Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 May 1;25(1):265.
doi: 10.1186/s12886-025-04075-y.

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

Ohisa Harley  1   2 , Yufilia Suci Amelia  3 , Elsa Gustianty  3   4   5 , Nanny N M Soetedjo  6 , Arief S Kartasasmita  3   4   5
Affiliations
Meta-Analysis

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

Ohisa Harley et al. BMC Ophthalmol. .

Abstract

Background: Diabetic retinopathy (DR) is increasingly prevalent and a major cause of irreversible blindness, particularly in developing countries. Limited access to ophthalmologists often leads to delayed diagnosis, emphasizing the need for more affordable and widely accessible screening methods to facilitate early identification. Recently, several studies have demonstrated variability in findings regarding the relationship between leukocyte differential count ratio biomarkers and DR. This study aims to investigate the association between leukocyte differential count ratios-NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), MLR (Monocyte-to-Lymphocyte Ratio), and SII (Systemic Immune-Inflammation Index)-and the stages of diabetic retinopathy (DR).

Methods: A comprehensive literature search was conducted across several databases up to September 2024, with a focus on identifying studies examining the relationship between the leukocyte differential count ratio profiles and diabetic retinopathy. Review Manager was used to conduct the meta-analyses. The Newcastle Ottawa Scale (NOS) were used to assess the included studies.

Results: A total of 38 studies were included in the systematic review and 27 studies were included in the meta-analysis. The mean differences in the NLR and PLR values were significantly different among the groups and were higher in the PDR group (0.68 (95%CI 0.42-0.95, p < 0.05) and 19.57 (95%CI 10.68-28.46, p < 0.05; respectively). These findings were followed by significant differences in SII value 202.53 (95% CI 196.19-208.86, p < 0.05). Moreover, the MLR values were not significantly different among the groups (p > 0.05).

Conclusion: NLR, PLR, and SII are associated with both the presence and progression of DR, with increasing levels of NLR and PLR reflecting a higher risk and severity of the disease. However, it is still necessary to justify the need to combine them with other clinical parameters to confirm the diagnosis.

Keywords: Biomarker; Diabetic retinopathy; Lymphocyte; Monocyte; Neutrophil; Platelet.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA diagram flow
Fig. 2
Fig. 2
Forrest plot and subgroup analysis of NLR in NPDR and PDR groups. NLR: Neutrophil-to-lymphocyte Ratio; NPDR: Non-Proliferative Diabetic Retinopathy; PDR: Proliferative Diabetic Retinopathy
Fig. 3
Fig. 3
Forrest plot and subgroup analysis of PLR in NPDR and PDR groups. PLR: Platelet-to-lymphocyte Ratio; NPDR: Non-Proliferative Diabetic Retinopathy; PDR: Proliferative Diabetic Retinopathy
Fig. 4
Fig. 4
Forrest plot and subgroup analysis of MLR in NPDR and PDR groups. MLR: Monocyte-to-lymphocyte Ratio; NPDR: Non-Proliferative Diabetic Retinopathy; PDR: Proliferative Diabetic Retinopathy
Fig. 5
Fig. 5
Forrest plot and subgroup analysis of SII in NPDR and PDR groups. Systemic immune-inflammation index; NPDR: Non-Proliferative Diabetic Retinopathy; PDR: Proliferative Diabetic Retinopathy
Fig. 6
Fig. 6
Risk of bias of included study
Fig. 7
Fig. 7
Funnel plots. A Funnel plots of NLR in DR. B Funnel Plots of NLR in NPDR and PDR. C Funnel plots of PLR in DR. D Funnel Plots of PLR in NPDR and PDR. E Funnel plots of MLR in DR. F Funnel Plots of MLR in NPDR and PDR. G Funnel Plots of SII in DR, NPDR and PDR. MLR: Monocyte-to-lymphocyte Ratio; NLR: Neutrophil-to-lymphocyte Ratio; PLR: Platelet-to-lymphocyte Ratio; NPDR: Non-Proliferative Diabetic Retinopathy; PDR: Proliferative Diabetic Retinopathy
Fig. 8
Fig. 8
Meta-regression analysis in DR subgroup. A and B Meta-regression of HbA1c and Duration of Diabetes based on NLR values. The regression line indicates a slight positive trend between HbA1c and NLR, while showing a slight negative trend between diabetes duration and NLR. C and D Meta-regression of HbA1c and Duration of Diabetes based on PLR values. The regression line demonstrates a negative trend between HbA1c and PLR, whereas it exhibits a positive trend between diabetes duration and PLR. HbA1c: Hemoglobin A1 C; NLR: Neutrophil-to-lymphocyte Ratio; PLR: Platelet-to-lymphocyte Ratio
See this image and copyright information in PMC

References

    1. Sasongko MB, Widyaputri F, Agni AN, Wardhana FS, Kotha S, Gupta P, et al. Prevalence of Diabetic Retinopathy and Blindness in Indonesian Adults With Type 2 Diabetes. Am J Ophthalmol. 2017;181:79–87. Available from: http://www.ajo.com/article/S0002939417302714/fulltext. Cited 2024 Jun 27. - PubMed
    1. Teo ZL, Tham YC, Yu M, Chee ML, Rim TH, Cheung N, et al. Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis. Ophthalmology. 2021;128(11):1580–91. Available from: http://www.aaojournal.org/article/S0161642021003213/fulltext. Cited 2024 Jul 3. - PubMed
    1. Bianco L, Arrigo A, Aragona E, Antropoli A, Berni A, Saladino A, et al. Neuroinflammation and neurodegeneration in diabetic retinopathy. Front Aging Neurosci. 2022Aug;16(14):937999. - PMC - PubMed
    1. Yu Y, Chen H, Su SB. Neuroinflammatory responses in diabetic retinopathy. J Neuroinflammation. 2015;12(1):1–15. Available from: https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-015.... Cited 2024 Mar 7. - DOI - PMC - PubMed
    1. Wu F, Phone A, Lamy R, Ma D, Laotaweerungsawat S, Chen Y, et al. Correlation of Aqueous, Vitreous, and Plasma Cytokine Levels in Patients With Proliferative Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2020;61(2). Available from: https://pubmed.ncbi.nlm.nih.gov/32084272/. Cited 2024 Aug 17. - PMC - PubMed

LinkOut - more resources