Background: Systematic literature searches are the cornerstone of systematic reviews. In this study, we evaluated database coverage of randomized clinical trials for central serous... Show moreBackground: Systematic literature searches are the cornerstone of systematic reviews. In this study, we evaluated database coverage of randomized clinical trials for central serous chorioretinopathy (CSC). Methods: We searched 12 databases (BIOSIS Previews, CINAHL, the Cochrane Central, Current Contents Connect, Data Citation Index, Derwent Innovations Index, EMBASE, KCI-Korean Journal Database, MEDLINE, PubMed, SciELO Citation Index, and Web of Science Core Collection) on 10 April 2023 for randomized clinical trials for CSC. After identifying all eligible studies across all databases, we investigated the coverage of these studies within each database, including the coverage of any combination of two databases. Results: The 12 databases yielded 848 records for screening, of which 76 were randomized clinical trials for CSC. No single database provided full coverage. The most comprehensive coverage was provided by EMBASE (88%), the Cochrane Central (87%), and PubMed (75%). A combined search in the Cochrane Central and PubMed led to complete coverage (100%) while reducing the number of records for screening from 848 to 279. Conclusions: Systematic review search design should include multiple databases. For randomized clinical trials for CSC, the combination of the Cochrane Central and PubMed provides an excellent balance between coverage and workload. Show less
Treatment of chronic central serous chorioretinopathy (cCSC) remains a topic of controversy. As cCSC is a disease that can wax and wane, treatment efficacy is difficult to assess especially when... Show moreTreatment of chronic central serous chorioretinopathy (cCSC) remains a topic of controversy. As cCSC is a disease that can wax and wane, treatment efficacy is difficult to assess especially when trials compare active treatments without any placebo/control group. In this study, we systematically reviewed short-term efficacies of any cCSC treatment tested in randomized controlled trials (RCT) and employed network meta-analyses to compare to non-treatment controls. We searched 11 literature databases on 20 March 2022 for RCTs of treatment of cCSC. We identified 17 RCTs including a total of 1172 eyes. Treatments included conventional laser (44 eyes), half-dose or half-fluence photodynamic therapy (PDT) (298 eyes), ranibizumab (16 eyes), antioxidants (50 eyes), mineralocorticoid receptor antagonists (187 eyes), rifampicin (91 eyes), selective retina therapy (SRT) (67 eyes) and subthreshold micropulse laser (192 eyes). Compared with controls, significant benefit on complete subretinal fluid resolution was only obtained from half-dose or half-fluence PDT (OR: 20.6; 95% CI: 6.3-66.7; p < 0.0001) and conventional laser (OR: 36.4; 95% CI: 2.0-655.7; p = 0.015), and at an order of magnitude lower degree from SRT (OR: 3.4; 95% CI: 1.7-6.8; p = 0.00075). Compared with controls and after sensitivity analyses, significant benefit in the change in best-corrected visual acuity was only obtained by half-dose/-fluence PDT (-0.13 logMAR; 95% CI: -0.20 to -0.06 logMAR; p = 0.00021). In conclusion, three treatment options provide significant improvement over no treatment: half-dose/-fluence PDT, conventional laser and to a much lesser degree SRT. Considering that conventional laser can only be applied for extrafoveal leaks, and the long-term data available for PDT-based treatments finding persisting treatment results, half-dose or half-fluence PDT is the only viable treatment option for patients with cCSC. Shortage issues with verteporfin should not lead to employment of ineffective treatment modalities, as they put patients at unnecessary risk of adverse events. Show less
Cushing's syndrome is a rare disease with an endogenous cause of excess cortisol secretion. More evidence substantially links cortisol levels to the pachychoroid spectrum diseases. In this... Show moreCushing's syndrome is a rare disease with an endogenous cause of excess cortisol secretion. More evidence substantially links cortisol levels to the pachychoroid spectrum diseases. In this systematic review and meta-analysis, we summarize available evidence on pachychoroid spectrum diseases in patients with Cushing's syndrome. We performed a systematic literature search in 11 databases on 21 May 2022. Studies were considered eligible if they performed retinal examination of a consecutive group of patients with Cushing's syndrome using optical coherence tomography (OCT) scans. We extracted data on subfoveal choroidal thickness in patients with Cushing's syndrome compared to matched controls. We also extracted data on the prevalence of pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), and polypoidal choroidal vasculopathy (PCV). We identified six eligible studies with a total of 159 patients with Cushing's syndrome. On average, patients with Cushing's syndrome have 49.5 mu m thicker subfoveal choroidal thickness compared to matched healthy individuals. Pachychoroid spectrum diseases were relatively common in these patients: PPE in 20.8%, CSC in 7.7%, and PCV in 2.8%. We conclude that there should be low threshold to recommend ophthalmic examination to patients with Cushing's syndrome, and that a macular OCT is recommended during this examination. Show less
Introduction: Since July 2021, a worldwide shortage of verteporfin (Visudyne (R)) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of... Show moreIntroduction: Since July 2021, a worldwide shortage of verteporfin (Visudyne (R)) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of indications in ophthalmology, including chronic central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal haemangioma. For these disorders, PDT is either the first-choice treatment or regarded as a major treatment option. Materials and methods: A questionnaire was sent to key opinion leaders in the field of medical retina throughout the world, to assess the role of PDT in their country and the effects of the shortage of verteporfin. In addition, information on the application of alternative treatments during shortage of verteporfin was obtained, to further assess the impact of the shortage. Results: Our questionnaire indicated that the shortage of verteporfin had a major impact on ophthalmic care worldwide and was regarded to be a serious problem by most of our respondents. However, even though there is ample evidence to support the use of PDT in several chorioretinal diseases, we found notable differences in its use in normal patient care throughout the world. Various alternative management strategies were noted during the verteporfin shortage, including lowering the dose of verteporfin per patient, the use of alternative treatment strategies and the use of a centralized system for allocating the remaining ampoules of verteporfin in some countries. Conclusion: The shortage of verteporfin has had a large effect on the care of ophthalmic patients across the world and may have resulted in significant and irreversible vision loss. Mitigation strategies should be developed in consultation with all stakeholders to avoid future medication shortages of verteporfin and other unique ophthalmic medications. These strategies may include mandatory stock keeping, compulsory licensing to an alternative manufacturer or incentivizing the development of competition, for example through novel public-private partnerships. Show less
Purpose: Comparing the effect of half-dose photodynamic therapy and high-density subthreshold micropulse laser treatment on retinal pigment epithelial detachments (PEDs) in chronic central serous... Show morePurpose: Comparing the effect of half-dose photodynamic therapy and high-density subthreshold micropulse laser treatment on retinal pigment epithelial detachments (PEDs) in chronic central serous chorioretinopathy. Methods: This study included data from the PLACE trial, a prospective randomized controlled trial comparing half-dose photodynamic therapy and high-density subthreshold micropulse laser treatment in chronic central serous chorioretinopathy. Main outcome measurements were changes in both the foveal PED and the highest PED within the macula at baseline compared with first and final evaluation visit. Results: At baseline, a macular PED was detected in 76.9% of patients (123/160), and a PED within 1,500 mu m from the foveal center in 37.5% of patients (60/160). In the half-dose photodynamic therapy arm (61 patients), there was a significantly larger decrease in the highest macular PED compared with the high-density subthreshold micropulse laser treatment arm (62 patients) at both first and final evaluation visits (P < 0.001 and P = 0.012, respectively). The decrease of highest foveal PED was significant at first visit (P = 0.025). Conclusion: Half-dose photodynamic therapy is superior to high-density subthreshold micropulse laser treatment with regard to a statistically significant reduction in the height of macular PEDs in active chronic central serous chorioretinopathy. These findings may also have implications for other diseases within the pachychoroid disease spectrum that can present with PEDs. Show less
Brinks, J.; Dijk, E.H.C. van; Kielbasa, S.M.; Mei, H.L.; Veen, I. van der; Peters, H.A.B.; ... ; Meijer, O.C. 2022
Context: Central serous chorioretinopathy (CSC) is a severe ocular disease characterized by fluid accumulation under the retina and abnormalities in the underlying vascular layer, the choroid. CSC... Show moreContext: Central serous chorioretinopathy (CSC) is a severe ocular disease characterized by fluid accumulation under the retina and abnormalities in the underlying vascular layer, the choroid. CSC has a striking prevalence in males of 80% to 90% of total patients. Corticosteroids are the most pronounced extrinsic risk factor for CSC. Choroidal endothelial cells (CECs) are important for the vascular integrity of the choroid, but the effects of corticosteroid effects in these cells are unknown.Objective: We aimed to reveal the potential steroidal contribution to CSC.Method: We characterized the expression of the glucocorticoid, mineralocorticoid, and androgen receptor in the human choroid using immunohistochemistry. Using RNA-sequencing, we describe the cortisol response in human CECs derived from 5 male and 5 female postmortem donors.Results: The glucocorticoid receptor was highly expressed in the human choroid, whereas no to minimal expression of the mineralocorticoid and androgen receptors was observed. The extensive transcriptional response to cortisol in human primary cultured CECs showed interindividual differences but very few sex differences. Several highly regulated genes such as ZBTB16(log2 fold change males 7.9; females 6.2) provide strong links to choroidal vascular regulation.Conclusions: The glucocorticoid receptor predominantly mediates the response to cortisol in human CECs. Interindividual differences are an important determinant regarding the cortisol response in human cultured CECs, whereas intrinsic sex differences appear less pronounced. The marked response of particular target genes in endothelial cells to cortisol, such as ZBTB16, warrants further investigation into their potential role in the pathophysiology of CSC and other vascular conditions. Show less
Ravenstijn, M.; Dijk, E.H.C. van; Haarman, A.E.G.; Kaden, T.R.; Vermeer, K.A.; Boon, C.J.F.; ... ; Yzer, S. 2021
Purpose: To increase insight into the myopic presentation of central serous chorioretinopathy (CSC) by comparing a large group of myopic patients with CSC with reference groups with only one of the... Show morePurpose: To increase insight into the myopic presentation of central serous chorioretinopathy (CSC) by comparing a large group of myopic patients with CSC with reference groups with only one of the diagnoses. Methods: Myopic patients with CSC (spherical equivalent <=-3D, n = 46), emmetropic patients with CSC (spherical equivalent -0.5 to 0.5 D, n = 83), and myopic, non-CSC patients (n = 50) were included in this multicenter cross-sectional study. Disease characteristics and imaging parameters, such as subfoveal choroidal thickness and indocyanine green angiography patterns, were compared between cases and reference groups. Results: In myopic patients with CSC, median subfoveal choroidal thickness (286 mu m [IQR 226-372 mu m]) was significantly thicker than subfoveal choroidal thickness in myopic, non-CSC patients (200 mu m [IQR 152-228 mu m], P < 0.001) but thinner than emmetropic patients with CSC (452 mu m [IQR 342-538 mu m], P < 0.001). They also had pachyvessels in 70% of the eyes comparable with emmetropic CSC (76%, P = 0.70). Choroidal hyperpermeability was frequently present on indocyanine green angiography in both myopic and emmetropic CSC eyes. Need for treatment, treatment success, and recurrence rate were not significantly different between CSC groups. Conclusion: Myopic CSC presents with similar imaging and clinical characteristics as emmetropic CSC, apart from their thinner choroids. Keeping in mind the structural changes of myopia, other imaging characteristics could aid the diagnostic process. Show less
Purpose: To investigate and compare the salivary alpha-amylase (sAA) activity as an indicator of the sympathetic activity and stress response in patients with central serous chorioretinopathy (CSC)... Show morePurpose: To investigate and compare the salivary alpha-amylase (sAA) activity as an indicator of the sympathetic activity and stress response in patients with central serous chorioretinopathy (CSC) and healthy control subjects. Methods: Prospective multicenter case series, including 80 CSC patients and 88 healthy control subjects. Central serous chorioretinopathy status was classified as either active or inactive, depending on the presence of subretinal fluid on optical coherence tomography. Salivary samples were collected in the morning from patients and control subjects of the main cohort and at midnight for the additional cohort. Salivary alpha-amylase activity was determined in all patients and control subjects. Results: Morning sAA activity was significantly higher in patients with active CSC compared with inactive CSC (P = 0.049) and to healthy control subjects (P = 0.012). There was no significant difference in sAA activity between patients with inactive CSC and control subjects (P = 1.0). Nocturnal sAA activity did not show any significant difference between patients with active CSC and either inactive CSC or control subjects (P = 0.139). Conclusion: Morning sAA activity is increased in patients with active CSC, although diurnal rhythmicity is preserved. Measurement of sAA is easy to perform and might be an eligible tool to further investigate the relation between stress and CSC. Show less
Purpose: To compare the effects of half-dose photodynamic therapy (PDT) and high-density subthreshold micropulse laser on choroidal dysfunction evaluated by degree and extent of hyperfluorescence... Show morePurpose: To compare the effects of half-dose photodynamic therapy (PDT) and high-density subthreshold micropulse laser on choroidal dysfunction evaluated by degree and extent of hyperfluorescence on indocyanine green angiography (ICGA) in chronic central serous chorioretinopathy. Methods: Data from the multicenter, randomized, controlled PLACE trial were used in this study. Hyperfluorescent and hypofluorescent areas on ICGA, their association with subretinal fluid and visual function were assessed. Results: In total, 146 patients were included (72 in the PDT and 74 in the high-density subthreshold micropulse laser treatment arm). A significantly greater decrease in the size of hyperfluorescent areas on ICGA at first visit after treatment was seen after PDT compared with high-density subthreshold micropulse laser (mean, -1.41 +/- 2.40 mm(2) vs. -0.04 +/- 0.73 mm(2), respectively; P < 0.001). A reduction in the degree of hyperfluorescence on ICGA decreased the odds of having persistent subretinal fluid on optical coherence tomography at first visit after treatment (B = 0.295; P = 0.019). There were no significant differences in best-corrected visual acuity and retinal sensitivity between the subgroup with novel hypofluorescence (n = 20, 28%) on ICGA at first visit post PDT, compared with the subgroup without novel hypofluorescence on ICGA after PDT. Conclusion: Choroidal abnormalities in chronic central serous chorioretinopathy can be effectively treated by ICGA-guided half-dose PDT but not with high-density subthreshold micropulse laser application. Show less
Subhi, Y.; Bjerager, J.; Boon, C.J.F.; Dijk, E.H.C. van 2021
Purpose To explore subretinal fluid (SRF) morphology in chronic central serous chorioretinopathy (cCSC) after one session of either high-density subthreshold micropulse laser (HSML) treatment or... Show morePurpose To explore subretinal fluid (SRF) morphology in chronic central serous chorioretinopathy (cCSC) after one session of either high-density subthreshold micropulse laser (HSML) treatment or half-dose photodynamic therapy (PDT).Methods We retrospectively obtained optical coherence tomography (OCT) scans from a subset of patients from a randomized controlled trial on treatment-naive eyes with cCSC allocated to either HSML treatment or half-dose PDT. OCT scans were evaluated prior to treatment and 6-8 weeks post-treatment, where we measured maximum SRF height and width, calculated the maximum height-to-maximum width-ratio (maxHWR) and calculated the total SRF volume.Results Forty-one eyes of 39 cCSC patients were included. SRF morphology ranged from flat to dome-shaped, quantified as maxHWR ranging between 0.02 and 0.12. SRF volume was median 0.373 mu l (range: 0.010-4.425 mu l) and did not correlate to maxHWR (rho = -0.004, p = 0.982). Half-dose PDT was superior to HSML treatment in complete SRF resolution (RR = 3.28, p = 0.003) and in morphological changes of SRF (Delta(maximum height), p = 0.001; Delta(maximum width), p < 0.001; Delta(volume), p = 0.025). SRF resolved completely in 19/22 PDT-treated eyes (86%) and 5/19 HSML-treated eyes (26%). SRF volume increased in five eyes (26%) after HSML treatment, and in none of the eyes after half-dose PDT. SRF morphology at baseline did not predict treatment outcomes.Conclusion SRF morphology changed after both HSML treatment and half-dose PDT in cCSC, with SRF disappearing in most PDT-treated patients, whereas SRF volume increased in a sizeable proportion of HSML-treated patients. Baseline SRF characteristics measured in this study were unable to predict outcomes after either HSML treatment or half-dose PDT. Show less
Purpose To describe the treatment outcomes and recurrence risk of chronic central serous chorioretinopathy (cCSC) in patients who had complete resolution of subretinal fluid (SRF) after either... Show morePurpose To describe the treatment outcomes and recurrence risk of chronic central serous chorioretinopathy (cCSC) in patients who had complete resolution of subretinal fluid (SRF) after either primary half-dose photodynamic therapy (PDT) or high-density subthreshold micropulse laser (HSML) in the PLACE trial.Methods This multicentre prospective follow-up study evaluated cCSC patients at 1 year after completion of the PLACE trial. Outcomes included: complete resolution of SRF on OCT, best-corrected visual acuity (BCVA) in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, retinal sensitivity on microperimetry and a visual function questionnaire (NEI-VFQ25).Results Twenty-nine out of 37 patients who received half-dose PDT and 15 out of 17 patients who received HSML could be evaluated at final visit. At final visit, 93% of the patients treated with half-dose PDT had complete resolution of SRF, compared with 53% of HSML-treated patients (p = 0.006). At final visit, the mean estimate increase in the PDT group compared with the HSML group was + 2.1 ETDRS letters, +0.15 dB for the retinal sensitivity and + 5.1 NEI-VFQ25 points (p = 0.103, p = 0.784 and p = 0.071, respectively). The mean estimated central retinal thickness in the half-dose PDT group was -7.0 mu m compared with the HSML group (p = 0.566). The mean estimated subfoveal choroidal thickness in the half-dose PDT group was -16.6 mu m compared with the HSML group (p = 0.359).Conclusion At 20 months after treatment, cCSC patients successfully treated with half-dose PDT are less likely to have recurrences of SRF compared with those successfully treated with HSML. However, functional outcomes did not differ. Show less
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... Show morePurpose 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. Show less
Karska-Basta, I.; Pociej-Marciak, W.; Chrzaszcz, M.; Wilanska, J.; Jager, M.J.; Markiewicz, A.; ... ; Kubicka-Trzaska, A. 2020
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 ... Show moreThe 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. Show less
