SII associated with PDR group. PLR were not associated with DR

10

Dogan, 2024 [22]

retrospective cohort

no DR 53.1 ± 6.9; NPDR 54.3 ± 7.1; PDR 55.7 ± 5.9; control 53.8 ± 7.4

Turkey

comprehensive examination include dilated fundus and fundus photography

control, no DR, NPDR and PDR

NLR, MLR, PLR, SII

NLR, PLR and SII were higher in NPDR and PDR groups. MLR were not significantly higher in NPDR or PDR group

11

El-Tawab, 2023 [23]

case–control

DR 50.48 ± 7.98; control 52.47 ± 8.85

Egypt

N/A

PDR and no PDR

NLR

NLR associated with DR

12

Fawwad, 2018 [24]

retrospective cohort

no DR 52.33 ± 11.05; microvascular complications 55.86 ± 10.72

Pakistan

digital retina photographs

no DR and DR

NLR

NLR associated with DR

13

Gao Y, 2024 [25]

retrospective cohort

no DR 53.78 ± 1.88; NPDR 51.72 ± 1.64; PDR 53.00 ± 1.52

China

fundus photography, FFA, and OCT based on ICDR severity scale

no DR, NPDR, PDR

NLR, PLR, SII

NLR, PLR and SII were associated with DR and DR stages

14

He X, 2022 [26]

cross-sectional

61.3 ± 13.2

US

comprehensive asessment based on ETDRS and ICDR severity scale

no DR and DR

NLR

NLR associated with DR

15

Huang Q, 2021 [27]

cross-sectional

61 ± 13.85

China

N/A

control, DM without DR, NPDR, PDR,

MLR

MLR were higher in PDR group

16

Ilhan C, 2019 [28]

Prospective case–control

Control 62.68 ± 10.40; NPDR 61.14 ± 9.33; PDR 59.63 ± 7.07

Turkey

based on IAO in 2002

control, severe NPDR, PDR

NLR, MLR, PLR

NLR associated with DR. MLR and PLR were not different among groups

17

Ilhan C, 2020 [29]

prospective cohort

control 63.54 ± 5.68; DME 58.22 ± 11.35; non-DME 61.92 ± 6.82

Turkey

fundus examination

control, NPDR with DME, NPDR without DME

NLR, MLR, PLR

NLR and MPV/L were higher in DME group. MLR and PLR were not different among groups

18

Lei C, 2023 [30]

cross-sectional

55.46 ± 10.08

China

medical records

PDR with DME, PDR without DME

NLR, PLR, MLR, SII

NLR, PLR, LMR, and SII were not associated with CMT/DME

19

Li J, 2024 [13]

cross-sectional

54.67 ± 12.86

China

non-mydriatic fundus photography based on ICDR severity scale

no DR and DR

NLR, PLR, SII

NLR, PLR and SII were associated with DR

20

Mahajan, 2023 [31]

prospective cohort

56.3 ± 13.24

India

dilated funduscopy based on ICDR severity scale

DR

NLR

Higher NLR in DR group. NLR associated with increased risk of microvascular complications

21

Moursy, 2015 [32]

retrospective cohort

DR 56.19 ± 7.27; no DR 53.60 ± 6.15; control 53.50 ± 6.66

Egypt

based on Global DR Project Group

no DR, NPDR, PDR

NLR

NLR were significantly higher in NPDR and PDR group compared to no DR. NLR were not significantly higher in PDR compared to NPDR

22

Ozturk, 2013 [33]

cross-sectional

DR 66.60 ± 4.20; no DR 66.78 ± 4.12

Turkey

non-mydriatic fundus photography based on ETDRS

no DR and DR

NLR

NLR were higher in diabetic group with complications

23

Rajendrakumar AL, 2023 [34]

retrospective cohort

61.7 ± 12.7

Scottish

based on ICDR severity scale

developed DR, death without DR, no DR

NLR

NLR associated with DR

24

Sari, 2021 [35]

case–control

N/A

Indonesia

based on ICDR severity scale

no DR, NPDR, PDR

NLR, PLR, MLR

NLR and PLR were not significantly higher in DR. MLR were insignificantly lower in DR compared to control

25

Tang Y, 2024 [36]

retrospective cohort

no DR 47.3 ± 11.2; DR 52.4 ± 10.9

China

dilated fundus, FA, and SD-OCT

no DR and DR

NLR

NLR associated with DR

26

Ulu SM, 2013 [37]

cross-sectional

control 48.38 ± 5.45; DM 50.31 ± 5.20

Turkey

undilated fundus

control, DM without DR, DM with DR

NLR

Higher NLR associated with DR and correlated with DR grades

27

Wan H, 2020 [38]

cross-sectional

67 ± 9

China

non-mydriatic fundus photography by ophthalmologist based on ICDR severity scale

DR, NPDR, PDR

NLR

Higher NLR were not associated with prevalence of DR

28

Wang H, 2022 [14]

cross-sectional

63.8 ± 10.8

US

dilated funduscopy and OCT based on ETDRS

no DR, NPDR, PDR

MLR

MLR were associated with PDR

29

Wang JR, 2020 [39]

cross-sectional

no DR 55.44 ± 11.27; DR 56.48 ± 9.86

China

dilated color fundus photography

no DR and DR

NLR, PLR, MLR

NLR and PLR associated with DR. MLR were not associated with DR

30

Wang RT, 2015 [40]

cross-sectional

control 58.7 ± 5.9; no DR 60.3 ± 6.0; DR 66.6 ± 5.8

China

N/A

control, DM without DR, DM with DR

NLR

NLR were higher in DR group

31

Wang S, 2023 [41]

cross-sectional

no DR 59 ± 4.25 DR 60, 3.43

China

N/A

no DR and DR

SII

SII were higher in DR groups and associate dwith DR

32

Xiaodong L, 2023 [42]

cross-sectional

57.8 ± 10.52

China

N/A

NPDR, PDR, NPDR with DN, and PDR with DN

NLR and PLR

NLR and PLR were higher in DR with DN compared to DR group only

33

Yanxia C, 2024 [43]

retrospective cohort

early 59.06 ± 11.74; advanced 60.34 ± 9.65; severe 61.37 ± 8.59; atrophic 61.71 ± 13.11

China

N/A

early, advanced, severe and atrophic DME

NLR, MLR, PLR, SII

SII and the decline in SRF and HRF ≥ were associated with DME stages

34

Yeter DY, 2022 [44]

retrospective cohort

63 ± 8.5

Turkey

N/A

DR without DME, DR with DME, DM without DR/DME

NLR and MHR

NLR and MHR were associated with DME

35

Yue Song, 2015 [45]

case–control

no DR 55.75 ± 11.11; NPDR 53.31 ± 10.56; PDR 56.00 ± 8.89

China

funduscopy based on ISO

DM without DR, NPDR, PDR

NLR, MLR, PLR

Higher NLR and PLR in DR group. Only MLR were associated with DR independently

36

Zeng J, 2022 [46]

retrospective cohort

no DR 55.23 ± 10.19; NPDR 57.69 ± 9.56; PDR 55.83 ± 8.18

China

Medical records

control, NPDR, PDR

NLR, MLR, PLR

NLR, PLR, MLR were higher in DR groups. Only PLR were associated with DR risk independently

37

Zhang P, 2021 [47]

cross-sectional

DR 68.33 ± 8.40; no DR 68.10 ± 8.47

China

dilated fundus

no DR and DR

NLR

NLR were higher in DR group

38

Zhu Y, 2022 [48]

retrospective cohort

no-DME 56.38 ± 10.51; DME 56.00 ± 8.25

China

OCT based on ESASO classification

severe DR with DME, severe DR without DME

NLR, MLR, PLR

NLR, PLR, MLR, MHR was not different among groups

  1. DME Diabetic Macular Edema, DR Diabetic Retinopathy, FFA Fundus Fluorescein Angiography, ICDR International Clinical Diabetic Retinopathy and Diabetic Macular Edema Disease, IAO International Academy of Ophthalmology, ISO International Society of Ophthalmology, MLR Monocyte-to-lymphocyte Ratio, NLR Neutrophil-to-lymphocyte Ratio, OCT Optical Coherence Tomography, PLR Platelet-to-lymphocyte Ratio, NPDR Non-Proliferative Diabetic Retinopathy, PDR Proliferative Diabetic Retinopathy; SII: Systemic Immune-Inflammation Index
  2. N/A Not available