DOI: https://doi.org/10.21203/rs.2.13585/v1
Background The concentrations of cytokines in the aqueous humor from neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) may vary. The study was conducted to compare various cytokine levels in the aqueous humor of eyes with PCV, nAMD and control.
Methods The present case control study included 49 treatment-naïve eyes from 49 patients (PCV 24, nAMD 11, and cataract 14 eyes). Totally 34 angiogenic and inflammatory cytokines in the aqueous humor were measured by Luminex bead-based multiplex array.
Results The aqueous humor levels of IL-8 and IL-12p70 in the nAMD group were significantly higher than the PCV group (p=0.031, p=0.012, respectively). The levels of IL-8, IL-18, IL-21, IL-31, LIF, SDF1-α, FGF-basic, VEGF-A, and VEGF-D in the aqueous humor were significantly higher in the nAMD group and PCV group than the control (nAMD vs control, p=0.004, 0.002, 0.005, <0.0001, <0.0001, <0.0001, 0.023, <0.0001, <0.0001, respectively, PCV vs control, p=0.031, <0.0001, <0.0001, <0.0001, <0.0001, <0.0001, 0.026, <0.0001, <0.0001, respectively). In contrast, the levels of BDNF, HGF, IP-10, MCP-1, and IL-13 in the aqueous humor were significantly lower in the nAMD group and PCV group than control (nAMD vs control, p=<0.0001, <0.0001, 0.003, <0.0001, <0.0001, respectively, PCV vs control, p=<0.0001, <0.0001, <0.0001, <0.0001, <0.0001, respectively). There were significant correlations among nAMD group, PCV group and control group in aqueous humor levels of HGF, IP-10, MCP-1, IL-13, IL-31, LIF, SDF1-α, VEGF-A, VEGF-D by multivariate logistic analysis.
Conclusions Various cytokines involved in inflammation and angiogenesis including HGF, IP-10, MCP-1, IL-13, IL-31, LIF, SDF1-α, VEGF-A and VEGF-D may contribute to the pathogenesis of nAMD and PCV. Measurement of IL-8 and IL-12p70 in the aqueous humor may help to differentiate nAMD and PCV.
Age-related macular degeneration (AMD) is a leading cause of irreversible visual disability and blindness among elderly in developed countries. Clinically, AMD is divided into two major types, the non-neovascular AMD and neovascular AMD (nAMD), and the latter is the major cause of severe visual loss. Polypoidal choroidal vasculopathy (PCV) is characterized by branching choroidal networks with polyp-like aneurysmal dilation, which can be clearly demonstrated by indocyanine green angiography (ICGA). PCV shares many similarities with nAMD, including clinical manifestations, genetic background, and both of them are choroidal vasculopathy associated with subretinal hemorrhage, scars and fibrosis [1], so some views support PCV is a subtype of nAMD. However, they still differ in pathophysiology, histopathological, epidemiology, some clinical characteristics, treatment responses, natural course and special genes [2-6]. There remain controversies as to whether PCV is merely a variant of nAMD or its own distinct entity [7]. Since PCV is mostly common in Asians, recent information supports the notion that angiogenesis and inflammation play an important and perhaps central role in the pathogenesis of nAMD and PCV [8]. There are some literatures on cytokines profile in aqueous humor of nAMD and PCV [9-11], but relatively few studies investigated the differences of both angiogenic and inflammatory cytokines in the aqueous humor among nAMD, PCV and controls. In the past, with the limitation of traditional ELISA consumables and aqueous humor contents, detecting the concentrations of cytokines in aqueous humor were restricted on a few selected cytokines [12, 13]. While the use of Luminex assay, a commercially available multiplex immunoassay with the advantages of high sensitivity and high throughput, makes evaluating a panel of cytokines in a small number of clinical samples comes to truth. Therefore, in this study, we first aim to further discover the differences between nAMD with PCV by analyzing cytokine profile. Next, we explored other new potential therapeutic targets besides blocking VEGF therapy via detecting various angiogenic and inflammatory cytokines levels in aqueous humor of nAMD and PCV.
This study was reviewed and approved by the Ethics Committee in Peking Union Medical College Hospital and adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants.
Patients
Forty-nine patients including twenty-four with treatment-naive PCV, eleven patients with treatment-naive nAMD and fourteen controls without any other associated sight-threatening pathology except for cataract who had been scheduled to undergo cataract surgery were recruited from the Department of Ophthalmology, Peking Union Medical College Hospital. All patients with PCV and nAMD were diagnosed specifically with fluorescein angiography (FFA) and ICGA. Eyes with PCV were indicated with clusters of polypoidal dilation of the vessels with or without abnormal vascular networks in the superficial choroid. Eyes with nAMD showed classic choroidal neovascularization (CNV) or occult CNV with FFA, with no polypoidal lesions in ICGA. Controls were selected among the patients undergoing cataract surgery. All collected subjects met inclusion criteria, which had no history or slit-lamp evidence of ocular trauma, no use of systemic corticosteroids, immunosuppressants, or antimetabolites, and no unrelated ocular diseases like any types of retinal diseases, pathological myopia, glaucoma, uveitis, vitreous hemorrhage, choroiditis, hereditary diseases and previous intraocular surgery.
Sample extraction and preparation
The aqueous humor samples were collected at the beginning of cataract surgery in the controls and at the time of intravitreal injection into the eyes with PCV or nAMD. After topical anesthesia, approximately 100μl aqueous humor was withdrawn aseptically using an insulin syringe with a 30-gauge needle at the corneal limbus and was rapidly frozen and stored at –80 ° C until final measurement.
Measurement of Cytokines
The concentrations of the cytokines in the aqueous humor samples were measured with Luminex platform following the manufacturer’s instructions. We measured 34 cytokines associated with inflammation and angiogenesis, including interleukin(IL)-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-13, IL-15, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IL-31, VEGF-A, VEGF-D, leukemia inhibitory factor(LIF), stromal-derived factor 1-α(SDF1-α), brain-derived neurotrophic factor(BDNF), interferon inducible protein 10(IP-10) , hepatocyte Growth Factor(HGF), interleukin-12p70(IL-12p70), PIGF, basic fibroblast growth factor(FGF-basic), granulocyte macrophage colony stimulating Factor(GMCSF), epidermal growth factor(EGF), macrophage inflammatory protein 1β(MIP-1β), Eotaxin, regulated upon the activation of normal T cell expressed and secreted(RANTES), platelet-derived growth factor-BB(PDGF-BB), MCP-1, nerve growth factor b(NGFb), stem cell factor(SCF), macrophage inflammatory protein-1α(MIP-1α), growth-related gene product α(GROα), interferon-γ(IFNγ), interferon-α(IFNα), tumor necrosis factor(TNF)α and TNFβ. Numbers on the Luminex plates were read by using Magpix system (Luminex Corp., Austin, TX, USA) following the manufacturer's instructions, and Bio-Plex manager 6.1 software (Bio-Rad Laboratories, Hercules, CA, USA) with a five-parameter curve-fitting algorithm was used to analyze the data.
Statistical Analysis
Statistical analyses were performed using SPSS 16.0 software. For the calculation of the mean and SD of the cytokines. Chi-square test was used to compare classification variables between the two groups, unpaired t-test was used for data measurement, and multivariate logistic regression analysis confirmed the correlation between cytokines in aqueous humor and nAMD or PCV. P < 0.05 was deemed to be statistically significant.
The details for all subjects including sex and age were listed in Table 1. The average age of the patients with nAMD, PCV and control was 75.55 ± 6.83 (mean ± SD), 67.46 ±8.79, 70.07 ± 12.65 years old, respectively. The mean age had no statistical difference among the 3 groups. Men in AMD, PCV and control group were 5 (45.6%), 21 (87.5%) and 4 (28.6%), respectively. However, sex showed statistical difference among 3 groups(P<0.05). Table 2 shows the concentrations of the 34 cytokines in the aqueous humor samples. Among the 34 cytokines, the concentrations of 9 cytokines, IL-8, IL-18, IL-21, IL-31, LIF, SDF1-α, FGF-basic, VEGF-A, VEGF-D, were significantly higher in nAMD and in PCV compared with controls (P<0.05). In contrast, the concentrations of 5 cytokines, BDNF, HGF, IP-10, MCP-1, IL-13 were significantly lower in the nAMD group and PCV group than in controls (P<0.05). Importantly, aqueous humor level of IL-8 and IL-12p70 investigated in the present study were significantly higher in nAMD group contrast with PCV group. Multivariate logistic regression analysis demonstrated that HGF, IP-10, MCP-1, IL-13, IL-31, LIF, SDF1-α, VEGF-A and VEGF-D concentrations was statistically significantly higher in nAMD and PCV respectively compared with controls after adjusted for age and gender (Table 3). Among them, HGF, IP-10, MCP-1, IL-13 concentrations were statistically significantly lower in nAMD and PCV compared with controls, while IL-31, LIF, SDF1-α, VEGF-A and VEGF-D concentrations were statistically significantly higher in nAMD and PCV compared with controls.
In the present study, we investigated the levels of 34 cytokines in aqueous humor from treatment-naïve eyes with nAMD, PCV and controls, and explored whether there were differences among the three groups. Our results revealed that the IL-8 and IL-12p70 were significantly higher in nAMD than in PCV, and that there were 9 cytokines levels increased associated with AMD and PCV. IL-8, IL-18, IL-21, IL-31, LIF, SDF1-α, FGF-basic, VEGF-A, VEGF-D levels were significantly higher in eyes with nAMD or PCV compared with control eyes, while BDNF, HGF, IP-10, MCP-1, IL-13 were significantly lower in nAMD and PCV in contrast with controls. nAMD group showed significantly difference with PCV group in higher aqueous concentrations of IL-8 and IL-12p70, which was different from previous studies [13, 14]. Sakurada et al. [13] reported biomarkers of inflammation, elevated CRP and IP-10, and suggested chronic inflammation might be involved in the pathogenesis of nAMD or PCV. However, Agrawal et al. [14] supported that there were no significant differences in cytokine levels observed between nAMD and PCV patients for aqueous humor, which was inconsistent with our findings. IL-8 are the chemokines produced by macrophages and other cells, which are primarily involved in the regulation of inflammatory responses. This result was consistent with previous study which revealed that elevated intraocular levels of IL‐8 and IL‐8 gene polymorphisms were associated with angiogenesis [15]. Balne et al. and Mimura et al. [10, 16] reported that aqueous humor cytokines IL-8 levels was significantly higher in nAMD and PCV patients than controls which was consistent with our findings. They may be the key cytokines to explain the differences of nAMD and PCV, and further studies are necessary to elucidate the pathogenetic role of IL-8 and IL-12p70.
We found that some cytokines levels in the aqueous humor of nAMD and PCV patients had seldom been reported in the past. Some pro-inflammatory and pro-angiogenic cytokines were increased in nAMD and PCV groups compared with controls, such as SDF1-α, IL-31, LIF, VEGF-D. SDF1-α, a potent stimulator of VEGF expression, acting as an angiogenic agent increased during inflammation, is the main candidate factor of neovascularization and vascular permeability [17, 18]. IL-31, an immunoregulatory protein belonging to the pro-inflammatory IL-6 cytokine family [19], might inhibit angiogenesis [19]. LIF, a member of the IL-6 family of cytokines, upregulated with inflammation having the function of both anti-angiogenic and pro-angiogenic, was reported to have the ability to protect the integrity of the vasculature and retinal away from degenerations [20, 21]. The function of these cytokines on the progress of the eyes of nAMD and PCV need further research in the future, which may offer alternative therapeutic approaches to treat visual defects associated with nAMD and PCV. VEGF-D and VEGF-A had been identified to play an important role in angiogenesis. The previous study reported that the high expression of VEGF-D, in addition to VEGF-A, exacerbated the angiogenic response of retinal pigment epithelium(RPE) cell in nAMD [22]. However, as far as we know, there was few research on the concentration of VEGF-D in PCV, let alone the comparison of aqueous humor levels of VEGF-D in three groups, even they seldomly distinguished VEGF family such as detecting VEGF-A and VEGF-D respectively [13, 16]. Our study reported that the mean aqueous humor concentration of not only VEGF-A but also VEGF-D tended to be higher in both nAMD and PCV than that in controls. According to these findings, we had reasons to suspect the possibility that VEGF-D expression in eye besides VEGF-A modify the ocular angiogenesis as angiogenic stimulators in both nAMD and PCV. Therefore, agent combined with anti-VEGFs such as OPT-302 (to inhibit VEGF-C and VEGF-D) may be one of the emerging anti-VEGF treatments in the future [23]. Nowadays, we should pay more attention to the function and concentration of VEGF-D in aqueous humor of nAMD and PCV. Thus, we may infer that development of procedures to neutralize elevated cytokines in the eye with nAMD or PCV may potentially be therapeutic targets, as anti-VEGF drugs to neutralize VEGF.
Some pro-inflammatory and pro-angiogenic cytokines had no change in nAMD and PCV groups compared with controls like IL-6. IL-6 may cause a breakdown of the blood-ocular barrier by inducing an increase of endothelial permeability, and promote CNV. While our study showed no differences between nAMD, PCV and control group, which is in agreement with prior research [24]. However, IL-6 was significantly higher in the AMD group than in the cataract group [10].
Some pro-inflammatory and pro-angiogenic cytokines were dramatically decreased in nAMD and PCV groups compared with controls, such as MCP-1, HGF, IL-13, IP-10. MCP-1, a potent factor that regulated the migration and infiltration of monocytes and macrophages, enhanced by pro-inflammatory molecules, and facilitated angiogenesis [25]. Previous studies have reported inconsistent results on the level of MCP-1. Some suggested that MCP-1 levels in the aqueous humor in eyes with nAMD or PCV were not significantly different from controls [10, 26, 27]. However, some investigators observed that MCP-1 levels in the aqueous humor showed statistically significant elevation in the AMD group compared with control group and then put forward that MCP-1 may be one of the future targets for the treatment of AMD [28-30]. Therefore, more research is still needed for the function and concentration of MCP-1. HGF was identified to stimulate the proliferation, migration, neovascularization and differentiation, which played an important role in ocular angiogenesis and increases leakage from retinal vessels [31]. Dramatically, in our study, aqueous humor concentration of HGF did show a significantly lower trend in nAMD and PCV patients compared with controls. IL-13 played pathophysiological roles in allergic inflammation and fibrosis formation. In the present study, IL-13 was significantly lower in the nAMD and PCV group than in the cataract group, while reports of aqueous humor IL-13 level in nAMD or PCV are still controversial according to recent reports. Fu and colleagues found that IL-13 of aqueous humor was significantly upregulated during AMD development, suggesting that IL-13 could have potent effects on the pathological process of this disease [12]. However, according to another research, aqueous humor levels of IL-13 showed no significant difference between AMD group and the cataract group [10], while there are few reports about IL-13 level in aqueous humor of PCV patient. Therefore, whether IL-13 makes sense in the pathogenic processes of nAMD and PCV or not still needs to be clarified in further research. IP-10 concentrations were reduced in the aqueous humor in eyes with nAMD and PCV in contrast to control group in the current study. However, some previous reports demonstrated that IP-10 expression was increased in AMD and PCV patients, highlighting the involvement of inflammatory pathways [13, 16, 24, 26, 32]. On the other hand, Funk et al. [33] reported that IP-10 concentrations in aqueous humor with AMD were similar to those in controls. This indicates that further studies are necessary to illuminate the role of IP-10 in the pathogenic process of nAMD and PCV.
Limitations of our study should be mentioned. Firstly, the main limitation of this study was the small number of subjects, which meant that our findings should be confirmed in a larger number of patients. Moreover, another limitation was that we did not compare the relationships between structure, function and aqueous humor cytokines concentrations, and further relative research is necessary to better understand the role of cytokines in the aqueous humor of nAMD and PCV. Besides, we didn’t take into account of the exact typing of the classic AMD or atypical AMD. Furthermore, as we reported above that inflammation and angiogenesis may have a common influence on the pathogenesis of nAMD and PCV, a treatment response targeting angiogenesis and inflammation should raise concern in the future study. Last but not least, there are maybe some other cytokines related to nAMD and PCV that was not covered in the present study, such that exploring new and more related-cytokines is needed in the future.
Our research studied the concentrations of 34 cytokines in aqueous humor of patients with nAMD, PCV and the controls. Findings of our study which have not been widely reported in previous researches were elevated intraocular levels of IL-31, LIF, SDF-α and VEGF-D, which may be associated with the pathogenesis of nAMD and PCV. Importantly, these various pro-inflammatory and pro-angiogenic cytokines may be potential novel therapeutic target for nAMD and PCV. Moreover, we found significant differences in aqueous humor IL-8 and IL-12p70 levels between nAMD and PCV, and these inflammatory factors may contribute to further explain the differences of nAMD and PCV.
nAMD: neovascular age-related macular degeneration; AMD: Age-related macular degeneration; PCV: polypoidal choroidal vasculopathy; ICGA: indocyanine green angiography; FFA: fluorescein angiography; CNV: choroidal neovascularization; IL: Interleukin; LIF: leukemia inhibitory factor; SDF1-α: stromal-derived factor 1-α; BDNF: brain-derived neurotrophic factor; IP-10: interferon inducible protein 10; HGF: hepatocyte Growth Factor; IL-12p70: interleukin-12p70; PIGF: placental growth factor; FGF-basic: basic fibroblast growth factor; GMCSF: granulocyte macrophage colony stimulating Factor; EGF: epidermal growth factor; MIP-1β: macrophage inflammatory protein 1β; RANTES: regulated upon the activation of normal T cell expressed and secreted; PDGF-BB: platelet-derived growth factor-BB; MCP-1: monocyte chemoattractant protein; NGFb: nerve growth factor b; SCF: stem cell factor; MIP-1α: macrophage inflammatory protein-1α; GROα: growth-related gene product α; IFNγ: interferon-γ; IFNα: interferon-α; TNF: tumor necrosis factor
Ethics approval and consent to participate
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The protocol was approved by the Ethics Committee of Peking Union Medical College Hospital (Beijing, China) with reference number ZS-1125. Written informed content was obtained from all patients before enrollment.
Consent for publication
Not applicable.
Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.
Competing interests
The authors declare that they have no competing interests.
Funding
The authors are thankful for the financial support of NSFC Grant No:81670879.
Authors’ Contributions
HZ was responsible for the concept, design, acquisition, analysis, interpretation of data and was a major contributor in writing the manuscript. XZ was responsible for the optimization of the manuscript. All authors (HZ, XZ, MY, YC) have been involved in revising and giving the final approval of the version to be published. All authors (HZ, XZ, MY, YC) agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors read and approved the final manuscript.
Acknowledgements
We want to express our gratitude to Mengmeng Shang for her help on guiding on statistics and Weihong Yu, Yong Tao for their help on editing manuscript.
Table 1. Demographic characteristics of patients
|
nAMD (n = 11) |
PCV (n = 24) |
Controls (n = 14) |
Male gender |
5 |
21 |
4 |
P* value versus controls |
0.434 |
<0.001 |
/ |
P* value versus PCV |
0.015 |
/ |
/ |
Mean age ± SD, years |
75.55 ± 6.83 |
67.46 ±8.79 |
70.07 ± 12.65 |
p value versus controls |
0.988 |
0.940 |
/ |
p value versus PCV |
0.986 |
/ |
/ |
SD=standard deviation, *=after Bonferroni correction |
Table 2. Levels of 34 cytokines (means ± SD) in the aqueous humor among 3 groups
cytokines |
nAMD (pg/ml) |
PCV (pg/ml) |
Control (pg/ml) |
P value (nAMD vs Control) |
P value (PCV vs Control) |
P value (nAMD vs PCV) |
BDNF |
4.58±2.90 |
4.82±2.83 |
18.69±4.58 |
<0.0001 |
<0.0001 |
0.816 |
EGF |
4.34±2.65 |
4.07±3.29 |
5.36±2.72 |
0.356 |
0.223 |
0.814 |
Eotaxin |
20.09±3.96 |
17.64±5.64 |
18.42±6.03 |
0.435 |
0.690 |
0.203 |
GMCSF |
31.62±18.47 |
20.04±17.93 |
40.07±11.66 |
0.204 |
<0.0001 |
0.088 |
HGF |
238.12±113.63 |
325.59±191.52 |
624.95±165.93 |
<0.0001 |
<0.0001 |
0.171 |
IL-1RA |
99.54±31.25 |
89.35±38.98 |
96.04±37.40 |
0.805 |
0.608 |
0.452 |
IP-10 |
49.57±36.70 |
33.44±29.05 |
100.99±38.55 |
0.003 |
<0.0001 |
0.170 |
MCP-1 |
61.57±43.04 |
91.56±88.82 |
274.24±63.01 |
<0.0001 |
<0.0001 |
0.298 |
MIP-1α |
8.91±4.55 |
8.94±5.46 |
8.72±5.48 |
0.928 |
0.904 |
0.985 |
MIP-1β |
50.91±10.24 |
53.34±17.27 |
55.47±12.22 |
0.331 |
0.688 |
0.669 |
IL-2 |
0.32±0.24 |
0.31±0.24 |
0.32±0.25 |
0.993 |
0.948 |
0.943 |
IL-4 |
0.03±0.01 |
0.03±0.01 |
0.03±0.01 |
0.766 |
0.760 |
0.944 |
IL-5 |
0.07±0.06 |
0.09±0.05 |
0.08±0.05 |
0.579 |
0.362 |
0.162 |
IL-6 |
0.72±0.55 |
0.79±0.48 |
0.96±0.53 |
0.291 |
0.318 |
0.724 |
IL-8 |
40.68±35.47 |
14.63±29.94 |
0.58±0.60 |
0.004 |
0.031 |
0.031 |
IL-12p70 |
2.89±1.99 |
1.17±1.67 |
3.49±0.34 |
0.347 |
<0.0001 |
0.012 |
IL-13 |
1.36±1.26 |
2.25±1.62 |
6.40±1.58 |
<0.0001 |
<0.0001 |
0.119 |
IL-15 |
0.02±0.01 |
0.02±0.01 |
0.02±0.01 |
0.558 |
0.828 |
0.656 |
IL-17A |
1.05±0.60 |
1.30±0.84 |
2.27±1.65 |
0.020 |
0.056 |
0.331 |
IL-18 |
40.98±32.69 |
51.18±37.16 |
0.41±0.32 |
0.002 |
<0.0001 |
0.441 |
IL-21 |
22.30±20.41 |
14.78±16.20 |
0.00±0.00 |
0.005 |
<0.0001 |
0.248 |
IL-23 |
0.05±0.02 |
0.03±0.02 |
0.04±0.03 |
0.643 |
0.185 |
0.068 |
IL-27 |
0.04±0.03 |
0.05±0.03 |
0.05±0.03 |
0.819 |
0.979 |
0.760 |
IL-31 |
10.11±6.34 |
8.83±5.13 |
0.17±0.49 |
<0.0001 |
<0.0001 |
0.529 |
LIF |
87.17±8.54 |
74.76±36.89 |
14.33±5.15 |
<0.0001 |
<0.0001 |
0.130 |
NGFβ |
11.10±6.64 |
9.78±6.55 |
8.82±5.09 |
0.340 |
0.640 |
0.586 |
PDGF-BB |
1.90±0.77 |
1.68±0.88 |
1.62±0.90 |
0.419 |
0.850 |
0.476 |
PIGF |
0.28±0.20 |
0.25±0.14 |
0.26±0.14 |
0.822 |
0.839 |
0.667 |
RANTES |
4.49±3.74 |
6.65±4.26 |
4.23±3.17 |
0.857 |
0.055 |
0.159 |
SCF |
5.75±3.34 |
23.66±3.34 |
5.89±3.92 |
0.923 |
0.323 |
0.378 |
SDF1-α |
285.56±73.64 |
273.10±135.54 |
41.10±10.58 |
<0.0001 |
<0.0001 |
0.728 |
FGF-basic |
0.11±0.14 |
0.05±0.10 |
0.00±0.00 |
0.023 |
0.026 |
0.148 |
VEGF-A |
175.71±36.29 |
154.43±87.56 |
38.69±17.26 |
<0.0001 |
<0.0001 |
0.446 |
VEGF-D |
242.49±28.96 |
221.50±96.24 |
43.66±23.61 |
<0.0001 |
<0.0001 |
0.337 |
Bold= P<0.05. SD = Standard deviation. IL=Interleukin, LIF=leukemia inhibitory factor, SDF1-α=stromal-derived factor 1-α, BDNF=brain-derived neurotrophic factor, IP-10=interferon inducible protein 10, HGF=hepatocyte Growth Factor, IL-12p70=interleukin-12p70, PIGF=placental growth factor, FGF-basic=basic fibroblast growth factor, GMCSF=granulocyte macrophage colony stimulating Factor, EGF=epidermal growth factor, MIP-1β=macrophage inflammatory protein 1β, RANTES=regulated upon the activation of normal T cell expressed and secreted, PDGF-BB=platelet-derived growth factor-BB, MCP-1= monocyte chemoattractant protein, NGFb=nerve growth factor b, SCF= stem cell factor, MIP-1α=macrophage inflammatory protein-1α, GROα=growth-related gene product α, IFNγ= interferon-γ, IFNα=interferon-α, TNF=tumor necrosis factor. |
Table 3. Association of nAMD or PCV with aqueous humor cytokines (multivariate logistic analysis)
|
HGF |
IP-10 |
MCP-1 |
IL-13 |
IL-31 |
LIF |
SDF1-α |
VEGF-A |
VEGF-D |
|
nAMD (vs. control)
|
|
|
|
|
|
|
|
|||
P value |
0.002 |
0.007 |
0.004 |
0.017 |
0.014 |
0.003 |
0.021 |
0.001 |
0.002 |
|
OR |
0.987 |
0.957 |
0.959 |
0.026 |
8.902 |
1.099 |
1.037 |
1.045 |
1.034 |
|
|
(0.978-0.995) |
(0.927-0.988) |
(0.932-0.987) |
(0.001-0.516) |
(1.552-51.065) |
(1.033-1.170) |
(1.005-1.069) |
(1.018-1.073) |
(1.012-1.056) |
|
PCV (vs. control)
|
|
|
|
|
|
|
|
|||
P value |
0.006 |
0.001 |
0.012 |
0.032 |
0.017 |
0.007 |
0.021 |
0.003 |
0.004 |
|
OR |
0.99 |
0.946 |
0.975 |
0.041 |
8.411 |
1.076 |
1.037 |
1.039 |
1.028 |
|
|
(0.983-0.997) |
(0.915-0.979) |
(0.956-0.994) |
(0.002-0.763) |
(1.468-48.198) |
(1.020-1.135) |
(1.005-1.069) |
(1.013-1.066) |
(1.009-1.047) |
|
p values are adjusted for age and gender. OR = Odds ratio. Figures in parentheses indicate 95% confidence intervals. |
|
|