Glaucoma is a leading cause of irreversible vision loss worldwide. Among its forms, primary open-angle glaucoma (POAG) is particularly insidious, often progressing unnoticed until significant and permanent optic nerve damage has occurred. This disease is commonly associated with increased intraocular pressure, and early detection is crucial to preserving vision before functional impairment becomes evident. Recent advancements in global risk assessment and diagnostic technologies have improved the early identification and management of glaucoma.1 Emerging evidence suggests that systemic inflammation plays a role in the pathogenesis of POAG. Inflammatory markers, including elevated counts of white blood cells (WBC), neutrophils, monocytes, and platelets, have been observed in affected patients. Ratios such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are inexpensive, readily available indicators of systemic inflammation. These markers have been explored as predictors in various conditions, including cancer, cardiovascular diseases, and chronic inflammatory disorders. However, studies examining their association with POAG remain limited. To date, only a few publications have investigated the potential of NLR and PLR as biomarkers in glaucoma, particularly in primary open-angle and pseudoexfoliation glaucoma.2-3 AIM: The aim of this study is to evaluate peripheral blood counts—WBC, neutrophils, monocytes, lymphocytes—as well as NLR, PLR, and LMR in patients with POAG, and to assess the utility of these ratios as simple, accessible indicators for predicting POAG.

This prospective, hospital-based case-control study was conducted over a period of 24 months in the Department of Ophthalmology, Sardar Patel Medical College and P.B.M. Hospital, Bikaner, Rajasthan. The study included 50 patients diagnosed with primary open-angle glaucoma (POAG) who consented to participate. Patients with systemic illnesses or those unwilling to participate were excluded from the study. A simple random sampling technique was used, and sample size determination was carried out using MEDCALC statistical software. A total of 50 cases and 50 age- and gender-matched controls were enrolled. Detailed demographic data and clinical history were recorded, including age, gender, history of surgery or trauma, systemic medical conditions, medication use, and smoking or alcohol consumption status. As part of routine preoperative workup, peripheral blood samples were collected from all participants on the morning of the second day of admission. Hematological parameters, including white blood cell (WBC) count, neutrophil count, lymphocyte count, monocyte count, platelet count, and mean platelet volume (MPV), were measured. Based on these values, several systemic inflammatory indices were calculated to provide additional insight into inflammatory status. These included the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR]. Data analysis was performed using SPSS version 22. For categorical variables, the chi-square test was applied, and for continuous variables, the independent sample t-test was used. A p-value < 0.05 was considered statistically significant.

The mean age of participants in the POAG group was 61.02 ± 9.68 years, while in the control group it was 61.23 ± 9.06 years. The age difference between the two groups was not statistically significant. In terms of gender distribution, males comprised 64.0% of the POAG group and 60.0% of the control group; females comprised 36.0% and 40.0%, respectively. This gender difference was also statistically insignificant. Inflammatory Ratios: Neutrophil-to-Lymphocyte Ratio (NLR): Higher in the POAG group (2.84 ± 1.91) than in controls (1.96 ± 0.84), statistically significant (Table 1). Table 1 Neutrophil to lymphocyte ratio (NLR) wise distribution NLR POAGgroup Control group p-value Mean 2.84 1.96 0.01 SD 1.91 0.84 Platelet-to-Lymphocyte Ratio (PLR): Elevated in the POAG group (2.7 ± 1.39) compared to controls (1.87 ± 0.84), statistically significant (Table 2). Table: 2 Platelet to lymphocyte ratio (PLR) wise distribution PLR POAGgroup Control group p-value Mean 137.96 117.63 0.01 SD 74.39 42.68 Lymphocyte-to-Monocyte Ratio (LMR): Significantly lower in the POAG group (4.34 ± 1.64) than in the control group (5.75 ± 2.22) (Table 3). Table: 3 Lymphocyte to monocytes ratio (LMR) wise distribution LMR POAGgroup Control group p-value Mean 4.32 5.75 0.01 SD 1.64 2.22 Severity Analysis: Neutrophil count, NLR, and WBC levels increased progressively from mild to severe POAG, with statistically significant differences across groups. Interestingly, platelet counts were higher in moderate POAG compared to severe cases (Table 4). Table: 4 Comparison of laboratory parameters with POAG severity Laboratory parameters Mild Moderate Severe p-value WBC(109/L) 5.84±1.63 6.02±1.59 6.31±2.03 0.001 Platelet(109/L) 194.02±52.36 207.42±56.34 193.63±54.32 0.04 Neutrophil(109/L) 3.84±1.40 3.54±1.21 4.21±1.68 0.03 Lymphocyte(109/L) 1.54±0.43 1.58±0.54 1.55±0.49 0.621 Monocyte(109/L) 0.36±0.13 0.37±0.14 0.40±0.16 0.541 NLR 2.56±1.58 2.61±0.98 2.94±1.54 0.01 PLR 132.18± 44.21 147.03± 120.02 135.24±56.32 0.21 LMR 4.39±1.51 4.21±1.52 4.26±1.75 0.01

This study aimed to analyze the peripheral counts of WBC, neutrophils, monocytes, lymphocytes, NLR, PLR, and LMR in patients with primary open-angle glaucoma (POAG), and to evaluate the predictive potential of NLR, PLR, and LMR as simple, accessible inflammatory markers for POAG diagnosis. Our findings revealed that patients with POAG exhibited significantly elevated levels of WBC, neutrophils, monocytes, NLR, and PLR, while platelet count, lymphocyte count, and LMR were significantly lower compared to controls. These results suggest a systemic inflammatory response in POAG, consistent with the hypothesis that inflammation plays a central role in its pathophysiology. Previous studies have supported the involvement of autoimmune mechanisms and active infection-induced inflammation in glaucoma development.4-9 Elevated NLR and PLR levels in POAG patients compared to controls (p < 0.001 and p = 0.04, respectively), along with significantly lower LMR values (p < 0.01), reinforce this inflammatory link. Subgroup analyses based on age and gender consistently demonstrated higher NLR and related inflammatory indices in the POAG group. Furthermore, stratification of POAG patients by disease severity revealed a stepwise increase in NLR and neutrophil levels, indicating a potential correlation between inflammation and disease progression. Our analysis revealed the predictive values (AUC) of NLR, PLR, and LMR for POAG to be 0.01, 0.21, and 0.621, respectively. Notably, NLR showed a positive association with mean deviation (MD) in visual field testing, indicating that it may serve as an independent marker correlated with disease severity. Leibovitch et al. reported elevated CRP levels in patients with normal-tension glaucoma (NTG), suggesting systemic inflammation as a shared feature among glaucoma subtypes. 10 Similar associations were reported by de Voogd et al., Mocan et al., and others, with increased levels of IL-6, IL-1β, TGF-β1, and IL-8 in both aqueous humor and peripheral blood of glaucomatous patients.11-12 These findings support the role of both local and systemic inflammation in glaucomatous optic neuropathy.13-14 Wong et al. further highlighted an increase in IL-2 and IFN-γ expression in the iris of patients with POAG and chronic angle-closure glaucoma, emphasizing immune activation.15 Other studies have reported increased WBC, neutrophil, monocyte, NLR, and PLR in PACG, further underlining the inflammatory basis of various glaucoma subtypes. Astafurov et al. reported that patients with glaucoma exhibited higher oral bacterial counts compared to healthy controls. Furthermore, administration of lipopolysaccharide in animal models of glaucoma led to enhanced axonal degeneration and neuronal loss, suggesting a link between systemic infection and glaucomatous neurodegeneration.16 Interestingly, systemic infections, including elevated oral bacterial counts and Helicobacter pylori infection, have been associated with higher WBC and neutrophil counts in glaucoma patients. A meta-analysis by Zeng et al. confirmed a significant association between H. pylori infection and open-angle glaucoma, suggesting systemic infections may contribute to glaucomatous inflammation.17 Inflammatory mediators can disrupt the trabecular meshwork, leading to increased intraocular pressure (IOP). While our study did not directly assess cytokine levels, prior research has shown that pro-inflammatory cytokines and acute-phase proteins may act not only as biomarkers but also as active mediators in glaucoma pathogenesis.18-21 Our findings align with those of Binghua Tang et al., who reported elevated NLR, PLR, and systemic immune-inflammation index (SII) in POAG patients. Similarly, Cem Ozgonul et al. demonstrated significant differences in NLR (p = 0.003) and PLR (p = 0.049) between POAG patients and controls, with ROC analysis yielding an AUC of 0.651 for NLR (cutoff: 2.1; sensitivity: 65%, specificity: 65%).22 Our results are consistent with these findings and support the potential use of NLR and PLR as clinical biomarkers. Additionally, we observed that WBC, neutrophils, and NLR were positively associated with POAG severity, whereas LMR was negatively associated. These results suggest that systemic inflammation may influence retinal ganglion cell damage in glaucoma. Secondary neurodegeneration, involving complement-mediated microglial activation, is increasingly recognized in glaucoma. Chronic inflammation, microglial priming, and prolonged exposure to pro-inflammatory cytokines may contribute to progressive optic nerve damage over time. This supports the observed association between inflammatory markers and disease severity in our study. We also found lower platelet counts in POAG patients, which may result from platelet activation and release of inflammatory mediators into ocular tissues. Platelets contribute to leukocyte recruitment and vascular inflammation, which may play a role in glaucoma development. Monocytes, as key cytokine producers, are known to mediate chronic inflammation. While monocyte counts were slightly elevated in POAG patients in our study, their exact role in disease progression remains to be fully elucidated and warrants further research. Currently, NLR and LMR are being increasingly recognized as reliable, cost-effective biomarkers for systemic inflammation in various ocular diseases, including POAG, pseudoexfoliation syndrome, age-related macular degeneration, and retinal vein occlusion.

This study demonstrates that systemic inflammatory markers—particularly WBC, neutrophils, NLR, and LMR—are significantly associated with the presence and severity of primary open-angle glaucoma (POAG). Elevated NLR and decreased LMR may serve as potential adjunctive indicators for POAG diagnosis and progression. While these markers alone are not diagnostic, they offer valuable insights when used in conjunction with traditional ophthalmologic assessments. Our findings support the hypothesis that inflammation contributes to glaucoma pathogenesis and highlight the potential utility of NLR and LMR as simple, cost-effective biomarkers in clinical practice. Further prospective, multicenter studies are warranted to validate their diagnostic and prognostic value.

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