Differential Expression of Sex-Steroid Receptors in the Choroid Aligns With Central Serous Chorioretinopathy Sex Prevalence Across Different Ages.

Purpose: The purpose of this study was to investigate the presence of sex-steroid receptors in human choroidal tissue across different ages and sex, aiming to better understand the pronounced sex difference in central serous chorioretinopathy (CSC) occurrence. Methods: Paraffin-embedded enucleated eyes of 14 premenopausal women, 15 postmenopausal women, 10 young men (<45 years), and 10 older men (>60 years) were used. A clinically certified immunostaining was performed to detect the presence of the androgen receptor (AR), progesterone receptor (PR; isoform A and B), and estrogen receptor (ERα). The stained slides were scored in a blinded manner for positive endothelial cells and stromal cells in consecutive sections of the same choroidal region. Results: Our analysis revealed the presence of AR, PR, and ERα in endothelial cells and stromal cells of choroidal tissue. The mean proportion of AR-positive endothelial cells was higher in young men (46% ± 0.15) compared to aged-matched women (29% ± 0.12; P < 0.05, 95% confidence interval [CI]). Premenopausal women showed markedly lower mean proportion of ERα (5% ± 0.02) and PR-positive endothelial cells (2% ± 0.01) compared to postmenopausal women (15% ± 0.07 and 19% ± 0.13; both P < 0.05, 95% CI), young men (13% ± 0.04 and 21% ± 0.10; both P < 0.05, 95% CI), and older men (18% ± 0.09 and 27% ± 0.14; both P < 0.05, 95% CI). Mean PR-positive stromal cells were also less present in premenopausal women (12% ± 0.07) than in other groups. Conclusions: The number of sex-steroid receptors in the choroidal tissue differs between men and women across different ages, which aligns with the prevalence patterns of CSC in men and postmenopausal women.

Chorioretinopathy Post COVID-19: A Systematic Review and Prevalence Assessment, Unveiling Insights into an Emerging Ocular Entity.

PURPOSE: To investigate the occurrence of chorioretinopathy post-COVID-19, emphasizing demographic characteristics, medication history, clinical presentation, diagnostic evaluation, and treatment approaches, with a specific focus on the role of corticosteroid use. METHODS: Our protocol was registered prospectively on PROSPERO (CRD42023457712). A systematic search of databases (PubMed, Cochrane, WOS, Scopus) from November 2020 to August 2023 were performed to identify any original research reporting chorioretinopathy in COVID-19 patients. Data extraction included patient demographics, COVID-19 timeline, medication history, symptoms, diagnostic tests, and treatment outcomes. We used Joanna Briggs Institute (JBI) critical appraisal tool to assess the quality of our included studies. RESULTS: We identified seven case reports and two case series including 10 patients, six females and four males (mean age 36.5 years), who exhibited chorioretinopathy after COVID-19. Onset varied from 6 days to three months post-infection (average = 24.3 days). Seven patients (70%) had a history of corticosteroid use during COVID-19 treatment. Symptoms included visual loss, blurred vision, and deterioration. Diagnostic assessments revealed central serous chorioretinopathy in seven patients (70%) and punctate inner choroidopathy in two (20%). Treatment approaches varied, with corticosteroid discontinuation leading to symptom improvement, while two patients were treated with corticosteroids. Five patients who discontinued corticosteroids were reported to have improvement in visual acuity, two of them changed to 20/25 after being 20/40, two changed to 6/6, and one changed to 20/20, while the visual acuity in the sixth patient was not reported. Regarding the two patients who were treated with corticosteroids, visual acuity was reported in one case only and it improved to 20/20. CONCLUSION: This systematic review states the prevalence and potential association between chorioretinopathy, and corticosteroid use in the context of COVID-19. This relation is still unclear because of the relief of symptoms in some cases after corticosteroid discontinuation, while two other cases were treated with corticosteroids and their symptoms improved.

Clinical Landscape of Central Serous Chorioretinopathy in Germany: Retina.net CSC Registry Report Number 1.

INTRODUCTION: The German Registry of central serous chorioretinopathy (CSC) collects data on CSC patients in a nationwide multicenter approach to analyze epidemiology, risk factors, clinical presentations, as well as diagnosis and treatment patterns. METHODS: In this multicenter cohort study, patients with CSC were enrolled in nine tertiary referral centers in Germany between January 2022 and June 2023. After consenting to the study, demographic data, risk factors, reported symptoms, best-corrected visual acuity (BCVA), funduscopic findings, disease severity, and diagnostic and treatment decisions were recorded and analyzed. RESULTS: A total of 539 eyes of 411 CSC patients were enrolled in this study including 308 males (75%) and 103 females (25%). Patients were predominantly of Caucasian origin and had a mean age of 55.5 years (IQR 41.0-70.0). 28% of eyes were classified as acute (<4 months duration) CSC, 28% as chronic (>4 months duration) CSC, 21% as inactive CSC, 11% as chronic atrophic CSC, and 12% as CSC with secondary CNV. 128 patients (31%) demonstrated bilateral CSC. The most common risk factors reported were psychological stress (52%), smoking (38%), arterial hypertension (38%), and a history of or current use of steroids (30%). Most frequently encountered symptoms included decreased visual acuity (76%), metamorphopsia (49%), relative scotoma (47%), blurred vision (19%), and dyschromatopsia (9%). The mean logMAR BCVA on initial examination was 0.2 (≈20/30, IQR 0.2-0.4) but showed significant variation with a tendency of lower BCVA in chronic cases. At the baseline visit, 74% of the overall cohort received no treatment, while 19% underwent local treatment and only 2% underwent systemic treatment. Of the local therapies, anti-VEGF injections were the most frequently performed procedure (33%, mainly for secondary CNV), followed by micropulse laser (28%), focal nonpulsed laser (23%), verteporfin photodynamic therapy (14%), and nonsteroidal anti-inflammatory eye drops (2%). Among intravitreal anti-VEGF agents, aflibercept was used most frequently, followed by bevacizumab and ranibizumab. CONCLUSION: This registry represents one of the largest cohorts of European patients with CSC to date. Patient age and the proportion of women were higher than expected and bilateral active disease was lower than anticipated, highlighting that neither age nor gender should be overemphasized when diagnosing CSC. Therapeutic interventions are heterogeneous and include verteporfin photodynamic therapy, micropulse laser, and anti-VEGF injections in case of secondary CNV.

Acute Central Serous Chorioretinopathy Outbreak during the COVID-19 Pandemic: A Pilot Study.

Background and Objectives: This study aims to investigate the potential association between the COVID-19 pandemic and a new presentation of central serous chorioretinopathy (CSCR). Materials and Methods: A retrospective analysis was conducted, comparing the incidence of new-onset CSCR cases among ophthalmology patients in a regional medical facility in southern Israel between two distinct periods: the COVID-19 pandemic era in Israel, which occurred from 27 February 2020 to 20 December 2020, and the non-pandemic period from calendar years 2018 to 2021, excluding the specific epidemic phase mentioned. Disease severity was evaluated based on recovery time, visual acuity loss, and central macular thickness via OCT. Results: Over the four-year period, 35 new cases of CSCR were recorded. During the COVID-19 pandemic, 17 new cases (0.005% per population) were identified, compared with 18 new cases (0.002% per population) in the preceding three years. The odds ratio for acute CSCR during the pandemic was 2.83 (95% CI, 1.46-5.50) with a p-value of 0.02. CSCR cases during the pandemic seemed to exhibit worse clinical characteristics, though not statistically significant. Additionally, 22.2% of the COVID-19 pandemic group had confirmed COVID-19 cases, which was statistically significantly higher than the general population's reported cases (6%). Conclusion: The study revealed a statistically significant increase of over 2.5 times in acute CSCR incidence during the COVID-19 pandemic compared with non-pandemic periods. The findings suggest that the pandemic's stressful changes may have unintended consequences on the occurrence of CSCR, highlighting the importance of mental health support and psychoeducation for affected patients.

Association of Central serous chorioretinopathy with type of personality, anxiety and depression.

PURPOSE: Central serous chorioretinopathy (CSCR) a relatively common cause of visual impairment, which is characterized by subretinal fluid accumulation in the macula and is more common in middle-aged males. Various risk factors have been reported in literature, among which substantial role of psychological factors is cited. Our aim was to look for the prevalence and association of the psychiatric factors in CSCR patients and to compare them with other non-chorioretinal ocular pathologies. METHODS: A cross-sectional correlational study was undertaken involving 91 CSCR patients, along with 91 patients with other non-chorioretinal diseases. Their risk factors, clinical history, ocular examination, and psychiatric assessments were done using standardized tools, and the groups were compared in terms of scoring of Framingham Type A scale (FTAS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HDRS). RESULTS: CSCR patients had a male:female ratio of 8:1. Chronic, bilateral, and recurrent diseases were found in 15%, 20%, and 23% cases, respectively. Anxiety disorder had a prevalence of 40%, followed by major depression with a prevalence of 24%, and these were significantly higher than non-chorioretinal disease patients (odds ratios 14.18 and 5.30, respectively). Also, these psychiatric disorders were significantly associated with an overall lower visual acuity and greater central macular thickness due to subretinal fluid accumulation. CONCLUSION: Psychiatric comorbidities like Type A personality trait and depression and anxiety disorders were significantly more prevalent in CSCR patients, compared to non-chorioretinal pathologies. Focus on psychological health would certainly benefit these patients in terms of better management of not only CSCR, but their psychiatric morbidity as well.

Increased risk of glaucoma development in patients with central serous chorioretinopathy: results of a 11-year population-based cohort study.

PURPOSE: To investigate whether patients with central serous chorioretinopathy (CSC) have increased risk of developing glaucoma. METHODS: Patients diagnosed with CSC between 1 January 2008 and 31 December 2018 were included in this study using data from the Taiwanese National Health Insurance Research Database (NHIRD). The CSC cohort was matched with a non-CSC cohort using the propensity score matching method, based on sex, age (in 10-year intervals), index date year, comorbidities, and steroid use, resulting in equal numbers of patients in both cohorts. Patients were followed up until 31 December 2019 or until they were withdrawn from the NHIRD. The incidence of glaucoma was compared between the two cohorts using the Cox regression model, and the risk of developing glaucoma was estimated using the Kaplan-Meier method. RESULTS: After adjusting for sex, age, comorbidities, and steroid use, the CSC cohort showed a significantly higher risk of developing glaucoma compared to those without CSC (adjusted HR = 3.99; 95% CI = 3.44-4.62). The cumulative incidence of glaucoma in the CSC cohort was also significantly higher than in the non-CSC cohort (log-rank test, p < 0.001). Among the glaucoma subtypes, normal tension glaucoma had the highest risk (adjusted HR = 5.79; 95% CI = 3.41-9.85), followed by primary open-angle glaucoma (adjusted HR = 2.77; 95% CI = 2.12-3.62). CONCLUSIONS: In conclusion, our study shows that CSC patients are at a higher risk of developing glaucoma, especially NTG. Awareness and regular glaucoma screenings are essential for patients with CSC.

[Central serous chorioretinopathy: A review]. / Choriorétinopathie séreuse centrale : une revue.

The central serous chorioretinopathy (CSCR) is characterized by serous retinal detachments SRD associated with one or several retinal pigment epithelium detachments/irregularities (PEDs). The choroid is thickened with dilated choroidal veins and choroidal hyperpermeability suggesting an underlying choroidopathy. CSCR belongs to the pachychoroid spectrum. CSCR affects mostly middle-aged men and the main risk factor is the corticosteroid intake. In most cases, the subretinal detachment resolves spontaneously with a good visual prognosis. However, recurrent or chronic form of the disease can lead to irreversible retinal damage and decreased visual acuity. Laser on an extra foveal leak point or half dose/half fluence photodynamic therapy are the first-line treatment options.

Risk of retinopathy in women with pregnancy-induced hypertension: a nationwide population-based cohort study of 9-year follow-up after delivery.

BACKGROUND: The retina is potentially associated with several physiological, hormonal, and metabolic changes during pregnancy. The few available epidemiologic studies of ocular changes in pregnancy have mainly concerned retinopathies. Pregnancy-induced hypertension, which leads to ocular manifestations including blurred vision, photopsia, scotoma, and diplopia, might induce reactive changes in the retinal vessels. Although several studies have suggested the existence of pregnancy-induced hypertension-related retinal ocular disease, there are few large cohort studies on this topic. OBJECTIVE: This study aimed to investigate the risk of major retinal diseases including central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, retinal artery occlusion, and hypertensive retinopathy in the long-term postpartum stage according to the presence of previous pregnancy-induced hypertension in a large cohort based on the Korean National Health Insurance Database. STUDY DESIGN: On the basis of Korean health data, 909,520 patients who delivered from 2012 to 2013 were analyzed. Among them, patients who had previous ocular diseases or hypertension and multiple births were excluded. Finally, 858,057 mothers were assessed for central serous chorioretinopathy (ICD-10: H35.70), diabetic retinopathy (ICD-10: H36.0, E10.31, E10.32, E11.31, E11.32, E12.31, E13.31, E13.32, E14.31, E14.32), retinal vein occlusion (ICD-10: H34.8), retinal artery occlusion (ICD-10: H34.2), and hypertensive retinopathy (ICD-10: H35.02) for 9 years after delivery. Enrolled patients were divided into 2 groups: 10,808 patients with and 847,249 without pregnancy-induced hypertension. The primary outcomes were the incidence of central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, retinal artery occlusion, and hypertensive retinopathy 9 years after delivery. Clinical variables were age, parity, cesarean delivery, gestational diabetes mellitus, and postpartum hemorrhage. In addition, pregestational diabetes mellitus, kidney diseases, cerebrovascular diseases, and cardiovascular diseases were adjusted. RESULTS: Postpartum retinal disease during the 9 years after delivery and total retinal diseases showed higher rates in patients with pregnancy-induced hypertension. In detail, the rates of central serous chorioretinopathy (0.3% vs 0.1%), diabetic retinopathy (1.79% vs 0.5%), retinal vein occlusion (0.19% vs 0.1%), and hypertensive retinopathy (0.62% vs 0.05%) were higher than those found in patients without pregnancy-induced hypertension. After adjusting for confounding factors, pregnancy-induced hypertension was associated with development of postpartum retinopathy, with a >2-fold increase (hazard ratio, 2.845; 95% confidence interval, 2.54-3.188). Furthermore, pregnancy-induced hypertension affected the development of central serous chorioretinopathy (hazard ratio, 3.681; 95% confidence interval, 2.667-5.082), diabetic retinopathy (hazard ratio, 2.326; 95% confidence interval, 2.013-2.688), retinal vein occlusion (hazard ratio, 2.241; 95% confidence interval, 1.491-3.368), and hypertensive retinopathy (hazard ratio, 11.392; 95% confidence interval, 8.771-14.796) after delivery. CONCLUSION: A history of pregnancy-induced hypertension increases the risk of central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, and hypertensive retinopathy according to 9-year long-term ophthalmologic follow-up.

Fuji sign: Prevalence and predictive power to photodynamic therapy in chronic central serous chorioretinopathy.

AIM: To determine the prevalence of Fuji sign in central serous chorioretinopathy (cCSC) patients and its predictive power of good response to photodynamic therapy (PDT). METHODS: Retrospective study, including 135 eyes of 130 patients diagnosed with cCSC treated with PDT between 2017 and 2021. Optical Coherence Tomography (OCT) images from these patients were compiled and analyzed. The presence of the Fuji sign, an anatomical finding recently described as a predictor of spontaneous resolution of the subretinal fluid (SRF) in cCSC, as assessed in basal images and the maximum height of SRF pre- and post-PDT OCT was measured. RESULTS: Mean age was 56.6 years, 69.4% were men and the percentage of partial or complete resolution of the SRF after PDT was 75.55%. Only 8.9% of patients (12/135) had positive Fuji sign at baseline OCT. Among them, 50% (6/12) presented a complete response to the PDT (pre-PDT SRF: 109.00 (29.61) µm), 8.3% (1/12) had a partial resolution of the SRF (127 µm to 66 µm) and 41.6% (5/12) did not respond to PDT (pre-PDT SRF: 71.00 (22.82) µm, post-PDT SRF: 83.60 (36.13) µm). CONCLUSIONS: Fuji sign has a low prevalence in cCSC and its presence is not associated with a good response to PDT.

Analysis of the pachychoroid phenotype in an Asian population: methodology and baseline study population characteristics.

AIM: To describe the clinical characteristics in a cohort of patients with the pachychoroid phenotype and to evaluate the association of ocular and systemic factors with type of complications observed. METHODS: We report baseline findings from a prospective observational study which recruited subjects with subfoveal choroidal thickness (SFCT) of ≥300 µm on spectral-domain optical coherence tomography (OCT). Multimodal imaging was used to classify eyes as uncomplicated pachychoroid (UP) or pachychoroid disease with pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC) or pachychoroid neovasculopathy (PNV) subtypes. RESULTS: Among 181 eyes of 109 participants (mean age 60.6 years, 33 (30.3%) female, 95 (7.2%) Chinese), 38 eyes (21.0%) had UP. Of 143 eyes (79.0%) with pachychoroid disease, 82 (45.3%), 41 (22.7%) and 20 (11.0%) had PPE, CSC and PNV, respectively. Addition of autofluorescence and OCT angiography to structural OCT led to reclassification of 31 eyes to a more severe category. Systemic and ocular factors evaluated, including SFCT, were not associated with disease severity. Comparison of PPE, CSC and PNV eyes showed no significant difference in OCT features of retinal pigment epithelial (RPE) dysfunction, but disruption of the ellipsoid zone (PPE 30.5% vs CSC 70.7% vs PNV 60%, p<0.001) and thinning of inner nuclear/inner plexiform layers (PPE 7.3% vs CSC 36.6% vs PNV 35%, p<0.001) were more frequent in CSC and PNV eyes. CONCLUSIONS: These cross-sectional associations suggest pachychoroid disease manifestations may reflect progressive decompensation from the choroid to the RPE then retinal layers. Planned follow-up of this cohort will be beneficial in clarifying the natural history of the pachychoroid phenotype.

Vigorous Physical Activity as a Risk Factor for Central Serous Chorioretinopathy.

PURPOSE: To evaluate whether frequent vigorous physical activity (PA) is significantly associated with active central serous chorioretinopathy (CSCR) and may represent a risk factor for CSCR. DESIGN: Case-control study. METHODS: This was a multicenter study. The patient population comprised consecutive patients with active CSCR and a comparable control group of healthy participants. Both groups were interrogated about their PA using a shortened version of the International Physical Activity Questionnaire. The Ainsworth Compendium of Physical Activities was taken as a reference for the activities requiring vigorous effort and to quantify the energy expended, expressed in metabolic equivalent of task (MET). As a main outcome measure, a moderate/high practice of vigorous PA was opposed to an absent/low practice of vigorous PA in the 2 groups. RESULTS: A total of 105 patients with CSCR and 105 healthy controls were included in the study. Moderate/high vigorous PA was observed in 63.5% of the patients with CSCR and in 26% of the controls (P = .0001). The MET values of vigorous PA were 2173.2 ± 2081.5 in the CSCR group and 1216.3 ± 524 in the control group (P = .029). The potential risk of disease associated with moderate/high vigorous PA was 5.58 (odds ratio; 95% confidence interval 3.01-10.69, P = .0001). CONCLUSIONS: This study demonstrates a significant association of vigorous PA with CSCR, indicating an increased probability of disease by 5.58 times. Frequent and intense PA, with the hypertensive episodes that it entails, can break the precarious hemodynamic balance in the choroid of individuals predisposed to CSCR, thereby favoring choroidal vascular decompensation and active disease.

A multicentre study of the risk factors associated with recurrence of central serous chorioretinopathy.

PURPOSE: To investigate potential clinical and multimodal imaging factors in central serous chorioretinopathy (CSC) recurrence. METHODS: The study was performed at nine Japanese medical institutions for patients who had experienced an active CSC episode. Demographic data and medical history were reviewed retrospectively. Significant differences in chronic manifestation, leakage site, leakage point number, leakage intensity, choroidal hyperpermeability, central retinal thickness (CRT) and subfoveal choroidal thickness were analysed between the recurrence and non-recurrence groups. RESULTS: In total, 538 eyes (538 patients) diagnosed with CSC (402 men, 136 women; mean age: 53.4 ± 11.9 years) were enrolled. Among them, 253 eyes (47.0%) developed ≥1 recurrence (follow-up: 15.9 ± 13.5 months, range 3-86 months). Univariate and multivariate analyses indicated that a history of corticosteroid use (odds ratio [OR], 5.52; 95% confidence interval [CI], 1.39-21.92; p = 0.015), bilateral disease (OR, 3.94; 95% CI, 1.47-10.6; p = 0.007), chronic manifestations (OR, 7.12; 95% CI, 2.93-17.28; p < 0.001), non-intense fluorescein leakage (OR, 3.34; 95% CI, 1.44-7.75; p = 0.005) and initial CRT (OR, 0.997; 95% CI, 0.993-0.999; p = 0.049) were significantly associated with CSC recurrence. Receiver operating characteristic curves were created, and the area under the curve for the multivariate logistic regression model of these five factors was 0.814. CONCLUSION: Patients with CSC who received corticosteroids and had bilateral disease, chronic manifestation, non-intense fluorescein leakage on fluorescein angiography or a relatively thinner CRT should be closely monitored to identify whether they are at high risk of recurrence.

RISK OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION IN PATIENTS WITH CENTRAL SEROUS CHORIORETINOPATHY: A Nationwide Cohort Study.

PURPOSE: To estimate the risk of incident age-related macular degeneration (AMD) in patients with central serous chorioretinopathy (CSC). METHODS: This population-based cohort study was finally conducted from January 2015 to December 2019. All patients with CSC from the entire population aged between 30 and 80 years were included. The incidence of CSC was estimated. Log-rank analysis and Cox proportional hazards regression analysis was used to evaluate the risk of exudative AMD in the CSC group compared with the non-CSC group. RESULTS: During a recent 5-year study period, 36,053 patients were identified as having incident CSC. The annual incidence in the latest year was 19.61 (95% confidence interval, 19.58 to 19.63) per 100,000 people. A total of 11,492 patients were included in the study group and 22,984 in the non-CSC group. The CSC and non-CSC groups included 166 (1.44%) and 73 (0.32%) cases of exudative AMD, respectively. The risk of exudative AMD was significantly higher in the CSC group than in the non-CSC group (adjusted hazard ratio: 4.86; 95% confidence interval: 2.98 to 5.88; P < 0.001). CONCLUSION: This study showed that subjects with CSC are at an increased risk of exudative AMD. This evidence supports a possible link between CSC and exudative AMD, particularly in Asian populations.

Relationship between Obstructive Sleep Apnea and Central Serous Chorioretinopathy: A Health Insurance Database Study.

PURPOSE: To evaluate the association between obstructive sleep apnea (OSA) and central serous chorioretinopathy (CSCR). METHODS: A retrospective, cohort, longitudinal study was conducted using the national health insurance database in Taiwan between 1996 and 2013. Patients diagnosed with OSA were enrolled after exclusion, and a control group with similar age, gender, and major systemic co-morbidities were included in a 1:1 ratio by propensity score matching. The primary outcome is the occurrence of CSCR, and patients with CSCR were categorized via severity for further analysis. The percentage of incident CSCR in the OSA group and control groups and the adjusted hazard ratios (aHR) of CSCR were determined by Cox proportional hazard regression. RESULTS: There were 13,084 patients enrolled in both the OSA group and control groups, respectively. The total event of CSCR was 50 (0.4%) in the OSA group and 25 (0.2%) in the control group (P < .001). Moreover, the OSA group has an increased aHR of 1.9 (P = .012) for developing CSCR. In the subgroup analysis, patients with OSA aged from 30 to 39 and 50 to 59 demonstrated higher risk of developing CSCR compared to the control group, and the presence of OSA would lead to a higher incidence of mild CSCR (all P < .05). CONCLUSIONS: OSA patients aged from 30 to 39 and 50 to 59 have a higher risk of developing CSCR, while the severity of CSCR will not be worsen by OSA.

Incidence of central serous chorioretinopathy (2011-2018): a nationwide population-based cohort study of Japan.

AIMS: The aim of this study was to elucidate the epidemiological background of central serous chorioretinopathy (CSC), including its incidence and treatment pattern. METHODS: This was a population-based longitudinal cohort study using a nationwide health insurance claims database of the Japan Ministry of Health, Labour and Welfare (MHLW). As Japan employs universal health coverage, the database covers more than 95% of claims issued in Japan. We accessed all data stored in the database with permission from the MHLW. We traced all individuals aged 30 years or older and identified individuals with new onset of CSC between January 2011 and December 2018. CSC cases were categorised by age and sex for each year, and incidence rate was calculated. We also identified major treatments for CSC to elucidate the initial treatment pattern. RESULTS: During the 8-year period, 247 930 incidences of CSC were identified, among which 75.9% were men. The crude incidence rate (per 100 000 person-years) in the general population aged 30 years or older was 34.0 (95% CI 33.9 to 34.2), in men was 54.2 (95% CI 53.9 to 54.4) and in women was 15.7 (95% CI 15.5 to 15.8). The mean age of onset was lower in men than in women (50.5±12.5 years vs 54.7±13.5 years). Most of the patients with newly diagnosed CSC (86.8%) did not receive major treatment. CONCLUSIONS: The current study provides the nationwide population-based evidence to clarify the detailed epidemiology of CSC. These results could help to understand the pathogenesis and mechanisms of CSC in the future.

Post-Traumatic Stress Disorder Is a Significant Risk Factor for Central Serous Chorioretinopathy in Male Veterans.

The primary aim of this study was to determine whether psychosocial factors, such as post-traumatic stress disorder (PTSD) and anxiety, are independently associated with the development of central serous chorioretinopathy (CSCR), a predominantly male eye disorder. A secondary aim was to verify previously determined risk factors in a veteran population. All CSCR subjects seen in one year at a veteran eye clinic were included. Chart review was performed to identify general health information as well as eye history. Univariate and multivariate analysis was performed to identify factors that were independently associated with the development of CSCR. Fifty-one cases of CSCR were identified and an additional 51 age-matched controls with healthy eyes were used for analysis. Multivariate analysis revealed that history of PTSD was strongly associated with the development of CSCR (OR = 9.43, p = .002), even more so than previously reported risk factors. Anxiety was significant at the univariate level (OR = 6.48, p = .001) but lost significance at the multivariate level. At the multivariate level, several existing risk factors were confirmed including sleep apnea (OR = 5.76, p = .004), heart disease (OR = 7.06, p = .004), smoking (OR = 5.52, p = .003) and steroid use (OR = 4.55, p = .005). PTSD was strongly associated with the development of CSCR in the veteran population studied and may represent an important modifiable risk factor.

Clinical characteristics of central serous chorioretinopathy in patients by age.

PURPOSE: To investigate the clinical characteristics of central serous chorioretinopathy (CSC) with age. STUDY DESIGN: Retrospective, cross-sectional study. METHODS: One-hundred and forty-seven CSC patients were classified into three age groups (aged <50 years (younger group; n=53), 50-70 years (middle group; n=68), and >70 years (senior group; n=26)) and the characteristics were compared. Bilateral ophthalmic evaluation included the best corrected visual acuity (BCVA), spherical equivalents, fundus examination, fundus autofluorescence, optical coherence tomography (OCT), fluorescein angiography (FA), and indocyanine green angiography. RESULTS: The male/female ratio became lower at more advanced ages (P=0.011). Bilateral macular abnormalities were observed more frequently in the senior group than the other groups (p=0.018) and multiple drusen were characteristic in the senior group (p<0.0001). The more advanced age groups displayed a worse BCVA (P=0.002). The rate of eyes with flat retinal pigment epithelium (RPE) elevation on OCT was significantly higher in the middle group than the other groups (P=0.024). The mean subfoveal choroidal thickness (SCT) was thickest in the younger group (P<0.0001). Unifocal leakage on FA and choroidal vascular hyperpermeability were mostly found in eyes of the younger group (P<0.001,P=0.020). CONCLUSION: CSC cases in those aged >70 years were associated with an increased proportion of women and having bilateral macular abnormalities, multiple drusen, and multifocal leakage sites. The BCVA and the SCT decreased with age. Patients with CSC aged 50-70 years had the highest rate of flat RPE elevation on OCT. These characteristics need to be considered to make an accurate diagnosis, particularly in elderly patients.

Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study.

BACKGROUND: Treatment options are sparse for patients with advanced cholangiocarcinoma after progression on first-line gemcitabine-based therapy. FGFR2 fusions or rearrangements occur in 10-16% of patients with intrahepatic cholangiocarcinoma. Infigratinib is a selective, ATP-competitive inhibitor of fibroblast growth factor receptors. We aimed to evaluate the antitumour activity of infigratinib in patients with locally advanced or metastatic cholangiocarcinoma, FGFR2 alterations, and previous gemcitabine-based treatment. METHODS: This multicentre, open-label, single-arm, phase 2 study recruited patients from 18 academic centres and hospitals in the USA, Belgium, Spain, Germany, Singapore, Taiwan, and Thailand. Eligible participants were aged 18 years or older, had histologically or cytologically confirmed, locally advanced or metastatic cholangiocarcinoma and FGFR2 fusions or rearrangements, and were previously treated with at least one gemcitabine-containing regimen. Patients received 125 mg of oral infigratinib once daily for 21 days of 28-day cycles until disease progression, intolerance, withdrawal of consent, or death. Radiological tumour evaluation was done at baseline and every 8 weeks until disease progression via CT or MRI of the chest, abdomen, and pelvis. The primary endpoint was objective response rate, defined as the proportion of patients with a best overall response of a confirmed complete or partial response, as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors, version 1.1. The primary outcome and safety were analysed in the full analysis set, which comprised all patients who received at least one dose of infigratinib. This trial is registered with ClinicalTrials.gov, NCT02150967, and is ongoing. FINDINGS: Between June 23, 2014, and March 31, 2020, 122 patients were enrolled into our study, of whom 108 with FGFR2 fusions or rearrangements received at least one dose of infigratinib and comprised the full analysis set. After a median follow-up of 10·6 months (IQR 6·2-15·6), the BICR-assessed objective response rate was 23·1% (95% CI 15·6-32·2; 25 of 108 patients), with one confirmed complete response in a patient who only had non-target lesions identified at baseline and 24 partial responses. The most common treatment-emergent adverse events of any grade were hyperphosphataemia (n=83), stomatitis (n=59), fatigue (n=43), and alopecia (n=41). The most common ocular toxicity was dry eyes (n=37). Central serous retinopathy-like and retinal pigment epithelial detachment-like events occurred in 18 (17%) patients, of which ten (9%) were grade 1, seven (6%) were grade 2, and one (1%) was grade 3. There were no treatment-related deaths. INTERPRETATION: Infigratinib has promising clinical activity and a manageable adverse event profile in previously treated patients with locally advanced or metastatic cholangiocarcinoma harbouring FGFR2 gene fusions or rearrangements, and so represents a potential new therapeutic option in this setting. FUNDING: QED Therapeutics and Novartis.

Increased risk for central serous chorioretinopathy in nephrotic syndrome patients: A population-based cohort study.

BACKGROUND: Nephrotic syndrome (NS) is characterized by various etiologies that damage the glomerulus. Central serous chorioretinopathy (CSCR) is a retinal disease characterized by neurosensory detachment of the retina. Several case reports have described the relationship between both. Therefore, we try to analyze the epidemiological associations between NS and CSCR using the National Health Insurance Research Database in Taiwan. METHODS: Data spanning 14 years were extracted from the National Health Insurance Research Database and sub-grouped. The variables were analyzed using Pearson's chi-squared test and Fisher's exact test. The risk factors for disease development with or without comorbidities were examined using an adjusted hazard ratio (aHR). Kaplan-Meier analysis was performed to evaluate the cumulative incidence of CSCR with or without NS. RESULTS: A total of 14 794 patients with NS and 14 794 matched controls without NS were enrolled in this cohort study. The incidence rate of CSCR was higher in the study cohort than in the control cohort (aHR = 3.349, p < 0.001). The overall incidence of CSCR was 44.51 per 100 000 person-years in the study cohort and 33.39 per 100 000 person-years in the control cohort. In both groups, CSCR occurred more frequently in males than in females. Patients aged 40-49, 50-59, and ≥60 years in the study cohort had a significantly higher risk of developing CSCR than those in the control cohort (aHR = 3.445, 5.421, and 4.957, all p < 0.001). NS patient with a 4-week history of steroid usage has a higher risk of developing CSCR (aHR = 2.010, p < 0.001). CONCLUSION: Our data showed that patients with NS have an increased risk of developing subsequent CSCR. Physician should routinely refer their NS patients to ophthalmologist for ophthalmic evaluation. This is the first nationwide epidemiological study reporting the association between these two diseases. Further studies are needed to clarify this relationship.