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Central serous chorioretinopathy (CSCR) is a retinal disease characterised by the accumulation of subretinal fluid, which often resolves spontaneously in acute cases. However, approximately one-third of patients experience recurrences that may cause severe and irreversible vision. This study aimed to identify parameters derived from optical coherence tomography (OCT) that are associated with CSCR recurrence. Our dataset included 5211 OCT scans from 344 eyes of 255 patients diagnosed with CSCR. 178 eyes were identified as recurrent, 109 as non-recurrent, and 57 were excluded. We extracted parameters using artificial intelligence algorithms based on U-Nets, convolutional kernels, and morphological operators. We applied inferential statistics to evaluate differences between the recurrent and non-recurrent groups, and we used a logistic regression predictive model, reporting the coefficients as a measure of biomarker importance. We identified nine predictive biomarkers for CSCR recurrence: age, intraretinal fluid, subretinal fluid, pigment epithelial detachments, choroidal vascularity index, integrity of photoreceptors and retinal pigment epithelium layer, choriocapillaris and choroidal stroma thickness, and thinning of the outer nuclear layer, and of the inner nuclear layer combined with the outer plexiform layer. These results could enable future developments in the automatic detection of CSCR recurrence, paving the way for translational medical applications., (© 2024. The Author(s).)

Current data suggest that oxidative stress may play an important role in the occurrence of acute central serous chorioretinopathy (CSC), as chorioretinal integrity may be affected by disruption of the patient's metabolic redox balance, indicating the need for biomarkers. In addition to oxidative stress, high-density lipoprotein (HDL) dysfunction due to dyslipidemia can also lead to many types of physical discomfort. However, little is known about the pathophysiology of the disease resulting from oxidative stress and HDL dysfunction in CSC. The aim of this study was to investigate whether serum oxidative stress and HDL functionality markers have an impact on CSC disease. The case series of this study included 33 consecutive patients with treatment-naïve acute CSC. Thirty-five healthy volunteers of similar age were included in this study as non-CSC controls. Serum samples of the participants were taken and routine lipid values, serum Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidized Low Density Lipoprotein (ox-LDL), and Paraoxonase (PON1) levels were measured quantitatively. Serum oxidative stress index (OSI) was then calculated. Serum Ox-LDL, TOS and OSI levels in the acute CSC group, consisting of patients who had never been treated before and had no other disease, were statistically significantly higher than the control group. Conversely, serum PON1 and TAS levels were lower in CSC than in the control group. The relationship between CSC and deterioration in serum redox balance and decrease in PON1 activity, an important marker of HDL functionality, was demonstrated for the first time through this study. According to the literature, serum levels of these biomarkers, which identify acute/chronic inflammation and oxidative stress, have not been measured before in CSC disease. Finally, it is conceivable that redox balance and HDL functionality may be important in the diagnosis and treatment of the acute phase of CSC., (© 2024. The Author(s).)

Background: Central Serous Chorioretinopathy (CSCR) manifests as fluid accumulation between the neurosensory retina and the retinal pigment epithelium (RPE). Elevated levels of steroid hormones have been implicated in CSCR pathogenesis. This investigation aims to delineate the gene expression patterns of CSCR-associated risk and steroid receptors across human choroidal cell types and RPE cells to discern potential underlying mechanisms., Methods: This study utilized a comprehensive query of transcriptomic data derived from non-pathological human choroid and RPE cells., Findings: CSCR-associated genes such as PTPRB , CFH , and others are predominantly expressed in the choroidal endothelium as opposed to the RPE. The androgen receptor, encoded by the AR gene, demonstrates heightened expression in the macular endothelium compared to peripheral regions, unlike other steroid receptor genes. AR -expressing endothelial cells display an augmented responsiveness to Transforming growth factor beta (TGF-β), indicating a propensity towards endothelial to mesenchymal transition (endMT) transcriptional profiling., Interpretation: These results highlight the proclivity of CSCR to manifest primarily within the choroidal vasculature rather than the RPE, suggesting its categorization as a vascular eye disorder. This study accentuates the pivotal role of androgenic steroids, in addition to glucocorticoids. The observed linkage to TGF-β-mediated endMT provides a potential mechanistic insight into the disease's etiology., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The purpose of this study was to investigate the presence of sex-steroid receptors in human choroidal tissue across different ages and sex, aiming to better understand the pronounced sex difference in central serous chorioretinopathy (CSC) occurrence., Methods: Paraffin-embedded enucleated eyes of 14 premenopausal women, 15 postmenopausal women, 10 young men (<45 years), and 10 older men (>60 years) were used. A clinically certified immunostaining was performed to detect the presence of the androgen receptor (AR), progesterone receptor (PR; isoform A and B), and estrogen receptor (ERα). The stained slides were scored in a blinded manner for positive endothelial cells and stromal cells in consecutive sections of the same choroidal region., Results: Our analysis revealed the presence of AR, PR, and ERα in endothelial cells and stromal cells of choroidal tissue. The mean proportion of AR-positive endothelial cells was higher in young men (46% ± 0.15) compared to aged-matched women (29% ± 0.12; P < 0.05, 95% confidence interval [CI]). Premenopausal women showed markedly lower mean proportion of ERα (5% ± 0.02) and PR-positive endothelial cells (2% ± 0.01) compared to postmenopausal women (15% ± 0.07 and 19% ± 0.13; both P < 0.05, 95% CI), young men (13% ± 0.04 and 21% ± 0.10; both P < 0.05, 95% CI), and older men (18% ± 0.09 and 27% ± 0.14; both P < 0.05, 95% CI). Mean PR-positive stromal cells were also less present in premenopausal women (12% ± 0.07) than in other groups., Conclusions: The number of sex-steroid receptors in the choroidal tissue differs between men and women across different ages, which aligns with the prevalence patterns of CSC in men and postmenopausal women.

Age-related macular degeneration (AMD) and central serous chorioretinopathy (CSC) are common diseases that can cause vision loss in older and younger populations. These diseases share pathophysiological conditions derived from retinal pigment epithelium (RPE) dysfunction. Tumor necrosis factor receptor superfamily 10A (TNFRSF10A)-LOC389641 with the same lead single-nucleotide polymorphism (SNP) (rs13278062) is the only overlapped susceptibility locus found in both AMD and CSC through genome-wide association studies. This lead SNP has been reported to alter the transcriptional activity of TNFRSF10A. This study aimed to elucidate the function of TNFRSF10A in RPE degeneration using human primary RPE cells and Tnfrsf10 knockout (Tnfrsf10-/-) mice. TNFRSF10A was found to be localized in human RPE. In vitro assays revealed that a T allele of rs13278062, the risk allele for AMD and CSC, downregulated TNFRSF10A transcription in RPE, leading to decreased cell viability and increased apoptosis through protein kinase C-α (PKCA) downregulation. Treatment with phorbol 12-myristate 13-acetate, a PKC activator, rescued the cell viability. Morphological RPE abnormality was found in the retina of Tnfrsf10-/- mice. Our data suggest that downregulation of TNFRSF10A expression inactivates PKCA signaling and causes cellular vulnerability of the RPE, which may contribute to the pathogenesis of AMD and CSC., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The purpose of this study was to investigate the factors of clinical outcome of selective retina therapy (SRT) for central serous chorioretinopathy (CSC). This retrospective study included 77 eyes of 77 patients, who were treated with SRT for CSC and observed at least 6 months after the treatment. SRT laser (527 nm, 1.7 µs, 100 Hz) was used for treatment. The mean best-corrected visual acuity (logMAR), central macular thickness (CMT) and central choroidal thickness were changed from baseline to at 6-months follow-up with significant difference. The multivariate analyses found that the rate of change (reduction) in CMT was associated with focal leakage type on fluorescein angiography (FA) (p = 0.03, coefficient 15.26, 95% confidence interval 1.72-28.79) and larger baseline CMT (p < 0.01, coefficient - 0.13, 95% confidence interval - 0.13 to - 0.05). Complete resolution of subretinal fluid was associated with nonsmoking history (p = 0.03, odds ratio 0.276, 95% confidence interval 0.086-0.887) and focal leakage type on FA (p < 0.01, odds ratio 0.136, 95% confidence interval 0.042-0.437). These results may be useful for predicting the therapeutic effectiveness of SRT.

Purpose: Central serous chorioretinopathy (CSCR) has been associated with oxidative stress-related risk factors. The objective of this study was to optimize an analytical method for evaluating the oxidative stress biomarker malondialdehyde (MDA) in human tears and determine its level in the tears of patients with CSCR., Methods: In this pilot study, tear samples were obtained from 34 healthy donors and 31 treatment-naïve CSCR male patients (eight with acute CSCR and 23 with chronic CSCR). Two analytical methods based on high-performance liquid chromatography followed by fluorescence detection were evaluated, with either 2-thiobarbituric derivative (TBA) or 2-aminoacridone (2-AA). Activity of CSCR was defined by the serous retinal detachment (SRD) height, which was measured by two independent observers on spectral-domain optical coherence tomography., Results: The 2-AA method showed higher sensitivity and precision compared to the TBA method. When the 2-AA method was applied to tears from healthy donors, the levels of MDA were statistically significantly higher in men compared to women (mean ± standard deviation, SD: 9,914 nM ± 6,126 versus 4,635 nM ± 1,173, p = 0.006). No difference was found in tear MDA levels between male patients with CSCR and age-matched control men (p = 0.17). However, MDA levels were statistically significantly higher in acute compared to chronic CSCR cases (mean ± SD: 12,295 nM ± 8,495 versus 6,790 ± 3,969 nM, p = 0.03). Additionally, there was a correlation between MDA levels and RPE leakage, quantified by the height of the serous retinal detachment (p = 0.02, r = 0.40)., Conclusions: Levels of MDA in tears, measured with an optimized analytical method, correlate with RPE leakage in CSCR., (Copyright © 2020 Molecular Vision.)

Purpose: Reduced-fluence photodynamic therapy (RFPDT) has proven effective for some patients with chronic central serous chorioretinopathy (cCSC). Several clinicodemographic factors influencing treatment response have been identified, but associations with genetic factors have not been examined. Therefore, we investigated the associations of single nucleotide polymorphisms (SNPs) implicated in cCSC pathogenesis with clinical outcome following RFPDT., Methods: This was a retrospective study of 87 eyes from 87 patients with cCSC who underwent RFPDT and were followed up for more than 12 months. Patients were divided into a good response group (53 patients) and a poor response group (34 patients) based on either persistence or recurrence of subretinal fluid detected with spectral domain optical coherence tomography after the first application of RFPDT. SNPs in the genes encoding age-related maculopathy susceptibility protein 2 ( ARMS2 , SNP rs10490924) and complement factor H ( CFH , SNP rs800292) were genotyped using TaqMan technology., Results: There were no statistically significant differences in the baseline characteristics between the response groups except the degree of hyperfluorescence on indocyanine green angiography (ICGA; p = 0.011). The minor (T) allele frequency of ARMS2 (rs10490924) were statistically significantly lower in the good response group than in the poor response group (24.0% versus 41.0%, p = 0.021). Further, the good response frequency was statistically significantly lower in patients with at least one minor allele (GT or TT) compared to the homozygous major allele group (GG; p<0.05). The baseline best-corrected visual acuity (BCVA) at 12 months after RFPDT was statistically significantly better in the GG carriers than in the GT or TT carriers (p<0.01). Logistic regression analysis showed less intense hyperfluorescence on ICGA, and the T allele of ARMS2 (rs10490924) was statistically significantly associated with poor response to PDT treatment (p = 0.012, p = 0.039, respectively)., Conclusions: Carriers of the ARMS2 rs10490924 minor allele (GT or TT) demonstrated a higher subretinal fluid persistence or recurrence rate and poorer visual outcome following RFPDT. In addition to the ICGA findings, genotyping of ARMS2 (rs10490924) may assist in the selection of patients with cCSC most likely to benefit from RFPDT., (Copyright © 2020 Molecular Vision.)

Purpose: Central serous chorioretinopathy (CSC), a distinct form of macular degeneration, has been associated with glucocorticoid use and possibly also with an increased endogenous activity of the hypothalamic-pituitary-adrenal (HPA) axis. To estimate long-term glucocorticoid exposure, measurement of hair cortisol concentrations (HCC) has emerged. This cross-sectional study aimed to investigate HCC, as a reflection of chronic endogenous steroid exposure, in a cohort of patients with chronic CSC (cCSC)., Methods: Hair cortisol concentrations (HCC) were determined in 48 patients with cCSC and 230 population-based controls (Lifelines cohort study), not using exogenous corticosteroids., Results: Increased HCC (defined as >10.49 pg/mg) were present in 2 (4%) patients with cCSC and 13 (6%) controls. Mean HCC values were not different between patients and controls, and no difference in HCC was found between patients with active cCSC disease and patients with inactive disease. No correlation between HCC and urinary free cortisol (UFC) levels in patients with cCSC was found., Conclusions: This study shows that HCC in patients with cCSC are not elevated compared to population-based controls, and no association between HCC and cCSC severity was found. This finding questions the previous suggestion that cCSC is associated with increased HPA axis activity. In line, HCC do not seem useful in monitoring cCSC disease activity., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the association between single nucleotide polymorphisms (SNPs) in the complement factor H (CFH) gene and response to PDT in patients with CSC., Methods: 103 eyes from 93 patients with CSC were enrolled from Department of Ophthalmology of the People's Hospital Peking University. Genotyping for selected SNPs in the CFH gene was performed, and multivariate linear analysis was used to identify factors influencing PDT treatment outcomes. Genetics associations between SNPs in the CFH gene and response to PDT in patients with CSC were analyzed., Results: None of the seven SNPs examined in this study (rs800292, rs1061170, rs3753394, rs3753396, rs2284664, rs1329428, and rs1065489) showed significant associations with 1-month outcomes after PDT in patients with CSC (P > 0.05). Baseline BCVA changed at 1 month after PDT (P < 0.001), and baseline retinal thickness was associated with changes in retinal thickness at 1 month after PDT (P < 0.001). Age was significantly associated with resolution of SRF at 1 month after PDT (P = 0.004)., Conclusions: There were no significant associations between SNPs in the CFH gene and 1-month outcomes after PDT in patients with CSC. However, baseline BCVA, baseline retinal thickness, and age were significantly associated with response to PDT in patients with CSC. Larger studies with more power are necessary to further determine whether an association exists between SNPs in the CFH gene and PDT in patients with CSC.

The aim of the study was to evaluate the prevalence of serum anti-retinal (ARAs) and anti-endothelial cell antibodies (ACEAs) in patients with acute and chronic central serous chorioretinopathy (CSC). We enrolled 28 patients with acute CSC, 42 patients with chronic CSC, and 40 healthy controls. The presence of ARAs was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECAs was determined using cultivated human umbilical vein endothelial cells (HUVECs) and primate skeletal muscle according to the manufacturer's instructions (Euroimmun AG). There were no differences in the prevalence of antibodies against rods, cones, cytoplasmic components of retinal nuclear layer cells, and retinal vessels between the acute and chronic CSC groups and the control group (P = 0.27, P = 0.16, P = 0.71, and P = 0.06, respectively). However, AECAs reactive with HUVECs were observed in 46% of patients with acute CSC, 45% of those with chronic CSC, and 22% of controls, whereas AECAs reactive with the skeletal muscle were present in 46%, 45%, and 15%, respectively (difference between groups: P = 0.045 for HUVECs and P = 0.005 for the skeletal muscle). Furthermore, AECA titers were higher in CSC patients than in controls (P = 0.004). This study provides evidence for the possible involvement of an autoimmune process directed against vessel antigens in the pathogenesis of CSC. AECAs may be more important than ARAs in this disease and may be involved in endothelial damage in the choroidal vessels and choriocapillaris, leading to hyperpermeability, which is central to the pathophysiology of CSC.

Purpose: To use swept-source optical coherence tomography and swept-source optical coherence tomography angiography to investigate potential relationships between choroidal vascular hyperpermeability (CVH) seen with indocyanine green angiography (ICGA), choriocapillaris flow density, and choroidal thickness in eyes with pachychoroid pigment epitheliopathy., Methods: Patients with pachychoroid pigment epitheliopathy were prospectively imaged with 12-mm × 12-mm swept-source optical coherence tomography, 12-mm × 12-mm swept-source optical coherence tomography angiographyA, and ICGA. Binarized choriocapillaris OCTA images were superimposed with ICGA images in which CVH area had been isolated. Choriocapillaris flow density within or outside the quadrants of CVH was calculated and the ratio of these two values was determined. The presence of CVH and choroidal thickness was evaluated at 9 locations within a central 3-mm × 3-mm area to explore the relationship between these 2 factors., Results: Ten eyes from 10 patients were enrolled in the present study. Choriocapillaris flow density within quadrants of CVH area was significantly lower compared with quadrants without CVH (P < 0.001). The mean choriocapillaris flow density ratio was 0.86 ± 0.10 (range: 0.65-0.99). From among the 90 locations in 10 study eyes, 48 were within areas of CVH. Choroidal thickness was greater in quadrants of CVH compared with areas without CVH (P < 0.001, 455 ± 122 µm vs. 297 ± 93 µm)., Conclusion: Reduced choriocapillaris flow density, increased choroidal thickness, and CVH appear to co-localize in eyes with pachychoroid pigment epitheliopathy.

Purpose: To investigate hair cortisol concentration (HCC), a biochemical correlate of long-term cortisol output patterns, and its relationship to active central serous chorioretinopathy (CSC)., Methods: Twenty-six participants were included in this observational pilot study (11 patients with active CSC and 15 healthy controls). Hair cortisol concentrations (HCCs) were determined from 3 cm hair strands collected near the scalp from patients and controls as an index of cumulative cortisol secretion over the 3-month period prior to hair sampling., Results: Patients with CSC exhibited higher HCCs (mean value: 20.14, 95% CI: 14.89-27.16 pg/mg) than healthy controls (mean value: 11.06, 95% CI: 8.63-14.22 pg/mg, p = 0.008). Group differences were not affected by relevant covariates (BMI, smoking status, sex)., Conclusion: Patients with active CSC have increased HCC, supporting the fact that cortisol is a major player in CSC pathogenesis., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To investigate subfoveal choroidal thickness and pachychoroid and their correlation with hormone level in patients with endogenous Cushing syndrome (CS)., Methods: We enrolled a consecutive series of patients with CS and healthy controls. All participants had swept-source optical coherence tomography. All patients with CS had hormone test including morning plasma-free cortisol, 24-hour urine-free cortisol (24UFC), and plasma adrenocorticotropic hormone. We compared subfoveal choroidal thickness and pachychoroid changes between two groups. We performed univariate and multivariate analysis to study correlation between hormone level and choroid thickness as well as pachychoroid in patients with CS., Results: Compared with control group, Cushing group had significantly greater subfoveal choroidal thickness (371.6 ± 114.9 and 320.0 ± 74.0, P = 0.002) and higher proportion of eyes with pachychoroid (53.1 and 14.3%, P < 0.001). Subfoveal choroidal thickness was significantly correlated with 24UFC (P = 0.007) but not with plasma-free cortisol (P = 0.48) or adrenocorticotropic hormone (P = 0.56). Pachychoroid was significantly correlated with 24UFC (P = 0.03) but not with plasma-free cortisol (P = 0.24) or adrenocorticotropic hormone (P = 0.32)., Conclusion: There was a positive correlation between elevated 24UFC and choroid thickening as well as pachychoroid, indicating the importance of normal endogenous cortisol level in maintaining the human choroid vasculature.

Purpose: To clarify the distinct molecular pathogenesis of central serous chorioretinopathy (CSC) and pachychoroid neovasculopathy (PNV)., Methods: Aqueous humor (AH) was collected from 18 acute CSC, 20 chronic CSC, and 20 PNV patients. Concentrations of 30 cytokines in the AH were analyzed using a multiplex bead immunoassay, and the cytokine profiles were compared among these three groups of patients. The areas of choroidal vascular hyperpermeability (CVH) and choroidal thickness (CT), including measurement of the vascular layers, were investigated to analyze the features of choroidal abnormality in acute CSC, chronic CSC, and PNV. Additionally, associations between cytokine profiles and choroidal abnormalities were analyzed., Results: Proinflammatory cytokines, IL-6 and IL-8 were significantly upregulated in the chronic CSC group compared with the acute CSC or PNV groups. Angiogenic cytokines and VEGF-A were upregulated at levels that almost reached significance along with disease progression from acute to chronic CSC, whereas the upregulation was not significant from chronic CSC to PNV. In the chronic CSC group, strong positive correlations were confirmed between VEGF-A and placental growth factor (PlGF) (r = 0.75, P < 0.001) and IL-6 and VEGF-A (r = 0.74, P < 0.001), and angiogenesis-related cytokines were positively correlated with the typical choroidal abnormalities, areas of CVH, mean CT, and mean large choroidal vessel layer thickness. However, there was no association between these choroidal abnormality parameters and AH cytokines in the PNV group., Conclusions: The results suggest that choroidal abnormalities in chronic CSC may be associated with upregulated angiogenesis.

Purpose: To evaluate the efficacy of navigated focal laser photocoagulation in patients with chronic central serous chorioretinopathy (CSCR) and active leakage on fluorescein angiography (FA)., Methods: Thirty-two eyes of 32 patients (age 48 ± 11, m/f = 24/8) with persistent or recurrent CSCR (> 3 months) who received navigated laser photocoagulation (Navilas®) of leaking point(s) between June 2013 and 2016 were included in this retrospective case series. Outcome parameters after 4 weeks and 3 months were the number of patients presenting with complete resolution of subretinal fluid, the volume of subretinal fluid measured on SD-OCT (Spectralis Heidelberg Engineering©), and best corrected visual acuity (BCVA/ (Snellen equivalent)., Results: Complete resolution of subretinal fluid was achieved in 17 eyes (50%) after 4 weeks and in 24 eyes (75%) after 3 months with an average number of 1.3 laser procedures (range 1-3). Five eyes displayed a nearly complete resolution with a reduction of over 80% of the subretinal fluid compared to baseline. Three eyes showed no reduction in subretinal fluid. BCVA improved from median 0.58 (range 0.16-1.25) to 0.66 (0.16-1.0) (p = 0.001). The seven patients who had been treated within the central 1 mm of the ETDRS-OCT Grid but outside the avascular foveal zone showed an improvement of BCVA from median 0.6 (range 0.2-1.0) to 0.8 (0.2-1.0). No patient experienced a treatment-induced visual loss., Conclusions: Laser treatment with Navilas® using eye tracking and FA-based planning is a safe and effective alternative therapy in patients with chronic CSCR.

Aim: To present a series of 2 cases of central serous chorioretinopathy and the changes in the macular pigment optical density during the evolution of the disease. Material and methods: A 32-year-old patient presented himself for blurred vision on his LE. The SD OCT imaging revealed serous macular detachment of the neurosensory retina on the LE. The MPOD results were 0.72 on RE and 0.91 on LE. After treatment and resorption of the subretinal fluid, the MPOD values were 0.72 on the RE and 0.82 on the LE. The second patient was a 36-year-old male with metamorphopsia on LE and serous macular detachment on this eye. The MPOD results were 0.43 on RE and 0.58 on the LE and, after treatment, they were 0.38 on the RE and 0.43 on the LE. Conclusions: Central serous chorioretinopathy is a disease of unknown pathophysiology in which we observed a higher MPOD on the eye with CSC than on the fellow eye and a decrease in the MPOD value after the resorption of the subretinal fluid. Abbreviations: L = lutein, Z = zeaxantin, MZ = mezozeaxantin, AMD = age related macular degeneration, MPOD = macular pigment optical density, MP = macular pigment, HFP = Heterochromatic Flicker Photometry, CSC = central serous chorioretinopathy, RE = right eye, LE = left eye.

Purpose: The aim of this study was to compare dynamic thiol/disulfide homeostatic status in acute central serous chorioretinopathy (CSCR) patients by using a novel and automated assay determining dynamic thiol/disulfide homeostasis., Methods: Fifty-one patients with acute CSCR (study group) and 65 healthy individuals (control group) were enrolled in this study. Diagnosis of acute CSCR was made clinically and using spectral-domain RTVue OCT (optical coherence tomography) (Optovue, Fremont, CA). Fluorescein angiography confirmed the diagnosis of acute CSCR in all subjects. Total thiol, native thiol, disulfide amount, and native thiol/disulfide ratio (TDR) were calculated in the blood samples., Results: Mean total thiol, native thiol, and native TDR values were lower in patients with acute CSCR (364.2 ± 14.1, 326.4 ± 13.2, 17.14 ± 1.9, respectively) than in healthy eyes (441.2 ± 16.3, 398.5 ± 16.4, 22.70 ± 2.15, respectively; mean total thiol, p = 0.017; native thiol, p = 0.011; native TDR, p = 0.031)., Conclusions: Total thiol, native thiol, and native TDR were significantly lower statistically in patients with acute CSCR when compared with healthy controls.

Importance: Chronic central serous chorioretinopathy (cCSC) is a chorioretinal disease with unknown disease etiology. The glucocorticoid receptor and the mineralocorticoid receptor, 2 glucocorticoid-binding receptors, might be involved in the pathogenesis of cCSC., Objective: To assess the association of functional variants and haplotypes in the glucocorticoid receptor (NR3C1) and mineralocorticoid receptor (NR3C2) genes with cCSC., Design, Setting, and Participants: In this case-control genetic association study, 336 patients with cCSC and 1314 unaffected controls, collected at 3 university medical centers from September 1, 2009, to May 1, 2016, underwent KASP genotyping for selected variants in NR3C1 (rs56149945, rs41423247, and rs6198) and NR3C2 (rs2070951 and rs5522)., Main Outcomes and Measures: Genetic associations of 3 NR3C1 variants and 2 NR3C2 variants with cCSC., Results: Among the 336 patients (274 men and 62 women; mean [SD] age, 52 [10] years), after correction for multiple testing, rs2070951 in the NR3C2 gene was significantly associated with cCSC (odds ratio, 1.29; 95% CI, 1.08-1.53; P = .004). Moreover, the GA haplotype of single-nucleotide polymorphisms rs2070951 and rs5522 in NR3C2 conferred risk for cCSC (odds ratio, 1.39; 95% CI, 1.15-1.68; P = .004), whereas the CA haplotype decreased risk for cCSC (odds ratio, 0.72; 95% CI, 0.60-0.87; P < .001). Three known variants in NR3C1 that alter the activity of the glucocorticoid receptor (rs56149945, rs41423247, and rs6198) were not associated with cCSC., Conclusions and Relevance: In this study, the variant rs2070951 and the GA haplotype in NR3C2 were associated with an increased risk for cCSC. Results of this genetic study support a possible role for the mineralocorticoid receptor in the pathogenesis of cCSC. Since these haplotypes have previously been associated with perceived stress, this study provides a clue to bridging clinical risk factors for cCSC to underlying genetic associations.

Purpose: To investigate long-term efficacy and prognostic factors of half-dose photodynamic therapy (PDT) in chronic central serous chorioretinopathy (CSCR)., Design: Retrospective multicenter interventional case series., Methods: Patients with chronic CSCR undergoing half-dose PDT between 2005 and 2011 were reviewed. Main outcome measures included resolution of serous retinal detachment (SRD) with single PDT, change in best-corrected visual acuities (BCVAs), and recurrence rate of CSCR at 36 months after PDT. Prognostic factors of visual outcome and recurrence of CSCR after PDT were identified with multivariate regression analysis., Results: A total of 136 eyes of 123 patients were followed up for 57.7 ± 16.2 months. At 36 months after PDT, 132 eyes (97.1%) achieved complete resolution of SRD with single PDT and 4 eyes (2.9%) had CSCR recurrence. The mean logMAR BCVA improved from 0.36 ± 0.29 (Snellen equivalent 20/46; range: 0.1-1.2) at baseline to 0.15 ± 0.23 at 36 months (Snellen equivalent 20/28; range: 0.1-1.5; P < .001) and 0.16 ± 0.24 (Snellen equivalent: 20/29; range: 0.1-1.5; P < .001) at final follow-up. Forty-four eyes (32.4%) had ≥3 lines of BCVA gain while 5 eyes (3.7%) had ≥3 lines of BCVA loss at 36 months after PDT. Nine eyes (6.6%) developed CSCR recurrence at final follow-up. Baseline BCVA was significantly associated with the BCVA (P = .009) and the improvement in BCVA (P < .001) at final follow-up. History of bilateral CSCR was significantly associated with CSCR recurrence at final follow-up (P = .036; odds ratio = 15.84, 95% confidence interval = 1.20-208.32). Eight eyes (5.9%) had complications related to PDT., Conclusions: Chronic CSCR patients treated with half-dose PDT can achieve long-term stable visual acuity and resolution of SRD. Patients with chronic CSCR are recommended to undergo half-dose PDT before they have significant visual deterioration. Patients with bilateral CSCR are more likely to develop CSCR recurrence after half-dose PDT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Importance: The use of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors has become more common in the treatment of systemic cancer. These agents have been associated with a central serous-like retinopathy in some patients. Recognition of such retinal findings and the relatively benign nature of these events is important to avoid unnecessary intervention, including the cessation of a potentially life-prolonging medication., Objectives: To evaluate the presence and characteristics of subretinal fluid (SRF) associated with the use of MEK inhibitors in the treatment of systemic cancer and to correlate the presence of SRF with visual acuity and symptoms over time., Design, Setting, and Participants: Post hoc analysis was conducted of prospectively collected data from 51 patients with locally advanced or metastatic cancer undergoing treatment with the MEK inhibitor binimetinib in 1 of 4 clinical trials. All clinical trial participants underwent complete ophthalmic examination by retina specialists at a private practice in Boston, Massachusetts, and were monitored between February 29, 2012, and January 8, 2014. The examination included Snellen-measured visual acuity, dilated fundus examination, and spectral-domain optical coherence tomography at baseline, biweekly for 2 months, then monthly for the remainder of their trial participation. Post hoc design and data analysis were performed between December 1, 2013, and June 20, 2014., Main Outcomes and Measures: Visual symptoms, visual acuity, fundus appearance, and the presence and characteristics of SRF noted on optical coherence tomography. The characteristics of angiograms performed at the discretion of the treating physician were reviewed., Results: Of the 51 participants, 18 (35%) were men; the mean (SD) age was 60 (13) years (range, 32-87 years). Forty-six (90%) study participants developed SRF during the study period, with 9 (20%) experiencing symptoms at any point. The mean (SD) central retinal thickness of 39 study participants who developed SRF at the first visit increased from 280 (26) µm at baseline to 316 (43) µm at the first visit after starting binimetinib treatment (paired t test, P < .001). On examination, SRF appeared as elevated, yellow-orange pockets in the fovea and/or along the arcades. Corresponding optical coherence tomographic imaging revealed SRF beneath the interdigitation zone. The fovea was affected in 37 of 46 (80%) individuals; the location of SRF accumulation varied. Visual symptoms were mild and mainly transient, occurring in 9 participants with SRF (20%; 95% CI, 10%-33%). Only 2 participants (4%) were found to have SRF at the last study visit after discontinuation of treatment with binimetinib. Both had Snellen-measured visual acuity of 20/25 or better., Conclusions and Relevance: The presence of SRF was common in study participants undergoing treatment with the MEK inhibitor binimetinib. Visual symptoms were mild and mainly transient. The presence of SRF did not lead to permanent ocular sequelae. Cessation of life-extending treatment with MEK inhibitors is not indicated when SRF is present.

Purpose: To evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, for nonresolving central serous chorioretinopathy., Methods: This is a prospective, randomized, double-blinded, placebo-controlled crossover study. Sixteen eyes of 16 patients with central serous chorioretinopathy and persistent subretinal fluid (SRF) for at least 3 months were enrolled. Patients were randomized to receive either spironolactone 50 mg or placebo once a day for 30 days, followed by a washout period of 1 week and then crossed over to either placebo or spironolactone for another 30 days. The primary outcome measure was the changes from baseline in SRF thickness at the apex of the serous retinal detachment. Secondary outcomes included subfoveal choroidal thickness and the ETDRS best-corrected visual acuity., Results: The mean duration of central serous chorioretinopathy before enrollment in study eyes was 10 ± 16.9 months. Crossover data analysis showed a statistically significant reduction in SRF in spironolactone treated eyes as compared with the same eyes under placebo (P = 0.04). Secondary analysis on the first period (Day 0-Day 30) showed a significant reduction in subfoveal choroidal thickness in treated eyes as compared with placebo (P = 0.02). No significant changes were observed in the best-corrected visual acuity. There were no complications related to treatment observed., Conclusion: In eyes with persistent SRF due to central serous chorioretinopathy, spironolactone significantly reduced both the SRF and the subfoveal choroidal thickness as compared with placebo.

Purpose: To compare the efficacy and safety of photodynamic therapy using reduced irradiation time or reduced verteporfin dose for chronic central serous chorioretinopathy., Methods: Between April 2011 and December 2013, 45 eyes with chronic central serous chorioretinopathy (43 consecutive patients) were treated with photodynamic therapy, using either half the irradiation time (18 eyes) or half the verteporfin dose (27 eyes). Outcome measures at follow-up, over at least 3 months, were complete resolution of serous retinal detachment, best-corrected visual acuity, and central retinal thickness., Results: After 3 months, serous retinal detachment had completely resolved in 88.8% of eyes in both treatment groups, which were therefore not significantly different. The logarithm of the minimal angle of resolution best-corrected visual acuity (Snellen equivalent) improved from 0.245 (20/35) to 0.130 (20/27) (P < 0.05, paired t-test) in the reduced time group and from 0.283 (20/38) to 0.138 (20/27) (P < 0.05) in the reduced verteporfin group. Final best-corrected visual acuities in the 2 groups were not significantly different. Central retinal thicknesses dropped from 337.0 μm to 146.6 μm (P < 0.05) in the reduced time group and from 343.5 μm to 166.9 μm (P < 0.05) in the reduced verteporfin group. No ocular or systemic side effects were observed., Conclusion: Reduced irradiation time and reduced verteporfin dose were equally effective and safe in photodynamic therapy for chronic central serous chorioretinopathy.

Purpose: Chronic central serous chorioretinopathy (cCSC) has recently been associated to variants in the complement factor H gene. To further investigate the role of the complement system in cCSC, the genomic copy number variations in the complement component 4 gene (C4) were studied., Methods: C4A and C4B copy numbers were analyzed in 197 cCSC patients and 303 healthy controls by using a Taqman copy number determination assay. Copy numbers of C4A, C4B, and the total C4 load were compared between cases and controls, by using a Fisher exact test. For this analysis Bonferroni correction was performed for three tests, and P values < 0.017 were considered to be significant. A logistic regression model was constructed to calculate the odds ratios (ORs) of each of the C4B copy numbers, using two copies as a reference. For this model P values < 0.05 were considered to be significant., Results: C4B genomic copy numbers differed significantly between cCSC patients and healthy controls (P = 0.0018). Absence of C4B significantly conferred risk of cCSC (P = 0.039, OR = 2.61 [95% confidence interval (CI) = 1.05-6.52]), whereas three copies of C4B significantly decreased the risk of cCSC (P = 0.014, OR = 0.45 [95% CI = 0.23-0.85]). The C4A genomic copy numbers and total C4 load did not significantly differ between cases and controls., Conclusions: This study showed that copy numbers of C4B are significantly associated with cCSC. Carrying no copies of C4B significantly increases the risk of cCSC, whereas carrying three C4B copies is protective. These findings reinforce the hypothesis of a possible involvement of the complement system in the pathogenesis of cCSC.

Significance: Inflammation is the standard double-edged defense mechanism that aims at protecting the human physiological homeostasis from devastating threats. Both acute and chronic inflammation have been implicated in the occurrence and progression of vascular diseases. Interference with components of the immune system to improve patient outcome after ischemic injury has been uniformly unsuccessful. There is a need for a deeper understanding of the innate immune response to injury in order to modulate, rather than to block inflammation and improve the outcome for vascular diseases., Recent Advances: Nucleotide-binding oligomerization domain-like receptors or NOD-like receptor proteins (NLRPs) can be activated by sterile and microbial inflammation. NLR family plays a major role in activating the inflammasome., Critical Issues: The aim of this work is to review recent findings that provided insights into key inflammatory mechanisms and define the place of the inflammasome, a multi-protein complex involved in instigating inflammation in neurovascular diseases, including retinopathy, neurodegenerative diseases, and stroke., Future Directions: The significant contribution of NLRP-inflammasome activation to vascular disease of the neurovascular unit in the brain and retina suggests that therapeutic strategies focused on specific targeting of inflammasome components could significantly improve the outcomes of these diseases.

Importance: A randomized clinical trial is needed to evaluate what is the best photodynamic therapy (PDT) protocol to use for acute central serous chorioretinopathy., Objective: To compare the efficacy and safety of a 50% dose of verteporfin (a method of PDT) with the efficacy and safety of a 30% dose for acute central serous chorioretinopathy., Design, Setting, and Participants: A multicenter, noninferiority, double-masked, randomized, controlled, clinical trial in which 131 patients (131 eyes) with acute central serous chorioretinopathy for less than 6 months were recruited with a follow-up of 12 months from university-based ophthalmology practices., Interventions: Patients were randomly assigned to either a 50% dose of verteporfin (the 50%-dose PDT group) or a 30% dose (the 30%-dose PDT group)., Main Outcomes and Measures: The 2 primary outcome measures were the proportion of eyes with complete absorption of subretinal fluid and the proportion of eyes with complete disappearance of fluorescein leakage at 6 and 12 months. The secondary outcome measures included the subretinal fluid recurrent rate, the fluorescein leakage recurrent rate at 12 months, the mean best-corrected visual acuity, the retinal thickness of the foveal center, and the maximum retinal thickness at each scheduled visit., Results: The noninferiority of the 30%-dose PDT compared with the 50%-dose PDT for the primary outcomes was not demonstrated. The optical coherence tomography-based improvement rate in the 30%-dose PDT group was less than that in the 50%-dose PDT group both at 6 months (73.8% vs 92.9%; α = 0.0125, P = .006) and at 12 months (75.4% vs 94.6%; α = 0.0125, P = .004). The fluorescein angiography-based improvement rate in the 30%-dose PDT group was less than that in the 50%-dose PDT group both at 6 months (68.9% vs 91.1%; α = 0.0125, P = .003) and at 12 months (68.9% vs 92.9%; α = 0.0125, P = .001). The subretinal fluid recurrence rate in the 30%-dose PDT group was greater than that in the 50%-dose PDT group (24.0% vs 5.7% at 12 months; P = .010, determined by use of the log-rank test). The fluorescein leakage recurrent rate in the 30%-dose PDT group was significantly higher than that in the 50%-dose PDT group (16.7% vs 3.8% at 12 months; P = .03, determined by use of the log-rank test). No ocular adverse event was encountered in the study., Conclusions and Relevance: A 50% dose of verteporfin may be more effective at resolving subretinal fluid and fluorescein leakage, and with better visual outcomes, than a 30% dose for acute central serous chorioretinopathy., Trial Registration: clinicaltrials.gov Identifier: NCT01574430.

Purpose: To investigate the differences in the optical density ratios between chronic central serous chorioretinopathy (CSC) and polypoidal choroidal vasculopathy (PCV) obtained from subretinal fluid (SRF) analyses to identify the diagnostic role of optical density ratios., Design: Retrospective cohort study., Methods: Patients with acute CSC (n = 36), chronic CSC (n = 38), and PCV (n = 32) were included in the study. Spectral-domain optical coherence tomography (SD OCT) images of SRF were analyzed. The optical density measurements were obtained by using ImageJ. The optical density ratios were calculated from the SRF to the vitreous, retinal pigment epithelium (RPE), and retinal nerve fiber layer (RNFL) reflectivity ratios., Results: Optical density ratios of SRF to the vitreous, RPE, and RNFL were significantly higher in patients with PCV than in those with chronic CSC (P = .002, P = .001, P = .001). There was no significant difference between acute and chronic CSC (P = .358, P = .433, P = .774). RPE reflectivity was significantly different between groups (P = .002) but no significant difference in vitreous and RNFL reflectivity were detected between groups (P = .172, P = .171)., Conclusions: The optical density ratio differs significantly between chronic CSC and PCV, but not between chronic and acute CSC. This suggests the usefulness of this parameter in differentiating between chronic CSC resembling PCV and PCV itself., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To evaluate whether half-dose verteporfin photodynamic therapy (PDT) is better than natural history for the treatment of central serous chorioretinopathy (CSC)., Methods: Retrospective review of consecutive CSC patients treated with half-dose verteporfin PDT or untreated with observation and a minimum follow-up of 36 months. The main outcome measures included mean change in visual acuity and CSC recurrence. Survival analysis was performed to compare the CSC recurrence rates between the two groups., Results: A total of 192 eyes of 192 patients were included; 75 eyes were treated with half-dose verteporfin PDT and 117 were untreated. The mean follow-up duration was 74.1 months. At the last follow-up, the mean logMAR visual acuity was significantly better in the half-dose verteporfin PDT group compared with the untreated control group (P=.005). The mean visual improvement of the half-dose verteporfin PDT group at the last follow-up was 1.8 lines, compared with 0.0 line in the untreated control group (P<.001). Recurrence of CSC developed in 15 eyes (20%) in the half-dose verteporfin PDT group compared with 63 eyes (53.8%) in the untreated control group (P<.001). Survival analysis demonstrated that eyes treated with half-dose verteporfin PDT were significantly less likely to develop CSC recurrence compared with untreated controls (P<.001). Regression analysis showed that half-dose verteporfin PDT was the only significant factor in reducing the risk of CSC recurrence., Conclusions: Half-dose verteporfin PDT for the treatment of CSC resulted in significantly better visual acuity outcomes and lower recurrence rate in the long term compared with untreated controls.

Purpose: To investigate the characteristics of subretinal exudation and consequent morphologic changes in acute central serous chorioretinopathy (CSC) using spectral-domain optical coherence tomography (OCT)., Design: Prospective, observational, cross-sectional case series., Methods: Patients with CSC with symptom duration of fewer than 3 months underwent visual acuity measurement, fundus observation and spectral-domain OCT examinations and then were evaluated for subretinal exudation and other changes., Results: A total of 123 patients (123 eyes) were included, all showing various retinal pigment epithelium (RPE) abnormalities on OCT. OCT also showed subretinal exudation (65 eyes, 52.8%); retinal dipping (14 eyes, 11.4%); and photoreceptor layer defects (88 eyes, 71.5%). Without exception, the locations of these pathologic changes were closely related to the abnormal sites in the RPE. Those with subretinal exudation showed shorter durations of symptoms, whereas those with photoreceptor layer defects showed longer durations. In most eyes with retinal dipping, exudation connected it to RPE abnormalities. The defects of the photoreceptor layer, which involved the photoreceptor outer segment in 68 eyes, the photoreceptor inner segment in 20 eyes, and the outer nuclear layer as well, were likely to be the consequence of retinal dipping., Conclusions: OCT findings suggested that in eyes with acute CSC subretinal exudation, which indicated fibrin leakage through the RPE defects, might cause retinal dipping, thus leading to photoreceptor layer defects, and that spectral-domain OCT could provide a better understanding of the pathologic changes in acute CSC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To investigate the effects of lutein supplementation on plasma lutein concentrations and the macular pigment optical density (MPOD) in central serous chorioretinopathy (CSC)., Methods: In this double-masked placebo-controlled study, 20 patients received lutein 20 mg/d and 19 received placebo. The plasma lutein concentration and MPOD using autofluorescence spectrometry (density unit, DU) were measured at baseline and 1 and 4 months., Results: The mean plasma lutein concentrations and MPOD values in the lutein and control groups, respectively, were 91.5 and 78.2 ng/mL and 0.444 and 0.437 DU at baseline; 204.9 and 79.3 ng/mL and 0.460 and 0.442 DU at 1 month; and 228.0 and 78.4 ng/mL and 0.441 and 0.421 DU at 4 months. The plasma concentration in the lutein group was significantly higher than in controls at 1 and 4 months (P < 0.0001 for both comparisons); however, the MPOD values did not differ significantly between groups at 1 (P = 0.479) or 4 months (P = 0.883). In patients with a plasma lutein concentration below the mean level in 20 age-matched healthy subjects (mean 105.3 ng/mL; n = 13 in lutein group, n = 15 in control group), the control MPOD values significantly (P = 0.0430) decreased at 4 months (mean baseline, 0.437 DU; 4 months, 0.404 DU). The MPOD in the lutein group remained at the baseline level (mean baseline, 0.426 DU; 4 months, 0.438 DU) (P = 0.6542)., Conclusions: The MPOD did not increase in patients with CSC with short-term lutein supplementation; however, among patients with low plasma lutein, supplemental lutein prevented a decline in MPOD that was observed in control subjects (www.umin.ac.jp/ctr number, UMIN000005849)., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Central serous chorioretinopathy (CSC) is characterized by leakage of fluid from the choroid into the subretinal space and, consequently, loss of central vision. The disease is triggered by endogenous and exogenous corticosteroid imbalance and psychosocial stress and is much more prevalent in men. We studied the association of genetic variation in 44 genes from stress response and corticosteroid metabolism pathways with the CSC phenotype in two independent cohorts of 400 CSC cases and 1,400 matched controls. The expression of cadherin 5 (CDH5), the major cell-cell adhesion molecule in vascular endothelium, was downregulated by corticosteroids which may increase permeability of choroidal vasculature, leading to fluid leakage under the retina. We found a significant association of four common CDH5 SNPs with CSC in male patients in both cohorts. Two common intronic variants, rs7499886:A>G and rs1073584:C>T, exhibit strongly significant associations with CSC; P = 0.00012; odds ratio (OR) = 1.5; 95%CI [1.2;1.8], and P = 0.0014; OR = 0.70; 95%CI [0.57;0.87], respectively. A common haplotype was present in 25.4% male CSC cases and in 35.8% controls (P = 0.0002; OR = 0.61, 95% CI [0.47-0.79]). We propose that genetically predetermined variation in CDH5, when combined with triggering events such as corticosteroid treatment or severe hormonal imbalance, underlie a substantial proportion of CSC in the male population., (© 2014 The Authors. *Human Mutation published by Wiley Periodicals, Inc.)

Background: This study aimed to investigate the levels of aqueous humour cytokines in the eyes of patients with central serous chorioretinopathy (CSC), who received an intravitreal injection of bevacizumab, and to evaluate the differences in cytokine levels between bevacizumab responders and non-responders., Methods: Aqueous humour samples were collected from 39 eyes of 39 patients with CSC and 25 eyes of 25 control patients undergoing cataract surgery and were analysed using Multiplex bead assays. We compared the cytokine levels in patients with CSC (responders and non-responders) and control subjects. After intravitreal injections of bevacizumab in patients with CSC, we evaluated the changes in visual acuity and optical coherence tomographic parameters., Results: Significantly increased levels of interferon gamma-induced protein (IP-10) were detected in the aqueous humour of eyes from patients with CSC compared to controls (p = 0.036). Vascular endothelial growth factor (VEGF) levels were significantly higher in bevacizumab responders than in non-responders (p = 0.021). The concentrations of the other cytokines investigated did not differ significantly between patients with CSC and control subjects or between responders and non-responders., Conclusion: The results of the present study suggest that IP-10 and VEGF may contribute to the pathogenesis of CSC. It is clear that intravitreal bevacizumab was helpful in some of the patients with CSC, who showed higher levels of VEGF in the aqueous humour. However, the true effect and the rationale of anti-VEGF injection treatment in patients with CSC remain to be elucidated. Our results suggest that patients with CSC may be more susceptible to VEGF and/or other cytokines than the normal population., (© 2014 The Authors. Clinical and Experimental Optometry © 2014 Optometrists Association Australia.)

Purpose: In this study, we aimed to evaluate the relation between obstructive sleep apnea (OSA) and central serous retinopathy (CSR)., Methods: Twenty-three consecutive subjects aged >18 years with the diagnosis of CSR were included in this prospective study. Overnight polysomnography was performed to all subjects. Desaturation index and apnea-hypopnea index (AHI) were recorded. Obstructive sleep apnea was classified according to AHI as mild, moderate, or severe. Statistical analysis was performed using chi-square test, Fisher's exact test, and Mann-Whitney U test., Results: Fourteen of 23 CSR patients (60.9%) had OSA. Prevalence of OSA was significantly higher in male subjects with CSR compared to female subjects with CSR (p = 0.018). One (16.7%) female subject with CSR had OSA whereas thirteen (76.5%) male subjects were found to have OSA. Desaturation index was found to be 5.1 ± 4.2 in females and 12.9 ± 11.1 in males (p = 0.036)., Conclusion: Obstructive sleep apnea is seen nearly in 2/3 of patients with the diagnosis of CSR. There are possible common pathophysiological mechanisms like oxidative stress, vasoconstriction, or blood coagulation abnormalities. Screening for OSA should be considered in subjects with the diagnosis of CSR.

Objective: We report the case of a patient with Cushing disease revealed by bilateral central serous chorioretinopathy (CSCR)., Methods: We present the clinical history, physical findings, laboratory results, and imaging studies of a 53-year-old Chinese woman with a Cushing disease revealed by bilateral CSCR. The association with CSCR and the pertinent literature are reviewed., Results: A 53-year-old patient initially presented to the Department of Ophthalmology with a 4-week history of decreased vision in the left eye. Standard ophthalmologic examination and fluorescein angiography established the diagnosis of bilateral CSCR. Systemic clinical signs and biochemical analysis indicated hypercortisolism. Magnetic resonance imaging (MRI) of the pituitary gland showed a left-side lesion compatible with a microadenoma. The diagnosis of Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome secondary to a pituitary microadenoma was selected. Endoscopic endonasal transsphenoidal surgery was performed and the pituitary adenoma was successfully removed. The histology confirmed the presence of ACTH-immunopositive pituitary adenoma. Early postoperative morning cortisol levels indicated early remission. At 6 weeks postoperatively, the patient's morning cortisol remains undetectable, and serous retinal detachments had regressed., Conclusion: CSCR is an uncommon manifestation of endogenous Cushing syndrome. It can be the first presentation of hypercortisolism caused by Cushing disease. CSCR should be considered when assessing patients with Cushing syndrome complaining of visual disorders. On the other hand, it is useful in patients with an atypical form of CSCR to exclude Cushing's syndrome.

Purpose: To evaluate the correlation between changes in fundus autofluorescence (AF) measured using 2 different sources (near-infrared fundus autofluorescence from melanin and short-wavelength fundus autofluorescence from lipofuscin) with changes in spectral-domain optical coherence tomography (SD OCT) and fluorescein angiography in resolved central serous chorioretinopathy (CSC)., Design: Retrospective, observational case study., Methods: A total of 91 eyes from 86 patients with a history of resolved CSC and abnormal AF imaging findings were included. In addition to AF, patients were assessed by means of SD OCT and fluorescein angiography. Outer retinal layer alterations in OCT images and abnormalities in fluorescein angiography were analyzed and correlated with the corresponding AF data., Results: All eyes with abnormal near-infrared AF showed a hyperfluorescent angiography window defect in the corresponding area. There was a significant association between the OCT and short-wavelength AF findings. An abnormal short-wavelength AF signal was significantly associated with loss of the ellipsoid portion of the inner segments (EPIS, previously known as the junction between the inner and outer segments of the photoreceptors) on SD OCT (χ(2) test; P < .0001). Near-infrared AF could not predict the status of EPIS without the short-wavelength AF image., Conclusions: Outer retinal layer changes in OCT images can be predicted by analyzing both short-wavelength AF and near-infrared AF images. Abnormal changes in the short-wavelength AF image were predictive of EPIS damage., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Macular pigment (MP) is the collective name for three isomeric carotenoids: lutein, zeaxanthin, and meso-zeaxanthin. Macular pigment density is greatest in the central retina, peaking at the fovea and falling to negligible levels at 7 degrees of eccentricity from the fovea. Several studies have documented the interocular symmetry of MP optical density (MPOD) spatial distribution. The ongoing University of Missouri-St. Louis study uses a novel, customized heterochromatic flicker photometer to map the spatial distribution of MPOD up to 8 degrees of eccentricity relative to the fovea. Here, we report the MPOD measurements in a subject with resolved central serous chorioretinopathy (CSC) in the right eye., Case Report: Two subjects performed the full MPOD spatial mapping. The test subject (WK) had a history of central serous CSC of the right eye. The control subject (CP) had an unremarkable ocular health history. Comprehensive exams were performed on each subject including Cirrus optical coherence tomography imaging and fundus photographs. Subject CP showed highly symmetric interocular MPOD profiles at the fovea and 2, 4, and 6 degrees of eccentricity. Subject WK showed interocular asymmetry at the fovea and at 2 degrees with relative symmetry at 4 and 6 degrees. A paired sample t test identified nonsignificant interocular values for subject CP and statistically significant differences of at 2 degrees for subject WK., Conclusions: We hypothesize that subject WK's interocular MPOD spatial distribution asymmetry resulted from his history of resolved CSC. This asymmetry is statistically significant at 2 degrees of retinal eccentricity and corresponds to the extent of retinal pigment epithelium changes observed on the fundus photographs. These findings suggest that MP and retinal pigment epithelium changes after a CSC episode are comparable in the area of the retina affected. These disruptions may also be measureable in other macular conditions in which the sensory retina is affected (e.g., cystoid macular edema and clinically significant macular edema).

Purpose: To perform qualitative and quantitative analyses of subretinal protein deposits (PDs), seen in acute central serous retinopathy (CSR) patients, using high-resolution spectral domain optical coherence tomography (SD-OCT), in order to investigate whether the present PDs have any significant impact on best corrected visual acuity (BCVA)., Methods: Patients diagnosed with acute CSR were included. Using SD-OCT, the following distances/heights were measured: central total retinal thickness, central neurosensory retinal thickness, the vertical and horizontal length of subfoveal subretinal fluid and subfoveal thickness of the PD layer, if present and could be measured., Results: Thirty-eight patients with acute CSR were included. A significant correlation was found between the subfoveal thickness of the PD layer and baseline/final visual acuities in the eyes (r = 0.60, p ≤ 0.001 and r = 0.45, p = 0.008, respectively)., Conclusions: The thickness of subfoveal PDs at baseline appears to be an important parameter related to the BCVA and time of CSR resolution., (Copyright © 2013 S. Karger AG, Basel.)

Purpose: To evaluate the utility of oral methotrexate (MTX) for the treatment of chronic central serous chorioretinopathy (CSCR)., Methods: Retrospective review of all eyes of patients on oral MTX as treatment for chronic CSCR in three different centers. Visual acuity as well as optical coherence tomography central macular thickness and total volume parameters were analyzed. Complete blood count and serum chemistry results were monitored., Results: Nine eyes of 9 patients treated with MTX for chronic CSCR met the criteria for analysis. Mean duration of CSCR was 28 months (range, 3-94 months). Mean starting dose of oral MTX was 7.04 mg (range, 5-10 mg), and mean final dose was 7.27 mg (range, 5-10 mg). The mean duration of treatment was 89 days. Mean visual acuity improved from 20/67 at baseline to 20/35 at 8 weeks (P < 0.01, paired t-test). Mean central macular thickness improved from 309 μm to 213 μm at 8 weeks (P < 0.01, paired t-test). Mean total macular volume improved from 8.14 to 7.21 at 8 weeks (P ≤ 0.02, paired t-test). Eighty-three percent of the patients achieved total resolution of subretinal fluid. No MTX-associated toxicity was evident., Conclusion: Methotrexate may have a role in the treatment of chronic CSCR as evidenced by these results. A randomized controlled clinical trial is warranted to better understand the effects of MTX in these patients.

Background and Objective: To compare the spectral-domain optical coherence tomography (SD-OCT) features of acute central serous chorioretinopathy (CSC) versus exudative age-related macular degeneration (AMD) and explore disease-specific features of each disease., Patients and Methods: SD-OCT images obtained at the time of diagnosis in 39 eyes with acute CSC (symptom onset < 2 months) and 52 eyes with exudative AMD were compared. Multiple regression analysis was performed to identify disease-specific features. The relationship between anatomical findings and visual function was also assessed., Results: There were significant morphologic differences on SD-OCT between the two diseases, including the presence and height of retinal fluid and morphologic changes of retinal pigment epithelium (RPE). Multiple regression analysis revealed that a reflective band with posterior shadowing was a disease-specific finding indicating exudative AMD; however, other SD-OCT findings were attributed to differences in age of onset between the two diseases. Visual acuity was correlated with subretinal fluid in CSC, whereas pigment epithelial detachment, intraretinal fluid, and diverse RPE morphologic abnormalities were associated with visual decline in exudative AMD., Conclusion: A reflective band with posterior shadowing is a disease-specific feature of exudative AMD that may be useful for the differential diagnosis. High-resolution SD-OCT images of the retinal layers identified distinguishing pathologic features of the outer retina between the two diseases. The OCT features associated with visual function were different between the two diseases., (Copyright 2012, SLACK Incorporated.)

Central serous chorioretinopathy (CSCR) is a vision-threatening eye disease with no validated treatment and unknown pathogeny. In CSCR, dilation and leakage of choroid vessels underneath the retina cause subretinal fluid accumulation and retinal detachment. Because glucocorticoids induce and aggravate CSCR and are known to bind to the mineralocorticoid receptor (MR), CSCR may be related to inappropriate MR activation. Our aim was to assess the effect of MR activation on rat choroidal vasculature and translate the results to CSCR patients. Intravitreous injection of the glucocorticoid corticosterone in rat eyes induced choroidal enlargement. Aldosterone, a specific MR activator, elicited the same effect, producing choroid vessel dilation -and leakage. We identified an underlying mechanism of this effect: aldosterone upregulated the endothelial vasodilatory K channel KCa2.3. Its blockade prevented aldosterone-induced thickening. To translate these findings, we treated 2 patients with chronic nonresolved CSCR with oral eplerenone, a specific MR antagonist, for 5 weeks, and observed impressive and rapid resolution of retinal detachment and choroidal vasodilation as well as improved visual acuity. The benefit was maintained 5 months after eplerenone withdrawal. Our results identify MR signaling as a pathway controlling choroidal vascular bed relaxation and provide a pathogenic link with human CSCR, which suggests that blockade of MR could be used therapeutically to reverse choroid vasculopathy.

Chronic central serous retinopathy (CSR) is characterised by frequent exacerbations and a poor visual prognosis. Very few therapies exist for chronic CSR, and the existing therapies are often ineffective. Thus, novel therapies to combat this frustrating disorder are needed. Presented here is a case detailing a patient with chronic CSR with persistent subfoveal fluid of 2 years' duration that completely resolved with 1 month of oral rifampin therapy. As a cytochrome P450, 3A4 inducer, rifampin is thought to favourably alter the metabolism of endogenous steroids, thereby leading to an improvement in CSR manifestations.

Background: Although it is known that antioxidants including lutein can affect macular pigment optical density (MPOD) and visual function, we still have much to learn about their effect. Our aim was to assess the 1-year changes in MPOD and visual function in response to supplementation containing lutein., Methods: We prospectively measured the MPOD level of those who received a supplement containing 6 mg of lutein daily for 1 year. MPOD level was measured every 3 months by using autofluorescence spectrometry with the two-wavelength method. Other examinations, including contrast sensitivity and retinal sensitivity were also measured every 3 or 6 months. Stepwise regression analysis was performed to determine the factors that correlated with the changes observed in those examinations., Results: Forty-three eyes of 43 Japanese subjects, including five normal eyes, five fellow eyes with central serous chorioretinopathy (CSC), and 33 fellow eyes with age-related macular degeneration (AMD) were enrolled. The higher baseline MPOD level was correlated with the eye with a clear intraocular lens (IOL). Although no time-dependent changes in the MPOD level were obtained in any area, subjects without cardiovascular diseases showed higher increase in the MPOD level. We observed significant increases in the contrast sensitivity at 1 year (p = 0.0124) and in the retinal sensitivity at 6 months (p < 0.0001) and 1 year (p < 0.0001). Stepwise regression analysis showed that nonsmokers had increased contrast sensitivity (p = 0.0173), and the fellow eye of those with CSC had less of an increase in retinal sensitivity (p = 0.0491)., Conclusions: Daily supplementation with 6 mg of lutein did not affect the MPOD level for 1 year, suggesting that 6 mg of lutein may be insufficient to increase the MPOD level. However, supplementation seems to improve visual functions such as contrast sensitivity and retinal sensitivity.

Purpose: To evaluate the levels of aqueous humor cytokines in the eyes of patients with central serous chorioretinopathy (CSC) before an intravitreal injection of bevacizumab., Methods: In a prospective interventional trial, 20 eyes of 20 patients with symptomatic CSC of at least 3 months duration and 20 eyes of 20 patients with cataract as control were included. Eyes with CSC received a single intravitreal injection of bevacizumab (1.25 mg/0.05 mL). Aqueous humor samples were collected from patients and controls. Multiplex bead assays were used for measurement of cytokines, including vascular endothelial growth factor and platelet-derived growth factor., Results: Similar vascular endothelial growth factor levels and significantly decreased platelet-derived growth factor levels were measured in the aqueous humor of eyes from patients with CSC compared with controls (P = 0.172 and P = 0.004, respectively). There was a significant inverse correlation between the vascular endothelial growth factor and platelet-derived growth factor in patients (r = -0.555; P = 0.026). Interleukin 6, interleukin 8, and monocyte chemoattractant protein-1 were detectable, but not significantly different between the patients and controls., Conclusion: The results of the current study suggest that platelet-derived growth factor contributes to the pathogenesis of CSC; however, the roles of vascular endothelial growth factor in CSC are unclear and warrant further investigation.

Purpose: To investigate functional abnormalities in eyes with central serous chorioretinopathy (CSC)., Design: Observational case series., Methods: Sixteen eyes with CSC were enrolled. Autofluorescence densitometry was performed to measure the optical density of the photopigments. Serial fundus autofluorescence (FAF) images were obtained by Heidelberg Retina Angiogram 2. We calculated the autofluorescence optical density difference from the FAF images. To compare the distribution pattern of autofluorescence optical density difference to the findings of outer retina, spectral-domain optical coherence tomography (SD-OCT) was performed in the acute phase and after resolution of CSC., Results: The autofluorescence optical density difference decreased at the serous retinal detachment (SRD) in all 16 eyes. After resolution, the photoreceptor inner and outer segment junction (IS/OS) was irregular in 13 eyes and defective in 3 eyes on SD-OCT. The autofluorescence optical density difference did not improve in any eyes. Five eyes were reexamined 3 month after resolution. In 4 of the 5 eyes, SD-OCT showed that the IS/OS was well delineated and 1 eye defective. The autofluorescence optical density difference improved in 2 of the 4 eyes, but not in the other 2 eyes. In the 1 eye without well-delineated IS/OS, the autofluorescence optical density difference did not improve., Conclusion: In eyes with CSC, the photopigment density decreased at the SRD. The density remained decreased immediately after resolution and showed delayed recovery. The photopigments decreased even in eyes with morphologic recovery of the outer retina., (Copyright © 2011 Elsevier Inc. All rights reserved.)