Clinical Diagnostic Study of Inflammatory Cytokines in Aqueous Humor of Patients with Posner-Schlossman Syndrome

Clinical Diagnostic Study of Inflammatory Cytokines in Aqueous Humor of Patients with Posner-Schlossman Syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Clinical Diagnostic Study of Inflammatory Cytokines in Aqueous Humor of Patients with Posner-Schlossman Syndrome Yu Liu, Xiangmei Kong, Shengjie Li, Zhujian Wang, Wenjun Cao, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4614672/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: To detect the levels of inflammatory cytokines in the aqueous humor (AH) of Posner-Schlossman syndrome (PSS) patients and to evaluate their correlation with ophthalmic parameters in PSS patients. Methods: Aqueous humor (AH) samples were obtained from 29 eyes of PSS patients and 16 eyes of age-related cataract (ARC) patients (control group) diagnosed in the Eye and ENT Hospital, Fudan University. Multiplex microsphere flow cytometric immunoassay was used to detect multiple inflammatory cytokines in AH, including interleukin 1β (IL-1β), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin 12 (IL-12), interleukin 17 (IL-17), tumor necrosis factor (TNF)α, and interferon (IFN) γ. We collected ophthalmic parameters, including corneal endothelial cell density, visual acuity, intraocular pressure (IOP), and visual field respectively. Independent sample t-tests/Mann-Whitney U tests were used for intergroup comparisons, and ROC curves were analyzed using MedCalc19.6. Results: The levels of IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-γ, and TNF-α in the AH of PSS patients were significantly higher than that in the control group ( P <0.05). IL-6 showed a positive correlation with PSS key ophthalmic parameters IOP ( r =0.430, P =0.025) and relative decrease in CECD loss between the affected eye and the fellow eye (RECL) ( r =0.453, P =0.039) and a negative correlation with corneal endothelial cell count ( r =-0.463, P =0.035). The ROC curves showed that IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-γ, and TNF-α had diagnostic value for PSS ( P <0.05). Conclusion: The cytokine levels in the AH of PSS patients were abnormal, suggesting that inflammatory cytokines may also be involved in the pathogenesis of PSS. Note: CECD, corneal endothelial cell density; RECL, relative decrease in CECD loss between the affected eye and the fellow eye Health sciences/Biomarkers Health sciences/Biomarkers/Diagnostic markers Posner-Schlossman syndrome intraocular pressure corneal endothelial cell density cytokines Figures Figure 1 Introduction Posner-Schlossman syndrome is a specific type of secondary glaucoma first described by Posner and Schlossman in 1948. [ 1 ] It is characterized by non-granulomatous anterior uveitis and recurrent episodes of elevated intraocular pressure (IOP), with the fellow eye typically maintaining normal IOP. The condition commonly presents with ocular pain and/or unilateral blurred vision, and corneal keratic precipitates (KP) may be present. Posner-Schlossman syndrome predominantly affects individuals between 20–50 years of age, with a higher prevalence in males. [ 2 ] Some patients may experience simultaneous or alternating involvement of both eyes. [ 3 , 4 ] The underlying etiology and pathogenesis of PSS remain incompletely understood. Due to the lack of characteristic ocular lesions and diagnostic biomarkers, the diagnosis is often delayed, precluding timely and effective etiological interventions. With increasing recognition of the protracted and recurrent nature of PSS in many patients, [ 4 ] leading to significant societal and economic burdens, there is a growing interest in uncovering disease-associated biomarkers for accurate diagnostic testing in PSS. Several studies have suggested that elevated levels of inflammatory mediators in the aqueous humor (AH) of PSS patients provide evidence for inflammation-induced, sustained impairment of aqueous outflow, leading to secondary glaucoma. A multitude of cytokines are involved in the immune regulation of inflammatory glaucomas. [ 5 , 6 , 7 , 8 ] An international study revealed that the majority of PSS patients exhibit structural alterations of the trabecular meshwork, resulting in impaired aqueous outflow and elevated IOP, and that elevated cytokine levels are a possible cause of these changes [ 6 ] . Pohlmann et al. [ 9 ] found significant changes in several cytokines in the AH of PSS patients with active inflammation. Similarly, Ren et al. [ 10 ] found that the frequencies of interleukin-17A (IL-17A)-secreting cells and IL-17A + CD4 + T cells were significantly higher in patients with glaucoma than in controls. This suggests that IL-17 is involved in the pathogenesis of glaucoma. These findings suggest that inflammatory cytokines may play an important role in the pathogenesis of PSS. However, due to the complex interplay and regulation of cytokine expression, further studies is necessary. The current study investigates multiple cytokines in the AH of PSS patients and explores their correlations with clinical parameters, including visual acuity, IOP, and corneal endothelial cell density, to assess their potential utility as biomarkers for future laboratory diagnostics of PSS and provide data for clinical laboratory investigations. Materials and methods 1. Materials This study included 29 patients (29 eyes) diagnosed with PSS at the Department of Ophthalmology and Otorhinolaryngology, Fudan University Affiliated Eye and ENT Hospital, between August 2018 and November 2020. All control eyes had normal IOP and were excluded for glaucoma. The diagnosis of PSS was based on the following criteria: recurrent elevated IOP > 21 mmHg, with normal IOP between episodes; mild anterior chamber inflammation, with small keratic precipitates visible on slit-lamp examination; open iridocorneal angle, and normal IOP, visual field, and optic disc in the unaffected eye. [ 11 ] This study was approved by the Medical Ethics Committee of Fudan University Affiliated Eye and ENT Hospital, and complied with the Declaration of Helsinki. Informed consent was obtained from all patients. 2. Methods 2.1 Reagents and Instruments: A 12-plex cytokine kit (catalog number: 191217) was purchased from Hangzhou R&D Biological Technology Co., Ltd. Multiplex bead-based flow cytometric immunoassays were performed to detect various inflammatory cytokines in the aqueous humor, including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, IFN-γ, and TNF-α. 2.2 Sample Collection: Aqueous humor samples (100 µl) were obtained from PSS patients and control group patients by anterior chamber paracentesis. All samples were stored at -80℃. 2.3 Collection of Ocular Clinical Parameters Visual Acuity: Visual acuity was measured using an international logMAR visual acuity chart. Visual Field Examination: Visual fields were measured using an Octopus 900 automated perimeter. Corneal Endothelial Cell Density: Corneal endothelial cell density was measured using a corneal endothelial microscope (NSP-9900II). 2.4 Statistical Analysis: Statistical analysis was performed using SPSS 21.0 software (IBM SPSS Statistics Product 21.0). The Shapiro-Wilk test was used to assess normality. Normally distributed data with equal variances were expressed as mean ± standard deviation (X ± SD) and analyzed using independent samples t-tests. Non-normally distributed data were expressed as median (first quartile, third quartile) and analyzed using the Mann-Whitney U test. Categorical data were analyzed using the chi-square test. Spearman's rank correlation analysis was used to assess the correlation between cytokine levels and ocular parameters, including age, gender, IOP, corneal endothelial cell density, and visual field defects. | r |≥0.8 indicating a strong correlation, 0.5–0.8 a moderate correlation, 0.3–0.5 a weak correlation, and < 0.3 no correlation. P < 0.05 was considered statistically significant. Receiver operating characteristic (ROC) curves were generated using MedCalc19.6 (MedCalc Software Ltd., Ostend, Belgium). Results There were 19 males and 10 females, the age range of the patients was 31–71 years, with a mean age of 48.7 ± 10.9 years. The control group consisted of 16 patients (16 eyes) with ARC, aged 53–77 years, with a mean age of 54.0 ± 10.2 years.There was no statistically significant difference in age or gender distribution between the PSS and control groups ( P > 0.05). Compared with the cataract control group, the PSS group exhibited significantly elevated levels of IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-γ, and TNF-α in the aqueous humor( P < 0.05). IL-2 and IL-12 were below the detection limit in both the control and PSS groups. The results of the aqueous humor cytokine assays are summarized in Table 1 . The comparisons of individual cytokine levels between the two groups are shown in Fig. 1 . Table 1 Aqueous humor cytokine levels in PSS and cataract control groups. Aqueous humor cytokine levels (pg/ml) Control n = 16 PSS n = 29 P value IL- 1β 1.82(1.07, 2.46) 11.01(6.59, 14.31) < 0.001* IL-4 1.43(1.43, 1.54) 1.66(1.51, 1.78) < 0.001* IL-5 1. 14(1.07, 1.64) 1.96(1.55, 2.40) < 0.001* IL-6 2. 15(1.60, 3.34) 9.82(2.99, 189.92) < 0.001* IL-8 1.00(1.00, 3.00) 93.82(83.31, 191.85) < 0.001* IL- 10 1.07(1.07, 1.32) 1.59(1.38, 1.97) < 0.001* IL- 17 3.31(2.28, 3.98) 3.90(2.99, 5.25) 0.027* IFN-γ 2.42(2.25, 2.68) 4.56(2.42, 7.91) 0.039* TNF-α 1.60(1.42, 2.06) 2.62(2.39, 3.25) < 0.001* Data were not normally distributed; cytokine group comparisons were made using the Mann-Whitney U test, and results are presented as median (interquartile range); * denotes significance. PSS patients were divided into two groups according to gender, age ( 0.05). The comparison results are shown in Table 2 . Table 2 Comparison of cytokine levels in PSS patients stratified by gender, age, and coexisting cataract. The aqueous humor cytokines with PSS Gender(males vs females) ( r value) Age(<50 vs ≥ 50) ( r value) Cataract(with vs without) ( r value) IL- 1β 0.368 0.356 0.713 IL-4 0.053 0.805 0.550 IL-5 0.735 0.471 0.713 IL-6 0.438 0.256 0.604 IL-8 0.822 0.529 0.614 IL- 10 0.357 0.589 0.582 IL- 17 0.702 0.753 0.963 IFN-γ 0.060 0.512 0.180 TNF- α 0.982 0.216 0.130 Data were not normally distributed; cytokine group comparisons were made using the Mann-Whitney U test; * denotes statistically significant difference ( p < 0.05). The correlation analysis between aqueous humor cytokine levels and ocular parameters in the PSS group is shown in Table 3 . The ROC analysis results for aqueous humor cytokines in PSS patients are presented in Table 4 . Table 3 Correlation analysis between aqueous humor cytokine levels and ocular parameters in the PSS group. ocular parameters IL- 1β IL-4 IL-5 IL-6 IL-8 IL- 10 IL- 17 TNF-α IFN-γ visual acuity r value -0.009 0.282 0.361 -0.062 0.044 0.325 -0.099 0.103 -0.137 P value 0.968 0.182 0.083 0.775 0.838 0. 121 0.647 0.630 0.523 IOP (mmHg) r value 0.178 0.211 -0.118 0.430 0.365 0.280 -0.015 -0.194 -0.063 P value 0.375 0.290 0.559 0.025* 0.061 0.157 0.943 0.332 0.755 Cup palte ratio r value -0.213 -0.022 -0. 112 -0.082 -0.148 -0.180 0.085 0.238 -0.196 P value 0.354 0.924 0.629 0.723 0.521 0.436 0.715 0.298 0.396 Axial length (mm ) r value -0.147 -0.152 -0.128 0.014 0.117 0.024 -0.035 0.055 0.050 P value 0.464 0.451 0.525 0.945 0.560 0.905 0.862 0.785 0.803 MD(dB) r value -0.052 0.057 0.012 0.310 0. 141 -0.101 -0.027 -0.029 0.100 P value 0.799 0.776 0.951 0.116 0.482 0.616 0.893 0.886 0.620 MS(dB) r value 0. 121 0.157 0.131 -0.076 -0.060 0.047 -0.115 -0.149 -0.207 P value 0.557 0.443 0.525 0.712 0.770 0.819 0.576 0.469 0.311 CECD (cell/mm2 ) r value -0.265 -0.385 -0.037 -0.463 -0.428 -0.356 -0.041 0.061 0.101 P value 0.246 0.085 0.874 0.035* 0.053 0.113 0.860 0.791 0.662 RECL (cell/mm2 ) r value 0.106 0.025 -0.329 0.453 0.330 0.036 -0.071 -0.322 0.110 P value 0.647 0.915 0.146 0.039* 0. 144 0.876 0.760 0.154 0.635 Course(years) r value P value 0.209 0.243 0.357 -0.072 0.091 -0.002 0.053 0.088 -0.145 0.295 0.222 0.068 0.722 0.651 0.993 0.792 0.663 0.470 Spearman's rank correlation coefficients ( r ) are shown, with corresponding P values in parentheses. * P < 0.05 Note IOP, intraocular pressure; CECD, corneal endothelial cell density; RECL, relative decrease in CECD loss between the affected eye and the fellow eye; MD, mean deviation; MS, mean sensibility. Table 4 ROC analysis results for aqueous humor cytokines in PSS patients. AUC 95% CI P value Youden’s index Cutoff Sensitivity Specifitcity IL- 1β 0.942 0.829–0.990 < 0.001 0.931 3.33 93.10 100.00 IL-2 0.612 0.455–0.754 0.071 0.220 1.46 34.48 87.50 IL-4 0.839 0.700–0.932 < 0.001 < 0.001 1.58 68.97 93.75 IL-5 0.793 0.646–0.899 < 0.001 0.584 1.35 89.66 68.75 IL-6 0.830 0.688–0.925 < 0.001 0.621 6.6 62.07 100.00 IL-8 1.000 0.921–1.000 < 0.001 1.000 8.26 100.00 100.00 IL- 10 0.844 0.705–0.935 < 0.001 0.606 1.32 79.31 81.25 IL- 12 0.527 0.373–0.678 0.744 0.345 1.75 34.48 100.00 IL- 17 0.699 0.544–0.827 0.011 0.386 4.28 44.83 93.75 TNF-α 0.889 0.760–0.963 < 0.001 0.772 2.18 89.66 87.50 IFN-γ 0.685 0.530–0.815 0.020 0.496 3.13 62.07 87.50 P values were derived using the Spearman rank correlation test; * P < 0.05. 2.2 Correlation Analysis of Different Cytokines in Aqueous Humor in PSS Patients Spearman's rank correlation analysis was performed on the levels of various cytokines in the aqueous humor of PSS patients. The results showed a strong positive correlation between IL-6 and IL-8 ( P < 0.001, r = 0.732, 95% CI 0.500-0.866), as well as between IL-6 and IL-10 ( P = 0.014, r = 0.453, 95% CI 0.104–0.703). Additionally, significant positive correlations were observed between IL-4 and IL-5 ( P = 0.002, r = 0.546, 95% CI 0.224–0.760), and between IL-4 and IL-10 ( P = 0.004, r = 0.523, 95% CI 0.194–0.747). These correlations are summarized in Table 5 . Table 5 Correlation analysis of different cytokines in aqueous humor. IL- 1β IL-4 IL-5 IL-6 IL-8 IL- 10 IL- 17 TNF- α IFN-γ IL- 1β - 0.162 0.462 0.213 0.398 0.264 0.362 0.612 0.494 IL-4 0.162 - 0.002* 0.074 0.618 0.004* 0.287 0.649 0.058 IL-5 0.462 0.002* - 0.844 0.387 0.088 0.554 0.337 0.031* IL-6 0.213 0.074 0.844 - < 0.001* 0.014* 0.579 0.162 0.959 IL-8 0.398 0.618 0.387 < 0.001* - 0.020* 0.781 0.312 0.161 IL- 10 0.264 0.004* 0.088 0.014* 0.020* - 0.231 0.264 0.874 IL- 17 0.362 0.287 0.554 0.579 0.781 0.231 - 0.260 0.183 TNF-α 0.612 0.649 0.337 0.162 0.312 0.264 0.260 - 0.212 IFN-γ 0.494 0.058 0.031* 0.959 0.161 0.874 0.183 0.212 - Note: Spearman's rank correlation coefficients ( r ) are shown, with corresponding P values in parentheses. * P < 0.05, ** P < 0.01 Discussion In this study, multiplex microsphere flow cytometric immunoassay was used to detect the levels of inflammatory cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ) in the aqueous humor of patients with PSS and cataract. By comparing the cytokine expression levels and their correlations with various clinical parameters between the two groups, we aimed to identify novel strategies for the laboratory diagnosis of PSS. Our results demonstrated that the levels of IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-γ, and TNF-α were significantly elevated in the aqueous humor of PSS patients compared with the cataract control group ( P < 0.05). IL-1β, which can stimulate almost all cell types, [ 12 ] is one of the most potent cytokines and a crucial mediator of immune and inflammatory responses in various conditions. [ 13 ] Elevated IL-1β expression has been reported in the blood and aqueous humor of patients with ocular diseases such as glaucoma and macular degeneration. IL-1β can also alter the extracellular matrix of trabecular meshwork cells and increase aqueous outflow, thereby affecting IOP. [ 14 – 16 ] Our findings of significantly elevated IL-1β in the aqueous humor of PSS patients suggest its involvement in the inflammatory mechanisms of PSS. Previous studies have reported significantly increased levels of cytokines such as interleukin IL-4 and IL-8 in the aqueous humor of patients with primary open-angle glaucoma or pseudoexfoliative glaucoma. [ 17 ] Li et al. [ 18 ] demonstrated that the levels of IL-5, IL-6, IL-8, and TNF-α were higher in the aqueous humor of PSS patients compared with controls, while IL-2 and IL-12 levels were lower in the PSS group. Although the difference in IL-4 levels was not statistically significant, its detection rate was higher in the PSS group than in the control group. Our results are consistent with these previous reports, suggesting that IL-4 and IL-5 may be involved in the pathogenesis of PSS. In a recent study, Li et al. [ 18 ] reported significantly elevated levels of IL-6 and IL-8 in the aqueous humor of PSS patients. Moreover, the concomitant elevation of IL-6 and IL-8 levels could serve as a cytokine indicator for predicting the development of secondary open-angle glaucoma in PSS patients. Another study demonstrated that IL-6 levels in the aqueous humor of patients with corneal endothelial dysfunction-induced graft failure were 179 times higher than those in cataract controls, and the elevated aqueous humor cytokine levels were associated with rapid corneal endothelial cell loss. [ 19 ] These findings suggest that the immune response is rapidly activated under these conditions and is closely related to the disease status and tissue damage. Such characteristics make inflammatory factors like IL-6 potential biomarkers for tissue damage, disease progression, and the pathological status. Our results showed that the levels of IL-6 and IL-8 in the aqueous humor of PSS patients were significantly higher than those in the cataract control group ( P < 0.05) and exhibited correlations with elevated IOP and corneal endothelial cell loss. Therefore, IL-6 and IL-8 play important roles in the anterior chamber inflammation associated with PSS and could serve as potential biomarkers for monitoring inflammation and as novel targets for future anti-inflammatory therapies in PSS. IL-10 is secreted by Th2 cell and mainly regulates cell proliferation and differentiation. As an important anti-inflammatory cytokine, it participates in inflammatory responses. Viruses have been detected in the aqueous humor of some PSS patients and play a role in PSS pathogenesis, potentially affecting IL-10 levels. [ 20 ] Studies have also reported significantly elevated IL-10 levels in the aqueous humor of patients with Fuchs' syndrome. [ 21 ] Similarly, our results showed elevated IL-10 levels in the PSS group, suggesting its clinical significance in the diagnosis and management of PSS. IL-10 is an anti-inflammatory cytokine, but our data suggest that the situation may be more complex and could be related to the sampling time. The eye is an immune-privileged site, and maintaining immune balance to prevent immune responses against viral infections from causing tissue damage is an inherent protective mechanism of the eye. Therefore, while the inflammatory cytokine levels induced by viruses increase, the expression of IL-10, which suppresses inflammation, is also upregulated to achieve immune balance. IL-17, mainly produced by Th17 cells, is an important pro-inflammatory cytokine involved in the pathogenesis of various diseases. It is associated with inflammation and autoimmune disorders, and its high expression usually leads to aggravated inflammation . [ 22 ] Our study found that the IL-17 level in the aqueous humor of PSS patients was significantly higher than that in the cataract control group (P < 0.05), suggesting that IL-17 may be an important cytokine involved in the pathological damage of PSS. Other studies have also reported upregulated IL-17 in the aqueous humor of secondary glaucoma, where it promotes the recruitment of inflammatory cells to the lesion and triggers inflammation. [ 23 ] Li et al. [ 24 ] demonstrated increased IL-17 expression in an animal model of acute IOP elevation. Furthermore, targeted inhibition of IL-17 can significantly relieve uveitis symptoms. [ 25 ] IFN-γ is a cytokine secreted by Th1 cells that can inhibit T cell and macrophage proliferation and promote the apoptosis of inflammatory cells. [ 26 – 29 ] Chua et al. [ 30 ] found that IFN-γ levels were upregulated in the aqueous humor of POAG patients. Another study demonstrated that intravitreal injection of IFN-γ could induce intraocular inflammation. [ 31 ] Compared with non-infectious uveitis, IFN-γ levels are more significantly elevated in the aqueous humor of infectious uveitis, indicating that IFN-γ is related to inflammation and infection. [ 32 , 33 ] In our study, the IFN-γ level in the aqueous humor of PSS patients was significantly higher than that in the control group, suggesting the clinical value of IFN-γ in the diagnosis of PSS. In an animal experiment, the TNF-α concentration in the aqueous humor increased after traumatic cataract surgery and developed into secondary increased IOP, suggesting that TNF-α may be involved in the development of glaucoma. Studies have found that TNF-α in the aqueous humor of glaucoma patients may damage trabecular meshwork cells by inducing inflammation and apoptosis. [ 34 ] It has also been reported that TNF-α can increase IOP by promoting nitric oxide synthesis and damaging trabecular meshwork cells. Elevated IOP can then stimulate TNF-α production, leading to a vicious cycle that exacerbates trabecular meshwork damage and IOP elevation. [ 35 ] Research has shown that TNF-α can contribute to the prolongation of inflammation, and its expression level is significantly increased during inflammatory responses. [ 36 ] TNF-α levels are upregulated in various types of uveitis, and this is particularly evident in PSS, which is presumably caused by inflammation-induced TNF-α expression. [ 37 ] Kelley et al. [ 36 ] found that TNF-α and IL-1 can act synergistically on the trabecular meshwork to upregulate MMP-3, which can degrade the extracellular matrix of trabecular meshwork cells, reducing the resistance to aqueous outflow. Our results showed that the TNF-α level in the aqueous humor of PSS patients was significantly higher than that in the control group, indicating that TNF-α plays a role in the pathogenesis of PSS. Moreover, we found that the aqueous humor cytokine levels of IL-6 and IL-8 were significantly elevated in PSS patients and were both correlated with clinical manifestations of IOP and RECL, suggesting that inflammatory changes in PSS are highly correlated with elevated IOP and corneal endothelial cell damage. Our study has several limitations.The incidence of PSS is relatively low, and the disease course is prolonged with recurrent episodes, resulting in a small sample size. Moreover, the strict inclusion criteria, high pre-analytical sample control and screening, and high technical requirements for detection led to a small number of eligible cases and control samples finally included in the study. In terms of detection, more sensitive detection techniques and high-throughput research methods are needed in the future to conduct multicenter prospective studies and investigate eye disease-related biomarkers more systematically. Conclusion our study found significantly increased levels of inflammatory factors such as IL-1β in the aqueous humor of PSS patients, indicating that these molecules undergo significant changes in the aqueous humor of PSS and may be closely related to ocular lesions. The cytokines IL-6 and IL-8 in the aqueous humor exhibited a significant positive correlation, suggesting a close relationship between ocular lesions and immune responses and inflammation in PSS patients. Declarations The authors report no conflicts of interest in this work. Author contributions Yu liu and Zhujian Wang wrote the main manuscript text and Yifan Gong prepared figures 1. All authors reviewed the manuscript. 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Mac- 1(+) myelopoiesis induced by CFA: a clueto the paradoxical effects of IFN-gamma in autoimmune disease models[J]. Trends Immunol, 2001, 22: 367–371. Matthys P, Froyen G, Verdot L, et al. IFN-gamma receptor-deficient mice arehypersensitive to the anti-CD3-induced cytokine release syndrome and thymocyteapoptosis. Protective role of endogenous nitric oxide[J]. J Immunol, 1995, 155: 3823–3829. Chua J, Vania M, Cheung CM, et al. Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes[J]. Mol Vis, 2012, 18:431–438. Tang ML, Varigos G, Kemp AS. Reduced interferon-gamma (IFN-gamma)secretion with increased IFN-gamma mRNA expression in atopic dermatitis: evidence for a post-transcriptional defect [J]. Clin Exp Immunol, 1994,97(3):483–90. Takase H, Futagami Y, Yoshida T, et al. Cytokine profile in aqueous humor and sera of patients with infectious or noninfectious uveitis[J]. Invest Ophthalmol Vis Sci, 2006,47:1557–1561. Novelli F, Casanova JL. The role of IL- 12, IL-23 and IFN-gamma in immunitytoviruses[J]. Cytokine Growth Factor Rev, 2004, 15: 367–377. Sarfarazi M, Rezaie T. Optineurin in primary open angle glaucoma[J]. Ophthalmol Clin NorthAm, 2003, 16(4):529–541. Schneemann A, Leusink Muis A, Vail den Berg T, et a1. Elevation of nitric oxide production in human trabecular meshwork by increased pressure[J]. Graefes Arch Clin Exp Ophthalmol, 2003,241(4):321–326. Kelley MJ, Rose AY, Song K, et al. Synergism of TNF and IL- 1 in the induction of matrix metalloproteinase-3 in trabecular meshwork[J]. Invest Ophthalmol Vis Sci, 2007, 48(6): 2634–2643. Lahdou IMAD, Engler C, Mehrke S, et a1. Role of Human Corneal Endothelial Cells in t-cell-mediated Alloimmune Attack in Vitro[J]. Invest Ophthalmol Vis Sci, 2014,55(3):1213–1221. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4614672","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":325867825,"identity":"e2f754e2-af9b-40d1-9f7c-2847c2134221","order_by":0,"name":"Yu Liu","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Liu","suffix":""},{"id":325867826,"identity":"0daca5f1-b7dc-4db9-8072-da01ee45b1c4","order_by":1,"name":"Xiangmei Kong","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Xiangmei","middleName":"","lastName":"Kong","suffix":""},{"id":325867827,"identity":"46ca8187-1ed0-466e-9aa5-e19bd2d19643","order_by":2,"name":"Shengjie Li","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Shengjie","middleName":"","lastName":"Li","suffix":""},{"id":325867828,"identity":"5824054b-0e5d-4611-bfa6-647f32573731","order_by":3,"name":"Zhujian Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYLACxgYGZjYg9SChooY0LcwGD84cI14LCLBJPmxhJqza4PjZwy9/7jjMzsd+9lhFYgMbA397dwJ+LWfy0iwkzxxmZuPJS7uRuEOGQeLM2Q14tZgdyDEzMGwDamHIMbuReIaNwUAil4CW82/MDBJBWvjfmBUktjEToeVGjvGDgyAtEjlmDERpsb/xxoyxsS0dqOWNsUTCmWM8BP0i2Z9j/PFnm3WyfH+O4ccfFTVy/O29+LUAAZsEkEiG8XgIKQcB5g9Awo4YlaNgFIyCUTBCAQB9Z0f8+euShwAAAABJRU5ErkJggg==","orcid":"","institution":"Fudan University","correspondingAuthor":true,"prefix":"","firstName":"Zhujian","middleName":"","lastName":"Wang","suffix":""},{"id":325867829,"identity":"037e7ae3-cf78-4dca-8b87-d30b14031135","order_by":4,"name":"Wenjun Cao","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Wenjun","middleName":"","lastName":"Cao","suffix":""},{"id":325867830,"identity":"566004e8-e6f3-4e2a-9f25-1442dfe1ffc6","order_by":5,"name":"Yifan Gong","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Yifan","middleName":"","lastName":"Gong","suffix":""}],"badges":[],"createdAt":"2024-06-21 03:44:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4614672/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4614672/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60624384,"identity":"ce92d74f-8974-4f74-b483-44c5f91e3597","added_by":"auto","created_at":"2024-07-18 22:13:58","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":56647,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of individual cytokine levels between the PSS and cataract control groups\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4614672/v1/b70bd859cf7af701fabf65f6.jpg"},{"id":75067284,"identity":"b35b7eac-d1f9-4620-b8af-c2d5f741245e","added_by":"auto","created_at":"2025-01-30 06:03:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":926699,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4614672/v1/7247b8ba-15b0-44d8-929c-5540ccd4a143.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Diagnostic Study of Inflammatory Cytokines in Aqueous Humor of Patients with Posner-Schlossman Syndrome","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePosner-Schlossman syndrome is a specific type of secondary glaucoma first described by Posner and Schlossman in 1948.\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e It is characterized by non-granulomatous anterior uveitis and recurrent episodes of elevated intraocular pressure (IOP), with the fellow eye typically maintaining normal IOP. The condition commonly presents with ocular pain and/or unilateral blurred vision, and corneal keratic precipitates (KP) may be present. Posner-Schlossman syndrome predominantly affects individuals between 20\u0026ndash;50 years of age, with a higher prevalence in males.\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e Some patients may experience simultaneous or alternating involvement of both eyes.\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe underlying etiology and pathogenesis of PSS remain incompletely understood. Due to the lack of characteristic ocular lesions and diagnostic biomarkers, the diagnosis is often delayed, precluding timely and effective etiological interventions. With increasing recognition of the protracted and recurrent nature of PSS in many patients,\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e leading to significant societal and economic burdens, there is a growing interest in uncovering disease-associated biomarkers for accurate diagnostic testing in PSS.\u003c/p\u003e \u003cp\u003eSeveral studies have suggested that elevated levels of inflammatory mediators in the aqueous humor (AH) of PSS patients provide evidence for inflammation-induced, sustained impairment of aqueous outflow, leading to secondary glaucoma. A multitude of cytokines are involved in the immune regulation of inflammatory glaucomas.\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e An international study revealed that the majority of PSS patients exhibit structural alterations of the trabecular meshwork, resulting in impaired aqueous outflow and elevated IOP, and that elevated cytokine levels are a possible cause of these changes\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Pohlmann et al.\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e found significant changes in several cytokines in the AH of PSS patients with active inflammation. Similarly, Ren et al.\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e found that the frequencies of interleukin-17A (IL-17A)-secreting cells and IL-17A\u003csup\u003e+\u003c/sup\u003e CD4\u003csup\u003e+\u003c/sup\u003eT cells were significantly higher in patients with glaucoma than in controls. This suggests that IL-17 is involved in the pathogenesis of glaucoma. These findings suggest that inflammatory cytokines may play an important role in the pathogenesis of PSS. However, due to the complex interplay and regulation of cytokine expression, further studies is necessary. The current study investigates multiple cytokines in the AH of PSS patients and explores their correlations with clinical parameters, including visual acuity, IOP, and corneal endothelial cell density, to assess their potential utility as biomarkers for future laboratory diagnostics of PSS and provide data for clinical laboratory investigations.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e1. Materials\u003c/p\u003e\n\u003cp\u003eThis study included 29 patients (29 eyes) diagnosed with PSS at the Department of Ophthalmology and Otorhinolaryngology, Fudan University Affiliated Eye and ENT Hospital, between August 2018 and November 2020. All control eyes had normal IOP and were excluded for glaucoma. The diagnosis of PSS was based on the following criteria: recurrent elevated IOP \u0026gt; 21 mmHg, with normal IOP between episodes; mild anterior chamber inflammation, with small keratic precipitates visible on slit-lamp examination; open iridocorneal angle, and normal IOP, visual field, and optic disc in the unaffected eye.\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e This study was approved by the Medical Ethics Committee of Fudan University Affiliated Eye and ENT Hospital, and complied with the Declaration of Helsinki. Informed consent was obtained from all patients.\u003c/p\u003e\n\u003cp\u003e2. Methods\u003c/p\u003e\n\u003cp\u003e2.1 Reagents and Instruments: A 12-plex cytokine kit (catalog number: 191217) was purchased from Hangzhou R\u0026amp;D Biological Technology Co., Ltd. Multiplex bead-based flow cytometric immunoassays were performed to detect various inflammatory cytokines in the aqueous humor, including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, IFN-γ, and TNF-α.\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e2.2 Sample Collection: Aqueous humor samples (100 µl) were obtained from PSS patients and control group patients by anterior chamber paracentesis. All samples were stored at -80℃.\u003c/p\u003e\u003cspan\u003e\n \u003cp\u003e2.3 Collection of Ocular Clinical Parameters\u003c/p\u003e\n\u003c/span\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eVisual Acuity: Visual acuity was measured using an international logMAR visual acuity chart. Visual Field Examination: Visual fields were measured using an Octopus 900 automated perimeter. Corneal Endothelial Cell Density: Corneal endothelial cell density was measured using a corneal endothelial microscope (NSP-9900II).\u003c/p\u003e\n\u003cp\u003e2.4 Statistical Analysis: Statistical analysis was performed using SPSS 21.0 software (IBM SPSS Statistics Product 21.0). The Shapiro-Wilk test was used to assess normality. Normally distributed data with equal variances were expressed as mean ± standard deviation (X ± SD) and analyzed using independent samples t-tests. Non-normally distributed data were expressed as median (first quartile, third quartile) and analyzed using the Mann-Whitney U test. Categorical data were analyzed using the chi-square test. Spearman's rank correlation analysis was used to assess the correlation between cytokine levels and ocular parameters, including age, gender, IOP, corneal endothelial cell density, and visual field defects. |\u003cem\u003er\u003c/em\u003e|≥0.8 indicating a strong correlation, 0.5–0.8 a moderate correlation, 0.3–0.5 a weak correlation, and \u0026lt; 0.3 no correlation. \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 was considered statistically significant. Receiver operating characteristic (ROC) curves were generated using MedCalc19.6 (MedCalc Software Ltd., Ostend, Belgium).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThere were 19 males and 10 females, the age range of the patients was 31–71 years, with a mean age of 48.7 ± 10.9 years. The control group consisted of 16 patients (16 eyes) with ARC, aged 53–77 years, with a mean age of 54.0 ± 10.2 years.There was no statistically significant difference in age or gender distribution between the PSS and control groups (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).\u003c/p\u003e\u003cp\u003eCompared with the cataract control group, the PSS group exhibited significantly elevated levels of IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-γ, and TNF-α in the aqueous humor(\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05). IL-2 and IL-12 were below the detection limit in both the control and PSS groups. The results of the aqueous humor cytokine assays are summarized in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The comparisons of individual cytokine levels between the two groups are shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAqueous humor cytokine levels in PSS and cataract control groups.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eAqueous humor cytokine levels\u003c/p\u003e\n \u003cp\u003e(pg/ml)\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003cp\u003en = 16\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003ePSS\u003c/p\u003e\n \u003cp\u003en = 29\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 1β\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.82(1.07, 2.46)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e11.01(6.59, 14.31)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001*\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-4\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.43(1.43, 1.54)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.66(1.51, 1.78)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001*\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-5\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1. 14(1.07, 1.64)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.96(1.55, 2.40)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001*\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-6\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e2. 15(1.60, 3.34)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e9.82(2.99, 189.92)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001*\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-8\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.00(1.00, 3.00)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e93.82(83.31, 191.85)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001*\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 10\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.07(1.07, 1.32)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.59(1.38, 1.97)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001*\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 17\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e3.31(2.28, 3.98)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e3.90(2.99, 5.25)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.027*\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIFN-γ\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e2.42(2.25, 2.68)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e4.56(2.42, 7.91)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.039*\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eTNF-α\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.60(1.42, 2.06)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e2.62(2.39, 3.25)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001*\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\n\u003c/div\u003e\u003cp\u003eData were not normally distributed; cytokine group comparisons were made using the Mann-Whitney U test, and results are presented as median (interquartile range); * denotes significance.\u003c/p\u003e\u003cp\u003ePSS patients were divided into two groups according to gender, age (\u0026lt; 50 years), and presence of coexisting cataract. The Mann-Whitney U test revealed no significant differences in any of the cytokines between the two groups (P \u0026gt; 0.05). The comparison results are shown in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u0026nbsp;\u003c/p\u003e\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of cytokine levels in PSS patients stratified by gender, age, and coexisting cataract.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eThe aqueous humor cytokines with PSS\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eGender(males vs females)\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003er\u003c/em\u003e value)\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eAge(\u0026lt;50 vs ≥ 50)\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003er\u003c/em\u003e value)\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eCataract(with vs without)\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003er\u003c/em\u003e value)\u003c/p\u003e\n \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 1β\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.368\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.356\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.713\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-4\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.805\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.550\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-5\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.735\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.471\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.713\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-6\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.438\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.256\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.604\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-8\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.822\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.529\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.614\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 10\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.357\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.589\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.582\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 17\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.702\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.753\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.963\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIFN-γ\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.060\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.512\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.180\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eTNF- α\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.982\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.216\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.130\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003cp\u003eData were not normally distributed; cytokine group comparisons were made using the Mann-Whitney U test; * denotes statistically significant difference (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05).\u003c/p\u003e\u003cp\u003eThe correlation analysis between aqueous humor cytokine levels and ocular parameters in the PSS group is shown in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. The ROC analysis results for aqueous humor cytokines in PSS patients are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCorrelation analysis between aqueous humor cytokine levels and ocular parameters in the PSS group.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eocular parameters\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL- 1β\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL-4\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL-5\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL-6\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL-8\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL- 10\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL- 17\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eTNF-α\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIFN-γ\u003c/p\u003e\n \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003evisual acuity\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003er\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.009\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.282\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.361\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.062\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.044\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.325\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.099\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.103\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.137\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.968\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.182\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.083\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.775\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.838\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0. 121\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.647\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.630\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.523\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eIOP\u003c/p\u003e\n \u003cp\u003e(mmHg)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003er\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.178\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.211\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.118\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.430\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.365\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.280\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.015\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.194\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.063\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.375\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.290\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.559\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.025*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.061\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.943\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.332\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.755\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eCup palte ratio\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003er\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.213\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.022\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0. 112\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.082\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.148\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.180\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.238\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.196\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.354\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.924\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.629\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.723\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.521\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.436\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.715\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.298\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.396\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eAxial length (mm )\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003er\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.147\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.152\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.128\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.117\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.035\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.050\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.464\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.451\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.525\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.945\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.560\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.905\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.862\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.785\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.803\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eMD(dB)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003er\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.052\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.310\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0. 141\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.101\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.027\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.029\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.799\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.776\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.951\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.482\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.616\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.893\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.886\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.620\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eMS(dB)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003er\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0. 121\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.131\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.076\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.060\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.115\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.149\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.207\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.557\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.443\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.525\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.712\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.770\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.819\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.576\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.469\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.311\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eCECD\u003c/p\u003e\n \u003cp\u003e(cell/mm2 )\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003er\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.265\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.385\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.037\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.463\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.428\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.356\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.041\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.061\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.101\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.246\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.874\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.035*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.860\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.791\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.662\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eRECL\u003c/p\u003e\n \u003cp\u003e(cell/mm2 )\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003er\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.106\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.329\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.453\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.330\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.071\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.322\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.647\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.915\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.146\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.039*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0. 144\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.876\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.760\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.154\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.635\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eCourse(years)\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003er\u003c/em\u003e value\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.209\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.243\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.357\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.072\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.002\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.145\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.295\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.222\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.068\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.722\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.651\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.993\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.792\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.663\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.470\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\n\u003c/div\u003e\u003cp\u003eSpearman's rank correlation coefficients (\u003cem\u003er\u003c/em\u003e) are shown, with corresponding P values in parentheses. *\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eNote\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eIOP, intraocular pressure; CECD, corneal endothelial cell density; RECL, relative decrease in CECD loss between the affected eye and the fellow eye; MD, mean deviation; MS, mean sensibility.\u0026nbsp;\u003c/p\u003e\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eROC analysis results for aqueous humor cytokines in PSS patients.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eAUC\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eYouden’s index\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eCutoff\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eSensitivity\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eSpecifitcity\u003c/p\u003e\n \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 1β\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.942\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.829–0.990\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.931\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e3.33\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e93.10\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-2\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.612\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.455–0.754\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.220\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.46\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e34.48\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e87.50\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-4\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.839\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.700–0.932\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.58\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e68.97\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e93.75\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-5\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.793\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.646–0.899\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.584\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.35\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e89.66\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e68.75\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-6\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.830\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.688–0.925\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.621\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e6.6\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e62.07\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-8\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.921–1.000\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e8.26\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 10\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.844\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.705–0.935\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.606\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.32\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e79.31\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e81.25\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 12\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.527\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.373–0.678\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.744\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.345\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1.75\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e34.48\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e100.00\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 17\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.699\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.544–0.827\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.386\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e4.28\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e44.83\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e93.75\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eTNF-α\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.889\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.760–0.963\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.772\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e2.18\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e89.66\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e87.50\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIFN-γ\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.685\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.530–0.815\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e0.496\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e3.13\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e62.07\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e87.50\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e values were derived using the Spearman rank correlation test; * \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e\u003cp\u003e2.2 Correlation Analysis of Different Cytokines in Aqueous Humor in PSS Patients\u003c/p\u003e\u003cp\u003eSpearman's rank correlation analysis was performed on the levels of various cytokines in the aqueous humor of PSS patients. The results showed a strong positive correlation between IL-6 and IL-8 (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001, \u003cem\u003er\u003c/em\u003e = 0.732, 95% CI 0.500-0.866), as well as between IL-6 and IL-10 (\u003cem\u003eP\u003c/em\u003e = 0.014, \u003cem\u003er\u003c/em\u003e = 0.453, 95% CI 0.104–0.703). Additionally, significant positive correlations were observed between IL-4 and IL-5 (\u003cem\u003eP\u003c/em\u003e = 0.002, \u003cem\u003er\u003c/em\u003e = 0.546, 95% CI 0.224–0.760), and between IL-4 and IL-10 (\u003cem\u003eP\u003c/em\u003e = 0.004, \u003cem\u003er\u003c/em\u003e = 0.523, 95% CI 0.194–0.747). These correlations are summarized in Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCorrelation analysis of different cytokines in aqueous humor.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL- 1β\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL-4\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL-5\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL-6\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL-8\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL- 10\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIL- 17\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eTNF- α\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eIFN-γ\u003c/p\u003e\n \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 1β\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.462\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.213\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.398\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.264\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.362\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.612\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.494\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-4\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.002*\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.618\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.287\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.649\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-5\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.462\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.844\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.387\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.554\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.337\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.031*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-6\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.213\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.844\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.014*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.579\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.959\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-8\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.398\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.618\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.387\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt; 0.001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.020*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.781\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.312\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.161\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 10\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.264\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.014*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.020*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.231\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.264\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.874\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIL- 17\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.362\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.287\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.554\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.579\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.781\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.231\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.260\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.183\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eTNF-α\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.612\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.649\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.337\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.312\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.264\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.260\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.212\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eIFN-γ\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.494\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.031*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.959\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.161\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.874\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.183\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e0.212\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"10\"\u003eNote: Spearman's rank correlation coefficients (\u003cem\u003er\u003c/em\u003e) are shown, with corresponding \u003cem\u003eP\u003c/em\u003e values in parentheses. *\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05, **\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.01\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, multiplex microsphere flow cytometric immunoassay was used to detect the levels of inflammatory cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ) in the aqueous humor of patients with PSS and cataract. By comparing the cytokine expression levels and their correlations with various clinical parameters between the two groups, we aimed to identify novel strategies for the laboratory diagnosis of PSS. Our results demonstrated that the levels of IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-γ, and TNF-α were significantly elevated in the aqueous humor of PSS patients compared with the cataract control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eIL-1β, which can stimulate almost all cell types,\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e is one of the most potent cytokines and a crucial mediator of immune and inflammatory responses in various conditions.\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e Elevated IL-1β expression has been reported in the blood and aqueous humor of patients with ocular diseases such as glaucoma and macular degeneration. IL-1β can also alter the extracellular matrix of trabecular meshwork cells and increase aqueous outflow, thereby affecting IOP.\u003csup\u003e[\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003eOur findings of significantly elevated IL-1β in the aqueous humor of PSS patients suggest its involvement in the inflammatory mechanisms of PSS.\u003c/p\u003e \u003cp\u003ePrevious studies have reported significantly increased levels of cytokines such as interleukin IL-4 and IL-8 in the aqueous humor of patients with primary open-angle glaucoma or pseudoexfoliative glaucoma.\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e Li et al. \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e demonstrated that the levels of IL-5, IL-6, IL-8, and TNF-α were higher in the aqueous humor of PSS patients compared with controls, while IL-2 and IL-12 levels were lower in the PSS group. Although the difference in IL-4 levels was not statistically significant, its detection rate was higher in the PSS group than in the control group. Our results are consistent with these previous reports, suggesting that IL-4 and IL-5 may be involved in the pathogenesis of PSS.\u003c/p\u003e \u003cp\u003eIn a recent study, Li et al. \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e reported significantly elevated levels of IL-6 and IL-8 in the aqueous humor of PSS patients. Moreover, the concomitant elevation of IL-6 and IL-8 levels could serve as a cytokine indicator for predicting the development of secondary open-angle glaucoma in PSS patients. Another study demonstrated that IL-6 levels in the aqueous humor of patients with corneal endothelial dysfunction-induced graft failure were 179 times higher than those in cataract controls, and the elevated aqueous humor cytokine levels were associated with rapid corneal endothelial cell loss.\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e These findings suggest that the immune response is rapidly activated under these conditions and is closely related to the disease status and tissue damage. Such characteristics make inflammatory factors like IL-6 potential biomarkers for tissue damage, disease progression, and the pathological status. Our results showed that the levels of IL-6 and IL-8 in the aqueous humor of PSS patients were significantly higher than those in the cataract control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and exhibited correlations with elevated IOP and corneal endothelial cell loss. Therefore, IL-6 and IL-8 play important roles in the anterior chamber inflammation associated with PSS and could serve as potential biomarkers for monitoring inflammation and as novel targets for future anti-inflammatory therapies in PSS.\u003c/p\u003e \u003cp\u003eIL-10 is secreted by Th2 cell and mainly regulates cell proliferation and differentiation. As an important anti-inflammatory cytokine, it participates in inflammatory responses. Viruses have been detected in the aqueous humor of some PSS patients and play a role in PSS pathogenesis, potentially affecting IL-10 levels.\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e Studies have also reported significantly elevated IL-10 levels in the aqueous humor of patients with Fuchs' syndrome.\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e Similarly, our results showed elevated IL-10 levels in the PSS group, suggesting its clinical significance in the diagnosis and management of PSS. IL-10 is an anti-inflammatory cytokine, but our data suggest that the situation may be more complex and could be related to the sampling time. The eye is an immune-privileged site, and maintaining immune balance to prevent immune responses against viral infections from causing tissue damage is an inherent protective mechanism of the eye. Therefore, while the inflammatory cytokine levels induced by viruses increase, the expression of IL-10, which suppresses inflammation, is also upregulated to achieve immune balance.\u003c/p\u003e \u003cp\u003eIL-17, mainly produced by Th17 cells, is an important pro-inflammatory cytokine involved in the pathogenesis of various diseases. It is associated with inflammation and autoimmune disorders, and its high expression usually leads to aggravated inflammation .\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e Our study found that the IL-17 level in the aqueous humor of PSS patients was significantly higher than that in the cataract control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), suggesting that IL-17 may be an important cytokine involved in the pathological damage of PSS. Other studies have also reported upregulated IL-17 in the aqueous humor of secondary glaucoma, where it promotes the recruitment of inflammatory cells to the lesion and triggers inflammation.\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e Li et al.\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e demonstrated increased IL-17 expression in an animal model of acute IOP elevation. Furthermore, targeted inhibition of IL-17 can significantly relieve uveitis symptoms.\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIFN-γ is a cytokine secreted by Th1 cells that can inhibit T cell and macrophage proliferation and promote the apoptosis of inflammatory cells.\u003csup\u003e[\u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e Chua et al.\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e found that IFN-γ levels were upregulated in the aqueous humor of POAG patients. Another study demonstrated that intravitreal injection of IFN-γ could induce intraocular inflammation.\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e Compared with non-infectious uveitis, IFN-γ levels are more significantly elevated in the aqueous humor of infectious uveitis, indicating that IFN-γ is related to inflammation and infection.\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e In our study, the IFN-γ level in the aqueous humor of PSS patients was significantly higher than that in the control group, suggesting the clinical value of IFN-γ in the diagnosis of PSS.\u003c/p\u003e \u003cp\u003eIn an animal experiment, the TNF-α concentration in the aqueous humor increased after traumatic cataract surgery and developed into secondary increased IOP, suggesting that TNF-α may be involved in the development of glaucoma. Studies have found that TNF-α in the aqueous humor of glaucoma patients may damage trabecular meshwork cells by inducing inflammation and apoptosis.\u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e It has also been reported that TNF-α can increase IOP by promoting nitric oxide synthesis and damaging trabecular meshwork cells. Elevated IOP can then stimulate TNF-α production, leading to a vicious cycle that exacerbates trabecular meshwork damage and IOP elevation.\u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eResearch has shown that TNF-α can contribute to the prolongation of inflammation, and its expression level is significantly increased during inflammatory responses.\u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003eTNF-α levels are upregulated in various types of uveitis, and this is particularly evident in PSS, which is presumably caused by inflammation-induced TNF-α expression.\u003csup\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/sup\u003e Kelley et al.\u003csup\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e found that TNF-α and IL-1 can act synergistically on the trabecular meshwork to upregulate MMP-3, which can degrade the extracellular matrix of trabecular meshwork cells, reducing the resistance to aqueous outflow. Our results showed that the TNF-α level in the aqueous humor of PSS patients was significantly higher than that in the control group, indicating that TNF-α plays a role in the pathogenesis of PSS.\u003c/p\u003e \u003cp\u003eMoreover, we found that the aqueous humor cytokine levels of IL-6 and IL-8 were significantly elevated in PSS patients and were both correlated with clinical manifestations of IOP and RECL, suggesting that inflammatory changes in PSS are highly correlated with elevated IOP and corneal endothelial cell damage.\u003c/p\u003e \u003cp\u003eOur study has several limitations.The incidence of PSS is relatively low, and the disease course is prolonged with recurrent episodes, resulting in a small sample size. Moreover, the strict inclusion criteria, high pre-analytical sample control and screening, and high technical requirements for detection led to a small number of eligible cases and control samples finally included in the study. In terms of detection, more sensitive detection techniques and high-throughput research methods are needed in the future to conduct multicenter prospective studies and investigate eye disease-related biomarkers more systematically.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eour study found significantly increased levels of inflammatory factors such as IL-1β in the aqueous humor of PSS patients, indicating that these molecules undergo significant changes in the aqueous humor of PSS and may be closely related to ocular lesions. The cytokines IL-6 and IL-8 in the aqueous humor exhibited a significant positive correlation, suggesting a close relationship between ocular lesions and immune responses and inflammation in PSS patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors report no conflicts of interest in this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYu liu and Zhujian Wang \u0026nbsp;wrote the main manuscript text and Yifan Gong prepared figures 1. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePosner A, Schlossman A. Syndrome of unilateral recurrent attacks of glaucoma with cyclitic symptoms[J]. Arch Ophthal, 1948,39(4):517\u0026ndash;535.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiang JH, Zhang SD, Dai ML, et al. Posner-Schlossman syndrome in Wenzhou, China: a retrospective review study[J]. 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Invest Ophthalmol Vis Sci, 2014,55(3):1213\u0026ndash;1221.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Posner-Schlossman syndrome, intraocular pressure, corneal endothelial cell density, cytokines","lastPublishedDoi":"10.21203/rs.3.rs-4614672/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4614672/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e To detect the levels of inflammatory cytokines in the aqueous humor (AH) of Posner-Schlossman syndrome (PSS) patients and to evaluate their correlation with ophthalmic parameters in PSS patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Aqueous humor (AH) samples were obtained from 29 eyes of PSS patients and 16 eyes of age-related cataract (ARC) patients (control group) diagnosed in the Eye and ENT Hospital, Fudan University. Multiplex microsphere flow cytometric immunoassay was used to detect multiple inflammatory cytokines in AH, including interleukin 1β (IL-1β), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin 12 (IL-12), interleukin 17 (IL-17), tumor necrosis factor (TNF)α, and interferon (IFN) γ. We collected ophthalmic parameters, including corneal endothelial cell density, visual acuity, intraocular pressure (IOP), and visual field respectively. Independent sample t-tests/Mann-Whitney U tests were used for intergroup comparisons, and ROC curves were analyzed using MedCalc19.6.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The levels of IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-γ, and TNF-α in the AH of PSS patients were significantly higher than that in the control group (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05). IL-6 showed a positive correlation with PSS key ophthalmic parameters IOP (\u003cem\u003er\u003c/em\u003e=0.430, \u003cem\u003eP\u003c/em\u003e=0.025) and relative decrease in CECD loss between the affected eye and the fellow eye (RECL) (\u003cem\u003er\u003c/em\u003e=0.453, \u003cem\u003eP\u003c/em\u003e=0.039) and a negative correlation with corneal endothelial cell count (\u003cem\u003er\u003c/em\u003e=-0.463, \u003cem\u003eP\u003c/em\u003e=0.035). The ROC curves showed that IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-γ, and TNF-α had diagnostic value for PSS (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The cytokine levels in the AH of PSS patients were abnormal, suggesting that inflammatory cytokines may also be involved in the pathogenesis of PSS.\u003c/p\u003e\n\u003cp\u003eNote: CECD, corneal endothelial cell density; RECL, relative decrease in CECD loss between the affected eye and the fellow eye\u003c/p\u003e","manuscriptTitle":"Clinical Diagnostic Study of Inflammatory Cytokines in Aqueous Humor of Patients with Posner-Schlossman Syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-18 22:13:53","doi":"10.21203/rs.3.rs-4614672/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"12ec28ce-d18e-46bd-a219-32474e8120f5","owner":[],"postedDate":"July 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":34478531,"name":"Health sciences/Biomarkers"},{"id":34478532,"name":"Health sciences/Biomarkers/Diagnostic markers"}],"tags":[],"updatedAt":"2025-01-30T05:53:44+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-18 22:13:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4614672","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4614672","identity":"rs-4614672","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}