Neutrophil-To-Lymphocyte Ratio Increases in Patients with Dry Eye

CLINICAL SCIENCE

Neutrophil-to-Lymphocyte Ratio Increases in Patients With Dry Eye

Berrak Sekeryapan, MD, Feyzahan Uzun, MD, Seyma Buyuktarakci, MD, Asker Bulut, MD, and Veysi Oner, MD

of lymphocytes in a peripheral blood sample, has been Purpose: To assess the neutrophil-to-lymphocyte ratio (NLR) as an proposed as an important measure of systemic inflamma- indicator of inflammation in patients with non-Sjögren dry eye disease. tion.8,9 It has also been shown that the NLR value may be fl Methods: Serum NLR and C-reactive protein values were deter- used as an indicator of in ammation in several ocular diseases, such as diabetic retinopathy (DR),10 age-related minedin33patientswithdryeyeandin32controls.TheNLRwas 11 calculated by dividing the neutrophil count by the lymphocyte count. macular degeneration (AMD), retinal vein occlusion (RVO),12 and keratoconus.13 In light of these findings, the Results: Characteristics of the dry eye and control groups were current study aims to assess the NLR in patients with DED similar. The mean NLR value was 2.8 6 1.4 (range: 1.1–6.1) in as an indicator of inflammation. thedryeyegroupand1.66 0.7 (range: 0.8–2.8) in the control group (P =0.002,t test). The mean C-reactive protein value was 0.6 6 0.7 mg/dL (range: 0–2.3 mg/dL) in the dry eye group and MATERIALS AND METHODS 6 – 0.5 0.6 mg/dL (range: 0 1.9 mg/dL) in the control group (P = In this prospective study, 33 patients with DED (DED 0.307, t test). group) and 32 healthy controls (control group) were enrolled. Conclusions: The NLR values were found to be higher in patients All participants were informed of the procedure, and they with non-Sjögren dry eye than in controls. This result suggests that gave written informed consent in accordance with the non-Sjögren dry eye disease may be associated with systemic institutional guidelines and the Declaration of Helsinki. The inflammation or the NLR values may increase in local inflammatory study received approval from the local ethics committee. ocular diseases. Patients with the following 3 criteria were considered to have DED: (1) symptoms of DED defined according to Key Words: dry eye disease, neutrophil-to-lymphocyte ratio, the ocular surface disease index (OSDI) questionnaire14 C-reactive protein {the 12 items of the OSDI questionnaire, translated to (Cornea 2016;35:983–986) Turkish, were graded on a scale of 0 to 4, and the total OSDI score was calculated using the following formula: OSDI = [(sum of scores for all questions answered) · 25]/ $ ry eye disease (DED) is a common ocular disorder total number of questions answered}; an OSDI score 13 Daffecting nearly 30% of those older than 50 years. was selected as the cutoff value for DED; (2) abnormal tear dynamics [when the Schirmer 1 test (without anesthesia) Although dry eye is a multifactorial disease, it is recognized # , that inflammation has a prominent role in its pathogenesis.1 was 5mm/5minutesand/orbreakuptime 10 seconds Studies have shown that several proinflammatory mediators in at least 1 eye]; and (3) ocular surface abnormalities, 2,3 which were identified by punctate staining of the cornea are increased in the tears of patients with DED. In addition, fl systemic inflammatory or rheumatologic diseases such as with uorescein and graded on a scale of 0 to 3. Following rheumatoid arthritis,4 systemic lupus erythematosus,5 chronic DED diagnosis, the patients were referred to the Interna- hepatitis C,6 and thyroid eye disease7 are frequently associ- tional Disease Department of the Recep Tayyip Erdogan ated with dry eye. University Education and Research Hospital to exclude the Recently, the neutrophil-to-lymphocyte ratio (NLR), possible diagnosis of Sjögren DED, and only patients with which is the number of neutrophils divided by the number non-Sjögren DED were included. According to The American-European Consensus Group Revised Interna- tional Classification criteria, the patients were questioned about ocular and oral symptoms.15 After detailed clinical Received for publication November 12, 2015; revision received February 23, 2016; accepted March 20, 2016. Published online ahead of print May 9, examination, the blood biochemistry and hematology pro- 2016. file, serum C-reactive protein (CRP), and erythrocyte From the Department of Ophthalmology, Recep Tayyip Erdogan University sedimentation rate were measured. Serum autoantibodies Medical School, Rize, Turkey. such as anti-Ro/La, antinuclear antibody, rheumatoid factor, The authors have no funding or conflicts of interest to disclose. – Reprints: Berrak Sekeryapan, MD, Fener Mah. Yesilkent Apt. No: 11, Rize and anti cyclic citrullinated peptideweremeasuredto 53100, Turkey (e-mail: [email protected]). exclude primary and secondary Sjögren syndrome. The Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. age of patients ranged from 45 to 65 years.

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The control group was selected from visitors who had The mean NLR value was 2.8 6 1.4 (range: 1.1–6.1) in regular medical checkups at the Health Promotion Center of the DED group, and 1.6 6 0.7 (range: 0.8–2.8) in the control the Recep Tayyip Erdogan University Education and group. The difference between the groups was statistically Research Hospital and who had age and sex distributions significant (P = 0.002, t test) (Table 2). similar to those of the dry eye group. All participants The mean CRP value was 0.6 6 0.7 mg/dL (range, 0– included in the control group fulfilled the following criteria: 2.3 mg/dL) in the DED group and 0.5 6 0.6 mg/dL (range, 0– (1)OSDIscore,13, (2) Schirmer I test .10 mm per 1.9 mg/dL) in the control group. The difference between the 5 minutes, (3) tear break up time .10 seconds, and (4) no groups was not statistically significant (P = 0.307, t test) fluorescein staining of the cornea. (Table 2). In both the DED and control groups, participants who The DED group was classified into 2 subgroups by the had a medical history of disorders influencing the NLR such OSDI score: mild to moderate dry eye (scores: 13–32) and as diabetes mellitus, cardiovascular diseases, arterial hyper- severe dry eye (scores: 33–100).14 When the subgroups were tension, chronic obstructive lung disease, malignancies, evaluated with regard to the NLR values, the mean NLR renal dysfunction, liver dysfunction, hematologic or auto- value was 2.3 6 1.2 (range: 1.1–4.8) in the mild to moderate immune disorders, and chronic systemic inflammatory group and 3.2 6 1.4 (range: 1.8–6.1) in the severe group. The diseases or those who had a history of prior ocular surgery, difference between the 2 groups was not statistically signif- ocular inflammation, AMD, retinal occlusive disease, icant (P = 0.09, t test). rubeosis iridis, or glaucoma were excluded. Patients who smoked habitually or were taking antiinflammatory therapies were also excluded. DISCUSSION Blood samples were obtained by venipuncture after As a result of clinical and experimental studies, the a fasting period of at least 12 hours. White blood cell inflammatory process has been shown to play an important subtypes were measured using a Cell-Dyn Ruby automatic role in DED pathogenesis. Although it is not clear whether blood counter (Abbott Diagnostics, Santa Clara, CA), and the inflammation is the cause or the consequence of the NLR values were calculated by dividing the neutrophil count pathogenesis of DED, it is well known that antiinflammatory by the lymphocyte count. therapies effectively treat the signs and symptoms of DED. CRP levels were measured with a Beckman Coulter Studies have reported increased concentrations of inflamma- Immage 800 in both groups as the acute-phase inflammation tory mediators such as interleukin-1, interleukin-6, tumor marker. Also, blood biochemistry and a hematology profile necrosis factor-a, and matrix metalloproteinase in the tears of were carried out in both groups. patients with DED.2,3 In addition, inflammatory mediators can The difference between groups was evaluated by t test be detected by immunostaining or flow cytometry in con- and the x2 test, and P value , 0.05 was considered junctival epithelial cells of patients with DED.16,17 It has been statistically significant. suggested that the measurement of the inflammatory mediators in tears and conjunctival cells can be used to define the RESULTS severity of DED and monitor the effects of therapy. However, fi fi The mean age of individuals was 58.2 6 5.3 years in technical dif culties such as insuf cient equipment for the DED group and 56.7 6 4.2 years in the control group; immune assay or inadequate tear volume or induction of reflex tearing during sample collection for tear assays limit 84.8% of patients with dry eye (n = 28) and 84.3% of control 18 patients (n = 27) were female. There were no differences the applications of these assay methods. between the 2 groups in terms of age, sex, or common clinical Recently, high neutrophil and low lymphocyte counts in the peripheral blood have been suggested as biomarkers of (hyperlipidemia and anemia) and lifestyle (caffeinated bev- fl erages, alcoholic drinks, and principal eating habits) factors systemic in ammation and poor prognosis in several diseases, . x2 such as coronary artery disease, myocardial infarction, (P 0.05, ). 19–23 The mean OSDI questionnaire scores, the Schirmer test diabetes mellitus, and cancer. Therefore, the NLR has fl been proposed as an indicator and prognostic marker for values, tear break up times, and uorescein staining scores of fl the 2 groups are shown in Table 1. systemic in ammatory conditions. Based on the importance of the NLR values in systemic inflammation, several ocular diseases with inflammatory pathogenesis, such as DR, AMD, and RVO have been evaluated for the importance of the TABLE 1. Dry Eye Examination Parameters of Dry Eye and Control Groups NLR values. Dry Eye Control P* OSDI score 40.4 6 7.3 7.3 6 1.8 ,0.001 TABLE 2. NLR and CRP Values of Dry Eye and Control Groups Schirmer 1 4.7 6 0.8 15.8 6 1.9 ,0.001 Dry Eye Control P* TBUT 5.7 6 1.8 10.9 6 1.0 ,0.001 6 6 Corneal staining score 1.9 6 0.5 0.1 6 0.3 ,0.001 NLR 2.8 1.4 1.6 0.7 0.002 CRP 0.6 6 0.7 0.5 6 0.6 0.307 *P value calculated by t test. TBUT, tear break up time. *P value calculated by t test.

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