Analysis of cytokine profiles in aqueous humor based on optical coherence tomography in pachychoroid spectrum diseases

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AH samples were analyzed using a multiplex bead assay for cytokines including vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), IL-8, IL-10, IP-10, and MCP-1. Results showed no significant differences in IL-6 (P = 0.122) and MCP-1 (P = 0.054) levels among groups. However, VEGF levels were significantly higher in CSC, PNV, and PCV compared to controls (all P < 0.05). In CSC and PNV, only VEGF was elevated without significant changes in other inflammatory cytokines, suggesting that inflammation was not a dominant factor. In contrast, PCV exhibited significantly higher levels of VEGF, IL-10, and IP-10, indicating distinct cytokine profiles. These findings suggest that elevated angiogenic and inflammatory cytokines may contribute to the pathogenesis of PCV. Health sciences/Diseases/Eye diseases Health sciences/Molecular medicine aqueous humor cytokine central serous chorioretinopathy pachychoroid neovasculopathy polypoidal choroidal vasculopathy Figures Figure 1 Figure 2 Introduction Pachychoroid disease spectrum, including pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), pachychoroid neovasculopathy (PNV), and polypoidal choroidal vasculopathy (PCV), has been widely described 1 . The clinical manifestations common to pachychoroid diseases include focal or diffuse choroidal thickening, dilated Haller’s layer vessels (pachyvessels) with thinning of the overlying inner choroid, and retinal pigment epithelium (RPE) abnormalities as well 2 . Although the pathophysiology of pachychoroid spectrum diseases remains controversial, abnormal choroidal changes with dilation of large choroidal vessels and increased permeability are recognized to play an important role 3 . There is growing evidence to suggest an overlap between CSC and other pachychoroid disorders such as PNV and PCV 4 . For instance, both serous detachments and RPE abnormalities could be seen in CSC and PCV, making it difficult to distinguish the two pachychoroid phenotypes. And these formerly independent disease entities are considered to represent a disease continuum, in which CSC might stage into PNV, and then ultimately into PCV 5,6 . However, not all patients with CSC could progress to PNV, nor do all PNV patients eventually develop PCV. The molecular mechanism explaining the progressions of these distinct pachychoroid phenotypes was not yet fully elucidated. Studies have shown that CSC is frequently complicated by choroidal neovascularization (CNV) 7,8 . And CNV was reportedly present as well above the pachyvessels in PNV and PCV 9–11 . It is well-established that vascular endothelial growth factor (VEGF) and other angiogenic factors contribute to CNV formation. To our knowledge, little is known about molecular pathological aspects of choroidal abnormality, which may be a major cause of CSC, PNV, and PCV. Measurement of cytokines in the aqueous humor (AH) may address the distinct molecular pathogenesis within the pachychoroid spectrum of macular disorders. In this study, we evaluated and compared cytokine profiles in the AH of CSC, PNV, and PCV patients. In addition, relationships between cytokine concentrations were analyzed among the three groups. Results Clinical features Table 1 shows the demographic and clinical characteristics of patients with CSC, PNV, PCV, and normal controls. A total of 172 AH samples were collected from 132 patients in the study group and 40 controls. Significant differences in age (P < 0.001), best-corrected visual acuity (BCVA) (P < 0.001), central macular thickness (CMT) (P = 0.005), and subfoveal choroidal thickness (SFCT) (P < 0.001) among the CSC, PNV, and PCV groups were confirmed by the Kruskal–Wallis test. CMT was greater in the PCV group than in the CSC (P = 0.001) and PNV (P = 0.041) groups, whereas there were no differences in CMT between the CSC and PNV groups (P = 0.335). SFCT was greater in the CSC group (P < 0.001) and the PNV group (P < 0.001) compared to the PCV group, whereas there were no differences in SFCT between the CSC and PNV groups (P = 0.254). Sex was not different among the three groups (P = 0.170). Table 1 Demographic and Clinical Characteristics Among the Pachychoroid Groups and the Controls. Pachychoroid Spectrum Diseases CSC (n = 65) PNV (n = 24) PCV (n = 43) P * Total (n = 132) Controls (n = 40) P † Age (y), mean ± SD 48.0 ± 8.1 49.2 ± 8.9 66.7 ± 10.7 < 0.001 54.3 ± 12.6 70.6 ± 7.5 < 0.001 Sex, male (%) 46 (70.8) 12 (50.0) 26 (60.5) 0.170 84 (63.6) 22 (55.0) 0.325 BCVA (logMAR) 0.22 (0.10–0.40) 0.46 (0.15–0.78) 0.70 (0.40-1.00) < 0.001 0.40 (0.15–0.70) 0.40 (0.22–0.52) 0.556 CMT (µm) 327.00 (242.50–425.00) 364.50 (272.75-457.25) 400.00 (321.00-536.00) 0.005 361.50 (276.00-476.50) / SFCT (µm) 475.00 (387.50–522.00) 382.50 (324.50-480.50) 205.00 (145.00-305.00) < 0.001 385.00 (284.50-492.25) / Variables with a skewed distribution are the median (interquartile range, [IQR]). CMT, central macular thickness; SFCT, subfoveal choroidal thickness. < 0.05 was considered significant (bold). * Kruskal–Wallis test among pachychoroid subtypes. † Mann–Whitney U test between the eyes with pachychoroid diseases and controls. Concentrations of cytokines In this study, six cytokines (VEGF, IL-6, IL-8, IL-10, IP-10, and MCP-1) stably detected in all AH samples were used for statistical analysis (Table 2 , Fig. 1 ). In the PCV group, levels of VEGF (P = 0.002), IL-10 (P < 0.001), and IP-10 (P < 0.001) were significantly higher than in controls. There were no significant differences in cytokine levels except for elevated VEGF levels between the CSC/PNV and control groups (P = 0.022 and P = 0.008, respectively). Table 2 Levels of Cytokines in the Aqueous Humor of Patients with Pachychoroid Spectrum Diseases and in Controls. Eyes with Pachychoroid Diseases CSC(n = 65) PNV(n = 24) PCV(n = 44) P* Total(n = 132) Controls(n = 40) P † VEGF 34.89 (24.50-47.28) 35.97 (28.71–47.53) 37.81 (25.71–49.09) 0.474 36.84 (25.77–47.28) 27.91 (20.71–35.42) 0.010 IL-6 4.51 (3.54–5.42) 5.56 (3.84–8.13) 2.95 (1.98–4.81) < 0.001 4.17 (2.99–5.66) 4.53 (1.56–7.96) 0.534 IL-8 7.49 (5.43–9.80) 9.89 (6.11–12.63) 9.90 (7.46–22.28) 0.018 8.27 (5.98–12.34) 8.09 (4.74–13.14) 0.645 IL-10 0.67 (0.64–0.67) 0.67 (0.59–0.79) 0.88 (0.79–1.41) < 0.001 0.67 (0.67–0.88) 0.63 (0.49–0.87) 0.008 IP-10 143.84 (93.87–214.30) 216.35 (165.84-363.33) 528.30 (340.31-842.44) < 0.001 221.37 (127.75-464.82) 147.70 (112.61-239.28) 0.003 MCP-1 409.84 (368.25-507.02) 479.52 (392.09-573.22) 491.74 (389.95-618.85) 0.054 442.48 (380.47-546.66) 396.99 (327.15-546.32) 0.389 Concentrations of cytokines are expressed as the median (interquartile range, [IQR]). VEGF, vascular endothelial growth factor; IL-6, interleukin 6; IL-8, interleukin 8; IL-10, interleukin 10; IP-10, interferon-inducible protein 10; MCP-1, monocyte chemotactic protein 1. P < 0.05 was considered significant (bold). * Kruskal–Wallis test among pachychoroid subtypes. † Mann–Whitney U test between the eyes with pachychoroid diseases and controls. Table 3 showed the relationships between cytokine concentrations in the AH among the groups via Spearman’s rank correlation coefficients. The concentrations of VEGF were not correlated with any detected cytokines in the study among the CSC, PNV, and PCV groups. Table 3 Spearman’s Rank Correlation Coefficient for Cytokines in the Aqueous Humor of Patients with Pachychoroid Diseases and in Controls. VEGF IL-6 IL-8 IL-10 IP-10 MCP-1 CSC VEGF 1 IL-6 -0.012 1 IL-8 0.097 0.534* 1 IL-10 -0.168 0.044 0.170 1 IP-10 0.014 0.522* 0.728* 0.141 1 MCP-1 0.073 0.541* 0.647* 0.101 0.556* 1 PNV VEGF 1 IL-6 -0.110 1 IL-8 0.405 0.532 ‡ 1 IL-10 0.108 -0.359 0.060 1 IP-10 0.005 0.301 0.402 0.251 1 MCP-1 0.396 0.574† 0.550† -0.215 0.288 1 PCV VEGF 1 IL-6 0.046 1 IL-8 0.019 0.746* 1 IL-10 0.299 0.236 0.018 1 IP-10 -0.058 0.331‡ 0.528* 0.057 1 MCP-1 -0.059 0.655* 0.798* -0.052 0.601* 1 Controls VEGF 1 IL-6 0.000 1 IL-8 0.071 0.598* 1 IL-10 0.446† -0.251 0.022 1 IP-10 -0.023 0.103 0.500† -0.017 1 MCP-1 0.060 0.488† 0.663* -0.033 0.328‡ 1 P < 0.05 was considered significant. *P < 0.001. †P < 0.01. ‡P < 0.05. Aqueous humor cytokines levels in CSC patients with different types of PED Retinal pigment epithelial detachment (PED) is a classical biomarker of CSC imaged by SD-OCT. Based on differences in shape, size, and reflectivity, PED can be classified into two subtypes: focal PED and flat irregular PED (FIPED) 12 . Cytokine levels in the AH of 65 eyes with CSC, including 34 FIPED eyes and 31 focal PED eyes, and 40 control eyes were analyzed (Table 4 ). The mean VEGF levels in the FIPED group were 36.95 (27.84–48.25) pg/ml, higher than those in the focal PED group [30.20 (19.97–40.88) pg/ml, P = 0.018] and the control group [27.91 (20.71–35.42) pg/ml, P = 0.001] (Fig. 2 ). The levels of VEGF were similar in the focal PED and controls (P = 0.401, Fig. 2 ). No significant differences were noted in the levels of IL-6, IL-8, IL-10, IP-10, and MCP-1 among the FIPED, the focal PED, and controls (all P > 0.05). Table 4 Levels of Cytokines Among Different Types of Pigment Epithelial Detachments (PEDs) in Patients with CSC. FIPED (n = 34) Focal PED (N = 31) Controls P ∗ VEGF 36.95 (27.84–48.25) 30.20 (19.97–40.88) 27.91 (20.71–35.42) 0.001 IL-6 4.93 (3.72–6.04) 4.02 (3.54–5.14) 4.53 (1.56–7.96) 0.468 IL-8 7.77 (6.02–11.62) 7.41 (5.43–9.16) 8.09 (4.74–13.14) 0.766 IL-10 0.67 (0.58–0.69) 0.67 (0.66–0.67) 0.63 (0.49–0.87) 0.185 IP-10 131.37 (91.78–319.10) 154.01 (91.60-207.46) 147.70 (112.61-239.28) 0.778 MCP-1 402.18 (370.21-504.39) 418.01 (352.77-514.39) 396.99 (327.15-546.32) 0.834 Values are the median (interquartile range, [IQR]). FIPED, flat irregular pigment epithelial detachment; PED, pigment epithelium detachment. VEGF, vascular endothelial growth factor; IL-6, interleukin 6; IL-8, interleukin 8; IL-10, interleukin 10; IP-10, interferon-inducible protein 10; MCP-1, monocyte chemotactic protein 1. P < 0.05 was considered significant (bold). ∗ Kruskal–Wallis test among the FIPED, the Focal PED, and Controls. Discussion This study provides the first comprehensive analysis of intraocular cytokines of patients with pachychoroid spectrum diseases including CSC, PNV, and PCV. In CSC and PNV, VEGF was elevated without the elevation of proinflammatory cytokines. In the PCV, VEGF and proinflammatory cytokines IL-10 and IP-10 were significantly higher than those in controls. Although a number of studies have described specific clinical and anatomical features of the four pachychoroid subtypes PPE, CSC, PNV, and PCV, their respective pathophysiology remains to be fully elucidated. The clinic manifestations common to the pachychoroid spectrum include choriocapillaris attenuation and abnormally dilated pachyvessels with choroidal vascular hyperpermeability 1 . The presence of choroidal morphologic changes as a key pathophysiologic mechanism was essential to diagnosing the pachychoroid spectrum of macular disorders. Cytokines were considered to be involved in ocular diseases that contributed to choroidal abnormalities 13 . This study aimed to investigate and compare various cytokine concentrations in the aqueous humor of patients with CSC, PNV, and PCV to better understand the respective molecular pathogenesis of these pachychoroid entities. CSC was the archetypal disease of the pachychoroid spectrum, characterized by serous neurosensory retinal detachment at the posterior pole 1 . Choroidal congestion and choroidal hyperpermeability were believed to contribute to CSC 1 . Our study showed that the proangiogenic cytokine VEGF levels were distinctly upregulated in the CSC group than in the control group. Liu et al have reported that the AH concentration of VEGF was significantly higher in various CNV diseases including CSC 14 . However, there was evidence that aqueous or plasma VEGF levels in patients with acute or chronic CSC were downregulated compared with the controls 15,16 . As the pathogenesis of CSC has not been fully elucidated, the true role of VEGF in CSC is unknown and warrants further investigation. No significant disparity was observed in other inflammatory factors between the CSC and control groups, suggesting that inflammatory mediators might play a minor role in CSC pathophysiology. Pigment epithelial detachment (PED) is a well-recognized feature of CSC and was commonly observed in all stages of CSC. According to the different morphologies, PED can be classified into two different types: typical focal PED and flat irregular PED (FIPED) 17 . Clinical features of CSC may vary depending on the diverse type of PED. Hwang et al found that CSC patients with FIPED involved more CNV and behaved with favorable anti-VEGF responsiveness in such cases 17 . It was unclear whether there was an association between the type of PED and cytokine levels. And the underlying molecular and cellular mechanisms of FIPED remain to be elucidated. We investigated and compared AH cytokine profiles according to PED type in CSC patients. In our study, the levels of VEGF were higher in eyes with FIPED than those in the focal PED and control groups, whereas no disparities were observed in IL-6, IL-8, IL-10, IP-10, and MCP-1 levels among the focal PED, FIPED and control groups. Our findings may explain why favorable treatment responses to anti-VEGF tend to occur in CSC patients with FIPED and the effect of inflammation mediators in CSC pathology was very minor. And this also showed that CSC was not an inflammatory disease. PNV is a newly proposed clinical entity within a spectrum of “pachychoroid driven disease”, characterized by thick choroid, RPE abnormalities, and/or choroidal vascular hyperpermeability 18 . PNV is often misdiagnosed as neovascular age-related macular degeneration (nAMD) because neovascularization is similar both in PNV and AMD 19 . It is well known that the activation of proinflammatory cytokines and subsequent upregulation of angiogenic factors, especially vascular endothelial growth factor (VEGF), play a pivotal role in CNV formation. In PNV, ischemia in the choriocapillaris or RPE dysfunction, resulting from compression of expanded choroidal vessels, led to overexpression of angiogenic factors and neovascularization. It was rational that proangiogenic cytokine VEGF was elevated in AH of patients with PNV than in the controls in our study. Terao et al. compared cytokine profiles in AH of PNV and nAMD and found that VEGF-A levels were significantly lower in the PNV group than in the nAMD group but were no disparity compared with normal controls 20 . Hata et al. found that the mean VEGF concentration in the AH of patients with PNV was significantly lower than that in nAMD 21 . Their study suggested that PNV and nAMD may have different pathophysiology and CNV in the pachychoroid phenotype was triggered by a lower VEGF concentration threshold than in nAMD. PCV, as one entity of the pachychoroid spectrum disease, is characterized by a branching vascular network with terminal aneurysmal (polypoidal) dilatations. It is increasingly thought to be a variant manifestation of type 1 neovascularization and may be closely correlated with CSC 22,23 . The etiology of PCV is still unclear. VEGF is considered a major stimulus for pathological angiogenesis in all eyes with CNV. Clinical studies have shown that intravitreal triamcinolone acetonide injection for the treatment of PCV was effective 24,25 , suggesting inflammation may play a contributing role in the pathogenesis of PCV. Other evidence indicated that proinflammatory factors such as IL-23, C-reactive protein, MCP-1, VEGF, and tumor necrosis factor-a were elevated in eyes with PCV 26–28 . In the present study, strong VEGF, IL-10, and IP-10 expression in AH was found in PCV eyes. We inferred that the disease continuum from CSC to PCV was also accompanied by the accumulation of inflammatory cytokines. This study has several limitations. First, the AH samples may not be as valuable as vitreous fluid for detecting cytokine concentrations at the site of pathology in the retina and choroid. Second, there may be many other cytokines associated with pachychoroid spectrum diseases that were not included in this study, so more relevant new cytokines need to be explored in the future. In summary, VEGF was elevated without the elevation of other inflammatory cytokines in CSC and PNV, indicating that inflammation was not the dominant factor on CSC and PNV diseases. PCV had significantly distinct cytokine profiles in the AH compared with controls. Elevated angiogenic and inflammatory cytokines, such as VEGF, IL-10, and IP-10, may contribute to the pathogenesis of PCV. In addition, higher VEGF levels in CSC patients with FIPED verified that VEGF contributed more to the pathogenesis of FIPED compared with focal PED. Methods This prospective, comparative, observational study was conducted in compliance with the tenets of the Declaration of Helsinki; the research was approved by the Institutional Review Board of Zhejiang Provincial People's Hospital (IRB number#KY2022022). Written informed consent was obtained from the subjects after detailed explanation of the study protocol. Study paticipants 65 eyes of patients with treatment-naïve CSC, 24 eyes had treatment-naïve PNV, and 43 eyes had treatment-naïve PCV were enrolled between January 2018 and June 2022 at Zhejiang Provincial People's Hospital and Affiliated Eye Hospital of Wenzhou Medical University. And 40 eyes who were scheduled to receive cataract surgery were recruited as controls. All patients received comprehensive ophthalmic examinations, including best-corrected visual acuity (BCVA) testing with the standard logarithmic visual acuity chart, slit-lamp biomicroscopy, color fundus photographs, fluorescein angiography (FA), indocyanine green angiography (ICGA), spectral-domain optical coherence tomography (SD-OCT) and OCT angiography. Diagnosis of CSC, PNV, and PCV The CSC diagnosis was based on: (1) OCT demonstrating the presence of subretinal fluid and/or serous pigment epithelium detachment involving the fovea; (2) FA showing the typical leakage points at the level of the RPE in the macular region; (3) symptom duration exceeding 3 months 4 . PNV was diagnosed using the following criteria based on the latest reports: (1) type-1 CNV detected in either eye; (2) no or only non-extensive drusen or hard drusen in both eyes; (3) dilated choroidal vessels or thicking below type 1 CNV detected by ICGA and OCT; (4) choroidal vascular hyperpermeability detected in the late phase of ICGA; and (5) RPE abnormality independent of CNV lesions detected by FA or a history of CSC 4 . PCV was diagnosed based on early subretinal ICGA hyperfluorescence and at least one of the following diagnostic criteria: (1) a sharply peaked pigment epithelium detachment (PED), subretinal pigment epithelium ring-like structures, double-layer sign, choroidal thickening with pachyvessels, and subretinal and subretinal pigment epithelium fluid on SD-OCT images. (2) nodular appearance of the polypoidal lesion on stereoscopic viewing, (3) hypofluorescent halo around the nodule, (4) abnormal vascular networks supplying the polypoidal lesion, (5) multiple aneurysmal staining or polypoidal lesions in the late phase of ICGA 4 . The exclusion criteria were (1) patients with any other systemic conditions including diabetes, cardiovascular diseases, cerebrovascular diseases, or malignancies. (2) history of other retinal disorders except for the inclusion were considered pachychoroid diseases. (3) previous anti-VEGF intravitreal injections or other intraocular procedures within the last 6 months. Aqueous Humor Collection AH samples (usually a volume of 0.1 ml) of eyes with CSC, PNV, or PCV were withdrawn before intravitreal conbercept (0.5 mg/0.05 ml; Kanghong Biotechnologies Co. Ltd, Chengdu, Sichuan Province, China) using a syringe with a 30-gauge needle (Nipro, Osaka, Japan) after topical anesthesia. The AH of controls was aspirated before cataract surgery in the same manner. All samples were transferred to a sterile tube and stored at − 80°C until cytokine analysis. Cytokine concentrations were analyzed using Multi-Analyte Profiling (xMAP; Luminex200, Hercules, CA, USA). All procedures were undertaken in the dark at room temperature, avoiding light-induced contamination. Image Analysis The central macula thickness (CMT) and subfoveal choroidal thickness (SFCT) were recorded using the caliper function of the Spectralis instrument. CMT was defined as the vertical distance between the RPE surface and the internal limiting membrane surface. Measuring SFCT from the hyperreflective line corresponding to Bruch’s membrane below the RPE to the inner surface of the sclera. Statistical Analysis Statistical analysis was performed using SPSS 26.0 software (IBM SPSS Inc., Chi cago, IL, USA). Continuous variables are presented as means ± standard deviation and categorical variables were assessed using Chi-squared tests. Quantitative variables were tested for normal distribution by the Shapiro–Wilk test. Data with a skewed distribution are expressed as the median and interquartile range (IQR). Intergroup comparisons of quantitative variables were made using the one-way analysis of variance (ANOVA) for normally distributed variables and the Kruskal–Wallis test for variables with nonnormal distribution. For the Kruskal–Wallis test, P values for multiple testing were corrected by the method of Bonferroni. Spearman’s rank correlation coefficients were used to evaluate the relationships between cytokine concentrations in the AH among the pachychoroid subtypes and control groups. P value < 0.05 was considered to be statistically significant. Declarations Date availability The data are not available for public access because of patient privacy concerns, but are available from the corresponding author upon reasonable request. Author Contributions C.Y.Z analyzed the data and wrote the original draft; J.B.M conceptualized and designed the study; Y.Z, S.A.Z, and Z.Y.X collected the data; L.J.S reviewed the draft and approved the final version of the manuscript. Funding This work was supported by the Medical and Health Research Project of Zhejiang Province (2023KY490). Competing interests The authors declare no competing interests. Additional information Correspondence and requests for materials should be addressed to J.B.M References Hua, R., Duan, J. & Zhang, M. Pachychoroid spectrum disease: Underlying pathology, classification, and phenotypes. Curr. Eye. Res. 46 , 1437–1448. http://doi.org/10.1080/02713683.2021.1942073 (2021). Mazzeo, T. J. M. M. et al. Pachychoroid disease spectrum: Review article. Graefes. Arch. Clin. 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Rep. 8 , 10520. http://doi.org/10.1038/s41598-018-28484-w (2018). Hata, M. et al. Intraocular vascular endothelial growth factor levels in pachychoroid neovasculopathy and neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 58 , 292–298. http://doi.org/10.1167/iovs.16-20967 (2017). Dansingani, K. K., Gal-Or, O., Sadda, S. R., Yannuzzi, L. A. & Freund, K. B. Understanding aneurysmal type 1 neovascularization (polypoidal choroidal vasculopathy): a lesson in the taxonomy of 'expanded spectra' - a review. Clin. Exp. Ophthalmol. 46 , 189–200. http://doi.org/10.1111/ceo.13114 (2018). Manayath, G. J., Shah, V. S., Saravanan, V. R. & Narendran, V. Polypoidal choroidal vasculopathy associated with central serous chorioretinopathy: Pachychoroid spectrum of diseases. Retina 38 , 1195–1204. http://doi.org/10.1097/IAE.0000000000001665 (2018). Liang, I. C., Lin, Y. R., Chien, H. W. & Liu, K. R. Vision preservation in eyes of polypoidal choroidal vasculopathy with low-dose intravitreal triamcinolone acetonide. J. Ocul. Pharmacol. Ther. 33 , 42–49. http://doi.org/10.1089/jop.2015.0150 (2017). Zhang, K. et al. Periocular triamcinolone acetonide injection for treating polypoidal choroidal vasculopathy concurrent with hemorrhagic retinal detachment. Medicine (Baltimore) 97 , 12464. http://doi.org/10.1097/MD.0000000000012464 (2018). Sasaki, S. et al. Associations of IL-23 with polypoidal choroidal vasculopathy. Invest. Ophthalmol. Vis. Sci. 53 , 3424–3430. http://doi.org/10.1167/iovs.11-7913 (2012). Zhou, H., Zhao, X., Yuan, M. & Chen, Y. Comparison of cytokine levels in the aqueous humor of polypoidal choroidal vasculopathy and neovascular age-related macular degeneration patients. BMC. Ophthalmol. 20 , 15. http://doi.org/10.1186/s12886-019-1278-8 (2020). Hu, J. et al. The features of inflammation factors concentrations in aqueous humor of polypoidal choroidal vasculopathy. PLoS. One. 11 , 0147346. http://doi.org/10.1371/journal.pone.0147346 (2016). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 01 Jul, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 29 Apr, 2025 Reviews received at journal 28 Apr, 2025 Reviews received at journal 16 Apr, 2025 Reviewers agreed at journal 08 Apr, 2025 Reviewers agreed at journal 06 Apr, 2025 Reviewers invited by journal 22 Mar, 2025 Editor invited by journal 17 Mar, 2025 Editor assigned by journal 13 Mar, 2025 Submission checks completed at journal 13 Mar, 2025 First submitted to journal 12 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-6212666","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":430132397,"identity":"0185bb92-59be-422d-96c5-36a737cee7b9","order_by":0,"name":"Caiyun Zhang","email":"","orcid":"","institution":"Zhejiang Provincial People's Hospital, Hangzhou Medical College","correspondingAuthor":false,"prefix":"","firstName":"Caiyun","middleName":"","lastName":"Zhang","suffix":""},{"id":430132399,"identity":"d17c811a-da0f-4af9-aef3-cf27a560144d","order_by":1,"name":"Yu Zhao","email":"","orcid":"","institution":"Hangzhou Medical College","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Zhao","suffix":""},{"id":430132400,"identity":"297a89b5-cb62-46b5-858d-7ac9b38e9498","order_by":2,"name":"Shian Zhang","email":"","orcid":"","institution":"Zhejiang Provincial People's Hospital, Hangzhou Medical College","correspondingAuthor":false,"prefix":"","firstName":"Shian","middleName":"","lastName":"Zhang","suffix":""},{"id":430132401,"identity":"86c9cfce-4a90-4779-963b-556b9a9efa93","order_by":3,"name":"Ziyi Xiang","email":"","orcid":"","institution":"Zhejiang Provincial People's Hospital, Hangzhou Medical College","correspondingAuthor":false,"prefix":"","firstName":"Ziyi","middleName":"","lastName":"Xiang","suffix":""},{"id":430132402,"identity":"0cb01f23-78b9-4d51-bf82-1ae55b088e6f","order_by":4,"name":"Lijun Shen","email":"","orcid":"","institution":"Zhejiang Provincial People's Hospital, Hangzhou Medical College","correspondingAuthor":false,"prefix":"","firstName":"Lijun","middleName":"","lastName":"Shen","suffix":""},{"id":430132403,"identity":"7e580a43-80b4-450b-ac72-35679193714c","order_by":5,"name":"Jianbo Mao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwUlEQVRIiWNgGAWjYHACZiC2keNnb2A4QIKWhDRjyZ4DpGk5nLjhRgKR6s3bmx8bfPzBzNhw8/nDwwU1DPL8YgQskzlzzDhxRgIbM+PsHIPDM44xGM6cTcA6CYkc5sM8CTxszNI5DId52BgSDG4To+VPggQPm+TxB4d5/hGpJRmoToJHgsHgMG8bMVp4jhkb9qSB9AD9wtsnQYRf2JsfS/yw+V+///jxx595vtnI80sT0IJhBGnKR8EoGAWjYBRgBwCQpz5fM6OCzgAAAABJRU5ErkJggg==","orcid":"","institution":"Zhejiang Provincial People's Hospital, Hangzhou Medical College","correspondingAuthor":true,"prefix":"","firstName":"Jianbo","middleName":"","lastName":"Mao","suffix":""}],"badges":[],"createdAt":"2025-03-12 13:53:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6212666/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6212666/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-04130-0","type":"published","date":"2025-07-01T15:58:02+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":78827971,"identity":"0b5c3883-0030-4ce5-808e-5758c01f8bff","added_by":"auto","created_at":"2025-03-19 13:00:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":73915,"visible":true,"origin":"","legend":"\u003cp\u003eColumn showing mean concentrations of six cytokines in aqueous humor of pachychoroiddiseases patients and controls. *P \u0026lt; 0.05, Kruskal–Wallis test. (A) The levels of VEGF were higher in pachychoroid entities than in controls (CSC vs controls, P = 0.022; PNV vs controls, P = 0.008; PCV vs controls, P = 0.002). (B) There were no significant differences in IL-6 among the four groups. (C) For IL-8, there was a statistically significant difference overall among the four groups (P = 0.041) but the difference between groups was not statistically significant. (D) IL-10 levels were higher in PCV compared to controls (P \u0026lt; 0.001). (E) IP-10 levels were higher in PCV than in controls (P \u0026lt; 0.001). (F) There were no significant differences in the levels of MCP-1 among the pachychoroidand control groups (P = 0.054). pg/ml, picogram per millilitre.\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6212666/v1/58871d615900ed9346f75a96.png"},{"id":78827242,"identity":"bcdb27c7-f786-4646-8c5f-dbfae52def9e","added_by":"auto","created_at":"2025-03-19 12:52:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":46189,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the VEGF levels in CSC patients with different PED types and controls. The mean VEGF levels in the FIPED group were higher than in the focal PED group (P = 0.018) and in the control group (P = 0.001), and no difference was observed between the focal and control groups (P = 0.401). *P \u0026lt; 0.05, one-way ANOVA. FIPED, flat irregular pigment epithelial detachment; PED, pigment epithelial detachment.\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6212666/v1/6f5375e7e73992465167e7fb.png"},{"id":86179093,"identity":"913e6425-6c16-4a8d-83e5-3eabe3dafc93","added_by":"auto","created_at":"2025-07-07 16:15:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1077397,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6212666/v1/c10c0774-514f-4004-a2b1-08be25c3f439.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of cytokine profiles in aqueous humor based on optical coherence tomography in pachychoroid spectrum diseases","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePachychoroid disease spectrum, including pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), pachychoroid neovasculopathy (PNV), and polypoidal choroidal vasculopathy (PCV), has been widely described\u003csup\u003e1\u003c/sup\u003e. The clinical manifestations common to pachychoroid diseases include focal or diffuse choroidal thickening, dilated Haller\u0026rsquo;s layer vessels (pachyvessels) with thinning of the overlying inner choroid, and retinal pigment epithelium (RPE) abnormalities as well\u003csup\u003e2\u003c/sup\u003e. Although the pathophysiology of pachychoroid spectrum diseases remains controversial, abnormal choroidal changes with dilation of large choroidal vessels and increased permeability are recognized to play an important role\u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThere is growing evidence to suggest an overlap between CSC and other pachychoroid disorders such as PNV and PCV\u003csup\u003e4\u003c/sup\u003e. For instance, both serous detachments and RPE abnormalities could be seen in CSC and PCV, making it difficult to distinguish the two pachychoroid phenotypes. And these formerly independent disease entities are considered to represent a disease continuum, in which CSC might stage into PNV, and then ultimately into PCV\u003csup\u003e5,6\u003c/sup\u003e. However, not all patients with CSC could progress to PNV, nor do all PNV patients eventually develop PCV. The molecular mechanism explaining the progressions of these distinct pachychoroid phenotypes was not yet fully elucidated. Studies have shown that CSC is frequently complicated by choroidal neovascularization (CNV)\u003csup\u003e7,8\u003c/sup\u003e. And CNV was reportedly present as well above the pachyvessels in PNV and PCV\u003csup\u003e9\u0026ndash;11\u003c/sup\u003e. It is well-established that vascular endothelial growth factor (VEGF) and other angiogenic factors contribute to CNV formation.\u003c/p\u003e \u003cp\u003eTo our knowledge, little is known about molecular pathological aspects of choroidal abnormality, which may be a major cause of CSC, PNV, and PCV. Measurement of cytokines in the aqueous humor (AH) may address the distinct molecular pathogenesis within the pachychoroid spectrum of macular disorders. In this study, we evaluated and compared cytokine profiles in the AH of CSC, PNV, and PCV patients. In addition, relationships between cytokine concentrations were analyzed among the three groups.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eClinical features\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the demographic and clinical characteristics of patients with CSC, PNV, PCV, and normal controls. A total of 172 AH samples were collected from 132 patients in the study group and 40 controls. Significant differences in age (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), best-corrected visual acuity (BCVA) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), central macular thickness (CMT) (P\u0026thinsp;=\u0026thinsp;0.005), and subfoveal choroidal thickness (SFCT) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) among the CSC, PNV, and PCV groups were confirmed by the Kruskal\u0026ndash;Wallis test. CMT was greater in the PCV group than in the CSC (P\u0026thinsp;=\u0026thinsp;0.001) and PNV (P\u0026thinsp;=\u0026thinsp;0.041) groups, whereas there were no differences in CMT between the CSC and PNV groups (P\u0026thinsp;=\u0026thinsp;0.335). SFCT was greater in the CSC group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and the PNV group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to the PCV group, whereas there were no differences in SFCT between the CSC and PNV groups (P\u0026thinsp;=\u0026thinsp;0.254). Sex was not different among the three groups (P\u0026thinsp;=\u0026thinsp;0.170).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and Clinical Characteristics Among the Pachychoroid Groups and the Controls.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c8\" namest=\"c2\"\u003e \u003cp\u003ePachychoroid Spectrum Diseases\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCSC\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;65)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003ePNV\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;24)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003ePCV\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;43)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eP\u003c/b\u003e\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;132)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eControls\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;40)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eP\u003c/b\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (y), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.7\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e54.3\u0026thinsp;\u0026plusmn;\u0026thinsp;12.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e70.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, male (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (70.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (60.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e84 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e22 (55.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.325\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCVA (logMAR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003cp\u003e(0.10\u0026ndash;0.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003cp\u003e(0.15\u0026ndash;0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.70\u003c/p\u003e \u003cp\u003e(0.40-1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003cp\u003e(0.15\u0026ndash;0.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003cp\u003e(0.22\u0026ndash;0.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.556\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCMT (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e327.00\u003c/p\u003e \u003cp\u003e(242.50\u0026ndash;425.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e364.50 (272.75-457.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e400.00\u003c/p\u003e \u003cp\u003e(321.00-536.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e361.50\u003c/p\u003e \u003cp\u003e(276.00-476.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e/\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSFCT (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e475.00 (387.50\u0026ndash;522.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e382.50 (324.50-480.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e205.00\u003c/p\u003e \u003cp\u003e(145.00-305.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e385.00\u003c/p\u003e \u003cp\u003e(284.50-492.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e/\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eVariables with a skewed distribution are the median (interquartile range, [IQR]). CMT, central macular thickness; SFCT, subfoveal choroidal thickness. \u0026lt; 0.05 was considered significant (bold).\u003c/p\u003e \u003cp\u003e \u003csup\u003e*\u003c/sup\u003e Kruskal\u0026ndash;Wallis test among pachychoroid subtypes.\u003c/p\u003e \u003cp\u003e \u003csup\u003e\u0026dagger;\u003c/sup\u003e Mann\u0026ndash;Whitney U test between the eyes with pachychoroid diseases and controls.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eConcentrations of cytokines\u003c/h3\u003e\n\u003cp\u003eIn this study, six cytokines (VEGF, IL-6, IL-8, IL-10, IP-10, and MCP-1) stably detected in all AH samples were used for statistical analysis (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In the PCV group, levels of VEGF (P\u0026thinsp;=\u0026thinsp;0.002), IL-10 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and IP-10 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were significantly higher than in controls. There were no significant differences in cytokine levels except for elevated VEGF levels between the CSC/PNV and control groups (P\u0026thinsp;=\u0026thinsp;0.022 and P\u0026thinsp;=\u0026thinsp;0.008, respectively).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLevels of Cytokines in the Aqueous Humor of Patients with Pachychoroid Spectrum Diseases and in Controls.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c7\" namest=\"c3\"\u003e \u003cp\u003eEyes with Pachychoroid Diseases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCSC(n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePNV(n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePCV(n\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTotal(n\u0026thinsp;=\u0026thinsp;132)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eControls(n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVEGF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e34.89\u003c/p\u003e \u003cp\u003e(24.50-47.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.97\u003c/p\u003e \u003cp\u003e(28.71\u0026ndash;47.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.81\u003c/p\u003e \u003cp\u003e(25.71\u0026ndash;49.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.474\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e36.84\u003c/p\u003e \u003cp\u003e(25.77\u0026ndash;47.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e27.91\u003c/p\u003e \u003cp\u003e(20.71\u0026ndash;35.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.010\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e4.51\u003c/p\u003e \u003cp\u003e(3.54\u0026ndash;5.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.56\u003c/p\u003e \u003cp\u003e(3.84\u0026ndash;8.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.95\u003c/p\u003e \u003cp\u003e(1.98\u0026ndash;4.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.17\u003c/p\u003e \u003cp\u003e(2.99\u0026ndash;5.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.53\u003c/p\u003e \u003cp\u003e(1.56\u0026ndash;7.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.534\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e7.49\u003c/p\u003e \u003cp\u003e(5.43\u0026ndash;9.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.89\u003c/p\u003e \u003cp\u003e(6.11\u0026ndash;12.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.90\u003c/p\u003e \u003cp\u003e(7.46\u0026ndash;22.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.27\u003c/p\u003e \u003cp\u003e(5.98\u0026ndash;12.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8.09\u003c/p\u003e \u003cp\u003e(4.74\u0026ndash;13.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.645\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003cp\u003e(0.64\u0026ndash;0.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003cp\u003e(0.59\u0026ndash;0.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003cp\u003e(0.79\u0026ndash;1.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003cp\u003e(0.67\u0026ndash;0.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003cp\u003e(0.49\u0026ndash;0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIP-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e143.84\u003c/p\u003e \u003cp\u003e(93.87\u0026ndash;214.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e216.35\u003c/p\u003e \u003cp\u003e(165.84-363.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e528.30\u003c/p\u003e \u003cp\u003e(340.31-842.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e221.37\u003c/p\u003e \u003cp\u003e(127.75-464.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e147.70\u003c/p\u003e \u003cp\u003e(112.61-239.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCP-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e409.84\u003c/p\u003e \u003cp\u003e(368.25-507.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e479.52\u003c/p\u003e \u003cp\u003e(392.09-573.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e491.74\u003c/p\u003e \u003cp\u003e(389.95-618.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e442.48\u003c/p\u003e \u003cp\u003e(380.47-546.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e396.99\u003c/p\u003e \u003cp\u003e(327.15-546.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.389\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eConcentrations of cytokines are expressed as the median (interquartile range, [IQR]). VEGF, vascular endothelial growth factor; IL-6, interleukin 6; IL-8, interleukin 8; IL-10, interleukin 10; IP-10, interferon-inducible protein 10; MCP-1, monocyte chemotactic protein 1. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant (bold).\u003c/p\u003e \u003cp\u003e \u003csup\u003e*\u003c/sup\u003e Kruskal\u0026ndash;Wallis test among pachychoroid subtypes.\u003c/p\u003e \u003cp\u003e \u003csup\u003e \u003cb\u003e\u0026dagger;\u003c/b\u003e \u003c/sup\u003e Mann\u0026ndash;Whitney U test between the eyes with pachychoroid diseases and controls.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e showed the relationships between cytokine concentrations in the AH among the groups via Spearman\u0026rsquo;s rank correlation coefficients. The concentrations of VEGF were not correlated with any detected cytokines in the study among the CSC, PNV, and PCV groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSpearman\u0026rsquo;s Rank Correlation Coefficient for Cytokines in the Aqueous Humor of Patients with Pachychoroid Diseases and in Controls.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVEGF\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIL-6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIL-8\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIL-10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIP-10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMCP-1\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCSC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVEGF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.534*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIP-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.522*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.728*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.141\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCP-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.073\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.541*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.647*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.556*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePNV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVEGF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.405\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.532 \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.359\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.060\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIP-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.301\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.402\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.251\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCP-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.396\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.574\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.550\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePCV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVEGF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.746*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.299\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.236\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIP-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.331\u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.528*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCP-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.059\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.655*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.798*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.601*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eControls\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVEGF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.598*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.446\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.251\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIP-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.500\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCP-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.060\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.488\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.663*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.328\u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e \u003cp\u003e*P\u0026thinsp;\u0026lt;\u0026thinsp;0.001.\u003c/p\u003e \u003cp\u003e\u0026dagger;P\u0026thinsp;\u0026lt;\u0026thinsp;0.01.\u003c/p\u003e \u003cp\u003e\u0026Dagger;P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\n\u003ch3\u003eAqueous humor cytokines levels in CSC patients with different types of PED\u003c/h3\u003e\n\u003cp\u003eRetinal pigment epithelial detachment (PED) is a classical biomarker of CSC imaged by SD-OCT. Based on differences in shape, size, and reflectivity, PED can be classified into two subtypes: focal PED and flat irregular PED (FIPED)\u003csup\u003e12\u003c/sup\u003e. Cytokine levels in the AH of 65 eyes with CSC, including 34 FIPED eyes and 31 focal PED eyes, and 40 control eyes were analyzed (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The mean VEGF levels in the FIPED group were 36.95 (27.84\u0026ndash;48.25) pg/ml, higher than those in the focal PED group [30.20 (19.97\u0026ndash;40.88) pg/ml, P\u0026thinsp;=\u0026thinsp;0.018] and the control group [27.91 (20.71\u0026ndash;35.42) pg/ml, P\u0026thinsp;=\u0026thinsp;0.001] (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The levels of VEGF were similar in the focal PED and controls (P\u0026thinsp;=\u0026thinsp;0.401, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). No significant differences were noted in the levels of IL-6, IL-8, IL-10, IP-10, and MCP-1 among the FIPED, the focal PED, and controls (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLevels of Cytokines Among Different Types of Pigment Epithelial Detachments (PEDs) in Patients with CSC.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFIPED (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFocal PED (N\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControls\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003csup\u003e\u0026lowast;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVEGF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.95 (27.84\u0026ndash;48.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.20 (19.97\u0026ndash;40.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.91 (20.71\u0026ndash;35.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.93 (3.72\u0026ndash;6.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.02 (3.54\u0026ndash;5.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.53 (1.56\u0026ndash;7.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.468\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.77 (6.02\u0026ndash;11.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.41 (5.43\u0026ndash;9.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.09 (4.74\u0026ndash;13.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.766\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.67 (0.58\u0026ndash;0.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.67 (0.66\u0026ndash;0.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.63 (0.49\u0026ndash;0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIP-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e131.37 (91.78\u0026ndash;319.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e154.01 (91.60-207.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e147.70 (112.61-239.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.778\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCP-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e402.18 (370.21-504.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e418.01 (352.77-514.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e396.99 (327.15-546.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.834\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eValues are the median (interquartile range, [IQR]). FIPED, flat irregular pigment epithelial detachment; PED, pigment epithelium detachment. VEGF, vascular endothelial growth factor; IL-6, interleukin 6; IL-8, interleukin 8; IL-10, interleukin 10; IP-10, interferon-inducible protein 10; MCP-1, monocyte chemotactic protein 1. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant (bold).\u003c/p\u003e \u003cp\u003e \u003csup\u003e \u003cb\u003e\u0026lowast;\u003c/b\u003e \u003c/sup\u003e Kruskal\u0026ndash;Wallis test among the FIPED, the Focal PED, and Controls.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study provides the first comprehensive analysis of intraocular cytokines of patients with pachychoroid spectrum diseases including CSC, PNV, and PCV. In CSC and PNV, VEGF was elevated without the elevation of proinflammatory cytokines. In the PCV, VEGF and proinflammatory cytokines IL-10 and IP-10 were significantly higher than those in controls.\u003c/p\u003e \u003cp\u003eAlthough a number of studies have described specific clinical and anatomical features of the four pachychoroid subtypes PPE, CSC, PNV, and PCV, their respective pathophysiology remains to be fully elucidated. The clinic manifestations common to the pachychoroid spectrum include choriocapillaris attenuation and abnormally dilated pachyvessels with choroidal vascular hyperpermeability\u003csup\u003e1\u003c/sup\u003e. The presence of choroidal morphologic changes as a key pathophysiologic mechanism was essential to diagnosing the pachychoroid spectrum of macular disorders. Cytokines were considered to be involved in ocular diseases that contributed to choroidal abnormalities\u003csup\u003e13\u003c/sup\u003e. This study aimed to investigate and compare various cytokine concentrations in the aqueous humor of patients with CSC, PNV, and PCV to better understand the respective molecular pathogenesis of these pachychoroid entities.\u003c/p\u003e \u003cp\u003eCSC was the archetypal disease of the pachychoroid spectrum, characterized by serous neurosensory retinal detachment at the posterior pole\u003csup\u003e1\u003c/sup\u003e. Choroidal congestion and choroidal hyperpermeability were believed to contribute to CSC\u003csup\u003e1\u003c/sup\u003e. Our study showed that the proangiogenic cytokine VEGF levels were distinctly upregulated in the CSC group than in the control group. Liu et al have reported that the AH concentration of VEGF was significantly higher in various CNV diseases including CSC\u003csup\u003e14\u003c/sup\u003e. However, there was evidence that aqueous or plasma VEGF levels in patients with acute or chronic CSC were downregulated compared with the controls\u003csup\u003e15,16\u003c/sup\u003e. As the pathogenesis of CSC has not been fully elucidated, the true role of VEGF in CSC is unknown and warrants further investigation. No significant disparity was observed in other inflammatory factors between the CSC and control groups, suggesting that inflammatory mediators might play a minor role in CSC pathophysiology.\u003c/p\u003e \u003cp\u003ePigment epithelial detachment (PED) is a well-recognized feature of CSC and was commonly observed in all stages of CSC. According to the different morphologies, PED can be classified into two different types: typical focal PED and flat irregular PED (FIPED)\u003csup\u003e17\u003c/sup\u003e. Clinical features of CSC may vary depending on the diverse type of PED. Hwang et al found that CSC patients with FIPED involved more CNV and behaved with favorable anti-VEGF responsiveness in such cases\u003csup\u003e17\u003c/sup\u003e. It was unclear whether there was an association between the type of PED and cytokine levels. And the underlying molecular and cellular mechanisms of FIPED remain to be elucidated. We investigated and compared AH cytokine profiles according to PED type in CSC patients. In our study, the levels of VEGF were higher in eyes with FIPED than those in the focal PED and control groups, whereas no disparities were observed in IL-6, IL-8, IL-10, IP-10, and MCP-1 levels among the focal PED, FIPED and control groups. Our findings may explain why favorable treatment responses to anti-VEGF tend to occur in CSC patients with FIPED and the effect of inflammation mediators in CSC pathology was very minor. And this also showed that CSC was not an inflammatory disease.\u003c/p\u003e \u003cp\u003ePNV is a newly proposed clinical entity within a spectrum of \u0026ldquo;pachychoroid driven disease\u0026rdquo;, characterized by thick choroid, RPE abnormalities, and/or choroidal vascular hyperpermeability\u003csup\u003e18\u003c/sup\u003e. PNV is often misdiagnosed as neovascular age-related macular degeneration (nAMD) because neovascularization is similar both in PNV and AMD\u003csup\u003e19\u003c/sup\u003e. It is well known that the activation of proinflammatory cytokines and subsequent upregulation of angiogenic factors, especially vascular endothelial growth factor (VEGF), play a pivotal role in CNV formation. In PNV, ischemia in the choriocapillaris or RPE dysfunction, resulting from compression of expanded choroidal vessels, led to overexpression of angiogenic factors and neovascularization. It was rational that proangiogenic cytokine VEGF was elevated in AH of patients with PNV than in the controls in our study. Terao et al. compared cytokine profiles in AH of PNV and nAMD and found that VEGF-A levels were significantly lower in the PNV group than in the nAMD group but were no disparity compared with normal controls\u003csup\u003e20\u003c/sup\u003e. Hata et al. found that the mean VEGF concentration in the AH of patients with PNV was significantly lower than that in nAMD\u003csup\u003e21\u003c/sup\u003e. Their study suggested that PNV and nAMD may have different pathophysiology and CNV in the pachychoroid phenotype was triggered by a lower VEGF concentration threshold than in nAMD.\u003c/p\u003e \u003cp\u003ePCV, as one entity of the pachychoroid spectrum disease, is characterized by a branching vascular network with terminal aneurysmal (polypoidal) dilatations. It is increasingly thought to be a variant manifestation of type 1 neovascularization and may be closely correlated with CSC\u003csup\u003e22,23\u003c/sup\u003e. The etiology of PCV is still unclear. VEGF is considered a major stimulus for pathological angiogenesis in all eyes with CNV. Clinical studies have shown that intravitreal triamcinolone acetonide injection for the treatment of PCV was effective\u003csup\u003e24,25\u003c/sup\u003e, suggesting inflammation may play a contributing role in the pathogenesis of PCV. Other evidence indicated that proinflammatory factors such as IL-23, C-reactive protein, MCP-1, VEGF, and tumor necrosis factor-a were elevated in eyes with PCV\u003csup\u003e26\u0026ndash;28\u003c/sup\u003e. In the present study, strong VEGF, IL-10, and IP-10 expression in AH was found in PCV eyes. We inferred that the disease continuum from CSC to PCV was also accompanied by the accumulation of inflammatory cytokines.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, the AH samples may not be as valuable as vitreous fluid for detecting cytokine concentrations at the site of pathology in the retina and choroid. Second, there may be many other cytokines associated with pachychoroid spectrum diseases that were not included in this study, so more relevant new cytokines need to be explored in the future.\u003c/p\u003e \u003cp\u003eIn summary, VEGF was elevated without the elevation of other inflammatory cytokines in CSC and PNV, indicating that inflammation was not the dominant factor on CSC and PNV diseases. PCV had significantly distinct cytokine profiles in the AH compared with controls. Elevated angiogenic and inflammatory cytokines, such as VEGF, IL-10, and IP-10, may contribute to the pathogenesis of PCV. In addition, higher VEGF levels in CSC patients with FIPED verified that VEGF contributed more to the pathogenesis of FIPED compared with focal PED.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This prospective, comparative, observational study was conducted in compliance with the tenets of the Declaration of Helsinki; the research was approved by the Institutional Review Board of Zhejiang Provincial People's Hospital (IRB number#KY2022022). Written informed consent was obtained from the subjects after detailed explanation of the study protocol.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStudy paticipants\u003c/h2\u003e \u003cp\u003e65 eyes of patients with treatment-na\u0026iuml;ve CSC, 24 eyes had treatment-na\u0026iuml;ve PNV, and 43 eyes had treatment-na\u0026iuml;ve PCV were enrolled between January 2018 and June 2022 at Zhejiang Provincial People's Hospital and Affiliated Eye Hospital of Wenzhou Medical University. And 40 eyes who were scheduled to receive cataract surgery were recruited as controls.\u003c/p\u003e \u003cp\u003eAll patients received comprehensive ophthalmic examinations, including best-corrected visual acuity (BCVA) testing with the standard logarithmic visual acuity chart, slit-lamp biomicroscopy, color fundus photographs, fluorescein angiography (FA), indocyanine green angiography (ICGA), spectral-domain optical coherence tomography (SD-OCT) and OCT angiography.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDiagnosis of CSC, PNV, and PCV\u003c/h3\u003e\n\u003cp\u003eThe CSC diagnosis was based on: (1) OCT demonstrating the presence of subretinal fluid and/or serous pigment epithelium detachment involving the fovea; (2) FA showing the typical leakage points at the level of the RPE in the macular region; (3) symptom duration exceeding 3 months \u003csup\u003e4\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePNV was diagnosed using the following criteria based on the latest reports: (1) type-1 CNV detected in either eye; (2) no or only non-extensive drusen or hard drusen in both eyes; (3) dilated choroidal vessels or thicking below type 1 CNV detected by ICGA and OCT; (4) choroidal vascular hyperpermeability detected in the late phase of ICGA; and (5) RPE abnormality independent of CNV lesions detected by FA or a history of CSC \u003csup\u003e4\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePCV was diagnosed based on early subretinal ICGA hyperfluorescence and at least one of the following diagnostic criteria: (1) a sharply peaked pigment epithelium detachment (PED), subretinal pigment epithelium ring-like structures, double-layer sign, choroidal thickening with pachyvessels, and subretinal and subretinal pigment epithelium fluid on SD-OCT images. (2) nodular appearance of the polypoidal lesion on stereoscopic viewing, (3) hypofluorescent halo around the nodule, (4) abnormal vascular networks supplying the polypoidal lesion, (5) multiple aneurysmal staining or polypoidal lesions in the late phase of ICGA \u003csup\u003e4\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe exclusion criteria were (1) patients with any other systemic conditions including diabetes, cardiovascular diseases, cerebrovascular diseases, or malignancies. (2) history of other retinal disorders except for the inclusion were considered pachychoroid diseases. (3) previous anti-VEGF intravitreal injections or other intraocular procedures within the last 6 months.\u003c/p\u003e\n\u003ch3\u003eAqueous Humor Collection\u003c/h3\u003e\n\u003cp\u003eAH samples (usually a volume of 0.1 ml) of eyes with CSC, PNV, or PCV were withdrawn before intravitreal conbercept (0.5 mg/0.05 ml; Kanghong Biotechnologies Co. Ltd, Chengdu, Sichuan Province, China) using a syringe with a 30-gauge needle (Nipro, Osaka, Japan) after topical anesthesia. The AH of controls was aspirated before cataract surgery in the same manner. All samples were transferred to a sterile tube and stored at \u0026minus;\u0026thinsp;80\u0026deg;C until cytokine analysis. Cytokine concentrations were analyzed using Multi-Analyte Profiling (xMAP; Luminex200, Hercules, CA, USA). All procedures were undertaken in the dark at room temperature, avoiding light-induced contamination.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eImage Analysis\u003c/h2\u003e \u003cp\u003eThe central macula thickness (CMT) and subfoveal choroidal thickness (SFCT) were recorded using the caliper function of the Spectralis instrument. CMT was defined as the vertical distance between the RPE surface and the internal limiting membrane surface. Measuring SFCT from the hyperreflective line corresponding to Bruch\u0026rsquo;s membrane below the RPE to the inner surface of the sclera.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS 26.0 software (IBM SPSS Inc., Chi cago, IL, USA). Continuous variables are presented as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and categorical variables were assessed using Chi-squared tests. Quantitative variables were tested for normal distribution by the Shapiro\u0026ndash;Wilk test. Data with a skewed distribution are expressed as the median and interquartile range (IQR). Intergroup comparisons of quantitative variables were made using the one-way analysis of variance (ANOVA) for normally distributed variables and the Kruskal\u0026ndash;Wallis test for variables with nonnormal distribution. For the Kruskal\u0026ndash;Wallis test, P values for multiple testing were corrected by the method of Bonferroni. Spearman\u0026rsquo;s rank correlation coefficients were used to evaluate the relationships between cytokine concentrations in the AH among the pachychoroid subtypes and control groups. P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to be statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDate availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data are not available for public access because of patient privacy concerns, but are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eC.Y.Z analyzed the data and wrote the original draft; J.B.M conceptualized and designed the study; Y.Z, S.A.Z, and Z.Y.X collected the\u0026nbsp;data;\u0026nbsp;L.J.S reviewed the draft and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the\u0026nbsp;Medical and Health Research Project of Zhejiang Province (2023KY490).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence and requests for materials should be addressed to J.B.M\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHua, R., Duan, J. \u0026amp; Zhang, M. 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The features of inflammation factors concentrations in aqueous humor of polypoidal choroidal vasculopathy. \u003cem\u003ePLoS. One.\u003c/em\u003e\u003cstrong\u003e11\u003c/strong\u003e, 0147346. http://doi.org/10.1371/journal.pone.0147346 (2016).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"aqueous humor, cytokine, central serous chorioretinopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy","lastPublishedDoi":"10.21203/rs.3.rs-6212666/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6212666/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study investigated cytokine profiles in the aqueous humor (AH) of 172 eyes with central serous chorioretinopathy (CSC, n\u0026thinsp;=\u0026thinsp;65), pachychoroid neovasculopathy (PNV, n\u0026thinsp;=\u0026thinsp;24), polypoidal choroidal vasculopathy (PCV, n\u0026thinsp;=\u0026thinsp;43), and controls (n\u0026thinsp;=\u0026thinsp;40). AH samples were analyzed using a multiplex bead assay for cytokines including vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), IL-8, IL-10, IP-10, and MCP-1. Results showed no significant differences in IL-6 (P\u0026thinsp;=\u0026thinsp;0.122) and MCP-1 (P\u0026thinsp;=\u0026thinsp;0.054) levels among groups. However, VEGF levels were significantly higher in CSC, PNV, and PCV compared to controls (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In CSC and PNV, only VEGF was elevated without significant changes in other inflammatory cytokines, suggesting that inflammation was not a dominant factor. In contrast, PCV exhibited significantly higher levels of VEGF, IL-10, and IP-10, indicating distinct cytokine profiles. These findings suggest that elevated angiogenic and inflammatory cytokines may contribute to the pathogenesis of PCV.\u003c/p\u003e","manuscriptTitle":"Analysis of cytokine profiles in aqueous humor based on optical coherence tomography in pachychoroid spectrum diseases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-19 12:52:03","doi":"10.21203/rs.3.rs-6212666/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-29T04:59:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-29T02:24:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-17T02:17:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"274156736507162120957440451445584786234","date":"2025-04-08T22:50:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"153878824618486410750153960915427643282","date":"2025-04-07T01:56:19+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-23T01:36:56+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-03-17T16:21:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-13T09:30:41+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-13T09:24:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-03-12T13:43:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"daf71042-8d0d-4d1d-91c2-dd7f64abce15","owner":[],"postedDate":"March 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":45812205,"name":"Health sciences/Diseases/Eye diseases"},{"id":45812206,"name":"Health sciences/Molecular medicine"}],"tags":[],"updatedAt":"2025-07-07T16:04:48+00:00","versionOfRecord":{"articleIdentity":"rs-6212666","link":"https://doi.org/10.1038/s41598-025-04130-0","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-07-01 15:58:02","publishedOnDateReadable":"July 1st, 2025"},"versionCreatedAt":"2025-03-19 12:52:03","video":"","vorDoi":"10.1038/s41598-025-04130-0","vorDoiUrl":"https://doi.org/10.1038/s41598-025-04130-0","workflowStages":[]},"version":"v1","identity":"rs-6212666","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6212666","identity":"rs-6212666","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}