Comparison of NLR, PLR, SII, and SIRI for Discriminating Severe Primary Open-Angle Glaucoma in a Cross-Sectional Study
Main Article Content
Introduction. Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness, with a 3.0% national blindness prevalence. Chronic low-grade inflammation is increasingly implicated in POAG, but few studies compare how these indices track severity rather than detect it. Objective. To compare the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammatory response index (SIRI) in discriminating severe from mild/moderate POAG. Methods. This cross-sectional study enrolled 45 patients (90 eyes) at Dr. Mohammad Hoesin Hospital. Severity was staged by the Hodapp-Parrish-Anderson classification and dichotomized as severe (48 eyes) versus mild/moderate (42 eyes), with the four indices derived from complete blood counts. Analyses used generalized estimating equations (GEE) for within-patient eye clustering. Results. Patients averaged 57.4±10.3 years, 60.0% female, with 53.3% of eyes (48/90) severe. All four indices remained associated with severity under GEE (p<0.05; SIRI p=0.043, the narrowest margin). On non-clustered ROC analysis, SII showed the highest AUC (0.803) and accuracy (80.0%), ahead of NLR (0.785), PLR (0.729), and SIRI (0.622). Bootstrap validation (500 replications) confirmed these cut-offs and AUCs; only the NLR-SIRI AUC gap reached significance (p=0.032–0.052), with SII-SIRI borderline (p=0.044–0.060). Conclusion. All four indices remained associated with severity after clustering adjustment, with SIRI's margin consistently the narrowest. SII showed the highest apparent discriminative performance, and bootstrap validation supports a real AUC disadvantage for SIRI versus NLR; broader superiority among the other three remains unestablished pending external validation. None of the four markers should replace intraocular pressure measurement or structural-functional evaluation.
Keywords:
Primary open-angle glaucoma
Neutrophil-to-lymphocyte ratio
Platelet-to-lymphocyte ratio
Systemic immune-inflammation index
Systemic inflammatory response index
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8. Ulhaq ZS, Istifiani LA, Pamungkas SA. Evaluation of Systemic IL-6 Trans-Signaling in Patients with Primary-Open Angle Glaucoma. J Fr Ophtalmol. 2023;46(6):622–9. doi:10.1016/j.jfo.2022.11.022 PubMed PMID: 37095023.
9. Jung Y, Ohn K, Shin H, Oh SE, Park CK, Park HYL. Factors Associated with Elevated Tumor Necrosis Factor-α in Aqueous Humor of Patients with Open-Angle Glaucoma. J Clin Med. 2022;11(17):5232. doi:10.3390/jcm11175232
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12. Li X, Sun YQ, Zhong XD, Zhang ZJ, Tang JF, Luo ZY. Association between systemic inflammatory response index and glaucoma incidence from 2005 to 2008. Front Med (Lausanne). 2025;12. doi:10.3389/FMED.2025.1542073 PubMed PMID: 39967596.
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18. Seth PK, Senthil S, Das AV, Garudadri C. Prevalence of glaucoma types, clinical profile and disease severity at presentation: Tertiary Institute based cross-sectional study from South India. Indian J Ophthalmol. 2023 Oct 1;71(10):3305–12. doi:10.4103/IJO.IJO_3305_22 PubMed PMID: 37787226.
19. Tang B, Li S, Han J, Cao W, Sun X. Associations between Blood Cell Profiles and Primary Open-Angle Glaucoma: A Retrospective Case-Control Study. Ophthalmic Res. 2020;63(4):413–22. doi:10.1159/000504450 PubMed PMID: 32018245.
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21. Thirunavukarasu AJ, Jain N, Sanghera R, Lattuada F, Mahmood S, Economou A, et al. A validated web-application (GFDC) for automatic classification of glaucomatous visual field defects using Hodapp-Parrish-Anderson criteria. NPJ Digit Med. 2024 Dec 1;7(1). doi:10.1038/S41746-024-01122-8 PubMed PMID: 38762669.
22. Poli M. Comparison of the Real-world Performance of Henson 9000 Perimeter and Humphrey Field Analyzer in Glaucoma Patients. J Curr Glaucoma Pract. 2025 Jan 1;19(1):55–63. doi:10.5005/JP-JOURNALS-10078-1470 PubMed PMID: 40417145.
23. Zaharia AC, Dumitrescu OM, Radu M, Rogoz RE. Adherence to Therapy in Glaucoma Treatment-A Review. J Pers Med. 2022 Apr 1;12(4). doi:10.3390/JPM12040514 PubMed PMID: 35455630.
24. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology. 2014 Nov 1;121(11):2081–90. doi:10.1016/j.ophtha.2014.05.013 PubMed PMID: 24974815.
25. Tezel G. Multifactorial Pathogenic Processes of Retinal Ganglion Cell Degeneration in Glaucoma towards Multi-Target Strategies for Broader Treatment Effects. Cells. 2021 Jun 1;10(6). doi:10.3390/CELLS10061372 PubMed PMID: 34199494.
26. Ehrlich JR, Burke-Conte Z, Wittenborn JS, Saaddine J, Omura JD, Friedman DS, et al. Prevalence of Glaucoma Among US Adults in 2022. JAMA Ophthalmol. 2024 Nov 21;142(11). doi:10.1001/JAMAOPHTHALMOL.2024.3884 PubMed PMID: 39418040.
27. Shi A, Berchuck SI, Jammal AA, Singh G, Hunt S, Roche K, et al. Identifying Risk Factors for Blindness From Glaucoma at First Presentation to a Tertiary Clinic. Am J Ophthalmol. 2023 Jun 1;250:130–7. doi:10.1016/j.ajo.2023.02.006 PubMed PMID: 36764425.
28. Wagner I V., Stewart MW, Dorairaj SK. Updates on the Diagnosis and Management of Glaucoma. Mayo Clin Proc Innov Qual Outcomes. 2022 Dec 1;6(6):618–35. doi:10.1016/j.mayocpiqo.2022.09.007
29. Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl Lek Listy. 2021;122(7):474–88. doi:10.4149/BLL_2021_078 PubMed PMID: 34161115.
30. Li S, Cao W, Han J, Tang B, Sun X. The diagnostic value of white blood cell, neutrophil, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio in patients with primary angle closure glaucoma. Oncotarget. 2017 Mar 25;8(40):68984–95. doi:10.18632/ONCOTARGET.16571 PubMed PMID: 28978173.
31. Siwicki M, Kubes P. Neutrophils in host defense, healing, and hypersensitivity: Dynamic cells within a dynamic host. Journal of Allergy and Clinical Immunology. 2023 Mar 1;151(3):634–55. doi:10.1016/j.jaci.2022.12.004 PubMed PMID: 36642653.
32. Wang H, Kim SJ, Lei Y, Wang S, Wang H, Huang H, et al. Neutrophil extracellular traps in homeostasis and disease. Signal Transduct Target Ther. 2024 Dec 1;9(1). doi:10.1038/S41392-024-01933-X PubMed PMID: 39300084.
33. Yu S, Liu J, Yan N. Endothelial Dysfunction Induced by Extracellular Neutrophil Traps Plays Important Role in the Occurrence and Treatment of Extracellular Neutrophil Traps-Related Disease. Int J Mol Sci. 2022 May 1;23(10). doi:10.3390/IJMS23105626 PubMed PMID: 35628437.
34. Li S, Qiu Y, Yu J, Shao M, Li Y, Cao W, et al. Association of systemic inflammation indices with visual field loss progression in patients with primary angle-closure glaucoma: potential biomarkers for 3P medical approaches. EPMA J. 2021 Dec 1;12(4):659–75. doi:10.1007/S13167-021-00260-3 PubMed PMID: 34745391.
35. Ebermeyer T, Cognasse F, Berthelot P, Mismetti P, Garraud O, Hamzeh-cognasse H. Platelet Innate Immune Receptors and TLRs: A Double-Edged Sword. Int J Mol Sci. 2021 Aug 1;22(15). doi:10.3390/IJMS22157894 PubMed PMID: 34360659.
36. Rawish E, Nording H, Münte T, Langer HF. Platelets as Mediators of Neuroinflammation and Thrombosis. Front Immunol. 2020 Oct 6;11. doi:10.3389/FIMMU.2020.548631 PubMed PMID: 33123127.
37. Tukenmez Dikmen N, Un Y. Systemic immuno-inflammatory index in patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma. Ther Adv Ophthalmol. 2023 Jan 1;15. doi:10.1177/25158414231197072 PubMed PMID: 37720205.
38. Elbeyli A, Kurtul B. Systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio levels are associated with keratoconus. Indian J Ophthalmol. 2021 Jul 1;69(7):1725–9. doi:10.4103/IJO.IJO_3011_20 PubMed PMID: 34146015.
39. Huang J, Wu H, Yu F, Wu F, Hang C, Zhang X, et al. Association between systemic immune-inflammation index and cataract among outpatient US adults. Front Med (Lausanne). 2024;11. doi:10.3389/FMED.2024.1469200 PubMed PMID: 39359932.
40. Üçer MB, Cevher S. Assessment of systemic inflammatory response index and other inflammatory indicators in retinal vein occlusion. Medicine. 2023 Dec 8;102(49):E36512. doi:10.1097/MD.0000000000036512 PubMed PMID: 38065869.
41. Bammidi S, Koontz V, Gautam P, Hose S, Sinha D, Ghosh S. Neutrophils in Ocular Diseases. Int J Mol Sci. 2024 Jul 1;25(14). doi:10.3390/IJMS25147736 PubMed PMID: 39062975.
42. Austermann J, Roth J, Barczyk-Kahlert K. The Good and the Bad: Monocytes’ and Macrophages’ Diverse Functions in Inflammation. Cells. 2022 Jun 1;11(12). doi:10.3390/CELLS11121979 PubMed PMID: 35741108.
2. Michael V. Boland 2024-2025 Basic and Clinical Science Course, Section 10 – Rarewaves.com [Internet]. [cited 2026 Nov 8]. Available from: https://www.rarewaves.com/products/9781681047928-2024-2025-basic-and-clinical-science?srsltid=AYCX9vJhbU2A9JpXy9HjPYXufR7RiQeLJPmTAflvzq-V32EiHjbMwLz_
3. Allison K, Patel D, Alabi O, Allison K, Patel D, Alabi O. Epidemiology of Glaucoma: The Past, Present, and Predictions for the Future. Cureus. 2020 Nov 24;12(11). doi:10.7759/cureus.11686 PubMed PMID: 33391921.
4. Steinmetz JD, Bourne RRA, Briant PS, Flaxman S, Taylor HR, Jonas JB, et al. Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: The Right to Sight: An analysis for the Global Burden of Disease Study. Lancet Glob Health. 2021 Feb 1;9(2):e144–60. doi:10.1016/S2214-109X(20)30489-7 PubMed PMID: 33275949.
5. Zhang N, Wang J, Li Y, Jiang B. Prevalence of primary open angle glaucoma in the last 20 years: a meta-analysis and systematic review. Sci Rep. 2021 Dec 1;11(1). doi:10.1038/S41598-021-92971-W PubMed PMID: 34215769.
6. Zhou LY, Liu ZG, Sun YQ, Li YZ, Teng ZQ, Liu CM. Preserving blood-retinal barrier integrity: a path to retinal ganglion cell protection in glaucoma and traumatic optic neuropathy. Cell Regeneration 2025 14:1. 2025 Apr 2;14(1):13-. doi:10.1186/S13619-025-00228-Y
7. Wang X, Wang M, Liu H, Mercieca K, Prinz J, Feng Y, et al. The Association between Vascular Abnormalities and Glaucoma-What Comes First? Int J Mol Sci. 2023 Sep 1;24(17). doi:10.3390/IJMS241713211 PubMed PMID: 37686017.
8. Ulhaq ZS, Istifiani LA, Pamungkas SA. Evaluation of Systemic IL-6 Trans-Signaling in Patients with Primary-Open Angle Glaucoma. J Fr Ophtalmol. 2023;46(6):622–9. doi:10.1016/j.jfo.2022.11.022 PubMed PMID: 37095023.
9. Jung Y, Ohn K, Shin H, Oh SE, Park CK, Park HYL. Factors Associated with Elevated Tumor Necrosis Factor-α in Aqueous Humor of Patients with Open-Angle Glaucoma. J Clin Med. 2022;11(17):5232. doi:10.3390/jcm11175232
10. Islam MM, Satici MO, Eroglu SE. Unraveling the clinical significance and prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index, and delta neutrophil index: An extensive literature r…. Turk J Emerg Med. 2024 Jan 1;24(1):8–19. doi:10.4103/TJEM.TJEM_198_23 PubMed PMID: 38343523.
11. ARIKAN S, ERSAN I, KARA S, TUFAN HA, KOCABIYIK Ö, GENCER B, et al. Neutrophil Lymphocyte Ratio in Different Types of Glaucoma.
12. Li X, Sun YQ, Zhong XD, Zhang ZJ, Tang JF, Luo ZY. Association between systemic inflammatory response index and glaucoma incidence from 2005 to 2008. Front Med (Lausanne). 2025;12. doi:10.3389/FMED.2025.1542073 PubMed PMID: 39967596.
13. Tang B, Li S, Han J, Cao W, Sun X. Associations between Blood Cell Profiles and Primary Open-Angle Glaucoma: A Retrospective Case-Control Study. Ophthalmic Res. 2020 Jul 4;63(4):413–22. doi:10.1159/000504450 PubMed PMID: 32018245.
14. Karahan M, Kilic D, Guven S. Systemic inflammation in both open-angle and angle-closure glaucoma: role of platelet-to-lymphocyte ratio. Bratisl Lek Listy. 2021 Oct 26;122(1):45–8. doi:10.4149/BLL_2021_005 PubMed PMID: 33393320.
15. Chuang SH, Chang CH. Platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio in glaucoma: a meta-analysis. Biomark Med. 2024 Jan 1;18(1):39–49. doi:10.2217/BMM-2023-0651 PubMed PMID: 38334411.
16. Ozgonul C, Sertoglu E, Mumcuoglu T, Kucukevcilioglu M. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Novel Biomarkers of Primary Open-Angle Glaucoma. J Glaucoma. 2016 Oct 1;25(10):e815–20. doi:10.1097/IJG.0000000000000392 PubMed PMID: 26918914.
17. Wang X, Jiang H, Zhang C. Association of systemic inflammatory biomarkers with ocular disease: a large population-based cross-sectional study. Eur J Med Res. 2025 Mar 26;30(1). doi:10.1186/S40001-025-02473-Y PubMed PMID: 40140856.
18. Seth PK, Senthil S, Das AV, Garudadri C. Prevalence of glaucoma types, clinical profile and disease severity at presentation: Tertiary Institute based cross-sectional study from South India. Indian J Ophthalmol. 2023 Oct 1;71(10):3305–12. doi:10.4103/IJO.IJO_3305_22 PubMed PMID: 37787226.
19. Tang B, Li S, Han J, Cao W, Sun X. Associations between Blood Cell Profiles and Primary Open-Angle Glaucoma: A Retrospective Case-Control Study. Ophthalmic Res. 2020;63(4):413–22. doi:10.1159/000504450 PubMed PMID: 32018245.
20. Parajuli A, Maharjan I. Severity of Primary Open Angle Glaucoma at First Presentation and Associated Factors in Tertiary Hospital. Nepalese Journal of Ophthalmology. 2026 Apr 3;18(35):15–22. doi:10.3126/nepjoph.v18i35.82846
21. Thirunavukarasu AJ, Jain N, Sanghera R, Lattuada F, Mahmood S, Economou A, et al. A validated web-application (GFDC) for automatic classification of glaucomatous visual field defects using Hodapp-Parrish-Anderson criteria. NPJ Digit Med. 2024 Dec 1;7(1). doi:10.1038/S41746-024-01122-8 PubMed PMID: 38762669.
22. Poli M. Comparison of the Real-world Performance of Henson 9000 Perimeter and Humphrey Field Analyzer in Glaucoma Patients. J Curr Glaucoma Pract. 2025 Jan 1;19(1):55–63. doi:10.5005/JP-JOURNALS-10078-1470 PubMed PMID: 40417145.
23. Zaharia AC, Dumitrescu OM, Radu M, Rogoz RE. Adherence to Therapy in Glaucoma Treatment-A Review. J Pers Med. 2022 Apr 1;12(4). doi:10.3390/JPM12040514 PubMed PMID: 35455630.
24. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology. 2014 Nov 1;121(11):2081–90. doi:10.1016/j.ophtha.2014.05.013 PubMed PMID: 24974815.
25. Tezel G. Multifactorial Pathogenic Processes of Retinal Ganglion Cell Degeneration in Glaucoma towards Multi-Target Strategies for Broader Treatment Effects. Cells. 2021 Jun 1;10(6). doi:10.3390/CELLS10061372 PubMed PMID: 34199494.
26. Ehrlich JR, Burke-Conte Z, Wittenborn JS, Saaddine J, Omura JD, Friedman DS, et al. Prevalence of Glaucoma Among US Adults in 2022. JAMA Ophthalmol. 2024 Nov 21;142(11). doi:10.1001/JAMAOPHTHALMOL.2024.3884 PubMed PMID: 39418040.
27. Shi A, Berchuck SI, Jammal AA, Singh G, Hunt S, Roche K, et al. Identifying Risk Factors for Blindness From Glaucoma at First Presentation to a Tertiary Clinic. Am J Ophthalmol. 2023 Jun 1;250:130–7. doi:10.1016/j.ajo.2023.02.006 PubMed PMID: 36764425.
28. Wagner I V., Stewart MW, Dorairaj SK. Updates on the Diagnosis and Management of Glaucoma. Mayo Clin Proc Innov Qual Outcomes. 2022 Dec 1;6(6):618–35. doi:10.1016/j.mayocpiqo.2022.09.007
29. Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl Lek Listy. 2021;122(7):474–88. doi:10.4149/BLL_2021_078 PubMed PMID: 34161115.
30. Li S, Cao W, Han J, Tang B, Sun X. The diagnostic value of white blood cell, neutrophil, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio in patients with primary angle closure glaucoma. Oncotarget. 2017 Mar 25;8(40):68984–95. doi:10.18632/ONCOTARGET.16571 PubMed PMID: 28978173.
31. Siwicki M, Kubes P. Neutrophils in host defense, healing, and hypersensitivity: Dynamic cells within a dynamic host. Journal of Allergy and Clinical Immunology. 2023 Mar 1;151(3):634–55. doi:10.1016/j.jaci.2022.12.004 PubMed PMID: 36642653.
32. Wang H, Kim SJ, Lei Y, Wang S, Wang H, Huang H, et al. Neutrophil extracellular traps in homeostasis and disease. Signal Transduct Target Ther. 2024 Dec 1;9(1). doi:10.1038/S41392-024-01933-X PubMed PMID: 39300084.
33. Yu S, Liu J, Yan N. Endothelial Dysfunction Induced by Extracellular Neutrophil Traps Plays Important Role in the Occurrence and Treatment of Extracellular Neutrophil Traps-Related Disease. Int J Mol Sci. 2022 May 1;23(10). doi:10.3390/IJMS23105626 PubMed PMID: 35628437.
34. Li S, Qiu Y, Yu J, Shao M, Li Y, Cao W, et al. Association of systemic inflammation indices with visual field loss progression in patients with primary angle-closure glaucoma: potential biomarkers for 3P medical approaches. EPMA J. 2021 Dec 1;12(4):659–75. doi:10.1007/S13167-021-00260-3 PubMed PMID: 34745391.
35. Ebermeyer T, Cognasse F, Berthelot P, Mismetti P, Garraud O, Hamzeh-cognasse H. Platelet Innate Immune Receptors and TLRs: A Double-Edged Sword. Int J Mol Sci. 2021 Aug 1;22(15). doi:10.3390/IJMS22157894 PubMed PMID: 34360659.
36. Rawish E, Nording H, Münte T, Langer HF. Platelets as Mediators of Neuroinflammation and Thrombosis. Front Immunol. 2020 Oct 6;11. doi:10.3389/FIMMU.2020.548631 PubMed PMID: 33123127.
37. Tukenmez Dikmen N, Un Y. Systemic immuno-inflammatory index in patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma. Ther Adv Ophthalmol. 2023 Jan 1;15. doi:10.1177/25158414231197072 PubMed PMID: 37720205.
38. Elbeyli A, Kurtul B. Systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio levels are associated with keratoconus. Indian J Ophthalmol. 2021 Jul 1;69(7):1725–9. doi:10.4103/IJO.IJO_3011_20 PubMed PMID: 34146015.
39. Huang J, Wu H, Yu F, Wu F, Hang C, Zhang X, et al. Association between systemic immune-inflammation index and cataract among outpatient US adults. Front Med (Lausanne). 2024;11. doi:10.3389/FMED.2024.1469200 PubMed PMID: 39359932.
40. Üçer MB, Cevher S. Assessment of systemic inflammatory response index and other inflammatory indicators in retinal vein occlusion. Medicine. 2023 Dec 8;102(49):E36512. doi:10.1097/MD.0000000000036512 PubMed PMID: 38065869.
41. Bammidi S, Koontz V, Gautam P, Hose S, Sinha D, Ghosh S. Neutrophils in Ocular Diseases. Int J Mol Sci. 2024 Jul 1;25(14). doi:10.3390/IJMS25147736 PubMed PMID: 39062975.
42. Austermann J, Roth J, Barczyk-Kahlert K. The Good and the Bad: Monocytes’ and Macrophages’ Diverse Functions in Inflammation. Cells. 2022 Jun 1;11(12). doi:10.3390/CELLS11121979 PubMed PMID: 35741108.
