Fundus autofluorescence abnormalities can predict fluorescein angiography abnormalities in patients with chronic central serous chorioretinopathy.

PURPOSE: This 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). METHODS: This 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. RESULTS: The median area of HF-FAF at first visit was 7.48 mm2 (1.41-27.9). The median area of HF-FA at first visit and last visit was 2.40 mm2 (0.02-17.27) and 5.22 mm2 (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. CONCLUSION: There 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.

The spectrum of polypoidal choroidal vasculopathy in Caucasians: clinical characteristics and proposal of a classification.

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, 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 µm (range: 71-420 µm). 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.

CLINICAL CHARACTERISTICS AND OUTCOME OF POSTERIOR CYSTOID MACULAR DEGENERATION IN CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To assess clinical characteristics and visual outcome in chronic central serous chorioretinopathy patients with posterior cystoid retinal degeneration (PCRD). METHODS: Patients' medical records were reviewed retrospectively in 62 cases (83 eyes, mean age = 59 years, 88% male). Data were collected at central serous chorioretinopathy diagnosis, at PCRD manifestation, and at final visit. All treatment modalities were reviewed. Main outcome measures were treatment efficacy in achieving PCRD resolution, and final best-corrected visual acuity. RESULTS: In 63 eyes (76%), subretinal fluid was present at first PCRD manifestation, whereas fluorescein angiography showed active focal or diffuse leakage in 65 eyes (78%). Seventy-six eyes (81%) received treatment, and PCRD had resolved completely in 31 eyes (37%) at the final visit. Photodynamic therapy was most successful in achieving a complete PCRD resolution. Best-corrected visual acuity did not improve, even after complete PCRD resolution (mean baseline best corrected visual acuity = 69 ± 19, and mean final best corrected visual acuity = 67 ± 20 ETDRS letters [20/40 and 20/50 in Snellen equivalent respectively], P = 0.354). CONCLUSION: Posterior cystoid retinal degeneration is a relatively common finding in chronic central serous chorioretinopathy, which is often accompanied by active subretinal fluid leakage. Treatment may be beneficial to stop the subretinal fluid leakage component, but is less likely to result in a complete PCRD resolution and/or a best-corrected visual acuity improvement.

GENETIC RISK FACTORS IN SEVERE, NONSEVERE AND ACUTE PHENOTYPES OF CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: 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 the ARMS2 (rs10490924), CFH (rs800292, rs1061170, rs1065489, rs1329428, rs2284664, rs3753394), and NR3C2 (rs2070951). Additionally, C4B gene copy numbers were analyzed. RESULTS: A significant association in 5 single-nucleotide polymorphisms in the CFH gene 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 × 10; OR = 0.49; 95% CI = 0.34-0.72), rs1329428 (P = 0.001; OR = 1.89; 95% CI = 1.49-2.40), rs2284664 (P = 1.21× 10; OR = 1.65; 95% CI = 1.28-2.13), and rs3753394 (P = 6.10× 10; OR = 0.61; 95% CI = 0.46-0.81). Carrying three C4B copies 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 the CFH and C4B genes, 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.

GENETIC RISK FACTORS IN ACUTE CENTRAL SEROUS CHORIORETINOPATHY.

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 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 × 10, 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.

FAMILIAL CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To assess ophthalmologic characteristics in patients and unaffected individuals in families with multiple members affected by central serous chorioretinopathy (CSC), both at presentation and long-term follow-up. METHODS: In 103 subjects from 23 families with at least 2 affected patients with CSC per family, prospective extensive ophthalmologic examination was performed, including best-corrected visual acuity, indirect ophthalmoscopy, digital color fundus photography, optical coherence tomography, fundus autofluorescence, and fluorescein angiography imaging. From these, 24 individuals from 6 families had undergone extensive ophthalmologic examination in either 1994 or 1995 and were followed up in this study. RESULTS: Subretinal fluid accumulation on optical coherence tomography and/or "hot spots" of leakage on fluorescein angiography indicative of CSC were detected in 45 of 103 phenotyped subjects (44%). Findings suggestive of CSC, but without the presence of subretinal fluid on optical coherence tomography and/or "hot spots" of leakage on fluorescein angiography, were observed in an additional 27 family members (26%). In 4 of 17 previously nonaffected subjects (24%) from the 24 individuals that were followed up after more than 20 years, we found more severe abnormalities. CONCLUSION: Extensive ophthalmologic phenotyping resulted in the detection of (suggestive) CSC in 52% of family members of patients with CSC. Genetic factors may play an important role in these specific CSC cases. Moreover, during follow-up, progressive disease can occur in a noteworthy number of patients.

Risk of Recurrence and Transition to Chronic Disease in Acute Central Serous Chorioretinopathy.

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 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.

Correlation between redefined optical coherence tomography parameters and best-corrected visual acuity in non-resolving central serous chorioretinopathy treated with half-dose photodynamic therapy.

PURPOSE: To assess parameters on optical coherence tomography (OCT), and their correlation with best-corrected visual acuity (BCVA) in patients with non-resolving central serous chorioretinopathy (CSC). METHODS: For 25 non-resolving CSC patients treated with photodynamic therapy (PDT), the thickness of retinal layers was assessed on the foveal spectral-domain (SD) OCT scan. Evaluated OCT parameters included the central retinal thickness (CRT), defined as the internal limiting membrane (ILM) to ellipsoid zone (EZ) distance, and the second band thickness (SBT), defined as the EZ to hyperreflective subretinal accumulation distance. Integrity of the external limiting membrane (ELM) and the EZ bands was also determined. These parameters, along with BCVA and CRT measured automatically by SD-OCT device software were obtained before PDT, after PDT, and at final visit. After Bonferroni correction, a p-value <0.007 was considered statistically significant. RESULTS: Twenty-five patients could be included at last visit before PDT and first visit after PDT. At final visit, 24 patients could be included, since 1 patients was lost to follow-up. Mean CRT was 112 µm at last visit before PDT, 118 µm at first visit after PDT (p = 0.030), and 127 µm at final visit (p<0.001compared to baseline). Mean SBT was 74 µm, 26 µm (p<0.001 compared to baseline), and 21 µm (p<0.001 compared to baseline), respectively. Mean BCVA in Early Treatment of Diabetic Retinopathy Study letters was 79 at baseline, 85 at first visit after PDT (p = 0.005 compared to baseline), and 87 at final visit (p = 0.001 compared to baseline). BCVA had an estimated correlation of ß = 0.103 (p = 0.114) with CRT, ß = -0.051 (p = 0.014) with SBT, ß = 0.615 (p = 0.600) with the integrity of the ELM, and ß = 4.917 with the integrity of the EZ (p = 0.001). CONCLUSIONS: In non-resolving CSC patients treated with half-dose PDT, the CRT increased at final visit in comparison to the last visit before PDT. The continuity of the EZ on SD-OCT was positively correlated with BCVA. We propose that the distance between ILM and EZ should be used as a reliable CRT measurement in non-resolving CSC patients treated with half-dose PDT.

Clinical characteristics and long-term visual outcome of severe phenotypes of chronic central serous chorioretinopathy.

PURPOSE: The aim of this study was to investigate disease onset and disease progression in patients with severe chronic central serous chorioretinopathy (cCSC). PATIENTS AND METHODS: The medical records of 143 cCSC patients (199 eyes) were reviewed. All cases had visual complaints for >6 months and showed signs of a severe disease phenotype on optical coherence tomography (OCT) and fluorescein angiography (FA). Clinical presentation at onset was evaluated, together with disease progression on multimodal imaging and final treatment outcome. RESULTS: Twenty-eight cases (14%) had a documented history of an acute episode of CSC, whereas 145 cases (73%) showed pre-existing features of chronicity already at first presentation. The first clinical presentation could not be evaluated in 13% of cases. Best-corrected visual acuity (BCVA) was 70 ± 18 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters at onset and 70 ± 22 ETDRS letters at final visit (p = 0.770). Among all studied cases, 173 eyes (87%) were treated, which resulted in complete resolution of subretinal fluid (SRF) in 76% of eyes at final visit. In eyes with fluorescein angiographic follow-up, the area of diffuse atrophic retinal pigment epithelium (RPE) abnormalities (diffuse atrophic RPE alterations [DARA]) had increased significantly in 43 eyes (68%) at final visit. CONCLUSION: CSC encompasses a clinical spectrum that includes a range of severe phenotypes, in which retinal abnormalities tend to be progressive. Nevertheless, the long-term visual acuity may remain fairly stable with treatment. Few patients with severe chronic CSC have a history of acute CSC, which could indicate that there may be pathogenetic differences between these 2 CSC variants.

Clinical spectrum of severe chronic central serous chorioretinopathy and outcome of photodynamic therapy.

PURPOSE: To describe a spectrum of severe chronic central serous chorioretinopathy (cCSC) cases and their response to photodynamic therapy (PDT). PATIENTS AND METHODS: A total of 66 patients (81 eyes) with active severe cCSC were studied, and their response to PDT was compared with a control group consisting of 35 active cCSCs (37 eyes) that did not display characteristics of severity. Best-corrected visual acuity (BCVA) and complete resolution of subretinal fluid (SRF) were considered as main outcome measures. RESULTS: In severe cCSC cases, we found cumulative areas of diffuse atrophic retinal pigment epithelium alterations in 48 eyes (59%), multiple "hot spots" of leakage in 36 eyes (44%), posterior cystoid retinal degeneration in 25 eyes (31%), and 13 eyes (16%) had a diffuse leakage on fluorescein angiography. After PDT treatment, BCVA increased in both groups, from 66 to 72 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters in the case group (P<0.001), and from 78 to 82 ETDRS letters in the control group (P<0.001). SRF had resolved completely in 87% of severe cCSC cases and 95% of controls at final follow-up visit. CONCLUSION: A spectrum of severe cCSC exists, and PDT seems to be an effective treatment in both severe cCSC and nonsevere cCSC in terms of resolution of SRF. Final BCVA shows a significant improvement in both groups after PDT treatment.

Neovascular age-related macular degeneration without drusen in the fellow eye: clinical spectrum and therapeutic outcome.

PURPOSE: To investigate the clinical characteristics and therapeutic outcome of patients with neovascular age-related macular degeneration (nAMD) in 1 eye, without drusen in the fellow eye. PATIENTS AND METHODS: Medical records of 381 patients were analyzed to identify the cases. The main outcomes included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) and change in central retinal thickness (CRT). These parameters were reviewed at baseline, first follow-up visit, and after 6, 12, and 24 months. RESULTS: Out of 381 patients, 29 cases (8%) were included (of whom 3 had polypoidal choroidal vasculopathy [PCV]) who were treated with anti-vascular endothelial growth factor (anti-VEGF) therapy which was supplemented by photodynamic therapy (PDT) in the PCV patients. Overall, no statistically significant change in mean BCVA was observed during follow-up. BCVA improved or remained stable (defined as a gain in BCVA, a stable BCVA, or a loss of <5 ETDRS letters) in 22 patients (76%), and 7 patients (23%) had lost ≥5 ETDRS letters at final follow-up. A gain of ≥15 ETDRS letters at final follow-up was seen in 5 patients (17%). Mean CRT had decreased significantly with 99 µm (P<0.001) at 24 months after the initial visit. CONCLUSION: There is a clinical spectrum of nAMD that is not associated with drusen in the fellow eye. Patients with nAMD without drusen in the fellow eye respond to anti-VEGF treatment and, in cases of PCV, to supplemental PDT. The pathophysiology of this spectrum of nAMD may be different from drusen-associated age-related macular degeneration.

Efficacy of photodynamic therapy in steroid-associated chronic central serous chorioretinopathy: a case-control study.

PURPOSE: To investigate whether patients who developed chronic central serous chorioretinopathy (cCSC) in association with corticosteroid treatment respond differently to photodynamic therapy (PDT) as compared to patients who have not used corticosteroids. METHODS: Clinical evaluation included visual acuity (VA), fundoscopy, optical coherence tomography (OCT), fluorescein and indocyanine green angiography. The main outcome measure was a complete resolution of subretinal fluid (SRF) on OCT after PDT. RESULTS: One hundred and twenty-three eyes (117 patients), including 35 steroid-associated cases (29%), who received PDT treatment with reduced settings for active cCSC were included. Complete resolution of SRF on OCT was seen in 69% of the steroid-associated cases and in 50% of the controls after PDT treatment (p = 0.062). At the final follow-up moment, 74% of the cases had a complete resolution of SRF compared to 60% in the control group (p = 0.142). The VA at the first visit after therapy showed an increase in both groups (mean VA before treatment; cases: 69 ± 14 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, controls: 74 ± 13 ETDRS letters, mean VA first visit after treatment; cases: 76 ± 13 ETDRS letters, controls: 75 ± 13 ETDRS letters). No significant differences were seen in response to PDT between the patients who continued corticosteroid treatment and those who ceased the use of corticosteroids. CONCLUSIONS: Photodynamic therapy appears to be equally effective in patients suffering from steroid-associated cCSC as compared to patients with cCSC who do not use corticosteroids. Continuation of corticosteroids at the time of PDT treatment does not seem to adversely affect PDT response.