Evaluation of the Systemic Inflammation in Patients with Pterygium: Monocyte-to- High-Density Lipoprotein Cholesterol Ratio and Hematologic Indexes of Inflammation.

PURPOSE: The purpose of this study is to evaluate systemic inflammation in patients with pterygium using the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and hematologic indexes of inflammation.
METHODS: Thirty-one patients with primary pterygium and 31 age-and sex-matched healthy participants were enrolled in this retrospective study. The MHR, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, eosinophil-to-lymphocyte ratio, monocyte-to-eosinophil ratio, mean platelet volume-to-platelet count ratio, platelet distribution width, and red cell distribution width were compared between the two groups.
RESULTS: There was not a statistically significant difference in terms of the MHR between the pterygium group and the control group (P = 0.693). The NLR was higher in the pterygium group than in the control group (P = 0.028). In the other hematologic indexes, there were no statistically significant differences between the two groups (P > 0.05 for all).
CONCLUSION: The MHR is not associated with the presence of pterygium. An increased NLR in patients with pterygium may be an indicator of systemic inflammation. Copyright:

Introduction

Pterygium is a wing-shaped conjunctival fibrovascular tissue that crosses over the limbus and invades the corneal surface. The prevalence of pterygium varies in different geographic regions and is higher in tropical areas around the equator, which are known as the “pterygium belt.”[1] A recent meta-analysis revealed that the prevalence of pterygium worldwide is 12%.[2] Sunlight exposure, male gender and older age are the most common risk factors.[2] The pathophysiological mechanisms that underlie the initiation and progression of the pterygium have not been fully understood. In addition to the well-known trigger effect of ultraviolet radiation, recent literature suggests the potential role of inflammatory mechanisms, immunological mechanisms, oxidative stress, genetic factors, and antiapoptotic mechanisms in the pterygium development.[34] Elevated inflammatory mediators in pterygium specimens are signs of the inflammatory process in the pterygium development.[567] In addition to local inflammation, studies suggest that systemic inflammation may also be involved in this process.[8910]

Monocytes are subtypes of leukocytes that have an important role in the inflammatory response, while high-density lipoprotein (HDL) cholesterol has anti-inflammatory effects. The monocyte-to-HDL cholesterol ratio (MHR) is examined as an indicator of inflammation in various systemic and ocular diseases.[111213]

The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-lymphocyte ratio (ELR), monocyte-to-eosinophil ratio (MER), mean platelet volume-to-platelet count ratio (MPV/PC), platelet distribution width (PDW), and red cell distribution width (RDW) have also been proposed as indicators of systemic inflammation in several studies.[14151617] These indicators are inexpensive and easily available parameters that are derived from complete blood count analyses. In this study, we aimed to evaluate the systemic inflammation in patients with pterygium using the MHR and hematologic indexes of inflammation, including NLR, MLR, PLR, ELR, MER, MPV/PC, PDW, and RDW.

Methods

In this study, the medical file records of patients over 18 years of age who applied to the ophthalmology department of a single university hospital between January 2019 and June 2019 and who were diagnosed with primary pterygium in one or two eyes were analyzed retrospectively. Thirty-one patients (16 males, 15 females; mean age: 48.16 ± 13.61 years, range: 25–74 years) who fulfilled the inclusion criteria and who had laboratory data including complete blood count and HDL cholesterol level simultaneously within the past 6 months were enrolled as the “Pterygium Group.” Thirty-one age-and sex-matched healthy participants (16 males, 15 females; mean age: 48.89 ± 11.08 years, range: 31–69 years) who fulfilled the inclusion criteria and who had laboratory data including complete blood count and HDL cholesterol level simultaneously within the past 6 months were enrolled as the “Control Group.” This study was approved by the local clinical research ethics committee and followed the tenets of the Declaration of Helsinki (Decision No: 2019/2187).

Participants in the control group had no ocular pathologies, and participants in the pterygium group had no ocular pathologies other than primary pterygium. Patients with recurrent pterygium were not included in this study. Patients were excluded if they had any systemic disorders that may affect the laboratory findings; if they had a history of ocular or systemic infections, and ocular or any other surgeries within the past 6 months before the laboratory tests; if they had used any form of corticosteroids (including ocular, dermal, inhaler, or systemic), lipid-lowering drugs, or any other medications that may affect the laboratory findings within the past 6 months before the laboratory tests and if they smoked cigarettes or consumed alcohol.

The inflammatory parameters evaluated in the study are (1) MHR: The ratio of monocyte count (/μL)-to-HDL cholesterol level (mg/dL) (2) NLR: the ratio of neutrophil count (/μL)-to-lymphocyte count (/μL)(3) MLR: the ratio of monocyte count (/μL)-to-lymphocyte count (/μL) (4) PLR: the ratio of platelet count (/μL)-to-lymphocyte count (/μL) (5) ELR: The ratio of eosinophil count (/μL)-to-lymphocyte count (/μL) (6) MER: the ratio of monocyte count (/μL)-to-eosinophil count (/μL) (7) MPV/PC: The ratio of mean platelet volume (fL)-to-mean platelet count (/μL) (8) PDW (%): the PDW (9) RDW (%): the RDW.

Statistical analyses of the data were performed using IBM SPSS statistics software version 20.0 (IBM Corp, Armonk, New York, USA). Normality was checked for each continuous variable using the Kolmogorov–Smirnov test. Continuous variables with normal distribution were expressed as the mean ± standard deviation. Continuous variables with nonnormal distribution were expressed as the median interquartile range. Categorical variables were expressed in terms of frequencies. Independent samples–t-test was performed for comparisons among normally distributed variables, and the Mann–Whitney U-test was conducted for comparisons among nonnormally distributed variables. A P < 0.05 was considered statistically significant.

Results

There were no statistically significant differences in terms of age and gender between the pterygium group and the control group (P < 0.05). The total number of cases, gender distribution and mean age in the pterygium and control groups are presented in Table 1.

Table 1

Total number of cases, gender distribution, and mean age in the pterygium and control groups

	Pterygium Group		Control Group		P
	n	Age (mean±SD)	n	Age (mean±SD)
Male	16	49.69±13.50	16	49.07±12.13	0.894
Female	15	46.53±14.01	15	48.69±10.23	0.650
Total	31	48.16±13.61	31	48.89±11.08	0.823

P value: Statistical significance in the independent samples t-test. SD: Standard deviation

There was no statistically significant difference in the MHR between the pterygium group and the control group (P = 0.693). The NLR was higher in the pterygium group than in the control group (P = 0.028). For the other hematologic indexes (MLR, PLR, ELR, MER, MPV/PC, PDW, and RDW), there were no statistically significant differences between the pterygium group and the control group (P = 0.693, (P = 0.163, P = 0.081, P = 0.721, P = 0.767, P = 0.606, P = 0.660, and P = 0.091, respectively). Absolute values of the parameters are presented in Table 2.

Table 2

Monocyte-to-high-density lipoprotein cholesterol ratio and hematologic indexes of inflammation in the pterygium and control groups

	Pterygium Group	Control Group	P
MHR	10.313 (8.676)	11.264 (7.320)	0.693
NLR	2.167 (4.004)	1.573 (0.735)	0.028
MLR	0.262 (0.231)	0.241 (0.083)	0.163
PLR	119.802 (71.867)	104.576 (36.127)	0.081
ELR	0.055 (0.064)	0.057 (0.053)	0.721
MER	4.857 (3.764)	4.817 (4.369)	0.767
MPV/PC (MPV/platelet count ratio) (×10-5)	3.802 (1.592)	3.830 (1.614)	0.606
PDW	11.700 (2.400)	12.150 (2.525)	0.660
RDW	13.300 (1.100)	12.750 (1.475)	0.091

Data are presented as median (IQR). P value: Statistical significance in the Mann-Whitney U-test, Bold: Statistically significant results, IQR: Interquartile range, NLR: Neutrophil/lymphocyte ratio, MLR: Monocyte/lymphocyte ratio, PLR: Platelet/lymphocyte ratio, ELR: Eosinophil/lymphocyte ratio, MER: Monocyte/eosinophil ratio, PDW: Platelet distribution width, RDW: Red cell distribution width, MHR: Monocyte-to-HDL cholesterol ratio, MPV/PC: Mean platelet volume-to-platelet count

Discussion

The main characteristics of pterygium development are inflammation, angiogenesis, and fibrosis.[89] Although the exact etiology of the pterygium is not known, ocular surface inflammation has an important role in the pathogenesis of pterygium, regardless of the initiating factor. Many studies in the literature show the locally elevated levels of proinflammatory mediators. Interleukin (IL)-1, IL-6, IL-8, IL-10, and IL-17 are the major interleukins with increased expression in pterygium tissue; these mediators are known to be closely related to inflammation.[3456] Kria et al. showed the expression of tumor necrosis factor-alpha in the epithelium, stromal cells, and vascular endothelial cells of the pterygium specimens.[18] Tekelioglu et al. showed the increased levels of inflammatory cells and mediators, including CD4 and CD8 positive lymphocytes, intercellular adhesion molecule-1 positive cells, vascular cell adhesion molecule-1 positive cells, and human leukocyte antigen-DR (HLA-DR) positive cells.[7]

In addition to local inflammation, recent studies have also evaluated the relationship of pterygium with systemic inflammation. Lee et al. showed increased levels of local and systemic endothelial progenitor cells (EPCs) and cytokines, including substance-P, stem cell factor, and vascular endothelial growth factor, in patients with pterygium.[10] EPCs are cells that have a role in postnatal neovascularization. The authors concluded that elevated levels of EPCs induced by the proinflammatory mediators might be associated with angiogenesis in pterygium pathogenesis.[10] Yoo et al. showed the increased serum immunoglobulin E (IgE) levels in patients with pterygium.[9] There is an increased number of mast cells in pterygium.[19] IgE mediates the degranulation of mast cells, and the release of proinflammatory and angiogenic mediators might contribute to the inflammation and angiogenesis in the pterygium pathogenesis.[920] Zidi et al. showed the elevated levels of IL-6, IL-17A, and nitric oxide in both the tear samples and serum samples of patients with pterygium.[8] Furthermore, the elevated systemic oxidant status of patients with pterygium, as shown in a study by Kilic-Toprak et al., may indicate the systemic relationship of pterygium.[21]

Monocytes are subtypes of leukocytes that differentiate into macrophages at the sites of inflammation and release proinflammatory cytokines. They have an important role in the inflammatory response and monocyte count increases in various inflammatory conditions. On the other hand, HDL cholesterol has anti-inflammatory and antioxidative effects. Therefore, in recent literature, MHR has been employed as an indicator of inflammation in various systemic diseases.[1122] An increased MHR has also been observed in ocular diseases, including dry eye, branch retinal vein occlusion, central serous chorioretinopathy, and keratoconus.[12132324] To the best of our knowledge, this is the first study to evaluate the MHR in patients with pterygium. We did not observe an increase in the MHR.

The NLR is a commonly investigated parameter in the evaluation of systemic inflammatory conditions.[1525] Ocular disorders, including age-related macular degeneration, retinal vascular diseases, glaucoma, uveitis, and keratoconus, are also associated with an elevated NLR.[26] We observed an elevated NLR in the patients with pterygium in contrast to the findings of Kurtul et al. and Üçgül-Atılgan et al.[1427] An elevated NLR may be an indicator of systemic inflammation in patients with pterygium.

In addition to the NLR, MLR (or lymphocyte-to-monocyte count), PLR, ELR, MER (or eosinophil-to-monocyte count), MPV/PC, PDW, and RDW are also employed as indicators of systemic inflammation.[151617282930] However, few studies evaluate these parameters in ocular diseases. In this study, we did not observe an increase in these parameters in the patients with pterygium. Kurtul et al. did not observe an increase in PLR and PDW but revealed an elevated RDW; they concluded that their findings support the role of inflammation in the pathogenesis of pterygium.[14]

This study has some limitations. The first limitation is the retrospective design of the study. Second, many factors can affect the evaluated parameters. We attempted to overcome this problem by strictly applying the inclusion and exclusion criteria to both the case group and the control group. The third limitation is the relatively small sample size.

Conclusion

The MHR is not associated with the presence of pterygium. The increased NLR may be an indicator of systemic inflammation in patients with pterygium. Further studies with larger sample sizes and prospective designs are needed to validate these findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.