Predictive factors of selective mineralocorticoid receptor antagonist treatment in chronic central serous chorioretinopathy.
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ABSTRACT:
SUBMITTER: Gergely R
PROVIDER: S-EPMC7538998 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Predictive factors of selective mineralocorticoid receptor antagonist treatment in chronic central serous chorioretinopathy.
Gergely Róbert R Kovács Illés I Récsán Zsuzsanna Z Sándor Gábor László GL Czakó Cecília C Nagy Zoltán Zsolt ZZ Ecsedy Mónika M
Scientific reports 20201006 1
To compare the macular morphology of good and poor responders to eplerenone treatment in chronic central serous chorioretinopathy (CSCR) patients. Thirty eyes of 29 patients with chronic CSCR were treated with 50 mg/day oral eplerenone and followed up for 1 year. The integrity of outer retinal layers at baseline was assessed using optical coherence tomography. Patients who showed complete resolution of subretinal fluid at 1 year were assigned to the good responder group (Group 1), whilst those w ...[more]
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Project description: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.
| S-EPMC5847108 | biostudies-literature
Project description:PurposeTo evaluate the efficacy and safety of oral mineralocorticoid-receptor antagonist (MRa) therapy in three clinical presentations of nonresolving central serous chorioretinopathy (CSCR) with chronic epitheliopathy.MethodsRetrospective case series of consecutive patients with nonresolving CSCR treated with oral eplerenone or spironolactone. Treatment criteria were: persistent CSCR with subretinal fluid (SRF) lasting longer than 4 months; recurrent CSCR with SRF lasting longer than 2 months; persistent CSCR (SRF ≥ 4 months) with fundus autofluorescence gravitational tracks. Outcomes at 1, 3, and 6 months were: foveal SRF height, central macular thickness (CMT), subfoveal choroidal thickness (SFCT), best-corrected visual acuity (BCVA), and occurrence of side effects.ResultsAmong 54 eyes from 42 patients (mean age: 53 years), mean foveal SRF, CMT, and SFCT decreased significantly at 1, 3, and 6 months after treatment initiation. Mean BCVA improved significantly at 6 months. In the subgroup analysis, mean foveal SRF, CMT, and SFCT decreased significantly at 3 and 6 months in the persistent and recurrent groups. In persistent cases with tracks, a significant diminution of mean CMT and SFCT was achieved at 6 months. Treatment-related side effects were observed in 6 patients, prompting treatment discontinuation in one case.ConclusionResponse to treatment was observed in the three subgroups. In persistent CSCR with tracks the response was delayed compared with persistent and recurrent cases, suggesting that longer treatment durations would be beneficial in patients with gravitational tracks of RPE alteration.Translational relevanceThe clinical response to oral MRa is consistent with the involvement of the mineralocorticoid pathway in CSCR pathogenesis.
| S-EPMC4782825 | biostudies-literature
Project description:Chronic central serous chorioretinopathy (cCSC) is a multifactorial eye disease characterized by subretinal fluid accumulation that leads to vision loss. Clinically, cCSC is associated with stress, hypercortisolism and corticosteroid use, and is more frequent in males (80%) than in females (20%). Current genetic studies on cCSC have thus far focussed on common variants, but familial occurrence of cCSC also suggests a role for rare variants in the disease susceptibility. Therefore, in this study, we performed exome sequencing of cCSC patients to elucidate the role of rare (protein-altering) variants in the disease. Exome sequencing was performed on 269 cCSC patients and 1,586 controls. Data were processed according to the Genome-Analysis-Toolkit (GATK) best practices. Principal component analysis was performed to check for genetic ancestry and only unrelated subjects of European descent were retained. Burden, SKAT and SKAT-O tests were performed using 2 different grouping criteria. One group included protein-altering variants only, while the other contained synonymous and splice site variants as well. The gene-based analyses were performed using the SKAT R-package correcting for two principal components using two approaches; (1) on the entire cohort correcting for sex and (2) on males and females separately. Additionally, the gene-based associations of genes at previously reported cCSC loci were investigated. After filtering, the dataset contained 263 cCSC patients (208 males [79%]) and 1352 controls (671 males [50%]) carrying 197,915 protein-altering variants in 16,370 genes and 330,689 exonic variants in 18,173 genes. Analysis stratified by sex identified significant associations with the PIGZ (PSKAT?=?9.19?×?10-7 & PSKAT-O?=?2.48?×?10-6), DUOX1 (PSKAT?=?1.03?×?10-6), RSAD1 (PSKAT?=?1.92?×?10-7 & PSKAT-O?=?8.57?×?10-8) and LAMB3 (PBurden?=?1.40?×?10-6 & PSKAT-O?=?1.14?×?10-6) genes in female cCSC patients, after correction for multiple testing. The number of rare variant carriers in these genes was significantly higher in the female cCSC cohort compared to female controls (45,5% vs. 18.5%, P?=?1.92?×?10-6, OR?=?3.67 [95% CI?=?2.09-6.46]). No significant associations were identified in the entire cohort nor in the male patients. In this exome study on cCSC patients, we have identified PIGZ, DUOX1, RSAD1 and LAMB3 as potential new candidate genes for cCSC in females. The sex-specific associations identified here suggest a possible interaction between rare genetic factors and sex for cCSC, but replication of these findings in additional cohorts of cCSC patients is necessary.
| S-EPMC6488596 | biostudies-literature
Project description:BackgroundCentral serous chorioretinopathy (CSC) is a chorioretinal disease characterized by fluid accumulation between the neuroretina and retinal pigment epithelium with unknown etiology. Family studies have suggested a heritable component for CSC with an autosomal dominant inheritance pattern. Therefore, exome sequencing was performed on familial cCSC to indentify the genetic components contributing to familial cCSC.MethodsExome sequencing was performed on 72 individuals of 18 families with CSC. In these families, we determined whether rare genetic variants (minor allele frequency < 1%) were segregated with CSC and also performed familial gene-burden analysis.ResultsIn total, 11 variants segregated in two out of 18 families. One of these variants, c.4145C>T; p.T1382I (rs61758735) in the PTPRB gene, was also associated with CSC in a large case-control cohort sequenced previously (p = 0.009). Additionally, in 28 genes two or more different heterozygous variants segregated in two or more families, but no gene showed consistent associations in both the family gene-burden results and gene-burden analysis in the case-control cohort.ConclusionWe identified potential candidate genes for familial CSC and managed to exclude Mendelian inheritance of variants in one or a limited number of genes. Instead, familial CSC may be a heterogeneous Mendelian disease caused by variants in many different genes, or alternatively CSC may represent a complex disease to which both environmental factors and genetics contribute.
| S-EPMC6465660 | biostudies-literature
Project description:Central serous chorioretinopathy is characterized by neurosensory detachment of the central retina secondary to fluid leakage through the retinal pigment epithelium. Though it has an incidence of 9,9 per 100.000 in men and 1,7 per 100.000 in women, it is the fourth most common retinal disorder. Central serous chorioretinopathy patients present with blurred vision, central scotoma, metamorphopsia, micropsia and mild color discrimination. It is usually a self-limited disorder with nearly none or minimal visual impairment but in some patients the disease persists and may cause severe visual impairment. Central serous chorioretinopathy pathophysiology is not well understood. Choroid, retinal pigment epithelium and hormonal pathways seem to play important roles in central serous chorioretinopathy pathophysiology. Also, familial cases of the disease indicate that there is a genetic background. The identification of certain disease genes could lead to the development of better diagnostic and therapeutic approaches for central serous chorioretinopathy patients.
| S-EPMC7806452 | biostudies-literature
Project description:Central serous chorioretinopathy (CSCR) is a common chorioretinal disease characterized by serous retinal detachment that most commonly involves the macular region. Although the natural history of the acute form shows a self-limiting course, a significant number of patients suffer from recurrent episodes leading to chronic disease, often leaving patients with residual visual impairment. Visual morbidity is often worsened by a delay in the diagnosis due to the incorrect understanding of the particular biomarkers of the disease. The aim of this review is to provide clinical understanding of the biomarkers of CSCR with an emphasis on the most recent findings in patient demographics, risk factors, clinical imaging findings, and management options. Patients with these biomarkers, age 30-44 years, male gender, increased stress levels, hypercortisolism (endogenous and exogenous exposures), sleep disturbance, pregnancy, and genetic predisposition have increased susceptibility to CSCR. Also, biomarkers on optical coherence tomography (OCT) such as choroidal thickness (CT) and choroidal vascularity index (CVI) showed good diagnostic and prognostic significance in the management of CSCR. There are nonspecific features of CSCR on OCT and OCT angiography such as choroidal neovascularization, photoreceptor alteration/cone density loss, and flat irregular pigment epithelium detachment. We described rare complications of CSCR such as cystoid macular edema (CME) and cystoid macular degeneration (CMD). Patients with CME recovered some vision when treated with anti-vascular endothelial growth factors (anti-VEGFs). Patients with CMD had irreversible macular damage even after treatment with anti-VEGFs.
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Project description:Bullous central serous chorioretinopathy (bCSCR) is a rare variant of the central serous chorioretinopathy, complicated by an exudative retinal detachment with shifting fluid. This systematic review aims to present the epidemiology, the pathogenesis, the clinical presentation, the imaging, the differential diagnosis, and the latest treatments of this disease. A total of 60 studies were identified following a literature search adhering to PRISMA guidelines. After full-text evaluation, 34 studies about bCSCR were included. bCSCR usually affects middle-aged men, and the principal risk factor is corticosteroid medications. Pathogenesis is related to an increased choroidal vessel and choriocapillaris permeability, with subsequent subretinal fluid accumulation, rich in fibrin, which may provoke the exudative retinal detachment. Clinical presentation and imaging are fundamental to distinguish bCSCR from other pathologies, avoiding unappropriated treatment. Corticosteroid withdraws (if assumed) and laser photocoagulation of leakage sites seen at angiography may speed up retinal reattachment. Verteporfin photodynamic therapy, transpupillary thermal therapy, oral eplerenone and scleral thinning surgery are other therapeutic options. An early diagnosis might prevent disease progression due to harmful medications as well as unnecessary surgery.
| S-EPMC7559580 | biostudies-literature
Project description:PurposeReduced-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.MethodsThis 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.ResultsThere 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).ConclusionsCarriers 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.
| S-EPMC7378327 | biostudies-literature
Project description:Central serous chorioretinopathy is one of the most frequent causes of vision reduction among middle-aged men. This disease usually has a self-limiting course, but sometimes it lasts more than 4-6 months or a second episode follows a complete resolution of the first one. Nevertheless, to date no consensus exists about the duration threshold and therapy protocols for these non-resolving central serous chorioretinopathy. Treatment as half-dose and half-fluence photodynamic therapy, subthreshold micropulse laser treatment, mineralocorticoid receptor antagonists, intravitreal anti-angiogenic drugs, transpupillary thermal therapy, anti-androgenic drugs, methotrexate, Rifampicin and melatonin are described in this review. Complications are very uncommon but end-point results like central macular thickness reduction and best-corrected visual acuity improvement are difficult to compare among different therapeutic modalities due to different duration of follow-up and lack of homogeneity in patient recruitment. The aim of this review is focusing on treatment modalities for these chronic forms with comprehensive recent management updates according to latest clinical trial results.
| S-EPMC6707196 | biostudies-literature
Project description:Currently, no general consensus exists regarding the management of central serous chorioretinopathy (CSC). Laser treatments include three different therapeutic approaches: conventional laser, subthreshold laser and photodynamic therapy. Conventional focal laser, addressed to seal the leaking points, as evidenced on fluorescein angiography, was largely used in the past, but now, it is almost completely abandoned, owing to the potential complications. Several studies confirmed the positive effects achieved by subthreshold laser treatment in CSC, even though its improper application in the PLACE trial has questioned the effectiveness.
| S-EPMC7692124 | biostudies-literature