TNFRSF10A downregulation induces retinal pigment epithelium degeneration during the pathogenesis of age-related macular degeneration and central serous chorioretinopathy.

Age-related macular degeneration (AMD) and central serous chorioretinopathy (CSC) are common diseases that can cause vision loss in older and younger populations. These diseases share pathophysiological conditions derived from retinal pigment epithelium (RPE) dysfunction. Tumor necrosis factor receptor superfamily 10A (TNFRSF10A)-LOC389641 with the same lead single-nucleotide polymorphism (SNP) (rs13278062) is the only overlapped susceptibility locus found in both AMD and CSC through genome-wide association studies. This lead SNP has been reported to alter the transcriptional activity of TNFRSF10A. This study aimed to elucidate the function of TNFRSF10A in RPE degeneration using human primary RPE cells and Tnfrsf10 knockout (Tnfrsf10-/-) mice. TNFRSF10A was found to be localized in human RPE. In vitro assays revealed that a T allele of rs13278062, the risk allele for AMD and CSC, downregulated TNFRSF10A transcription in RPE, leading to decreased cell viability and increased apoptosis through protein kinase C-α (PKCA) downregulation. Treatment with phorbol 12-myristate 13-acetate, a PKC activator, rescued the cell viability. Morphological RPE abnormality was found in the retina of Tnfrsf10-/- mice. Our data suggest that downregulation of TNFRSF10A expression inactivates PKCA signaling and causes cellular vulnerability of the RPE, which may contribute to the pathogenesis of AMD and CSC.

Factors affecting resolution of subretinal fluid after selective retina therapy for central serous chorioretinopathy.

The purpose of this study was to investigate the factors of clinical outcome of selective retina therapy (SRT) for central serous chorioretinopathy (CSC). This retrospective study included 77 eyes of 77 patients, who were treated with SRT for CSC and observed at least 6 months after the treatment. SRT laser (527 nm, 1.7 µs, 100 Hz) was used for treatment. The mean best-corrected visual acuity (logMAR), central macular thickness (CMT) and central choroidal thickness were changed from baseline to at 6-months follow-up with significant difference. The multivariate analyses found that the rate of change (reduction) in CMT was associated with focal leakage type on fluorescein angiography (FA) (p = 0.03, coefficient 15.26, 95% confidence interval 1.72-28.79) and larger baseline CMT (p < 0.01, coefficient - 0.13, 95% confidence interval - 0.13 to - 0.05). Complete resolution of subretinal fluid was associated with nonsmoking history (p = 0.03, odds ratio 0.276, 95% confidence interval 0.086-0.887) and focal leakage type on FA (p < 0.01, odds ratio 0.136, 95% confidence interval 0.042-0.437). These results may be useful for predicting the therapeutic effectiveness of SRT.

Levels of the oxidative stress biomarker malondialdehyde in tears of patients with central serous chorioretinopathy relate to disease activity.

Purpose: Central serous chorioretinopathy (CSCR) has been associated with oxidative stress-related risk factors. The objective of this study was to optimize an analytical method for evaluating the oxidative stress biomarker malondialdehyde (MDA) in human tears and determine its level in the tears of patients with CSCR. Methods: In this pilot study, tear samples were obtained from 34 healthy donors and 31 treatment-naïve CSCR male patients (eight with acute CSCR and 23 with chronic CSCR). Two analytical methods based on high-performance liquid chromatography followed by fluorescence detection were evaluated, with either 2-thiobarbituric derivative (TBA) or 2-aminoacridone (2-AA). Activity of CSCR was defined by the serous retinal detachment (SRD) height, which was measured by two independent observers on spectral-domain optical coherence tomography. Results: The 2-AA method showed higher sensitivity and precision compared to the TBA method. When the 2-AA method was applied to tears from healthy donors, the levels of MDA were statistically significantly higher in men compared to women (mean ± standard deviation, SD: 9,914 nM ± 6,126 versus 4,635 nM ± 1,173, p = 0.006). No difference was found in tear MDA levels between male patients with CSCR and age-matched control men (p = 0.17). However, MDA levels were statistically significantly higher in acute compared to chronic CSCR cases (mean ± SD: 12,295 nM ± 8,495 versus 6,790 ± 3,969 nM, p = 0.03). Additionally, there was a correlation between MDA levels and RPE leakage, quantified by the height of the serous retinal detachment (p = 0.02, r = 0.40). Conclusions: Levels of MDA in tears, measured with an optimized analytical method, correlate with RPE leakage in CSCR.

Genetic factors associated with treatment response to reduced-fluence photodynamic therapy for chronic central serous chorioretinopathy.

Purpose: Reduced-fluence photodynamic therapy (RFPDT) has proven effective for some patients with chronic central serous chorioretinopathy (cCSC). Several clinicodemographic factors influencing treatment response have been identified, but associations with genetic factors have not been examined. Therefore, we investigated the associations of single nucleotide polymorphisms (SNPs) implicated in cCSC pathogenesis with clinical outcome following RFPDT. Methods: This was a retrospective study of 87 eyes from 87 patients with cCSC who underwent RFPDT and were followed up for more than 12 months. Patients were divided into a good response group (53 patients) and a poor response group (34 patients) based on either persistence or recurrence of subretinal fluid detected with spectral domain optical coherence tomography after the first application of RFPDT. SNPs in the genes encoding age-related maculopathy susceptibility protein 2 (ARMS2, SNP rs10490924) and complement factor H (CFH, SNP rs800292) were genotyped using TaqMan technology. Results: There were no statistically significant differences in the baseline characteristics between the response groups except the degree of hyperfluorescence on indocyanine green angiography (ICGA; p = 0.011). The minor (T) allele frequency of ARMS2 (rs10490924) were statistically significantly lower in the good response group than in the poor response group (24.0% versus 41.0%, p = 0.021). Further, the good response frequency was statistically significantly lower in patients with at least one minor allele (GT or TT) compared to the homozygous major allele group (GG; p<0.05). The baseline best-corrected visual acuity (BCVA) at 12 months after RFPDT was statistically significantly better in the GG carriers than in the GT or TT carriers (p<0.01). Logistic regression analysis showed less intense hyperfluorescence on ICGA, and the T allele of ARMS2 (rs10490924) was statistically significantly associated with poor response to PDT treatment (p = 0.012, p = 0.039, respectively). Conclusions: Carriers of the ARMS2 rs10490924 minor allele (GT or TT) demonstrated a higher subretinal fluid persistence or recurrence rate and poorer visual outcome following RFPDT. In addition to the ICGA findings, genotyping of ARMS2 (rs10490924) may assist in the selection of patients with cCSC most likely to benefit from RFPDT.

Differences in anti-endothelial and anti-retinal antibody titers: implications for the pathohysiology of acute and chronic central serous chorioretinopathy.

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 (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.

Association between CFH single nucleotide polymorphisms and response to photodynamic therapy in patients with central serous chorioretinopathy.

PURPOSE: To evaluate the association between single nucleotide polymorphisms (SNPs) in the complement factor H (CFH) gene and response to PDT in patients with CSC. METHODS: 103 eyes from 93 patients with CSC were enrolled from Department of Ophthalmology of the People's Hospital Peking University. Genotyping for selected SNPs in the CFH gene was performed, and multivariate linear analysis was used to identify factors influencing PDT treatment outcomes. Genetics associations between SNPs in the CFH gene and response to PDT in patients with CSC were analyzed. RESULTS: None of the seven SNPs examined in this study (rs800292, rs1061170, rs3753394, rs3753396, rs2284664, rs1329428, and rs1065489) showed significant associations with 1-month outcomes after PDT in patients with CSC (P > 0.05). Baseline BCVA changed at 1 month after PDT (P < 0.001), and baseline retinal thickness was associated with changes in retinal thickness at 1 month after PDT (P < 0.001). Age was significantly associated with resolution of SRF at 1 month after PDT (P = 0.004). CONCLUSIONS: There were no significant associations between SNPs in the CFH gene and 1-month outcomes after PDT in patients with CSC. However, baseline BCVA, baseline retinal thickness, and age were significantly associated with response to PDT in patients with CSC. Larger studies with more power are necessary to further determine whether an association exists between SNPs in the CFH gene and PDT in patients with CSC.

RELATIONSHIP BETWEEN CHOROIDAL VASCULAR HYPERPERMEABILITY, CHORIOCAPILLARIS FLOW DENSITY, AND CHOROIDAL THICKNESS IN EYES WITH PACHYCHOROID PIGMENT EPITHELIOPATHY.

PURPOSE: To use swept-source optical coherence tomography and swept-source optical coherence tomography angiography to investigate potential relationships between choroidal vascular hyperpermeability (CVH) seen with indocyanine green angiography (ICGA), choriocapillaris flow density, and choroidal thickness in eyes with pachychoroid pigment epitheliopathy. METHODS: Patients with pachychoroid pigment epitheliopathy were prospectively imaged with 12-mm × 12-mm swept-source optical coherence tomography, 12-mm × 12-mm swept-source optical coherence tomography angiographyA, and ICGA. Binarized choriocapillaris OCTA images were superimposed with ICGA images in which CVH area had been isolated. Choriocapillaris flow density within or outside the quadrants of CVH was calculated and the ratio of these two values was determined. The presence of CVH and choroidal thickness was evaluated at 9 locations within a central 3-mm × 3-mm area to explore the relationship between these 2 factors. RESULTS: Ten eyes from 10 patients were enrolled in the present study. Choriocapillaris flow density within quadrants of CVH area was significantly lower compared with quadrants without CVH (P < 0.001). The mean choriocapillaris flow density ratio was 0.86 ± 0.10 (range: 0.65-0.99). From among the 90 locations in 10 study eyes, 48 were within areas of CVH. Choroidal thickness was greater in quadrants of CVH compared with areas without CVH (P < 0.001, 455 ± 122 µm vs. 297 ± 93 µm). CONCLUSION: Reduced choriocapillaris flow density, increased choroidal thickness, and CVH appear to co-localize in eyes with pachychoroid pigment epitheliopathy.

Hair cortisol concentrations in chronic central serous chorioretinopathy.

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 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.

Quetiapine associated Central Serous Chorioretinopathy: Implicit role of serotonin and dopamine pathways.

A 30-year-old insomniac, an off-label user of quetiapine, presented with blurring of central vision, eventually diagnosed as central serous chorioretinopathy. A potential association was suspected based on the drug's actions on the autonomic nervous system. He showed improvement on drug withdrawal; then he unwittingly resumed quetiapine and had a recurrence. Possible underlying mechanisms that include alteration in choroidal perfusion through serotonin and dopamine receptors are discussed. Although retinal vein occlusions and pigment epithelial detachment have been described with quetiapine, to the author's knowledge, this is the first case report of quetiapine-associated central serous chorioretinopathy.

CHOROIDAL THICKENING AND PACHYCHOROID IN CUSHING SYNDROME: Correlation With Endogenous Cortisol Level.

PURPOSE: To investigate subfoveal choroidal thickness and pachychoroid and their correlation with hormone level in patients with endogenous Cushing syndrome (CS). METHODS: We enrolled a consecutive series of patients with CS and healthy controls. All participants had swept-source optical coherence tomography. All patients with CS had hormone test including morning plasma-free cortisol, 24-hour urine-free cortisol (24UFC), and plasma adrenocorticotropic hormone. We compared subfoveal choroidal thickness and pachychoroid changes between two groups. We performed univariate and multivariate analysis to study correlation between hormone level and choroid thickness as well as pachychoroid in patients with CS. RESULTS: Compared with control group, Cushing group had significantly greater subfoveal choroidal thickness (371.6 ± 114.9 and 320.0 ± 74.0, P = 0.002) and higher proportion of eyes with pachychoroid (53.1 and 14.3%, P < 0.001). Subfoveal choroidal thickness was significantly correlated with 24UFC (P = 0.007) but not with plasma-free cortisol (P = 0.48) or adrenocorticotropic hormone (P = 0.56). Pachychoroid was significantly correlated with 24UFC (P = 0.03) but not with plasma-free cortisol (P = 0.24) or adrenocorticotropic hormone (P = 0.32). CONCLUSION: There was a positive correlation between elevated 24UFC and choroid thickening as well as pachychoroid, indicating the importance of normal endogenous cortisol level in maintaining the human choroid vasculature.

Hair cortisol concentration in patients with active central serous chorioretinopathy is elevated - a pilot study.

PURPOSE: To investigate hair cortisol concentration (HCC), a biochemical correlate of long-term cortisol output patterns, and its relationship to active central serous chorioretinopathy (CSC). METHODS: Twenty-six participants were included in this observational pilot study (11 patients with active CSC and 15 healthy controls). Hair cortisol concentrations (HCCs) were determined from 3 cm hair strands collected near the scalp from patients and controls as an index of cumulative cortisol secretion over the 3-month period prior to hair sampling. RESULTS: Patients with CSC exhibited higher HCCs (mean value: 20.14, 95% CI: 14.89-27.16 pg/mg) than healthy controls (mean value: 11.06, 95% CI: 8.63-14.22 pg/mg, p = 0.008). Group differences were not affected by relevant covariates (BMI, smoking status, sex). CONCLUSION: Patients with active CSC have increased HCC, supporting the fact that cortisol is a major player in CSC pathogenesis.

Association of Upregulated Angiogenic Cytokines With Choroidal Abnormalities in Chronic Central Serous Chorioretinopathy.

Purpose: To clarify the distinct molecular pathogenesis of central serous chorioretinopathy (CSC) and pachychoroid neovasculopathy (PNV). Methods: Aqueous humor (AH) was collected from 18 acute CSC, 20 chronic CSC, and 20 PNV patients. Concentrations of 30 cytokines in the AH were analyzed using a multiplex bead immunoassay, and the cytokine profiles were compared among these three groups of patients. The areas of choroidal vascular hyperpermeability (CVH) and choroidal thickness (CT), including measurement of the vascular layers, were investigated to analyze the features of choroidal abnormality in acute CSC, chronic CSC, and PNV. Additionally, associations between cytokine profiles and choroidal abnormalities were analyzed. Results: Proinflammatory cytokines, IL-6 and IL-8 were significantly upregulated in the chronic CSC group compared with the acute CSC or PNV groups. Angiogenic cytokines and VEGF-A were upregulated at levels that almost reached significance along with disease progression from acute to chronic CSC, whereas the upregulation was not significant from chronic CSC to PNV. In the chronic CSC group, strong positive correlations were confirmed between VEGF-A and placental growth factor (PlGF) (r = 0.75, P < 0.001) and IL-6 and VEGF-A (r = 0.74, P < 0.001), and angiogenesis-related cytokines were positively correlated with the typical choroidal abnormalities, areas of CVH, mean CT, and mean large choroidal vessel layer thickness. However, there was no association between these choroidal abnormality parameters and AH cytokines in the PNV group. Conclusions: The results suggest that choroidal abnormalities in chronic CSC may be associated with upregulated angiogenesis.

Macular pigment density changes in central serous chorioretinopathy.

Aim: To present a series of 2 cases of central serous chorioretinopathy and the changes in the macular pigment optical density during the evolution of the disease. Material and methods: A 32-year-old patient presented himself for blurred vision on his LE. The SD OCT imaging revealed serous macular detachment of the neurosensory retina on the LE. The MPOD results were 0.72 on RE and 0.91 on LE. After treatment and resorption of the subretinal fluid, the MPOD values were 0.72 on the RE and 0.82 on the LE. The second patient was a 36-year-old male with metamorphopsia on LE and serous macular detachment on this eye. The MPOD results were 0.43 on RE and 0.58 on the LE and, after treatment, they were 0.38 on the RE and 0.43 on the LE. Conclusions: Central serous chorioretinopathy is a disease of unknown pathophysiology in which we observed a higher MPOD on the eye with CSC than on the fellow eye and a decrease in the MPOD value after the resorption of the subretinal fluid. Abbreviations: L = lutein, Z = zeaxantin, MZ = mezozeaxantin, AMD = age related macular degeneration, MPOD = macular pigment optical density, MP = macular pigment, HFP = Heterochromatic Flicker Photometry, CSC = central serous chorioretinopathy, RE = right eye, LE = left eye.

Navigated laser photocoagulation in patients with non-resolving and chronic central serous chorioretinopathy.

PURPOSE: To evaluate the efficacy of navigated focal laser photocoagulation in patients with chronic central serous chorioretinopathy (CSCR) and active leakage on fluorescein angiography (FA). METHODS: Thirty-two eyes of 32 patients (age 48 ± 11, m/f = 24/8) with persistent or recurrent CSCR (> 3 months) who received navigated laser photocoagulation (Navilas®) of leaking point(s) between June 2013 and 2016 were included in this retrospective case series. Outcome parameters after 4 weeks and 3 months were the number of patients presenting with complete resolution of subretinal fluid, the volume of subretinal fluid measured on SD-OCT (Spectralis Heidelberg Engineering©), and best corrected visual acuity (BCVA/ (Snellen equivalent). RESULTS: Complete resolution of subretinal fluid was achieved in 17 eyes (50%) after 4 weeks and in 24 eyes (75%) after 3 months with an average number of 1.3 laser procedures (range 1-3). Five eyes displayed a nearly complete resolution with a reduction of over 80% of the subretinal fluid compared to baseline. Three eyes showed no reduction in subretinal fluid. BCVA improved from median 0.58 (range 0.16-1.25) to 0.66 (0.16-1.0) (p = 0.001). The seven patients who had been treated within the central 1 mm of the ETDRS-OCT Grid but outside the avascular foveal zone showed an improvement of BCVA from median 0.6 (range 0.2-1.0) to 0.8 (0.2-1.0). No patient experienced a treatment-induced visual loss. CONCLUSIONS: Laser treatment with Navilas® using eye tracking and FA-based planning is a safe and effective alternative therapy in patients with chronic CSCR.

A novel marker in acute central serous chorioretinopathy: thiol/disulfide homeostasis.

PURPOSE: The aim of this study was to compare dynamic thiol/disulfide homeostatic status in acute central serous chorioretinopathy (CSCR) patients by using a novel and automated assay determining dynamic thiol/disulfide homeostasis. METHODS: Fifty-one patients with acute CSCR (study group) and 65 healthy individuals (control group) were enrolled in this study. Diagnosis of acute CSCR was made clinically and using spectral-domain RTVue OCT (optical coherence tomography) (Optovue, Fremont, CA). Fluorescein angiography confirmed the diagnosis of acute CSCR in all subjects. Total thiol, native thiol, disulfide amount, and native thiol/disulfide ratio (TDR) were calculated in the blood samples. RESULTS: Mean total thiol, native thiol, and native TDR values were lower in patients with acute CSCR (364.2 ± 14.1, 326.4 ± 13.2, 17.14 ± 1.9, respectively) than in healthy eyes (441.2 ± 16.3, 398.5 ± 16.4, 22.70 ± 2.15, respectively; mean total thiol, p = 0.017; native thiol, p = 0.011; native TDR, p = 0.031). CONCLUSIONS: Total thiol, native thiol, and native TDR were significantly lower statistically in patients with acute CSCR when compared with healthy controls.

Association of a Haplotype in the NR3C2 Gene, Encoding the Mineralocorticoid Receptor, With Chronic Central Serous Chorioretinopathy.

Importance: Chronic central serous chorioretinopathy (cCSC) is a chorioretinal disease with unknown disease etiology. The glucocorticoid receptor and the mineralocorticoid receptor, 2 glucocorticoid-binding receptors, might be involved in the pathogenesis of cCSC. Objective: To assess the association of functional variants and haplotypes in the glucocorticoid receptor (NR3C1) and mineralocorticoid receptor (NR3C2) genes with cCSC. Design, Setting, and Participants: In this case-control genetic association study, 336 patients with cCSC and 1314 unaffected controls, collected at 3 university medical centers from September 1, 2009, to May 1, 2016, underwent KASP genotyping for selected variants in NR3C1 (rs56149945, rs41423247, and rs6198) and NR3C2 (rs2070951 and rs5522). Main Outcomes and Measures: Genetic associations of 3 NR3C1 variants and 2 NR3C2 variants with cCSC. Results: Among the 336 patients (274 men and 62 women; mean [SD] age, 52 [10] years), after correction for multiple testing, rs2070951 in the NR3C2 gene was significantly associated with cCSC (odds ratio, 1.29; 95% CI, 1.08-1.53; P = .004). Moreover, the GA haplotype of single-nucleotide polymorphisms rs2070951 and rs5522 in NR3C2 conferred risk for cCSC (odds ratio, 1.39; 95% CI, 1.15-1.68; P = .004), whereas the CA haplotype decreased risk for cCSC (odds ratio, 0.72; 95% CI, 0.60-0.87; P < .001). Three known variants in NR3C1 that alter the activity of the glucocorticoid receptor (rs56149945, rs41423247, and rs6198) were not associated with cCSC. Conclusions and Relevance: In this study, the variant rs2070951 and the GA haplotype in NR3C2 were associated with an increased risk for cCSC. Results of this genetic study support a possible role for the mineralocorticoid receptor in the pathogenesis of cCSC. Since these haplotypes have previously been associated with perceived stress, this study provides a clue to bridging clinical risk factors for cCSC to underlying genetic associations.

A Multicenter Study on the Long-term Outcomes of Half-dose Photodynamic Therapy in Chronic Central Serous Chorioretinopathy.

PURPOSE: To investigate long-term efficacy and prognostic factors of half-dose photodynamic therapy (PDT) in chronic central serous chorioretinopathy (CSCR). DESIGN: Retrospective multicenter interventional case series. METHODS: Patients with chronic CSCR undergoing half-dose PDT between 2005 and 2011 were reviewed. Main outcome measures included resolution of serous retinal detachment (SRD) with single PDT, change in best-corrected visual acuities (BCVAs), and recurrence rate of CSCR at 36 months after PDT. Prognostic factors of visual outcome and recurrence of CSCR after PDT were identified with multivariate regression analysis. RESULTS: A total of 136 eyes of 123 patients were followed up for 57.7 ± 16.2 months. At 36 months after PDT, 132 eyes (97.1%) achieved complete resolution of SRD with single PDT and 4 eyes (2.9%) had CSCR recurrence. The mean logMAR BCVA improved from 0.36 ± 0.29 (Snellen equivalent 20/46; range: 0.1-1.2) at baseline to 0.15 ± 0.23 at 36 months (Snellen equivalent 20/28; range: 0.1-1.5; P < .001) and 0.16 ± 0.24 (Snellen equivalent: 20/29; range: 0.1-1.5; P < .001) at final follow-up. Forty-four eyes (32.4%) had ≥3 lines of BCVA gain while 5 eyes (3.7%) had ≥3 lines of BCVA loss at 36 months after PDT. Nine eyes (6.6%) developed CSCR recurrence at final follow-up. Baseline BCVA was significantly associated with the BCVA (P = .009) and the improvement in BCVA (P < .001) at final follow-up. History of bilateral CSCR was significantly associated with CSCR recurrence at final follow-up (P = .036; odds ratio = 15.84, 95% confidence interval = 1.20-208.32). Eight eyes (5.9%) had complications related to PDT. CONCLUSIONS: Chronic CSCR patients treated with half-dose PDT can achieve long-term stable visual acuity and resolution of SRD. Patients with chronic CSCR are recommended to undergo half-dose PDT before they have significant visual deterioration. Patients with bilateral CSCR are more likely to develop CSCR recurrence after half-dose PDT.