Expression of nuclear receptor co­activator 7 protein is associated with poor prognosis of breast cancer.

Nuclear receptor coactivator 7 (NCOA7) is an estrogen receptor binding protein. Its role in breast cancer progression has so far remained elusive. The present study aimed to determine the expression levels of NCOA7 in breast tumor samples and confirmed its potential utility as a breast cancer prognostic biomarker. The expression of NCOA7 was detected by immunohistochemical staining in 241 breast cancer tumor samples and 163 adjacent normal tissue samples. The association of NCOA7 expression with the clinicopathological characteristics and overall survival were statistically analyzed. Cell proliferation was determined by Cell Counting Kit-8 and colony-formation assays. Cell migration was detected using wound-healing and Transwell assays. NCOA7 was positively expressed in 44% of breast tumor tissues. The expression of NCOA7 was positively associated with tumor size (T-stage; P=0.005) and lymph node metastasis (N-stage; P=0.008). Additional statistical analysis indicated that the expression of NCOA7 was associated with patient age, tumor size and lymph node metastasis in patients with triple-negative breast cancer (TNBC) compared with that in patients with non-TNBC. The overall survival of patients with NCOA7-positive breast cancer was significantly lower than that of patients with NCOA7-negative breast cancer (P=0.006). Among the patients with lymph node metastasis, the overall survival was reversely associated with the expression of NCOA7 (P=0.042). Furthermore, knockdown of NCOA7 expression in breast cancer T47D and MCF7 cells significantly inhibited both cell proliferation and migration, suggesting that this protein may exert a role in driving breast cancer progression. Taken together, these results indicate that the expression of NCOA7 is associated with poor prognosis of breast cancer and suggest that this protein may be a driver for metastasis and a potential therapeutic target for advanced breast cancer.

A clinical study of liposuction followed by lymphovenous anastomosis for treatment of breast cancer-related lymphedema.

Objective: In this work, we studied the clinical effect of liposuction followed by lymphovenous anastomosis (LVAs) for the treatment of breast cancer-related lymphedema (BCRL). Methods: We analyzed 158 patients with unilateral upper limb BCRL who underwent liposuction followed by LVAs 2-4 months later. Arm circumferences before and 7 days after the combined treatments were prospectively recorded. Circumferences of different upper extremities were measured before the procedure, 7 days after LVAs, and during the follow-ups. Volumes were calculated with the frustum method. During the follow-ups, the conditions of patients' treated arms, i.e., the frequency of erysipelas episodes and dependence on compression garments, were recorded. Results: The mean circumference difference between two upper limbs decreased significantly from M (P25, P75) of 5.3 (4.1, 6.9) preoperatively to 0.5 (-0.8, 1.0) (P < 0.05) 7 days after treatments, while at follow-up 0.3 (-0.4, 1.0). The mean volume difference decreased significantly from M (P25, P75) of 838.3 (662.4, 1,129.0) preoperatively to 7.8 (-120.3, 151.4) (P < 0.05) 7 days after treatments, while at follow-up 43.7 (-59.4, 161.1). The incidence of erysipelas also significantly decreased (P < 0.05). 6.3% of patients were already independent of compression garments during the past six months or even more. Conclusion: Liposuction followed by LVAs is an effective method for the treatment of BCRL.

Phospholipase A2 (PLA2) injured lymphatic endothelial cells leading to progression of secondary lymphoedema.

Secondary lymphoedema is one of the common complications after lymph node dissection for gynecologic malignancies and breast cancer. In this study, the relationship between PLA2 and postoperative lymphoedema in cancer at the molecular level has been explored through transcriptomics and metabolomic assays. Transcriptome sequencing technology, as well as metabolomic assays, were utilized to explore the expression of PLA2 in lymphoedema patients, and search for potential pathways in the pathogenesis and exacerbation mechanism of lymphoedema. The effect of sPLA2 on human lymphatic endothelial cells was investigated by culturing human lymphatic endothelial cells. Secretory phospholipases A2 (sPLA2) showed high expression levels in lymphoedema tissues, however, cytoplasmic phospholipases A2 (cPLA2), showed low expression in lymphoedema, as demonstrated by RT-qPCR. By culturing human lymphatic vascular endothelial cells, the study found that sPLA2 causes HLEC vacuolization and has an inhibitory effect on HLEC proliferation and migration. By detecting sPLA2 in the serum of lymphoedema patients and analyzing clinical data, it was found that sPLA2 was positively correlated with the severity of lymphoedema. Secretory Phospholipase A2 (sPLA2) is highly expressed in lymphoedema tissue, damages lymphatic vessel endothelial cells, is strongly associated with disease severity, and can be used as a potential predictor of disease severity.Abbreviations: PLA2: Phospholipase A2; DEGs: differentially expressed genes; DMP: differential metabolic production.

ETS1 is a prognostic biomarker of triple-negative breast cancer and promotes the triple-negative breast cancer progression through the YAP signaling.

E26 transcription factor-1 (ETS1) is involved in extracellular matrix remodeling, migratory infiltration and angiogenesis in tumors and known to play an important role in tumor progression. However, the mechanism by which ETS1 promotes tumor progression remains elusive. In this report, we show that ETS1 is highly expressed in breast tumor tissues and specifically associated with the tumor metastasis and poor survival in triple negative breast cancer (TNBC) tumors, upon analysis by immunohistochemical (IHC) staining of tumor samples from 240 breast cancer cases. Depletion of ETS1 in TNBC cells by shETS1 significantly inhibited the cell proliferation and migration. Mechanistically, knockdown of ETS1 in TNBC cells dramatically reduced expression of YAP and the YAP target genes, and overexpression of YAP in the ETS1 knockdown cells restored the cell proliferation and migration. These data indicate that YAP is a downstream effector mediating the ETS1-promoted TNBC cell proliferation and migration. Taken together, our results suggest that ETS1 promotes TNBC progression through the YAP signaling.

Bioinformatics analysis of inflammation and oncology in pulmonary lymphangioleiomyomatosis.

This study investigates the molecular markers and biological pathways of pulmonary lymphangioleiomyomatosis. We analyzed 2 gene expression profiles in the gene expression omnibus Gene Expression Omnibus database for normal lung tissue and lymphangioleiomyomatosis and identified differential expressed genes in pulmonary lymphangioleiomyomatosis. Ninety-one differentially expressed genes were identified, including 36 upregulated genes and 55 downregulated genes. Hub genes and pathogenic pathways associated with disease development were subsequently identified by enrichment analysis and protein-protein interaction network. Analysis showed that differential expressed genes are mainly involved in the biological behavior of tumor cell proliferation and invasion as well as the inflammatory response. We have identified 10 hub genes in the protein-protein interaction network. Hub genes play an important role in the proliferation and inflammatory response involved in tumor cell proliferation. This study deepens the understanding of lymphangioleiomyomatosis disease and provides a biological basis for further clinical diagnosis and treatment.

Estrogen Receptor Bio-Activities Determine Clinical Endocrine Treatment Options in Estrogen Receptor-Positive Breast Cancer.

In estrogen receptor positive (ER+) breast cancer therapy, estrogen receptors (ERs) are the major targeting molecules. ER-targeted therapy has provided clinical benefits for approximately 70% of all breast cancer patients through targeting the ERα subtype. In recent years, mechanisms underlying breast cancer occurrence and progression have been extensively studied and largely clarified. The PI3K/AKT/mTOR pathway, microRNA regulation, and other ER downstream signaling pathways are found to be the effective therapeutic targets in ER+ BC therapy. A number of the ER+ (ER+) breast cancer biomarkers have been established for diagnosis and prognosis. The ESR1 gene mutations that lead to endocrine therapy resistance in ER+ breast cancer had been identified. Mutations in the ligand-binding domain of ERα which encoded by ESR1 gene occur in most cases. The targeted drugs combined with endocrine therapy have been developed to improve the therapeutic efficacy of ER+ breast cancer, particularly the endocrine therapy resistance ER+ breast cancer. The combination therapy has been demonstrated to be superior to monotherapy in overall clinical evaluation. In this review, we focus on recent progress in studies on ERs and related clinical applications for targeted therapy and provide a perspective view for therapy of ER+ breast cancer.

Geranylgeranylation signaling promotes breast cancer cell mitosis via the YAP-activated transcription of kinetochore/centromere genes.

Geranylgeranylation signaling plays an important role in cancer cell proliferation. Our previous studies have shown that the YAP is one of the geranylgeranylation signal transducers in breast cancer cells (Mi W, et al., Oncogene. 2015; 34(24): 3095-3106). However, the downstream effectors that mediate the promoting effect of the geranylgeranylation/YAP signal axis on breast cancer cell proliferation remain elusive. In this report, we investigated the pathway that mediates the effect of the geranylgeranylation on breast cancer cell proliferation. The results have shown that inhibition of geranylgeranyl biosynthesis inactivates transcription of a set of kinetochore/centromere genes. Further biochemical and cell biological studies demonstrated that inhibition of geranylgeranyl biosynthesis significantly reduced the level of key kinetochore/centromere proteins, thus caused a defect in mitosis. Knockdown of YAP caused similar inhibitory effects on the kinetochore/centromere gene expression and mitosis to that of inhibition of geranylgeranyl biosynthesis. Furthermore, we found that E2F1, the gene coding for E2F1 that is known to activate expression of cell cycle genes, is a target gene of YAP. Knockdown of E2F1 also reduced expression of the kinetochore/centromere genes, suggesting that the activation effect of YAP on expression of the kinetochore/centromere genes may be mediated by E2F1. Our studies have proposed a novel geranylgeranylation-dependent cancer cell proliferation signaling pathway in which geranylgeranylation signaling promotes cancer cell mitosis via the YAP-activated transcription of kinetochore/centromere genes.

Liposuction in cancer-related lower extremity lymphedema: an investigative study on clinical applications.

BACKGROUND: Lymphedema is a progressive, noncurable condition consisting of increases in subcutaneous fat and interstitial fluid in the limbs and fibrosis during later stages. The disease most commonly affects the limbs following injury to or removal of the lymph nodes. The aim of this study was to investigate the therapeutic outcomes of liposuction for cancer-related lower extremity lymphedema. METHODS: Sixty-two patients with cancer-related lymphedema in the unilateral lower extremity were recruited for this study, and all patients underwent liposuction. The volume of hemorrhage and lipids, the operation time, and the volume changes of the affected extremity were compared by applying the t tests, and the subjective feelings of patients were compared with the chi-square tests. RESULTS: The total lipid volume was 2539 ± 1253.5 ml, and the hemorrhage volume was 828 ± 311.8 ml. For the comparison of objective indices, (1) the percent volume differences (PVDs) before surgery, intraoperatively, and at the 3-month follow-up were 5.5 ± 12.2 vs. 11.6 ± 18.4 vs. 43.2 ± 23.7, P < 0.05, respectively; (2) greater lipid volumes and higher liposuction rates were observed for female patients, as was a smaller volume of hemorrhage; (3) greater hemorrhage volumes were observed in patients with a history of recurrent erysipelas; and (4) greater lipid volumes and liposuction rates (LRs) and smaller hemorrhage volumes were observed for stage II than for stage III patients. CONCLUSIONS: Liposuction is an effective therapy for cancer-related lower extremity lymphedema. Sex, stage, and recurrent erysipelas history influence the course and effect of liposuction.

MEKK5 Interacts with and Negatively Regulates the E3 Ubiquitin Ligase NEDD4 for Mediating Lung Cancer Cell Migration.

Our previous studies have shown that the HECT E3 ubiquitin ligase NEDD4 and kinase MEKK5 both play an essential role in lung cancer migration. A report predicts that MEKK5 may be ubiquitinated by NEDD4; however, interaction of MEKK5 with NEDD4 and ubiquitination of MEKK5 by NEDD4 have not been characterized. In this report, we show that NEDD4 interacts with MEKK5 through a conserved WW3 domain by the co-immunoprecipitation and the GST-pulldown assays. The ubiquitination assay indicates that MEKK5 is not a ubiquitination substrate of NEDD4, but negatively regulates NEDD4-mediated ubiquitination. Furthermore, overexpression of MEKK5 significantly reduced the NEDD4-promoted lung cancer cell migration. Taken together, our studies have defined an inhibitory role of MEKK5 in regulation of NEDD4-mediated ubiquitination.

[Analysis of DNAH1 gene variant in two infertile males with multiple morphological abnormalities of sperm flagella].

OBJECTIVE: To explore the clinical feature and gene variant for two cases of primary male infertility caused by severe asthenospermia and to analyze the etiology of the disease. METHODS: Genomic DNA of peripheral blood samples of patients and their parents was extracted and gene variant analysis of the patients was conducted by using whole exome sequencing. Suspected pathogenic variant was verified by Sanger sequencing and pathogenic analysis. RESULTS: Whole exome sequencing showed that the DNAH1 gene of patient 1 had two heterozygous variants of c.2016T>G(p.Y672X) and c.6017T>G (p.V2006G). The DNAH1 gene of patient 2 had a homozygous variant of c.2610G>A(p.W870X), which were inherited from his father and mother, respectively. According to American College of Medical Genetics and Genomics standards and guidelines, the c.2016T>G (p.Y672X) and c.2610G>A (p.W870X) varaints of DNAH1 gene were predicted to be pathogenic (PVS1+PM2+PM3+PP3). CONCLUSION: The two patients of multiple morphological abnormalities of the sperm flagella may be caused by DNAH1 gene variant, which has resulted in primary male infertility.

Lymphedema complicated by protein-losing enteropathy with a 22q13.3 deletion and the potential role of CELSR1: A case report.

INTRODUCTION: 22q13.3 deletion syndrome is a well-known syndrome characterized by typical clinical findings including neonatal hypotonia, absent or severely delayed speech, intellectual disability, and other various features, and detection of a heterozygous deletion of chromosome 22q13.3 with the involvement of at least part of SHANK3. It is reported that 10% to 29% of patients with 22q13.3 deletion syndrome present lymphedema. Protein-losing enteropathy (PLE) has never been reported in 22q13.3 deletion syndrome. PATIENT CONCERNS: The patient presented to our institution for refractory hypoalbuminemia and chronic lymphedema in both legs. DIAGNOSIS: The patient manifested intellectual disability, absent speech, tooth grinding, dysmorphic face, and abnormal hands and toenails. Copy-number variation sequencing confirmed the maternal deletion in 22q13.31-q13.33 (chr22:46285592-51244566, hg19). The patient was genetically diagnosed with 22q13.3 deletion syndrome. INTERVENTIONS: Low-fat diets and medium-chain triglycerides supplements were prescribed. The patient was recommended to wear compression garments and elevate legs. OUTCOMES: The symptom of diarrhea was resolved, but hypoalbuminemia persisted. Lower extremities lymphedema was gradually becoming severe. CONCLUSIONS: Primary lymphedema and PLE can occur simultaneously in a patient with 22q13.3 deletion syndrome. The 2 phenotypes could share the same genetic etiology of congenital lymphatic abnormalities. CELSR1 deletion may play a role in lymphatic dysplasia. The case also provides additional proof of the pathogenic effect of CELSR1 on hereditary lymphedema.

New application of direct lymphangiography in the diagnosis and treatment of chylothorax after lung cancer surgery: a case series.

BACKGROUND: Chylothorax is caused by accumulation of chylous fluid in the thoracic cavity following injury to the thoracic duct or its tributaries. It is a rare but relatively severe complication of lung cancer surgery, especially after lung resection and mediastinal lymph node dissection. If chylothorax is not treated promptly and effectively, it may result in relatively high mortality rate. Although the majority of patients with chylothorax secondary to lung cancer surgery can be treated with conservative measures, there are still some patients who fail to respond to conservative treatment or suffer from recurrent episodes. This study aims to explore the causes of postoperative chylothorax and how targeted treatment can help achieve better outcomes. METHODS: Four cases of chylothorax secondary to lung cancer surgery are reported in which patients underwent direct lymphangiography (DLG) after failed conservative treatment. RESULTS: Thoracic duct obstruction was found in all patients on DLG, as well as dilated intrathoracic part of the thoracic duct. Thoracic duct reconstruction was performed to successfully treat 3 of the 4 patients. CONCLUSIONS: DLG is of great value in the diagnosis of chylothorax secondary to lung cancer surgery, for which thoracic duct reconstruction proves to be an effective procedure. DLG provides a new objective basis for the diagnosis and treatment of chylothorax. It is our best wish to help more patients with chylothorax secondary to lung cancer surgery.

Effect of Lactobacillus plantarum fermented barley on plasma glycolipids and insulin sensitivity in subjects with metabolic syndrome.

Fermented barley (FB) flour by Lactobacillus plantarum is richer in dietary fiber, polyphenols, gamma-aminobutyric acid, and other biologically active ingredients. This study aimed to determine the impacts of fermented barley - wheat flour compound noodle (FBWN) on glucose and fat metabolism in subjects with metabolic syndrome. This was a single-blinded and parallel 10-week clinical trial study. Subjects were randomly assigned into the trial group (FBWN) and whole wheat noodles group (WWN), and were measured on the beginning of week 3 and the ending of week 10. The glucose level at 30 and 60 min was significantly decreased after FBWN intervention. Levels of fasting blood glucose, HbA1c, and TG were all declined after FBWN intervention compared to before in the trial group. Moreover, the fat mass, fat rate, and visceral fat were decreased by 6.48, 7.19, 6.3 kg after FBWN intervention, respectively, while muscle mass and basal metabolic rate rose 7.44 kg and 252.60 kcal. PRACTICAL APPLICATIONS: Many studies have illustrated that the extraction of fermented barley held the activities of anti-obesity, antitumor, and so on. Moreover, this present study evaluated the effects of fermented barley by Lactobacillus plantarum on patients with metabolic syndrome. Results indicated that FB benefits the subjects on improving plasma glycolipids and insulin sensitivity, decreasing visceral fat level, and increasing satiety. The findings showed that the products of FB may be beneficial to dietary manipulations, thus, reducing the burden of patients.

Analysis of choroidal morphology and comparison of imaging findings of subtypes of polypoidal choroidal vasculopathy: a new classification system.

AIM: To classify polypoidal choroidal vasculopathy (PCV) into 2 subtypes based on the subfoveal choroidal thickness (SFCT) and to further evaluate their multimodal image features. METHODS: A retrospective observational case series study. Sixty-four eyes of 64 patients with PCV were enrolled and classified into 2 groups based on SFCT (thick-choroid group/thin-choroid group). Then further analyze the spectrum domain optical coherence tomography (SD-OCT) and indocyanine green angiography (ICGA) differences of the two subtypes. Imaging analysis included measurement of SFCT, maximum vascular diameter ratio (MVDR), choroidal vascularity index (CVI), central macular thickness (CMT), and the presence of pigment epithelial detachment (PED) on SD-OCT. Polypoidal lesions (polyps) number, branching vascular network (BVN) area, greatest linear dimension (GLD), and the choroidal vascular hyperpermeability (CVH) were analyzed by ICGA. RESULTS: The distribution of SFCT was bimodal with two peaks at 195 and 285 µm, and a trough at 225 µm. The 225 µm was taken as the cutoff point for the following classification of thick/thin choroid groups. The PCV eyes in the thick-choroid group presented with greater MVDR, CVI within 3 and 6 mm of the fovea, but lower CMT, less PED, small PED diameters on SD-OCT scans, and fewer polyps, smaller BVN and GLD, but more frequency of CVH on ICGA. CONCLUSION: The SFCT at 225 µm can be used as a readily available indicator for the classification of PCV subtypes. The thick-choroid group presents much apparent enlargement of the choroidal layer and vasculature expansion, which indicates different pathogenesis of the two subtypes.

ROLE OF DIAGNOSTIC PARS PLANA VITRECTOMY IN DETERMINING THE ETIOLOGY OF UVEITIS INITIALLY UNKNOWN.

PURPOSE: To estimate the success and safety of diagnostic pars plana vitrectomy (PPV) in determining the etiology of uveitis initially unknown and analyze their characteristics. METHODS: The PubMed, Embase, and Ovid were searched up to October 2017 to identify relevant studies. The PRISMA guidelines were followed. Statistical analyses were performed with R version 3.3.1. Result in proportion were transformed by the Freeman-Tukey variant of arcsine square to attain symmetry of confidence intervals (CIs). The statistical heterogeneity was assessed by the chi-square test and I statistics. Sensitivity analysis and subgroup analyses were performed to identify the source of heterogeneity. Publication bias was assessed by the Egger test. RESULTS: Sixteen studies involving 1,195 patients were finally included. The pooling result showed the successful rate of diagnostic PPV was 44% (95% CI [39%∼50%]). Among patients whose diagnostic PPV yielded a definitive diagnosis, 69% were infectious uveitis (95% CI [61%∼77%]), 23% were lymphoma (95% CI [17%∼30%]), and 4% were metastatic carcinoma (95% CI [2%∼10%]). Among patients diagnosed with infectious uveitis, the most frequent pathogens identified were viruses, followed by bacteria, Toxocara canis, Toxoplasma gondii, tuberculosis, and fungus. The incidence of postoperative cataract and postoperative retinal detachment was 19% (95% CI [8%∼29%]) and 5% (95% CI [1%∼10%]), respectively, and the rate of secondary vitrectomy surgery was 10% (95% CI [2%∼22%]). Postoperative visual improvement rate was 46% (95% CI [39%∼52%]), and the postoperative treatment strategy was changed in light of the results of diagnostic PPV in 20% of cases (95% CI [10%∼29%]). CONCLUSION: For uveitis of unknown cause, diagnostic PPV is an effective, reliable, and relatively safe procedure for establishing the definite diagnosis and guiding further treatment. Positive therapeutic effect could also be achieved.

THE OCCURRENCE, CHARACTERISTICS, MANAGEMENT, AND PROGNOSIS OF RETINAL PIGMENT EPITHELIUM TEARS IN PATIENTS WITH POLYPOIDAL CHOROIDAL VASCULOPATHY: A Retrospective Study of 397 Patients.

PURPOSE: To investigate retinal pigment epithelium (RPE) tears in patients with polypoidal choroidal vasculopathy. METHOD: A retrospective review of polypoidal choroidal vasculopathy cases with confirmed RPE tears was conducted. Patients' comprehensive clinical data were collected and analyzed. The treatment strategy was a loading dose of one intravitreal antivascular endothelial growth factor injection, combined with additional injections if exudative activities or visual deterioration were detected. RESULTS: Among 397 polypoidal choroidal vasculopathy patients, 33 patients with RPE tears (8.3%) were included. 42.4% of them happened spontaneously. Pigment epithelial detachment (PED) occurred more frequently in RPE tear patients and most of them had serous vascularized or hemorrhagic PED. The height and greatest linear diameter of PED, and the subfoveal choroidal thickness of these cases were significantly larger, whereas the central foveal thickness was significantly smaller. Most of the RPE tears occurred at the edge of the PED. After our treatment strategy, patients' best-corrected visual acuity improved significantly from 2.13 ± 1.24 (median 20/52) to 1.32 ± 1.31 (median 20/166). Large subretinal hemorrhage may increase the risk of the formation of subretinal fibrosis (P < 0.05). CONCLUSION: Retinal pigment epithelium tears in polypoidal choroidal vasculopathy are associated with high subRPE hydrostatic pressure, produced by a large PED or hemorrhage. After our intervention strategy, this condition may not necessarily result in poor prognosis.

Five-year real-world outcomes of anti-vascular endothelial growth factor monotherapy versus combination therapy for polypoidal choroidal vasculopathy in a Chinese population: a retrospective study.

BACKGROUND: To evaluate 5-year outcomes of anti-vascular endothelial growth factor (VEGF) monotherapy and combination therapy of anti-VEGF agents and photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV) in a real-world Chinese population. METHODS: Retrospective study. Fifty-three eyes of 46 patients with subtype 1 and 2 PCV followed up for at least 60 months were grouped into three regimens: anti-VEGF monotherapy, PDT combining with anti-VEGF therapy initially, and PDT combining with deferred anti-VEGF therapy. Main outcome measure was best-corrected visual acuity (BCVA) using logarithm of minimal angle of resolution (logMAR). RESULTS: The mean BCVA of eyes with subtype 1 PCV (n = 28) deteriorated from 0.69 logMAR at baseline to 1.25 logMAR at months 60 (P = 0.001), while the mean BCVA of eyes with subtype 2 PCV (n = 25) sustained stable from 0.62 logMAR at baseline to 0.57 at months 60 (P = 0.654). No significant differences of visual outcomes were found between the 3 treatment regimens for subtype 1 PCV. Anti-VEGF monotherapy and initial combination treatment had better visual outcomes in eyes with subtype 2 PCV than deferred combination group during part of follow-up significantly. Initial combination group needed a less number of PDT than deferred combination group (P < 0.001). CONCLUSIONS: Compared with subtype 1 PCV, subtype 2 PCV has a more favorable visual outcome in real world. All the regimens presented unfavorable visual outcomes for subtype 1 PCV. Anti-VEGF monotherapy and initial combination therapy should be superior to deferred combination therapy in the long-term management of subtype 2 PCV. Prospective randomized studies of larger size are needed to determine the long-term efficacy and safety of various treatment for PCV in real world.

Noninvasive multimodal imaging in diagnosing polypoidal choroidal vasculopathy.

PURPOSE: To investigate the diagnostic accuracy of noninvasive multimodal imaging methods in diagnosing polypoidal choroidal vasculopathy (PCV) and distinguishing PCV from typical neovascular age-related macular degeneration (nvAMD). METHODS: Retrospective study. Imaging features of noninvasive multimodal imaging methods, including fundus photography (FP), B-scan optical coherence tomography (OCT), en face OCT, OCT angiography, and autofluorescence, of 103 eyes with PCV or typical nvAMD were reviewed. Diagnostic strategy was established based on imaging features and was validated in other 105 eyes with PCV or typical nvAMD. RESULTS: Features of subretinal orange nodule on FP, thumb-like PED on OCT, notched PED on OCT, bubble sign on OCT, and Bruch's membrane depression under serosanguinous PED on OCT were more common. When the diagnostic strategy of using at least 2 of 5 features was performed, there is 0.88 sensitivity and 0.92 specificity for diagnosing PCV. The results of the validation test further confirmed the diagnostic strategy with 0.94 sensitivity and 0.93 specificity. CONCLUSIONS: Noninvasive multimodal imaging, especially FP and B-scan OCT, provide high sensitivity and specificity for diagnosing PCV and distinguishing PCV from typical nvAMD, when at least 2 of 5 suggestive imaging features are present.

Optical coherence tomography angiography analysis of the choriocapillary layer in treatment-naïve diabetic eyes.

PURPOSE: To evaluate the capillary flow density (CFD) of choriocapillary (CC) microvasculature using optical coherence tomography angiography (OCT-A) in diabetic eyes and the association of CFD and systemic and metabolic factors. METHODS: Cross-sectional study. This study enrolled 282 eyes of 146 subjects, including 43 healthy control eyes, 56 diabetic eyes without diabetic retinopathy (DR), 43 eyes with mild nonproliferative DR (NPDR), 54 eyes with moderate NPDR, 38 eyes with severe NPDR, and 48 eyes with proliferative DR (PDR). CFD was measured in the CC layer. Clinical data were collected. Multiple linear regression analyses were performed to identify associated clinical variables. RESULTS: CFD in the CC layer presented a downward trend with DR progression. Comparisons of CFD in the CC layer between adjacent stages of DR revealed significant differences between severe NPDR and PDR using both 3-mm and 6-mm scan patterns (P = 0.003, P = 0.001). CFD in the CC layer in DR with diabetic macular edema (DME) was less than that in DR without DME using both 3-mm and 6-mm scan patterns (P < 0.001, P < 0.001). Coronary artery disease and atherosclerosis in other locations, estimated glomerular filtration rate, and increased HbA1c were associated with CFD in the CC layer using both 3-mm and 6-mm scan patterns (all P values < 0.05). CONCLUSIONS: OCT-A revealed decreased CFD in the CC layer in the PDR stage and the presence of DME. Diabetic patients with apparently decreased CFD should be assessed carefully under general conditions.