==== Front Medicine (Baltimore) MD Medicine 0025-7974 1536-5964 Lippincott Williams & Wilkins Hagerstown, MD 37390242 00014 10.1097/MD.0000000000034225 3 5800 Research Article Observational Study Blood inflammatory biomarkers in participants with idiopathic epiretinal membrane: A retrospective case series study https://orcid.org/0000-0003-1596-7970 Qin Guanghao MD qinguanghao2020@163.com a Lin Tiezhu MD, PhD 360970814@qq.com a You Yue MD youyue20220311@163.com b Shang Mingxin MD shangmingxin@hsyk.com.cn a He Wei MD, PhD hewei@hsyk.com.cn a https://orcid.org/0000-0002-0848-827X Pazo Emmanuel Eric MD, MSc, PhD a * a He Eye Specialist Hospital, Shenyang, China b Sinqi Eye Hospital, Shenyang, China. * Correspondence: Emmanuel Eric Pazo, Department of Ophthalmology, He Eye Specialist Hospital, No. 128 Huanghe Street, Yuhong District, Shenyang, Liaoning Province 110000, China (e-mail: ericpazo@outlook.com). 30 6 2023 30 6 2023 102 26 e342255 4 2023 15 6 2023 15 6 2023 Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. 2023 https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The objective was to evaluate the levels of monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with idiopathic epiretinal membrane (iERM). This retrospective case series study comprised of participants with iERM and participants with cataract. The values of MLR, NLR, PLR and from participants’ peripheral blood were assessed among groups. The best cutoff value of MLR, NLR, and PLR in iERM was found by performing a receiver operating characteristic curve analysis and determining the optimum cutoff value for each variable. In total, 95 participants with iERM were included in the study group, and 61 participants with senile cataract were included as controls. The lymphocyte count in the iERM group was significantly lower than the control group (1.69 ± 0.63 vs. 1.95 ± 0.53, P = .003). The monocyte count in the iERM group was significantly higher than the control group (0.39 ± 0.11 vs. 0.31 ± 0.10, P < .001). The area under the curve of MLR, NLR, and PLR in differentiating patients with IERM and controls was 0.782, 0.645, and 0.657, respectively, according to receiver operating characteristic. The best cutoff value of MLR was > 0.18, with sensitivity and specificity of 74.7% and 75.4%, respectively. The NLR was > 2.06, with a sensitivity and specificity of 50.5% and 83.6%, respectively. The PLR was > 95.89, with a sensitivity and specificity of 86.3% and 41.0%, respectively. The findings of this study suggest that systemic inflammation may be associated with iERM. IERM patients may be prone to have high MLR, NLR, and PLR values. idiopathic epiretinal membrane monocyte-to-lymphocyte ratio neutrophil-to-lymphocyte ratio platelet-to-lymphocyte ratio OPEN-ACCESSTRUE ==== Body pmc1. Introduction Epidemiology studies show that the incidence of Idiopathic Epiretinal Membrane (iERM) increases as we age. It affects roughly 1.9% of those under 60 years, and 7.2% of individuals older than 60 years of age, with a slightly higher proportion of females being affected.[1,2] iERM is a non-vascular membrane that covers the fundus and adjacent retina and is usually related to advanced age and posterior vitreous detachment (PVD).[3] Participants can experience signs and symptoms such as reduced visual acuity, metamorphopsia, and monocular diplopia. Although the exact cause of iERM is unclear, it is broadly accepted that anomalous PVD and inflammation are essential factors in its development.[4,5] PVD may damage the internal limiting membrane of the retina and disrupt the blood-retinal barrier, activating the migration, proliferation, and aggregation of various retinal cells, as well as the secretion of a variety of growth and inflammatory factors that promote the formation of the anterior membrane.[6,7] As an inexpensive and convenient marker of inflammation, monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have gained increasing attention in various disorders such as multiple types of cancers, COVID-19, Alzheimer disease, and acute coronary disease.[8–13] Furthermore, these serum inflammatory biomarkers have been linked to the onset of ocular disorders such as dry eye disease, keratoconus, retinal vein occlusion, and retinal artery occlusion.[14–18] While the role of NLR and PLR has been previously explored in iERM,[19,20] the current study aimed to evaluate the probable relationship between MLR, NLR, and PLR serum inflammatory biomarkers in participants with iERM. 2. Material and method 2.1. Study design and participants Participants diagnosed with iERM at the He Eye Specialist Hospital between January 2016 and October 2020 had their medical data evaluated retrospectively. The Ethics Committee at He Eye Specialist Hospital (Liaoning, China) approved this study, which followed the Declaration of Helsinki (IRB2022K004.01). As a control group, 61 age- and gender-matched cataract participants with normal fundus were enrolled. ERM is defined as fibroblastic pre retinal membrane, which is diagnosed by an experienced retinal specialist using indirect ophthalmoscopy after dilating the pupil in conjunction with digital retinal imaging techniques using a 45° non-mydriatic camera (TRC-NW300, Topcon, Tokyo, Japan) and Cirrus HD-OCT 5000 (Carl Zeiss Meditec, Dublin, USA). Macular edema (ME) was diagnosed at the same time during the examination. The study excluded participants who had any systemic diseases other than diabetes and hypertension, including infection, giant cell arteritis, any tumor, any blood disease, autoimmune disease, failure of the kidney and liver, heart disease, cerebrovascular disease, a history of surgery, drinking alcohol and smoking, family history of diabetic retinopathy, trauma, retinal artery or vein occlusion, glaucoma, or any other ocular disease. Anticoagulants, anti-inflammatory medications, anti-hyperlipidemia medications, and cancer-related treatments or medications were also excluded from this study. 2.2. Clinical evaluation Intraocular pressure, slit lamp biomicroscopy, best corrected visual acuity, and indirect ophthalmoscopy following dilation of the pupil were all part of the thorough ophthalmological examination. Blood routine investigation (Auto-Blood Cell Analys BC-5180; Mindray, ShenZhen, China), as well as blood glucose and lipid profile analysis (Auto-chemistry Analys CS-1200; Mindray), were performed on overnight fasting blood samples of all participants in the same laboratory. The blood cell count, blood lipid profile, and fasting blood glucose level were all assessed. PLR, NLR, and MLR were manually calculated. Age, gender, weight, height, hypertension, diabetes, and body mass index was assessed. 2.3. Statistical analysis The statistical analysis was carried out with the help of the SPSS statistical software (ver. 25.0; SPSS Inc., Chicago, USA). Among the descriptive statistics employed were the mean standard deviation (mean SD) and percentage. Categorical data was provided as percentages, and the Chi-square test was used to examine the data. The Kolmogorov–Smirnov test was used to determine whether or not the data was normally distributed. A Student t test was employed to determine whether or not there was any homogeneity of variance between the 2 groups. An examination of the receiver operating characteristics curve (ROC) was done to determine the sensitivity and specificity of baseline MLR, NLR, and PLR, and even the best cutoff value of iERM. The area under the ROC was used to predict validity. To determine statistical significance, a P value of less than .05 was employed, and the confidence interval was set at 95% CI. 3. Results 3.1. Patient characteristics The final analysis of the study included 95 iERM participants (63 females and 32 males with a mean age of 65.91 ± 9.34 years) Forty-seven of the iERM participants had macular edema. Sixty-one senile cataract participants (40 females and 21 males with a mean age of 65.69 ± 6.67 years) were collected as control (Table 1). Table 1 Baseline characteristics of participants. iERM (n = 95) Control (n = 61) P value Age (yr) 65.91 ± 9.34 65.69 ± 6.67 .875 Gender, male (%) 32 (33.68) 21 (34.43) .924 Hypertension, n (%) 21 (22.11) 12 (19.67) .717 Diabetes, n (%) 9 (9.47) 6 (9.84) .940 BMI (kg/m2) 23.82 ± 3.17 24.12 ± 3.32 .582 BMI = body mass index, iERM = idiopathic epiretinal membranes. 3.2. Parameters of the blood test The parameters of the blood test are summarized in Table 2 in 2 groups. The study group’s lymphocyte count was considerably lower than the control group’s (1.69 ± 0.63 vs 1.95 ± 0.53, P = .003). The iERM group had a substantially higher monocyte count than the control group (0.39 ± 0.11 vs 0.31 ± 0.10, P < .001). The MLR, NLR, and PLR of the iERM group were considerably greater than those of the control group (all P < .001). Table 2 The comparation of parameters of blood routine. iERM (n = 95) Mean ± SD Control (n = 61) Mean ± SD P value* White blood cell count (109/µL) 5.55 ± 1.34 5.69 ± 1.43 .540 Neutrophil count (109/µL) 3.36 ± 1.03 3.25 ± 0.99 .501 Lymphocyte count (109/µL) 1.69 ± 0.63 1.95 ± 0.53 .003 Platelet count (109/µL) 214.17 ± 45.57 214.62 ± 50.21 .954 Monocyte count (109/µL) 0.39 ± 0.11 0.31 ± 0.10 <.001 High-density lipoprotein, mg/dL 1.59 ± 0.34 1.62 ± 0.36 .492 Low-density lipoprotein, mg/dL 3.62 ± 0.96 3.74 ± 0.99 .466 Total cholesterol (mg/dL) 5.39 ± 1.04 5.53 ± 1.14 .431 Triglyceride (mg/dL) 1.74 ± 0.97 1.74 ± 0.83 .992 Fasting glucose (mg/dL) 5.71 ± 0.91 5.77 ± 0.83 .680 MLR 0.26 ± 0.11 0.16 ± 0.10 <.001 NLR 2.23 ± 1.00 1.70 ± 0.51 <.001 PLR 140.71 ± 51.97 113.94 ± 34.98 <.001 iERM = idiopathic epiretinal membranes, MLR = monocyte to lymphocyte ratio, NLR = neutrophil to lymphocyte ratio, PLR = platelet to lymphocyte ratio, SD = stand deviation. * iERM compared to control group. The iERM participants were subgrouped according to the presence or absence of macular edema, and there was no statistical difference in NLR, PLR, and MLR between participants with ME and non-ME (Table 3). Table 3 The comparation of parameters of blood test in ME and non-ME groups. ME (n = 47) Mean ± SD Non-ME (n = 48) Mean ± SD P value* Age (yr) 67.15 ± 6.98 64.69 ± 11.11 .200 White blood cell count (109/µL) 5.72 ± 1.32 5.39 ± 1.35 .231 Neutrophil count (109/µL) 3.44 ± 1.11 3.28 ± 0.94 .458 Lymphocyte count (109/µL) 1.76 ± 0.69 1.63 ± 0.56 .303 Platelet count (109/µL) 220.04 ± 46.17 208.42 ± 44.70 .216 Monocyte count (109/µL) 0.40 ± 0.11 0.38 ± 0.11 .478 High-density lipoprotein, mg/dL 1.64 ± 0.39 1.53 ± 0.29 .097 Low-density lipoprotein, mg/dL 3.73 ± 1.06 3.52 ± 0.85 .300 Total cholesterol (mg/dL) 5.45 ± 1.07 5.32 ± 1.02 .547 Triglyceride (mg/dL) 1.78 ± 1.11 1.70 ± 0.82 .681 Fasting glucose (mg/dL) 5.77 ± 0.83 5.66 ± 1.01 .580 MLR 0.26 ± 0.12 0.26 ± 0.10 .861 NLR 2.26 ± 1.15 2.19 ± 0.84 .718 PLR 139.96 ± 51.38 141.44 ± 53.07 .890 iERM = idiopathic epiretinal membranes, ME = macular edema, MLR = monocyte to lymphocyte ratio, NLR = neutrophil to lymphocyte ratio, PLR = platelet to lymphocyte ratio, SD = stand deviation. * iERM compared to control group. The area under the curve of MLR, NLR, and PLR in differentiating patients with IERM and controls was 0.782, 0.645, and 0.657, respectively, according to ROC. The best cutoff value of MLR was >0.18, with sensitivity and specificity of 74.7% and 75.4% respectively. The NLR was >2.06, with a sensitivity and specificity of 50.5% and 83.6% respectively. The PLR was >95.89, with a sensitivity and specificity of 86.3% and 41.0% respectively (Fig. 1). Figure 1. MLR, NLR, and PLR receiver operating characteristic curves for iERM predictors. iERM = idiopathic epiretinal membrane, MLR = monocyte-to-lymphocyte ratio, NLR = neutrophil-to-lymphocyte ratio, PLR = platelet-to-lymphocyte ratio. 4. Discussion iERM is a relatively common condition affecting the vitreous-macular junction. The patient has no clear history of eye disease, and the condition is most prevalent in the elderly. It has been established that the formation of iERM is associated with PVD, inflammation, and renin-angiotensin (RAS) system activation.[4,21–23] According to previous reports, approximately 95% of clinically significant iERM occurs following vitreous body detachment.[24] The iERM is primarily composed of retinal pigment epithelial cells and retinal glial cells (astrocytes and Müller cells).[25] Histological studies have revealed that myofibroblasts, fibroblasts, clear cells, and macrophages may play roles in the occurrence and progression of iERM.[25] Myojin et al[26] examined the vitreous lavage fluid of participants with iERM (15 eyes) and found that pro-inflammatory genes were overexpressed (IL-6, GFAP, VEGFA, TGFB2, CXCL1, TNC, and RELA). Multiple interleukins (IL-1 IL-6, IL-13, IL-17) and TGF-β1, TGFβ2 interferon necrosis factor and other inflammatory factors are also involved in the formation of iERM.[23,26] Furthermore, in the development of iERM, the RAS system is implicated.[23,27] RAS can induce retinal vascular inflammation and mediate and regulate the factors involved in iERM fibrosis (FGF2, GDNF, NGF, TGF-β1). Monocytes are pro-inflammatory during inflammation, whereas lymphocytes can help regulate inflammation.[28,29] MLR has been used to investigate the staging and prognosis of COVID-19 and cardiovascular disease.[9,13] In the current study, we found the monocyte count was significantly higher, and the lymphocyte count was significantly lower in the iERM participants. We used MLR to predict the development of iERM, and found good sensitivity and specificity. According to Joshi et al[4] and Zhao et al,[30] the major cell types in iERM are hyalocytes and müller cells. Hyalocytes are classified as macrophages (a kind of inflammation cells).[31] Other 2 popular markers associated with the prognosis of systemic inflammatory diseases are NLR and PLR.[32] Previous studies have established a link between NLR, PLR, retinal artery occlusion, retinal vein occlusion, and Keratoconus.[15,18,33,34] Additionally, NLR and PLR were also used to classify the severity of dry eye.[14] Though we found that iERM participants had significantly higher PLR and NLR values than the control group in the current study, that is inconsistent with the previous studies,[33] in which the sensitivity or specificity was low. However, the lower sensitivity (52.6%) of NLR in predicting iERM was also reported in the study by Uzlu et al[20] They attributed this difference to the small sample size. Macular edema and macular holes could be caused by iERM traction. Triamcinolone acetonide (a long-acting adrenaline glucocorticoid) has the effects of anti-inflammatory, inhibiting cell proliferation, reducing the capillary permeability, stabilizing the retinal barrier, etc., and can reduce and control the progression of macular edema. Past studies have suggested that intravitreal injection of triamcinolone acetonide while removing the macular membrane can effectively reduce macular edema.[35,36] That hint suggests that eyes with macular edema might be more associated with inflammation than usual. In addition, some clinical studies suggest that NLR and MLR can be used as inflammatory markers for diabetic macular edema.[37,38] But we didn’t find any significant difference in MLR, PLR, and NLR between iERM participants with macular edema and those without macular edema in this study. The possible explanation is that macular edema in iERM eyes might be due to the physical traction, and inflammation might play a comparable role in the iERM with or without macular edema. This study was limited by a number of factors. First, the vitreous fluid and postoperative macular membrane tissue tests were not available due to retrospective design. Second, we were unable to compare additional inflammatory markers simultaneously, such as interleukin-1 and TGF. However, to our knowledge, this is the first research to examine the link between MLR and iERM using a large sample size. To summarize, it is possible that systemic inflammation may be associated with iERM. IERM patients may be prone to have high MLR, NLR, and PLR values. Additional laboratory studies on iERM’s mechanism are necessary to gain a better understanding of the relationship between iERM and blood biomarkers. Acknowledgments We thank the participants in this study. This manuscript has not been published and is not under consideration for publication elsewhere. Author contributions Conceptualization: Mingxin Shang, Wei He. Data curation: Guanghao Qin, Yue You. Formal analysis: Guanghao Qin. Investigation: Tiezhu Lin, Wei He. Methodology: Guanghao Qin, Wei He. Project administration: Tiezhu Lin. Resources: Mingxin Shang, Wei He, Emmanuel Eric Pazo. Software: Yue You, Mingxin Shang. Supervision: Mingxin Shang, Emmanuel Eric Pazo. Validation: Yue You. Writing – original draft: Guanghao Qin. Writing – review & editing: Tiezhu Lin, Emmanuel Eric Pazo. Abbreviations: iERM idiopathic epiretinal membrane ME macular edema MLR monocyte-to-lymphocyte ratio NLR neutrophil-to-lymphocyte ratio PLR platelet-to-lymphocyte ratio PVD posterior vitreous detachment RAS renin-angiotensin ROC receiver operating characteristic curve SD standard deviation This study was supported by He Eye Specialist Hospital, Shenyang, China. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published. The authors have no conflicts of interest to disclose. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. How to cite this article: Qin G, Lin T, You Y, Shang M, He W, Pazo EE. Blood inflammatory biomarkers in participants with idiopathic epiretinal membrane: A retrospective case series study. Medicine 2023;102:26(e34225). ==== Refs References [1] Mitchell P Smith W Chey T . Prevalence and associations of epiretinal membranes: the blue mountains eye study, Australia. Ophthalmology. 1997;104 :1033–40.9186446 [2] Kim JY Rim TH Kim SS . Trends of pars plana vitrectomy rates in South Korea: a nationwide cohort study. Korean J Ophthalmol. 2017;31 :446.28914000 [3] Ruberto G Parisi V Vandelli G . Surgery for Idiopathic epimacular membrane: morpho-functional outcomes based on the preoperative macular integrity of the photoreceptoral junction. A prospective pilot study. Adv Ther. 2020;37 :566–77.31828609 [4] Joshi M Agrawal S Christoforidis JB . Inflammatory mechanisms of idiopathic epiretinal membrane formation. Mediators Inflamm. 2013;2013 :1–6. [5] Sebag J . Anomalous posterior vitreous detachment: a unifying concept in vitreo-retinal disease. Graefes Arch Clin Exp Ophthalmol. 2004;242 :690–8.15309558 [6] Gilbert C Hiscott P Unger W . Inflammation and the formation of epiretinal membranes. Eye (Basingstoke). 1988;2 :S140–56. [7] Harada T Harada C Mitamura Y . Neurotrophic factor receptors in epiretinal membranes after human diabetic retinopathy. Diabetes care. 2002;25 :6. [8] Chen C Yang H Cai D . Preoperative peripheral blood neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratio (PLR) related nomograms predict the survival of patients with limited-stage small-cell lung cancer. Transl Lung Cancer Res. 2021;10 :866–77.33718028 [9] Li YX Chang JY He MY . Neutrophil-to-Lymphocyte Ratio (NLR) and Monocyte-to-Lymphocyte Ratio (MLR) predict clinical outcome in patients with stage IIB cervical cancer. J Oncol. 2021;2021 :2939162.34539781 [10] Budzianowski J Pieszko K Burchardt P . The role of hematological indices in patients with acute coronary syndrome. Dis Markers. 2017;2017 :1–9. [11] Guclu K Celik M . Prognostic value of inflammation parameters in patients with Non-ST elevation acute coronary syndromes. Angiology. 2020;71 :825–30.32597198 [12] Kuyumcu ME Yesil Y Oztürk ZA . The evaluation of neutrophil-lymphocyte ratio in Alzheimer’s disease. Dement Geriatr Cogn Disord. 2012;34 :69–74.22922667 [13] Citu C Gorun F Motoc A . The Predictive Role of NLR, d-NLR, MLR, and SIRI in COVID-19 Mortality. Diagnostics. 2022;12 :2–11. [14] Ozcan DO Kurtul BE Ozcan SC . Increased systemic immune-inflammation index levels in patients with dry eye disease. Ocul Immunol Inflamm. 2022;30 :588–92.32990489 [15] Bozkurt E Ucak T . Serum inflammation biomarkers in patients with keratoconus. Ocul Immunol Inflamm. 2021;29 :1164–7.32255702 [16] Kumral ET Yenerel NM Ercalik NY . Neutrophil/lymphocyte ratio and mean platelet volume in branch retinal vein occlusion. Saudi J Ophthalmol. 2016;30 :105–8.27330385 [17] Qin G He F Zhang H . Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) are more prominent in retinal artery occlusion (RAO) compared to retinal vein occlusion (RVO). PLoS One. 2022;17 :e0263587.35113973 [18] Guven S Kilic D . Neutrophil to Lymphocyte Ratio (NLR) is a better tool rather than Monocyte to High-Density Lipoprotein Ratio (MHR) and Platelet to Lymphocyte Ratio (PLR) in central retinal artery occlusions. Ocul Immunol Inflamm. 2021;29 :997–1001.32078399 [19] Dikkaya F Karaman Erdur S Ozsutcu M . The significance of neutrophil-to-lymphocyte ratio in idiopathic epiretinal membrane. Int Ophthalmol. 2018;38 :1393–7.28608032 [20] Uzlu D Erdöl H Somuncu AM . The role of simple inflammatory blood parameters in idiopathic epiretinal membrane patients. Int Ophthalmol. 2021;41 :107–12.32851557 [21] Klein R Klein BEK Wang Q . The epidemiology of epiretinal membranes. Trans Am Ophthalmol Soc. 1994;92 :403–25.7886875 [22] Gandorfer A Rohleder M Kampik A . Epiretinal pathology of vitreomacular traction syndrome. Br J Ophthalmol. 2002;86 :902–9.12140213 [23] Dong Y Kanda A Noda K . Pathologic roles of receptor-associated prorenin system in idiopathic epiretinal membrane. Sci Rep. 2017;7 :44266.28276504 [24] Wiznia RA . Posterior vitreous detachment and idiopathic preretinal macular gliosis. Am J Ophthalmol. 1986;102 :196–8.3740180 [25] Bu SC Kuijer R van der Worp RJ . Immunohistochemical evaluation of idiopathic epiretinal membranes and in vitro studies on the effect of TGF-β on müller cells. Invest Ophthalmol Vis Sci. 2015;56 :6506–14.26447986 [26] Myojin S Yoshimura T Yoshida S . Gene expression analysis of the irrigation solution samples collected during vitrectomy for idiopathic epiretinal membrane. PLoS One. 2016;11 :e0164355.27736918 [27] Limb GA Kapur S Woon H . Expression of mRNA for interleukin 6 by cells infiltrating epiretinal membranes in proliferative vitreoretinopathy. Agents Actions. 1993;38 Spec No :C73-6.8317327 [28] Angkananard T Anothaisintawee T McEvoy M . Neutrophil lymphocyte ratio and cardiovascular disease risk: a systematic review and meta-analysis. Biomed Res Int. 2018;2018 :2703518.30534554 [29] Linton MF Fazio S . Macrophages, inflammation, and atherosclerosis. Int J Obes. 2003;27 Suppl 3 :S35–40. [30] Zhao F Gandorfer A Haritoglou C . Epiretinal cell proliferation in macular pucker and vitreomacular traction syndrome: analysis of flat-mounted internal limiting membrane specimens. Retina. 2013;33 :77–88.22914684 [31] Kohno RI Hata Y Kawahara S . Possible contribution of hyalocytes to idiopathic epiretinal membrane formation and its contraction. Br J Ophthalmol. 2009;93 :1020–6.19429593 [32] Balta S Demirkol S Kucuk U . The platelet lymphocyte ratio may be useful inflammatory indicator in clinical practice. Hemodial Int. 2013;17 :668–9.23763539 [33] Şahin M Elbey B Şahin A . Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in retinal vein occlusion. Clin Exp Optom. 2020;103 :490–4.31773807 [34] Zhu D-d Liu X . Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in branch retinal vein occlusion. J Ophthalmol. 2019;2019 :6043612.31885890 [35] Byon IS Pak GY Kwon HJ . Natural history of idiopathic epiretinal membrane in eyes with good vision assessed by spectral-domain optical coherence tomography. Ophthalmologica. 2015;234 :91–100.26302864 [36] Shukla D . Management of macular epiretinal membrane by vitrectomy and intravitreal triamcinolone. Indian J Ophthalmol. 2014;62 :511–2.23571236 [37] Yeter DY Eroglu S Sariakcali B . The usefulness of Monocyte-to-High Density Lipoprotein and Neutrophil-to-Lymphocyte Ratio in diabetic macular edema prediction and early anti-VEGF treatment response. Ocul Immunol Inflamm. 2021;30 :901–6.33596398 [38] Hu Y Cheng Y Xu X . Pretreatment neutrophil-to-lymphocyte ratio predicts prognosis in patients with diabetic macular edema treated with ranibizumab. BMC Ophthalmol. 2019;19 :194.31455273