Changes in neutrophil-to-lymphocyte ratio in different subtypes of diabetic retinopathy

Authors:Wang Manqiao, Liu Boshi, Li Xiaorong

Corresponding author: Li Xiaorong, Email: xiaorli@163.com

Published:2026-09-10

DOI: 10.3760/cma.j.cn115989-20260331-00149

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ABSTRACT 

Objective To investigate the changes in the neutrophil-to-lymphocyte ratio (NLR) in different subtypes of diabetic retinopathy (DR).

Methods A case-control study was conducted. From September 2023 to May 2024, 174 patients with DR and 57 patients with simple age-related cataract were enrolled at Tianjin Medical University Eye Hospital. According to the DR subtype, the patients were divided into a chronic progression group ( n=52), an inflammatory leakage group ( n=68), and a neovascular group ( n=54). Hematological parameters were collected, including glycated hemoglobin, triglycerides, cholesterol, creatinine, urea, hemoglobin, mean platelet volume, hematocrit, neutrophils, lymphocytes, NLR, platelets, and the platelet-to-lymphocyte ratio (PLR). Differences in these parameters among the groups were compared. Logistic regression analysis was used to assess the association between NLR and DR subtypes under different models. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance of different models for discriminating DR subtypes. After gradual adjustment of variables, an unadjusted univariate model and models Ⅰ and Ⅱ after adjusting different parameters were constructed. Glycated hemoglobin, triglycerides, cholesterol, urea, and creatinine were adjusted in Model Ⅰ. Hemoglobin, mean platelet volume, hematocrit, and platelets were adjusted in Model Ⅱ based on Model Ⅰ. The study adhered to the principles of the Declaration of Helsinki. The research protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No. 2024KY-15). Written informed consent was obtained from all patients.

Results No statistically significant differences were found among the control, chronic progression, inflammatory leakage, and neovascular groups in triglycerides, platelets, or cholesterol ( H=6.347, 2.039; F=2.538; all P>0.05). However, significant differences were observed among the four groups in urea, creatinine, mean platelet volume, absolute neutrophil count, absolute lymphocyte count, NLR, PLR, hemoglobin, and hematocrit ( H=28.162, 15.537, 12.602, 23.095, 12.017, 41.923, 12.587; F=4.153, 4.614; all P<0.05). Regarding the inflammatory markers NLR and PLR, NLR showed a progressively increasing trend across the control, chronic progression, inflammatory leakage, and neovascular groups, with statistically significant pairwise comparison differences (all P<0.05). The PLR in the neovascular group was higher than that in the control group and the chronic progression group, and the PLR in the inflammatory leakage group was higher than that in the chronical progression group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that NLR was independently related to the occurrence and subtype progression of DR, and the intensity of the association increased with the severity of the disease. Compared with the control group, the odds ratios ( OR) of DR group in univariate model, Model Ⅰ, and Model Ⅱ were 3.274, 19.211, and 96.640, respectively (all P<0.01). In the comparison of subtypes, chronic progression group compared with the inflammatory leakage group, NLR was an independent risk factor after adjusting for confounding factors (Model Ⅰ: OR=1.553, P=0.032; Model Ⅱ: OR=1.622, P=0.026); chronic progression group compared with the neovascular group, all the models suggested that the NLR and DR subtypes were independently correlated ( OR=2.259-2.354, all P<0.01); there was no statistically correlation between NLR and DR subtypes in the inflammatory leakage group and the neovascular group ( P>0.05). ROC curve analysis showed that, compared the control group and the DR group, the area under the ROC curve (AUC) of univariate model for NLR in diagnosing DR was 0.711, and the AUC of Model Ⅰ and Model Ⅱ was 0.992 and 0.996 respectively (all P<0.001); in the chronic progression group and the inflammatory leakage group, the AUC of univariate model for NLR in diagnosing DR subtypes was 0.613 ( P=0.056), and the AUC of Model Ⅰ and Model Ⅱ were 0.689 and 0.724 respectively (both P<0.01); in the chronic progression group and the neovascular group, the AUC of univariate model, Model I, and Model Ⅱ for NLR in diagnosing DR subtypes were 0.740, 0.783, and 0.780 respectively (all P<0.001). The AUC of each model for NLR in diagnosing DR subtypes ranged from 0.596 to 0.642 in the inflammatory leakage group and the neovascular group, among which there was no statistical significance in model Ⅰ ( P=0.102), but there were statistical significances in the univariate model and Model Ⅱ (both P<0.05).

Conclusions Significant differences in NLR exist among different DR subtypes, and NLR shows good diagnostic efficacy in distinguishing various DR subtypes.KEYWORDS：

KEYWORDS：

Diabetic retinopathy;Neutrophil-to-lymphocyte ratio;Platelet-to-lymphocyte ratio;Regression analysis;ROC curve

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Authors Info & Affiliations 

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Figures & Tables

Table 1 Comparison of baseline characteristics among different groups Note: (*: Kruskal-Wallis rank-sum test; #: χ² test)　Diabetes duration and HbA1c levels were only analyzed in the chronic progression, inflammatory leakage, and neovascular groups　HbA1c: glycated hemoglobin

Table 2 Comparison of hematological parameters among the four groups Note: Compared with control group, ^aP<0.05; compared with chronic progression group, ^bP<0.05; compared with inflammatory leakage group, ^cP<0.05 (*: Kruskal-Wallis rank-sum test, Dunn test; #: One-way ANOVA)　MPV: mean platelet volume; HCT: hematocrit; NEUT: absolute neutrophil count; LYMPH: absolute lymphocyte count; NLR: neutrophil-to-lymphocyte ratio; PLR: platelet-to-lymphocyte ratio

Table 3 Multivariable logistic regression analysis of the association between NLR and DR subtypes under different models Note: Model Ⅰ adjusted HbA1c, triglcerides, cholesterol, urea, and creatinine; Model Ⅱ adjusted hemoglobin, MPV, HCT, and platelets based on Model Ⅰ　NLR: neutrophil-to-lymphocyte ratio; DR: diabetic retinopathy; OR: odds ratio; CI: confidence interval; HbA1c: glycated hemoglobin; MPV: mean platelet volume; HCT: hematocrit

Figure 1 Schematic diagram of fundus changes in patients with different subtypes of DR 　A: Chronic progression type　B: Inflammatory leakage type　C: Neovascular type　DR: diabetic retinopathy

Figure 2 ROC curve analysis results for the diagnostic value of NLR in differentiating DR subtypes under different models 　A: Control group vs all DR subtypes combined　B: Chronic progression group vs inflammatory leakage group　C: Chronic progression group vs neovascular group　D: Inflammatory leakage group vs neovascular group　NLR: neutrophil-to-lymphocyte ratio; DR: diabetic retinopathy; ROC: receiver operating characteristic

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