non-SS Dry Eye Research Articles

Comparison of corneal biomechanics in Sjögren's syndrome and non-Sjögren's syndrome dry eyes by Scheimpflug based device.

To compare the corneal biomechanics of Sjögren's syndrome (SS) and non-SS dry eyes with Corneal Visualization Scheimpflug Technology (CorVis ST). Corneal biomechanics and tear film parameters, namely the Schirmer I test value, tear film break-up time (TBUT) and corneal staining score (CSS) were detected in 34 eyes of 34 dry eye patients with SS (SSDE group) and 34 dry eye subjects without SS (NSSDE group) using CorVis ST. The differences of the above parameters between the two groups were examined, and the relationship between corneal biomechanics and tear film parameters were observed. The differences in age, sex, intraocular pressure (IOP) and central corneal thickness (CCT) were not significant between the two groups (P>0.05). The tear film parameters had significant differences between the SSDE group and NSSDE group (all P<0.05). Patients in the SSDE group had significantly lower A1-time and HC-time, but higher DA (P=0.01, 0.02, and 0.02, respectively) compared with the NSSDE group. In the SSDE group, DA was negatively correlated with TBUT (rho=-0.38, P=0.03); HC-time was negatively correlated with CSS (rho=-0.43, P=0.02). In the NSSDE group, HC-time was again negatively correlated with CSS (rho=-0.39, P=0.02). There are differences in corneal biomechanical properties between SSDE and NSSDE. The cornea of SSDE tends to show less "stiffness", as seen by a significantly shorter A1-time and HC-time, but larger DA, compared with the cornea of NSSDE. Biomechanical parameters can be influenced by different tear film parameters in both groups.

The Efficacy of Diquafosol Ophthalmic Solution in Non-Sjögren and Sjögren Syndrome Dry Eye Patients Unresponsive to Artificial Tear.

This study evaluates the efficacy of 3% diquafosol tetrasodium ophthalmic solution in Sjögren's syndrome (SS) and non-SS dry eye patients unresponsive to conventional artificial tear. This retrospective study included 38 dry eye patients (11 with SS and 27 with non-SS) who were treated with 3% diquafosol due to lack of response to artificial tear treatment for more than 3 months. Signs such as tear film break-up time (TBUT), Schirmer-I test, and total ocular staining score (OSS), which consisted of corneal OSS and conjunctival OSS, were evaluated at baseline and the first visit after treatment. Symptoms were quantified using visual analog scale (VAS) and ocular surface disease index (OSDI) scores. Changes of parameters after treatment in all the patients and differences of changes in SS and non-SS were evaluated. In total population, total OSS and corneal OSS improved average 6 weeks after diquafosol treatment (all P < 0.05, paired t-test), although conjunctival OSS had no improvement. TBUT increased after treatment (P = 0.036), while Schirmer-I test, OSDI, and VAS showed no improvement. With respect to comparisons, total and corneal OSS improved in non-SS patients and TBUT improved in SS patients (all P < 0.05). Three percent diquafosol tetrasodium treatment could be considered as an additive or substitute treatment when artificial tear treatment is insufficient, as it improved OSS and TBUT. This study also demonstrated that diquafosol treatment is beneficial for TBUT improvement in SS, while it is beneficial for OSS improvement in non-SS dry eye patients.

Association of IL-21 cytokine with severity of primary Sjögren syndrome dry eye.

IL-21 plays an important role in primary Sjögren syndrome (SS) pathogenesis. The purpose of this study was to evaluate IL-21 expression in tears and the conjunctiva and to analyze the impact of IL-21 on primary SS dry eyes. Eighty subjects were enrolled in this study: 30 patients with primary SS dry eye (30 eyes); 30 patients with non-SS dry eye (30 eyes), and 20 normal controls. Tear IL-21 levels were measured by flow cytometry, and IL-21 gene expression in the conjunctiva from impression cytology was evaluated by quantitative polymerase chain reaction. Ocular Surface Disease Index, tear film breakup time, Schirmer I test, and ocular surface staining scores were obtained for all patients. Primary SS dry eyes had significantly higher tear IL-21 levels than non-SS dry eyes and normal controls (P < 0.01). In addition, IL-21 gene expression in the conjunctiva was also higher in primary SS dry eyes than in non-SS dry eyes and normal controls (P < 0.01). However, there were no significant differences in IL-21 expression in tears and the conjunctiva between non-SS dry eyes and controls. The tear IL-21 level was significantly correlated with ocular surface stain scores (r = 0.54, P < 0.01) and Schirmer I test values (r = -0.23, P < 0.05) in primary SS dry eyes. Our findings suggest that severity of primary SS dry eye is associated with IL-21.

Expression of Th17 related cytokines on ocular surface of dry eye and its significance

Background The pathogenesis of dry eye has not been clearly established.There are more and more evidences to suggest that it is associated with ocular surface inflammation mediated by immunity.But how T helper cell 17 (Th17) plays its role in dry eye remains unclear.Objective The aim of this study was to investigate the expressions of Th17 related cytokines in ocular surface with dry eye.Methods A prospective cohortl study was designed.This protocol was approved by Ethic Commission of Peking University Third Hospital,and written informed consent was obtained from each subject prior to entering this cohort.Twenty female patients with Sjigren syndrome (SS group),20 patients with non-SS dry eyes and 20 normal volunteers were recruited in Peking University Third Hospital during 2011-2012 duration and all the subjects were menopausal female with the age 50 years old or more.The ocular surface disease index (OSDI)questionnaire designed by Schiffman was performed firstly,and then tear breakup time (BUT),corneal fluorescein staining and Schirmer Ⅰ test (S Ⅰ t) were carried out in the subjects.Expression of Th17 related cytokines mRNA were measured using PCR-Array.The correlation between IL-17A and ocular surface parameters was analyzed.Results The OSDI scores of the SS dry eye group,non-SS dry eye group and normal control group were 50.00 (33.50,66.50),45.00 (35.50,55.00) and 3.00 (0.00,5.00),the S Ⅰ t values were 2.50 (1.00,4.00),5.00 (2.00,5.00) and 15.50 (10.00,18.50),the BUT were 2.00 (1.00,4.00),4.00 (3.00,5.00) and 10.00 (10.00,12.00),the corneal fluorescein staining score were 8.50 (6.00,12.00),5.50 (4.00,7.00)and 0.00 (0.00,0.00),respectively,and significant differences were seen among the SS group,non-SS dry eye group and normal control group (x2=34.11,28.13,93.66,92.25,all at P＜0.01).The relative expression values of IL-17A mRNA,IL-6 mRNA,IL-8 mRNA,IL-22 mRNA and IL-23 mRNA in the ocular surface were 1.98±0.16,11.64±1.32,6.67±1.12,1.88±0.18 and 1.78±0.17 in the SS group patients,and 1.45±0.17,1.32±0.14,1.12 ±0.13,1.23 ±0.15 and 1.23 ±0.13 in the non-SS dry eye group patients,respectively,with significant differences between the two groups (all at P＜0.01).IL-17A level on the ocular surface was significantly negative correlated with BUT (r =-0.56,P＜0.01) and positive correlation with corneal fluorescein staining scores (r=0.44,P=0.01).Conclusions Expressions of Th17 related cytokines in the ocular surface increased in patients with dry eye,especially in those with SS.IL-17A level in ocular surface is associated with BUT and corneal fluorescein staining scores,suggesting that immune is involved in the pathogenesis and devlopment of dry eye. Key words: Dry eye; Sj(o)gren syndrome; Immunity; CD4-positive T-lymphocyte; Cytokine; Inflammation; Female; Prospective study

Proteomic analysis revealed the altered tear protein profile in a rabbit model of Sjögren's syndrome-associated dry eye

Sjögren's syndrome (SS) is an autoimmune disease that results in pathological dryness of mouth and eye. The diagnosis of SS depends on both clinical evaluation and specific antibodies. The goal of this study was to use quantitative proteomics to investigate changes in tear proteins in a rabbit model of SS-associated dry eye, induced autoimmune dacryoadenitis (IAD). Proteomic analysis was performed by iTRAQ and nano LC-MS/MS on tears collected from the ocular surface, and specific proteins were verified by high resolution MRM. It was found that in the tears of IAD rabbits at 2 and 4 weeks after induction, S100 A6, S100 A9, and serum albumin were upregulated, whereas serotransferrin (TF), prolactin-inducible protein (PIP), polymeric immunoglobulin receptor (pIgR), and Ig gamma chain C region were downregulated. High resolution MRM with mTRAQ labeling verified the changes in S100 A6, TF, PIP, and pIgR. Our results indicated significant changes of tear proteins in IAD rabbits, suggesting these proteins could potentially be used as biomarkers for the diagnosis and prognosis of dry eye. Several of these proteins were also found in the tears of non-SS dry eye patients indicating a common basis of ocular surface pathology, however, pIgR appears to be unique to SS.

Analysis of Tear Cytokines and Clinical Correlations in Sjögren Syndrome Dry Eye Patients and Non–Sjögren Syndrome Dry Eye Patients

To compare concentrations of tear cytokines in 3 groups composed of Sjögren syndrome (SS) dry eye, non-Sjögren syndrome (non-SS) dry eye, and normal subjects. Correlations between ocular surface parameters and tear cytokines were also investigated. Prospective cross-sectional study. SS dry eye patients (n = 24; 40 eyes) were diagnosed with primary SS according to the criteria set by the American-European Consensus Group. Non-SS dry eye patients (n = 25; 40 eyes) and normal subjects (n = 21; 35 eyes) were also enrolled. Tear concentrations of interleukin (IL)-17, IL-6, IL-10, IL-4, IL-2, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) were measured by a multiplex immunobead assay. Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), Schirmer I test, and fluorescein staining scores were obtained from dry eye patients. All cytokine levels except for IL-2 were highest in the SS group, followed by non-SS dry eye group and control subjects. Concentrations of IL-17, TNF-α, and IL-6 were significantly different among the 3 groups (IL-17: SS > control P < .001, non-SS > control P = .042, SS > non-SS P < .001; TNF-α: SS > control P = .006, non-SS > control P = .034, SS > non-SS P = .029; IL-6: SS > control P = .002, non-SS > control P = .032, SS > non-SS P = .002). IL-17 was significantly correlated with TBUT (R = -0.22, P = .012) and Schirmer I test (R = -0.36, P = .027) scores in the SS group. IL-6 was significantly correlated only with TBUT (R = -0.38, P = .02) in the non-SS group. Differences in tear cytokine levels and correlation patterns between SS dry eye and non-SS dry eye patients suggest the involvement of different inflammatory processes as causes of dry eye syndrome.

Tear Evaporation Rates in Sjögren Syndrome and non-Sjögren Dry Eye Patients

To reinvestigate tear evaporation rates in Sjögren syndrome (SS) and non-Sjögren (non-SS) dry eye patients with a recently reported ventilated chamber evaporimeter system. Prospective case-control study. A ventilated chamber evaporimeter system was used to measure tear evaporation rates. A DR-1 camera (Kowa, Nagoya, Japan) was used for tear lipid layer interference image acquisition. The Yokoi severity grading system was used for DR-1 image evaluation. Twenty-four aqueous tear deficiency (ATD) eyes of 21 consecutive patients with SS were studied (SS ATD group). Twenty-one ATD eyes of 12 non-SS patients (non-SS ATD group) were examined as control subjects. Tear evaporation rates of the SS ATD group (5.9 +/- 3.5 [10(-7) g/cm(2) per second]) were significantly higher than those of the non-SS ATD group (2.9 +/- 1.8 [10(-7) g/cm(2) per second]; P = .0009). The severity grading of DR-1 tear interference images of the SS ATD group was significantly higher (P = .03), along with significantly worse meibomian gland expressibility and vital staining scores, compared with those of the non-SS ATD group. Tear evaporation rates were higher in eyes of the SS ATD group compared with the non-SS ATD group. Tear evaporation assessed in conjunction with tear lipid layer findings and meibomian gland expressibility provides an increased understanding in the differential diagnosis of dry eye states.

Reflex tearing in dry eye not associated with Sjögren's syndrome.

Dry eye with tear deficiency is now classified into two categories: associated with Sjögren’s syndrome (SS), and not associated with Sjögren’s syndrome (non-SS).1 SS is an autoimmune disorder characterized by lymphocytic infiltration and destruction of exocrine glands.2 SS dry eye is more severe than non-SS dry eye, with the former showing more vital staining, squamous metaplasia, and lymphocytic infiltration of the conjunctival epithelium (Fig. 1).3–5

Decrease in Corneal Sensitivity and Change in Tear Function in Dry Eye

Our purpose was to investigate the relationship between insufficient tear secretion and decreased corneal sensitivity. We studied 59 patients with dry eye, 15 of whom had Sjögren's syndrome (SS), and 26 healthy subjects. Corneal sensitivity was measured by the esthesiometer of Cochet and Bonnet. Schirmer test with or without anesthesia, tear clearance rate, tear function index, and rose bengal and fluorescein staining were also evaluated. The mean corneal sensitivity of either dry-eye group (4.6 +/- 1.2 and 4.5 +/- 1.2 cm for non-SS and SS dry eye, respectively) was significantly lower than that of the control (5.8 +/- 0.4 cm, p < 0.001). Corneal sensitivity correlated significantly with the Schirmer values with anesthesia and the tear function index in the two dry-eye groups and the control (p < 0.05). There were significant relationships between corneal sensitivity and the rose bengal and fluorescein scores in the three groups (p < 0.05). Hyposecretion of tears in dry eye may lead to pathologic changes in corneal epithelium and a decline in corneal sensitivity. Prompt treatment of dry eye is essential to maintain a normal corneal protective mechanism.