Half-dose PDT is superior to HSML for treating cCSC, leading to a significantly higher proportion of patients with complete resolution of SRF and functional improvement.

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PURPOSE. Abnormal choroidal blood flow is considered important in the pathogenesis of chronic central serous chorioretinopathy (CSC). Optical coherence tomography (OCT) angiography can image ocular blood cell flow and could thus provide novel insights in disease mechanisms of CSC. We evaluated depth-resolved flow in chronic CSC by OCT angiography compared to fluorescein angiography (FA) and indocyanine green angiography (ICGA).METHODS. Eighteen eyes with chronic CSC, and six healthy controls, were included. Two human observers annotated areas of staining, hypofluorescence, and hotspots on FA and ICGA, and areas of abnormal flow on OCT angiography. Interobserver agreement in annotating OCT angiography and FA/ICGA was measured by Jaccard indices (JIs). We assessed colocation of flow abnormalities and subretinal fluid visible on OCT, and the distance between hotspots on ICGA from flow abnormalities.RESULTS. Abnormal areas were most frequently annotated in late-phase ICGA and choriocapillary OCT angiography, with moderately high (median JI, 0.74) and moderate (median JI, 0.52) interobserver agreement, respectively. Abnormalities on late-phase ICGA and FA colocated with those on OCT angiography. Aberrant choriocapillary OCT angiography presented as foci of reduced flow surrounded by hyperperfused areas. Hotspots on ICGA were located near hypoperfused spots on OCT angiography (mean distance, 168 lm). Areas with current or former subretinal fluid were colocated with flow abnormalities.CONCLUSIONS. On OCT angiography, chronic CSC showed irregular choriocapillary flow patterns, corresponding to ICGA abnormalities. These results suggest focal choriocapillary ischemia with surrounding hyperperfusion that may lead to subretinal fluid leakage.

PurposeTo describe the clinical findings and long-term outcome of patients with chronic central serous chorioretinopathy (cCSC).Materials and methodsThis was a retrospective case series in 52 eyes of 36 patients with a follow-up period of at least 1 year. Extensive ophthalmic examination and a validated questionnaire concerning vision-related quality of life (National Eye Institute Visual Function Questionnaire [NEI-VFQ]-39) were analyzed.ResultsMean visual acuity showed a significant decline over time of 0.16 logarithm of minimum angle of resolution ([logMAR] range: −0.22 to 1.3; P=0.009) after a mean follow-up period of 10.6 years. Also, patients reported lower vision-related quality of life based on the NEI-VFQ-39 for almost all categories compared to healthy controls. Macular atrophy was diagnosed more often on optical coherence tomography compared to other diagnostic entities. Retinal pigment epithelium detachments in the macula were documented on optical coherence tomography in 56% of the patients. A significant thinning of foveal thickness was measured over time compared to unaffected fellow eyes (P=0.002). On long-term follow-up, 13 eyes (37%) showed an increase in number of hot spots on fluorescein angiography.ConclusionThis study indicates that cCSC is a progressive disease in many patients, causing a progressive decline in visual acuity, accompanied by lower reported vision-related quality of life. In deciding whether or not to treat, the progressive nature of cCSC should be taken into account in this relatively young and often still professionally active patient group.

IMPORTANCE To date, several targeted genetic studies on chronic central serous chorioretinopathy (cCSC) have been performed; however, unbiased genome-wide studies into the genetics of cCSC have not been reported. To discover new genetic loci associated with cCSC and to better understand the causative mechanism of this disease, we performed a genome-wide association study (GWAS) on patients with cCSC. OBJECTIVE To discover new genetic loci and pathways associated with cCSC and to predict the association of genetic variants with gene expression in patients with cCSC. DESIGN, SETTING, AND PARTICIPANTS This case-control GWAS was completed in the general community, 3 referral university medical centers, and outpatient care on Europeans individuals with cCSC and population-based control participants. Genotype data was collected from May 2013 to August 2017, and data analysis occurred from August 2017 to November 2017. MAIN OUTCOMES AND MEASURES Associations of single-nucleotide polymorphisms, haplotypes, genetic pathways, and predicted gene expression with cCSC. RESULTS A total of 521 patients with cCSC (median age, 51 years; interquartile range [IQR], 44-59 years; 420 [80.6%] male) and 3577 European population-based control participants (median age, 52 years; IQR, 37-71 years; 1630 [45.6%] male) were included. One locus on chromosome 1 at the complement factor H (CFH) gene reached genome-wide significance and was associated with an increased risk of cCSC (rs1329428; odds ratio [OR], 1.57 [95% CI, 1.38-1.80]; P = 3.12 × 10 −11). The CFH haplotypes H1 and H3 were protective for cCSC (H1: OR, 0.64 [95% CI, 0.

BackgroundChronic central serous chorioretinopathy (cCSC) is an eye disease characterized by an accumulation of serous fluid under the retina. It is postulated that this fluid accumulation results from hyperpermeability and swelling of the choroid, the underlying vascular tissue of the eye, causing a dysfunction of the retinal pigment epithelium. This fluid accumulation causes neuroretinal detachment. A prolonged neuroretinal detachment in the macula can lead to permanent vision loss. Therefore, treatment is aimed primarily at achieving resolution of subretinal fluid, preferably within the first 4 months after diagnosis of the disease. A broad spectrum of treatment modalities has been investigated in cCSC, but no consensus exists on the optimal treatment of cCSC. Currently, photodynamic therapy (PDT) and high-density subthreshold micropulse laser treatment (HSML) are among the most frequently cited treatments in obtaining successful neuroretinal reattachment.Methods/DesignThis is a randomized, controlled, open-label, multicenter trial comparing the efficacy of half-dose PDT to HSML in treating patients with cCSC. A total of 156 patients will be recruited, 78 patients in each treatment arm, with a maximum follow-up duration of 8 months after the first treatment. A complete ophthalmological examination with vision-related quality of life (NEI VFQ-25) and stress questionnaires, will be performed at baseline, 6 to 8 weeks after the first treatment, 6 to 8 weeks after a second treatment (if necessary), and at the final follow-up visit at 7 to 8 months after the first treatment. Treatment visits will be scheduled within 3 weeks after the baseline visit, and within 3 weeks after the first control visit, if a second treatment is required.DiscussionBoth half-dose PDT and HSML may be effective treatments in cCSC, but because of the lack of prospective randomized controlled trials, which treatment should be the first choice remains unclear. The aim of this study is to compare the efficacy of half-dose PDT to HSML. The primary endpoint to evaluate efficacy will be a complete absence of subretinal fluid on optical coherence tomography after treatment. Secondary functional endpoints include change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity, retinal sensitivity on microperimetry, and NEI VFQ-25 questionnaire of visual functioning.Registration number Institutional Review Board (CMO Arnhem-Nijmegen, the Netherlands): 2013/203 NL nr.: 41266.091.13Trial registrationClinicalTrials.gov identifier: NCT01797861. Date of registration: 21 February 2013.

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 PARTICIPANTSIn 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.

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.