Risk Factors and VEGF, hs-CRP, and ESR in Central Serous Chorioretinopathy.

Background: The pathogenesis of central serous chorioretinopathy (CSC) remains a subject of intensive research. We aimed to determine correlations between plasma levels of selected angiogenic factors and different forms of CSC. Methods: Eighty patients were enrolled in the study including 30 with a chronic form of CSC, 30 with acute CSC, and 20 controls. Presence of active CSC was determined by fluorescein angiography (FA), indocyanine green angiography (ICGA), and swept-source optical coherence tomography (SS-OCT). Plasma concentrations of angiopoietin-1, endostatin, fibroblast growth factor, placental growth factor (PlGF), platelet-derived growth factor (PDGF-AA), thrombospondin-2, vascular endothelial growth factor (VEGF), VEGF-D, and pigment epithelium–derived factor were measured, and the results were compared between groups. Additionally, mean choroidal thickness (CT) was measured in all patients. Results: Levels of angiopoietin-1 (p = 0.008), PlGF (p = 0.045), and PDGF-AA (p = 0.033) differed significantly between the three groups. Compared with the controls, VEGF (p = 0.024), PlGF (p = 0.013), and PDGF-AA (p = 0.012) were downregulated in the whole CSC group, specifically PDGF-AA (p = 0.002) in acute CSC and angiopoietin-1 (p = 0.007) in chronic CSC. An inverse correlation between mean CT and VEGF levels was noted in CSC patients (rho = −0.27, p = 0.044). Conclusions: Downregulated angiopoietin-1, VEGF, PDGF-AA, and PlGF levels may highlight the previously unknown role of the imbalanced levels of proangiogenic and antiangiogenic factors in the pathogenesis of CSC. Moreover, downregulated VEGF levels may suggest that choroidal neovascularization in CSC is associated with arteriogenesis rather than angiogenesis.

Purpose To investigate the association between central serous chorioretinopathy (CSC) and the risk of developing depression. The risk factors associated with depression in CSC patients were also assessed. Methods A population-based retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from the beginning of 2001 through the end of 2013. CSC patients and age- and gender-matched (1 : 4 matched) control subjects without CSC were enrolled in the study. Kaplan–Meier curves were generated to compare the cumulative hazard of subsequent depression between the CSC and control groups. A Cox regression analysis estimated the crude and adjusted hazard ratios (HRs) for depression. Risk factors leading to depression were investigated among the CSC patients. Results 25,939 CSC patients and 103,756 controls were enrolled in the study. The CSC group had a significantly higher cumulative hazard for depression compared to the control group (p value < 0.0001). The Cox regression model indicated that the CSC group had a significantly higher risk for depression (adjusted HR = 1.33). Within the CSC group, significant risk factors for depression included age, female gender, low income, first-onset CSC, peptic ulcer, and smoking. The recent use of steroids prior to CSC, by all routes of administration, also significantly increased the risk for depression. However, treatment of CSC did not significantly reduce the risk for depression. Conclusion Patients with CSC are at significantly greater risk of developing depression. Among CSC patients, age, female gender, low income, first-onset CSC, peptic ulcer, smoking, and recent use of steroids prior to CSC were significant risk factors for depression.

Diagnostic value of blood platelet (PLT) and serum total bilirubin (TBIL) for central serous chorioretinopathy (CSC) was investigated. A total of 537 patients with CSC and 182 people with normal physical conditions were selected from June 2012 to August 2016. The 537 patients included 294 males and 243 females with an average age of 45.5±17.8 years, and all patients were treated in the Department of Ophthalmology of Yantai Hospital of Traditional Chinese Medicine and the Department of Ophthalmology of Yantai Liuhuangding Hospital. Clinical data of the patients were retrospectively analyzed. The 182 people with normal physical conditions included 103 males and 79 females with an average age of 43.6±15.2 years, and they were set as the control group. PLT and TBIL tests at admission and after treatment were collected and compared between CSC and the control group to analyze the diagnostic values of PLT and TBIL for CSC. PLT level in the CSC group was significantly higher than that in the control group, but TBIL level in the CSC group was significantly lower than that in the control group (p<0.05). Linear correlation analysis showed that PLT was a risk factor for CSC, and TBIL was a protective factor for CSC. The sensitivity of PLT and TBIL in diagnosis of CSC was 75.2 and 72.7%, respectively, and the specificity of PLT and TBIL in diagnosis of CSC was 65.8 and 63.3%, respectively. PLT of CSC patients was significantly higher than that of the control group, and TBIL of CSC patients was significantly lower than that of the control group, but they both gradually reduced to normal levels after treatment, which can be regarded as the index for the clinical diagnosis of CSC in the future.

Objective To compare the differences of optic nerve head (ONH) parameters and the thickness of circumpapillary retinal nerve fiber layer (CP-RNFL) between acute Vogt-Koyanagi-Harada syndrome (VKH) and acute central serous chorioretinopathy (CSC) patients. Methods Retrospective clinical case control analysis. This study included 38 eyes of 20 acute VKH patients (VKH group) and 37 eyes of 37 acute CSC patients (CSC group). Seventy five eyes of 57 normal healthy subjects, matching patients with age and gender, were collected as control group. The disc RPE angle, the thickness of average CP-RNFL, the nasal, superior, temporal and inferior quadrant CP-RNFL thickness, and ONH parameters including optic disc area, cup area, rim area, C/D area ratio, linear CD ratio (CDR), vertical CDR were measured by 3D-OCT. Analysis of variance was performed for comparison among three groups. Minimum significant difference t test was performed for comparison between two groups. Results The differences of ONH parameters between VKH group and CSC group: 29 eyes of VKH group appeared retinal detachment next to disc, only 12 eyes appeared in CSC group. Twenty one eyes of VKH group appeared optic disc hyperemia while none in CSC group. The three groups’ disc RPE angles were (138.62±11.96)°, (154.09±5.85)° and (153.41±5.77)°. VKH group were significantly smaller than CSC group (t=-2.05, P=0.00) and control group (t=-1.68, P=0.00), while there was no significant difference between CSC group and control group (t=-1.88, P=0.72). The optic cup area and rim area were significantly bigger in VKH group than in CSC group (t=4.61, 2.71; P=0.00, 0.01), and the thickness of mean CP-RNFL, all quadrants of CP-RNFL were significantly thicker in VKH group than in CSC group (t=6.25, 4.40, 3.53, 5.48, 2.69; P=0.00, 0.00, 0.00, 0.00, 0.01). Conclusion Compared with the acute CSC, VKH patients are likely to appear retinal detachment next to disc, their disc RPE angles are smaller, their optic cup area and rim area are bigger, and their CP-RNFL thickness are thicker. Key words: Uveomeningoencephalitic syndrome; Central serous chorioretinopathy; Optic disk; Nerve fibers; Tomography, optical coherence

The purpose of the study is to investigate the characteristics of choriocapillaris flow based on the underlying choroidal vasculature in fellow eyes with central serous chorioretinopathy (CSC). We included 57 patients with CSC and normal controls. Characteristics of choriocapillaris flow were evaluated using swept-source optical coherence tomography (OCT) angiography. We divided the choroidal layer into the vascular and stromal beds according to the choroid vessels on en-face OCT images. We compared the flow void area and mean vascular density of the choriocapillaris according to the underlying choroidal beds in the CSC and control group. The mean vascular density of the choriocapillaris in the CSC group was not different from that of the control group (P = 0.289). The flow void area was more frequently found in the CSC group (59.6%) than in the control group (29.8%, P = 0.002). The presence of the flow void area in the CSC group was associated with greater macular choroidal thickness (P = 0.004). In the CSC group, the mean flow void area and ratio of the choriocapillaris over the vascular bed were larger than those over the stromal bed (all P < 0.001). The location of the flow void area of the choriocapillaris was associated with the distribution of the underlying choroidal vessels. This suggests that the underlying choroidal vessels may affect choriocapillaris perfusion in pachychoroid eyes.

PurposeThis study aimed to evaluate mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR) values and their relationship with clinical findings in patients with central serous chorioretinopathy (CSCR).MethodsOverall, 87 patients fulfilling inclusion criteria and 320 age- and sex-matched healthy individuals as controls were included in the study. The CSCR patients (n=87) were classified into 2 groups as acute CSCR (group 1, n=43) and chronic CSCR (group 2, n=44).ResultsIt was found that NLR (P<0.05) and C-reactive protein (CRP) (P<0.05) values were higher in acute CSCR group than the other groups. MPV value was found to be higher in chronic CSCR group than the other groups (P<0.001).ConclusionIt seems that neutrophils play a major role in acute CSCR while platelets are involved in progression to chronic CSCR. Larger, prospective studies are needed on this topic.

Vascular endothelial growth factor and nitric oxide are both related to tumor progression. This study was designed to measure preoperative plasma vascular endothelial growth factor and nitrite levels in patients with colorectal cancer to evaluate their clinical applications as tumor markers. In total, 279 patients with primary colorectal cancer and 20 patients with hemorrhoids (as a control) were included in this study. Plasma vascular endothelial growth factor was measured by quantitative, solid-phase, enzyme-linked immunosorbent assay (R&D Systems), whereas nitrite was measured by a high-performance liquid chromatographic method. The vascular endothelial growth factor (mean, 220.6 pg/ml, P < 0.005) and nitrite (mean, 29.4 microM, P = 0.043) levels of patients with cancer were significantly higher than those of controls (mean vascular endothelial growth factor, 67 pg/ml; mean nitrite, 23 microM). Preoperative plasma vascular endothelial growth factor levels were positively correlated with tumor stage, T class, M class, and tumor size (Spearman correlation, P < 0.01), but were not associated with gender, N class, tumor location, histology type, or grade. There were no statistical differences in nitrite levels among different groups of patients with cancer. Higher vascular endothelial growth factor levels also were correlated with leukocytosis, elevated carcinoembryonic antigen, and a higher platelet count. The positive rates of vascular endothelial growth factor elevation (>148.6 pg/ml) compared with carcinoembryonic antigen elevation were 36.9 to 14.6 percent in Stage I, 60.9 to 33 percent in Stage II, 62.9 to 48.7 percent in Stage III, and 86 to 70.2 percent in Stage IV, respectively. The overall positive rate of vascular endothelial growth factor elevation also was higher than that of carcinoembryonic antigen elevation (63 percent for vascular endothelial growth factor vs. 42.5 percent for carcinoembryonic antigen, P = 0.016). More than one-half of the patients without carcinoembryonic antigen elevation still had elevated vascular endothelial growth factor levels. The combined assessment using vascular endothelial growth factor and carcinoembryonic antigen was superior to individual assessment using vascular endothelial growth factor or carcinoembryonic antigen. In node-negative tumor, the patients with vascular endothelial growth factor elevation had worse disease-free survival than those without vascular endothelial growth factor elevation (P = 0.0367). There was no association of vascular endothelial growth factor elevation with survival in patients with node-positive tumor. Plasma vascular endothelial growth factor is a useful complementary tumor marker; however, synchronous measurement of white blood cells, platelets, and carcinoembryonic antigen is suggested in the clinical application of vascular endothelial growth factor to colorectal cancer.

Purpose:To compare the anterior scleral thickness in eyes with central serous chorioretinopathy (CSC) and healthy eyes.Design:Cross-sectional observational study.Methods:The study included patients with CSC and age and gender-matched healthy individuals. The subfoveal choroidal thickness (SFCT) and scleral thickness at 3 mm, 4 mm, and 8 mm posterior to the scleral spur were measured using swept source optical coherence tomography (Topcon DRI-OCT Triton plus).Results:The study included 35 eyes with CSC and 35 control eyes. In CSC group, 82.86% were simple and 17.14% were complex. There was no statistically significant difference in the scleral thickness in CSC and control groups. Though the sclera was thicker in the complex CSC group compared to simple CSC at 3 mm (nasal: 724.33 ± 180.53 vs 658.48 ± 57.63, temporal: 696.17 ± 212.91 vs 628.83 ± 107.7) and 4 mm (nasal: 656.67 ± 109.34 vs 621.62 ± 79.31, temporal: 640.17 ± 191.31 vs 616.48 ± 86.30), the difference was not statistically significant. A moderate negative correlation was noted between SFCT and scleral thickness at 8 mm (r -0.349) and 3 mm on the nasal side (r -0.388) in the control group. A moderate negative correlation was noted between SFCT and scleral thickness at 4 mm (r -0.377) and 3 mm (r -0.403) on the temporal side in CSC group.Conclusion:The anterior scleral thickness was similar in CSC and healthy eyes. As the study sample predominantly included simple CSC, the findings indicate that the anterior scleral thickness may not be involved in the pathogenesis of simple CSC.

Inhibition of vascular endothelial growth factor (VEGF) by gene transfer techniques was effectively applied to control experimental tumor growth, whereas effects on systemic VEGF levels had not been investigated. Therefore, we evaluated the effect of VEGF inhibition by adenoviral-mediated gene delivery of a dominant-negative soluble fragment of FLK-1 (sFlk-1) on systemic VEGF levels, organ-specific VEGF-RNA expression and antitumor efficacy in a murine colorectal cancer (CRC) tumor model. Vector function of AdsFlk-1 was shown by Western blot analysis and transgene expression was documented over a time period of 42 days in the serum of treated mice. Although cell supernatant of CT26 cells contained considerable levels of VEGF, systemic VEGF levels in the serum of tumor-bearing mice remained unaffected. Interestingly, mice that were systemically treated with AdsFlk-1 showed a strong upraise of circulating VEGF, whereas VEGF remained at background levels in the control. Vascular endothelial growth factor was increased not only in tumor bearing but also in healthy, tumor-free mice. Vascular endothelial growth factor determination in liver tissue homogenates showed a 16.5-fold upraise in AdsFlk-1-treated animals as compared to the AdLacZ control. Consecutively, systemic small interfering RNA injection targeted against VEGF reverted elevated VEGF levels almost back to normal levels. In spite of elevated VEGF levels, AdsFlk-1 administration showed significant antitumor effects in a subcutaneous metastatic CRC tumor model. There was no significant correlation between antitumour treatment response and VEGF levels in this model. Collectively, we conclude that the systemic administration of AdsFlk-1 had significant inhibitory effects on metastatic CRC tumor growth in spite of elevated systemic VEGF levels and that VEGF serum concentrations did not correlate to tumor burden and antitumor treatment response in this model.

To analyze the long-term visual outcomes of pachychoroid spectrum diseases (PSD). Retrospective study. We reviewed the medical charts of consecutive patients with PSD, including focal choroidal excavation (FCE), pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), and pachychoroid neovasculopathy (PNV). The patients initially visited the Tokyo University Hospital from January 2008 to March 2021. Survival analyses were performed, in which loss of vision was defined as visual acuity (VA) of 0.2 logarithm of minimal angle of resolution (logMAR) or worse, 0.5 logMAR or worse, or VA worsening by 0.3 logMAR or greater. Moreover, we further investigated factors associated with visual prognosis, particularly in the CSC group. A total of 741 eyes of 638 patients were included in this analysis. The CSC or PNV group showed significantly worse visual prognosis than the FCE&PPE group for VA to 0.2 logMAR or worse (P = 0.0117 or 0.0001, respectively) and for VA worsening by 0.3 logMAR or greater (P = 0.0283 or 0.0037, respectively). In the CSC group, unlike age, sex, or treatment history, the accumulative duration of subfoveal fluid existence ≥ 12 months (continuous or intermittent) was significantly associated with visual prognosis (P < 0.0001). Among PSD, CSC and PNV were associated with a higher risk of vision loss in the long term than FCE and PPE. The duration of subretinal fluid existence was identified as a significant factor affecting long-term visual outcomes in CSC.

To estimate the risk of incident age-related macular degeneration (AMD) in patients with central serous chorioretinopathy (CSC). This population-based cohort study was finally conducted from January 2015 to December 2019. All patients with CSC from the entire population aged between 30 and 80 years were included. The incidence of CSC was estimated. Log-rank analysis and Cox proportional hazards regression analysis was used to evaluate the risk of exudative AMD in the CSC group compared with the non-CSC group. During a recent 5-year study period, 36,053 patients were identified as having incident CSC. The annual incidence in the latest year was 19.61 (95% confidence interval, 19.58 to 19.63) per 100,000 people. A total of 11,492 patients were included in the study group and 22,984 in the non-CSC group. The CSC and non-CSC groups included 166 (1.44%) and 73 (0.32%) cases of exudative AMD, respectively. The risk of exudative AMD was significantly higher in the CSC group than in the non-CSC group (adjusted hazard ratio: 4.86; 95% confidence interval: 2.98 to 5.88; P < 0.001). This study showed that subjects with CSC are at an increased risk of exudative AMD. This evidence supports a possible link between CSC and exudative AMD, particularly in Asian populations.

PurposeTo investigate the impact of central serous chorioretinopathy on sleep and mood in patients with acute and chronic central serous chorioretinopathy.MethodsThis cross-sectional study compared sleep and mood differences between central serous chorioretinopathy and control patients recruited from Ophthalmology clinics at the John Radcliffe Hospital, Oxford between 2012 and 2020. Data including visual acuity, type of central serous chorioretinopathy (acute or chronic; aCSC/cCSC), sex, and chronotype were obtained. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI); the Hospital Anxiety and Depression Scale (HADS) was used to evaluate anxiety (HADS-A) and depression (HADS-D).ResultsA total of 247 age matched controls and 109 patients with central serous chorioretinopathy participated. There were no significant differences in PSQI or HADs (P > 0.05) between the two groups. Females exhibited significantly higher PSQI scores than males both for control and central serous chorioretinopathy groups (P < 0.05). Within the central serous chorioretinopathy group, 88 (81%) had chronic central serous chorioretinopathy and 21 (19%) had acute central serous chorioretinopathy, and an increase in daytime dysfunction was seen in the acute phenotype compared to chronic (P = 0.018).ConclusionIn our study, no significant differences in sleep quality or mood scores were identified in central serous chorioretinopathy patients, when compared to controls. Worsened sleep for females was present when compared to males, both in central serous chorioretinopathy and control groups. Within central serous chorioretinopathy groups, worsened daytime function was observed in acute versus chronic – a larger study would help distinguish the effect of chronicity on sleep.

Background and Objectives: Retinal pigment epitheliopathy and hyperpermeability of choroidal vessels were postulated to be involved in the pathogenesis of central serous chorioretinopathy (CSC). Imbalanced levels of vascular endothelial growth factor (VEGF) and pigment-epithelium–derived factor (PEDF) were previously implicated in the development of chorioretinal diseases characterized by increased vascular permeability. We aimed to compare the plasma levels of proangiogenic VEGF and antiangiogenic PEDF for 26 patients with acute CSC, 26 patients with chronic CSC, and 19 controls. Materials and Methods: VEGF and PEDF levels were measured using a multiplex immunoassay or enzyme-linked immunosorbent assay. Correlations with disease duration were assessed. Results: VEGF levels differed between groups (p = 0.001). They were lower in patients with acute CSC (p = 0.042) and chronic CSC (p = 0.018) than in controls. PEDF levels were similar in all groups. The VEGF-to-PEDF ratio was lower in CSC patients than in controls (p = 0.04). A negative correlation with disease duration was noted only for PEDF levels in the group with chronic CSC (rho = −0.46, p = 0.017). Discussion: Our study confirmed that patients with CSC have imbalanced levels of VEGF and PEDF. This finding may have important implications for the pathogenesis of CSC. VEGF-independent arteriogenesis rather than angiogenesis may underlie vascular abnormalities in these patients.

Interplay between p53 and VEGF: how to prevent the guardian from becoming a villain

The purpose of this study was to determine if there is an association between obstructive sleep apnea (OSA) and central serous chorioretinopathy (CSCR). Patients with CSCR without a history of steroid use or secondary retinal disease were matched based on age/gender/body mass index with control patients and administered the Berlin Questionnaire to assess for OSA risk. Patients were scored "OSA+" if they were at "high risk" on the Berlin Questionnaire or reported a previous OSA diagnosis. Rates of OSA+ were compared between the 2 groups, odds ratio and its 95% confidence interval was calculated using exact conditional logistic regression. Forty-eight qualifying patients with CSCR were identified. There were no statistically significant differences between the CSCR and control groups by age (mean = 55 years), gender (79% male), body mass index (mean = 28.2), history of diabetes, or hypertension. Within the CSCR group, 22 patients (45.8%) were OSA+ versus 21 control patients (43.8%) (difference = 2.1%; 95% confidence interval, -18.2% to 22.2%; exact odds ratio = 1.08, 95% confidence interval, 0.47-2.49; P = 1.00). When compared with matched controls, patients with CSCR did not have statistically significant higher rates of OSA risk or previous diagnosis. This finding contrasts with previous work showing a strong association between the diseases. The divergence is likely due to our matching controls for body mass index, a significant risk factor for OSA.