Central serous chorioretinopathy (CSC) is a multifactorial disease of the retina and the choroid in the human eye. The disease is characterized by a serous detachment of the neurosensory retina in... Show moreCentral serous chorioretinopathy (CSC) is a multifactorial disease of the retina and the choroid in the human eye. The disease is characterized by a serous detachment of the neurosensory retina in the central macula, which causes visual complaints including blurred vision, a central relative scotoma, metamorphopsia, and alterations in color and contrast vision. Multimodal imaging techniques have revealed that abnormally thickened, leaking choroidal blood vessels cause an excessive fluid outflow into the interstitial space, which presumably causes the characteristic thickened choroid. This thesis addresses the clinical spectrum of CSC including the acute CSC, the chronic CSC and the severe chronic CSC. Here we suggest a strict but practical classification of CSC phenotypes based on findings on multimodal imaging techniques. We also report on the outcome of treatment, especially photodynamic therapy (PDT), in all phenotypes of CSC and provide recommendation regarding disease management and therapy. Furthermore, in this thesis we assess the roll of genetic variations among different phenotypes of CSC for a better understanding of the pathogenesis of the disease. Despite the genetic associations found in CSC phenotypes, we conclude that the so far known genetic variations do not explain the different clinical disease presentation of CSC phenotypes. Show less
PurposeThis study is to assess the possible correlation between findings on fundus autofluorescence (FAF) and fluorescein angiography (FA) in patients with chronic central serous chorioretinopathy ... Show morePurposeThis study is to assess the possible correlation between findings on fundus autofluorescence (FAF) and fluorescein angiography (FA) in patients with chronic central serous chorioretinopathy (cCSC).MethodsThis multicentre retrospective cohort study included 71 cCSC patients (92 eyes) with at least 6 months of follow-up, who had a FAF-FA imaging discrepancy larger than 0.5 optic disc diameters in size in the corresponding areas of hyperfluorescent abnormalities. A comparison was performed between progression in size of areas of hyperautofluorescent retinal pigment epithelium (RPE) abnormalities on FAF (HF-FAF) and the hyperfluorescent areas on FA (HF-FA) at first visit and last visit. The possible correlations were estimated between FAF-FA discrepancy and disease characteristics.ResultsThe median area of HF-FAF at first visit was 7.48 mm(2) (1.41-27.9). The median area of HF-FA at first visit and last visit was 2.40 mm(2) (0.02-17.27) and 5.22 mm(2) (0.53-25.62), respectively. FAF-FA discrepancy was associated with follow-up duration and the area of HF-FAF at first visit. A mathematical algorithm for grading FAF-FA discrepancy in time was suggested, which predicted the enlargement of hyperfluorescent RPE abnormalities on FA in 82.6% of cases.ConclusionThere is a statistically significant relationship between the areas of HF-FAF and HF-FA in cCSC patients with FAF-FA imaging discrepancy at first presentation. Long-term changes in RPE alterations in cCSC on FA can be predicted based on baseline HF-FAF and follow-up duration. Show less
Purpose: To study genetic predispositions and differences between severe chronic central serous chorioretinopathy (cCSC), nonsevere cCSC, and acute central serous chorioretinopathy (aCSC). Methods:... Show morePurpose: To study genetic predispositions and differences between severe chronic central serous chorioretinopathy (cCSC), nonsevere cCSC, and acute central serous chorioretinopathy (aCSC). Methods: One hundred seventy-three severe cCSC patients, 272 nonsevere cCSC patients, 135 aCSC patients, and 1,385 control individuals were included. Eight single-nucleotide polymorphisms were genotyped in theARMS2(rs10490924),CFH(rs800292, rs1061170, rs1065489, rs1329428, rs2284664, rs3753394), andNR3C2(rs2070951). Additionally,C4Bgene copy numbers were analyzed. Results: A significant association in 5 single-nucleotide polymorphisms in theCFHgene could be reproduced among severe cCSC patients, including rs800292 (P= 0.0014; odds ratio [OR] = 1.93; 95% confidence interval [CI] = 1.51-2.47), rs1065489 (P= 2.22 x 10(-4); OR = 0.49; 95% CI = 0.34-0.72), rs1329428 (P= 0.001; OR = 1.89; 95% CI = 1.49-2.40), rs2284664 (P= 1.21x 10(-4); OR = 1.65; 95% CI = 1.28-2.13), and rs3753394 (P= 6.10x 10(-4); OR = 0.61; 95% CI = 0.46-0.81). Carrying threeC4Bcopies was protective for severe cCSC (P= 0.001; OR = 0.29; 95% CI = 0.14-0.61). No significant differences in allele frequencies could be found among the CSC phenotypes. Conclusion: Acute CSC, nonsevere cCSC, and severe cCSC all showed a similar association with theCFHandC4Bgenes, and the three phenotypes could not be distinguished based on the genetics. This shows that despite the differences in clinical presentation and severity, there is an overlap in the genetic predisposition of different CSC phenotypes. Nongenetic factors may play a more important role in determining the clinical course of CSC. Show less
Purpose To describe the clinical characteristics and outcome of polypoidal choroidal vasculopathy (PCV), also known as aneurysmal type 1 (sub-retinal pigment epithelium (RPE)) neovascularization,... Show morePurpose To describe the clinical characteristics and outcome of polypoidal choroidal vasculopathy (PCV), also known as aneurysmal type 1 (sub-retinal pigment epithelium (RPE)) neovascularization, in Caucasian patients. Methods Single-centre study in 66 Caucasian patients with a diagnosis of PCV based on optical coherence tomography scan and indocyanine green angiography. Clinical characteristics and multimodal imaging were collected and assessed by an experienced retina specialist. Results This study involved 74 eyes of 66 patients with PCV, with a mean age at onset of 73 years and a female preponderance of 66%. The mean number of polypoidal lesions per eye was 1 (range: 1-5 lesions), out of which 75% was located in the macula and 19% in the peripapillary region. Of the 74 eyes, 37 eyes (50%) had PCV associated with a drusenoidal neovascular age-related macular degeneration (AMD) phenotype (PCV-AMD) and 18 eyes (24%) had PCV associated with non-polypoidal type 1 choroidal neovascularization/branching vascular network (PCV-BVN) without signs of drusenoidal AMD, while 19 eyes (26%) had idiopathic, isolated PCV (iPCV). The mean subfoveal choroidal thickness measured in 22 patients was 245 mu m (range: 71-420 mu m). In 51% of patients, the initially performed therapy showed good anatomical recovery (resolution of intra- and subretinal fluid). Conclusions A spectrum of PCV (aneurysmal type 1/sub-RPE neovascularization) can be seen in Caucasian patients. PCV associated with a drusenoidal neovascular AMD phenotype in Caucasians is phenotypically and presumably pathophysiologically more associated with neovascular AMD (PCV-AMD: type A PCV). However, this may not be the case for patients with PCV with non-polypoidal type 1 choroidal neovascularization or BVN and no signs of drusenoidal AMD (PCV-BVN: type B PCV), and for patients with idiopathic PCV without associated drusen or BVN (iPCV; type C PCV). Most patients have a thin choroid, even when drusen are absent. For the entire patient group, a moderate anatomical recovery was observed after treatment. Show less
Purpose: To study the risk of recurrence in acute central serous chorioretinopathy (aCSC) and to evaluate the risk of transitioning to chronic CSC.Patients and Methods: The medical records and... Show morePurpose: To study the risk of recurrence in acute central serous chorioretinopathy (aCSC) and to evaluate the risk of transitioning to chronic CSC.Patients and Methods: The medical records and multimodal imaging data of 295 aCSC cases were reviewed. Typical aCSC was defined as the presence of serous subretinal fluid (SRF), one focal leakage spot on fluorescein angiography (FA), retinal pigment epithelium (RPE) alterations limited in area to less than one optic disc diameter, and complete recovery from this first CSC episode. An increase in RPE alterations combined with persistent SRF was considered a sign of chronicity, which was determined in cases with >12 months follow-up. The main outcome measures included final visual acuity, percentage of disease recurrence, and percentage of cases moving toward a chronic phenotype. Treatment strategies and their efficacy were also reviewed.Results: A total of 295 eyes in 291 patients with aCSC were included. Spontaneous recovery was awaited in 154 eyes (52%), whereas 141 eyes (48%) recovered following treatment. SRF recurrence occurred in 24% of untreated cases and in 4% of treated cases (p<0.001). An analysis of 61 eyes that underwent an FA after >= 12 months of follow-up revealed increased RPE alterations in 22 eyes (36%), and 14 eyes (23%) had both an increase in RPE alterations and SRF recurrence.Conclusion: All aCSC cases recovered from the first disease episode, and none of the cases developed persistent SRF leakage. Among the cases for which long-term follow-up information was available, 36% showed a tendency toward chronicity in terms of increased RPE alterations, whereas 23% showed both an increase in RPE alterations and recurrent SRF. Early photodynamic therapy (PDT) may decrease the risk of recurrences. Show less
Purpose: To investigate genetic associations in white patients with acute central serous chorioretinopathy (aCSC) and to assess genetic differences between aCSC and chronic CSC (cCSC).Methods: A... Show morePurpose: To investigate genetic associations in white patients with acute central serous chorioretinopathy (aCSC) and to assess genetic differences between aCSC and chronic CSC (cCSC).Methods: A total of 135 aCSC patients, 272 cCSC patients, and 1,385 control individuals were included. Eight single nucleotide polymorphisms were genotyped for ARMS2 (rs10490924), CFH (rs800292, rs1061170, rs1065489, rs1329428, rs2284664, rs3753394), and NR3C2 (rs2070951). Also, C4B gene copy numbers were analyzed.Results: Three single nucleotide polymorphisms in the CFH gene were significantly associated with aCSC: rs800292 (P = 0.003, odds ratio = 1.53 [95% confidence interval = 1.15-2.03]), rs1061170 (P = 0.002, odds ratio = 0.64 [95% confidence interval = 0.48-0.86]), and rs1329428 (P = 5.87 x 10(-6), odds ratio = 1.83 [95% confidence interval = 1.40-2.38]). A significant difference was found in the distribution of C4B gene copy numbers in aCSC patients compared with controls (P = 0.0042). No differences could be found among the selected variants between aCSC and cCSC patients.Conclusion: Three variants in the CFH gene and copy number variations in C4B were found to be significantly associated with the risk of aCSC development. Despite the differences in clinical presentation, acute and chronic CSC may share a similar genetic predisposition based on our present analysis. Other genetic and/or nongenetic risk factors may be more influential in the differentiation toward an acute or a chronic phenotype of CSC. Show less
