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Background: Up to the present time, there has remained a lack of strong evidence as to whether sentinel lymph node biopsy can replace lymphadenectomy for early endometrial cancer. The traditional surgery for endometrial cancer includes pelvic lymphadenectomy and paraaortic lymph node resection, but complications often seriously affect patients' quality of life. Two randomized controlled trials with large samples have proved that lymphadenectomy does not improve the overall recurrence rate and survival rate of patients. On the contrary, it increases the incidence of complications and even mortality. The current trial is designed to clarify whether sentinel lymph node biopsy can replace lymphadenectomy for early endometrial cancer patients with negative lymph nodes. Methods: This study is a randomized, open-label, multicenter and non-inferiority controlled clinical trial in China. Potential participants will be patients with pathologically confirmed endometrial cancer at the Zhejiang Cancer Hospital, Jiaxing Maternity and Child Health Care Hospital, and the First Hospital of Jiaxing in China. The total sample size for this study is 722. Patients will be randomly assigned in a 1:1 ratio to two groups. Patients in one group will undergo sentinel lymph node biopsy + total hysterectomy + bilateral salpingo-oophorectomy ± paraaortic lymph node resection. Patients in the other group will undergo sentinel lymph node biopsy + total hysterectomy + bilateral salpingo-oophorectomy + pelvic lymphadenectomy ± paraaortic lymph node resection. The 3-year disease-free survival rate, overall survival rate, quality of life (use EORTC QLQ-C30 + QLQ-CX24), and perioperative related indexes of the two groups will be compared. Results: We expect to find that for patients with early endometrial cancer, the 3-year disease-free survival rate following sentinel lymph node biopsy with indocyanine green combined with near-infrared fluorescence imaging is similar to that following lymphadenectomy. The operation time, as well as incidence of pelvic lymphocyst, lymphedema of lower limb, and edema of vulva in patients who only undergo sentinel lymph node biopsy are expected to be significantly lower than in patients who undergo lymphadenectomy. The quality of life of patients who undergo sentinel lymph node biopsy alone will be significantly better than that of patients who undergo lymph node dissection. Conclusion: This will prove that the prognosis of sentinel lymph node biopsy alone with indocyanine green combined with near-infrared fluorescence imaging is not inferior to that of sentinel lymph node biopsy plus lymphadenectomy for early stage endometrial cancer with negative nodal assessment intraoperatively. In addition, sentinel lymph node biopsy alone with indocyanine green combined with near-infrared fluorescence imaging results in fewer surgical complications and gives patients better quality of life. Trial registration: chictr.org.cn, ChiCTR1900023161. Registered 14 May 2019, http://www.chictr.org.cn/edit.aspx?pid=38659&htm=4. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the main etiological factors and visual outcomes in patients with dense vitreous hemorrhage (DVH) aged ≥80 years. We retrospectively included patients with DVH aged ≥80 years who were admitted to our ophthalmology department between January 1, 2010, and December 31, 2019. All patients underwent pars plana vitrectomy (PPV). Data regarding demographic characteristics; preoperative and postoperative best-corrected visual acuity (BCVA), intraocular pressure (IOP), and ophthalmic B-scan ultrasonography findings; intraoperative conditions; and postoperative complications were collected and analyzed. A total of 44 patients (44 eyes) were enrolled, with a median age of 82 years; among them, 25 patients (56.82%) were men. The median preoperative BCVA was 2.3 (1.1–3.0). The main etiological factors included retinal vein occlusion (RVO) (20 eyes, 45.45%), polypoidal choroidal vasculopathy (PCV) (15 eyes, 34.09%), proliferative diabetic retinopathy (PDR) (7 eyes, 15.90%), retinal arterial macroaneurysm (RAM) (1 eye, 2.27%), and posterior vitreous detachment (PVD) (1 eye, 2.27%). The median final BCVA was 1.92 (0.5–2.6). There was a significant postoperative improvement in the BCVA; moreover, branch RVO (BRVO) had a better postoperative visual prognosis than central RVO (CRVO), PCV, and PDR (P < 0.05). The final postoperative BCVA was significantly better when the initial BCVA was above hand motion (HM) than when it was HM or lower (P < 0.05). Our findings indicate that RVO, PCV, and PDR were the main causes of DVH. Microinvasive PPV is a safe and effective method that can clarify diagnosis and improve BCVA. Patients with BRVO and preoperative BCVA > HM may have a relatively good visual prognosis. For patients aged ≥80 years who have an appropriate general condition, PPV can be timely performed to treat DVH. [ABSTRACT FROM AUTHOR]

In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV. A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-naive PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Six evidence-based recommendations support optimal care for PCV patients' management. [ABSTRACT FROM AUTHOR]

Background: Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are major causes of blindness in aged people. 30% of the patients show unsatisfactory response to anti-vascular endothelial growth factor (anti-VEGF) drugs. This study aims to investigate the relationship between serum metabolome and treatment response to anti-VEGF therapy. Methods: A prospective longitudinal study was conducted between March 2017 and April 2019 in 13 clinical sites in China. The discovery group were enrolled from Shanghai General Hospital. The validation group consisted of patients from the other 12 sites. Participants received at least one intravitreal injection of 0.5 mg anti-VEGF drug, conbercept, and were divided into two groups - responders and non-responders. Serum samples of both groups were processed for UHPLC-MS/MS analysis. We constructed principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models to investigate the metabolic differences between two groups using SIMCA-P. Area under curve (AUC) was calculated to screen the biomarkers to predict treatment response. Metabolites sub-classes and enriched pathways were obtained using MetaboAnalyst5.0. Results: 219 eyes from 219 patients (nAMD = 126; PCV = 93) were enrolled. A total of 248 metabolites were detected. PCA and PLS-DA models of the discovery group demonstrated that the metabolic profiles of responders and non-responders clearly differed. Eighty-five differential metabolites were identified, including sub-classes of diacylglycerophosphocholines, lysophosphatidylcholine (LPC), fatty acids, phosphocholine, etc. Responders and non-responders differed most significantly in metabolism of LPC (p = 7.16 x 10-19) and diacylglycerophosphocholine (p = 6.96 x 10-17). LPC 18:0 exhibited the highest AUC, which is 0.896 with 95% confidence internal between 0.833 and 0.949, to discriminate responders. The predictive accuracy of LPC 18:0 was 72.4% in the validation group. Conclusions: This study suggests that differential metabolites may be useful for guiding treatment options for nAMD and PCV. Metabolism of LPC and diacylglycerophosphocholine were found to affect response to conbercept treatment. LPC 18:0 was a potential biomarker to discriminate responders from non-responders. [ABSTRACT FROM AUTHOR]

Background: Indocyanine green (ICG) is becoming a frequently used sentinel lymph node (SLN) tracer of breast cancer in China. However, there is still a lack of data on its safety. We reported the clinical outcome of ICG as a tracer of SLN over a median 67-month follow-up period to evaluate its feasibility in clinically node-negative patients with breast cancer. Methods: A total of 194 consecutive patients underwent sentinel lymph node biopsy (SLNB) with ICG, radioisotopes (RI) and methylene blue (MB), or with ICG and MB. The SLN mapping data by each tracer was recorded, and safety outcomes were analyzed through follow-up. Results: With the triad mapping (N = 44), the identification rate of SLN by ICG was 95.5%, slightly higher than that of MB (86.4%) and comparable with RI (95.5%) and combined methods (95.5%, 100%) (p = 0.068). Analysis of all candidates (N = 194) demonstrated that the identification rate of SLN by ICG or by ICG and MB was 99%, significantly higher than that by MB (92.8%) (p < 0.0001). No tracer-related allergic reaction and permanent skin staining of ICG were observed. Local disease progression was reported in 2 of the 194 patients at the ipsilateral axilla. After remedial axillary lymph node dissection, no disease progression was detected at follow-up. Conclusions: ICG as an SLN tracer is more accurate than MB and comparable to the combined methods and has good clinical safety. ICG can be considered a useful supplement or suitable alternative to traditional tracers. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the safety, effectiveness, and feasibility of indocyanine green (ICG) tracing in guiding lymph-node (LN) dissection during laparoscopic D2 radical gastrectomy in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NAC). Method: We retrospectively analyzed data on 313 patients with clinical stage of cT1-4N0-3M0 who underwent laparoscopic radical gastrectomy after NAC between February 2010 and October 2020 from two hospitals in China. Grouped according to whether ICG was injected. For the ICG group (n = 102) and non-ICG group (n = 211), 1:1 propensity matching analysis was used. Results: After matching, there was no significant difference in the general clinical pathological data between the two groups (ICG vs. non-ICG: 94 vs. 94). The average number of total LN dissections was significantly higher in the ICG group and lower LN non-compliance rate than in the non-ICG group. Subgroup analysis showed that among patients with LN and tumor did not shrink after NAC, the number of LN dissections was significantly more and LN non-compliance rate was lower in the ICG group than in the non-ICG group. Intraoperative blood loss was significantly lesser in the ICG group than in the non-ICG group, while the recovery and complications of the two groups were similar. Conclusion: For patients with poor NAC outcomes, ICG tracing can increase the number of LN dissections during laparoscopic radical gastrectomy, reduce the rate of LN non-compliance, and reduce intraoperative bleeding. Patients with AGC should routinely undergo ICG-guided laparoscopic radical gastrectomy. [ABSTRACT FROM AUTHOR]

Purpose: To provide a detailed review on the therapeutic efficacy of conbercept for the management of ocular vasculopathies. Methods: A comprehensive literature search of various electronic databases was performed. Results: Ocular vasculopathy is one of the major causes of visual impairment and blindness which includes a range of disorders. Vascular endothelial growth factor (VEGF) regulates angiogenesis, enhances vascular permeability, and drives the formation of neovascularization. Anti-VEGF therapy has been shown to prevent vision loss or potentially improve vision in patients with exudative or neovascular retinal disease. The most recent anti-VEGF drug in China is conbercept. In the USA and Europe, bevacizumab is the most recently approved anti-VEGF agent. Conclusions: Conbercept serves as another anti-VEGF option for patients with neovascular AMD and other retinal vascular disorders. There have not been many clinical trials that study conbercept as compared with other currently available anti-VEGF drugs. There is a need for large-scale, well-designed, randomized clinical trials to ensure its long-term safety and efficacy and to determine if it has any advantages over other anti-VEGF agents. [ABSTRACT FROM AUTHOR]

Chromoblastomycosis is a chronic skin and subcutaneous fungal infection caused by dematiaceous fungi and is associated with low cure and high relapse rates. In southern China, Fonsecaea monophora and Fonsecaea pedrosoi are the main causative agents. We treated 5 refractory and complex cases of chromoblastomycosis with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with oral antifungal drugs. The lesions improved after 4 to 9 sessions of ALA-PDT treatment at an interval of one or two weeks, and in some cases, mycological testing results became negative. The isolates were assayed for susceptibility to antifungal drugs and ALA-PDT in vitro, revealing sensitivity to terbinafine, itraconazole and voriconazole, with ALA-PDT altering the cell wall and increasing reactive oxygen species production. These results provide the basis for the development of a new therapeutic approach, and ALA-PDT combined with oral antifungal drugs constitutes a promising alternative method for the treatment of refractory and complex cases of chromoblastomycosis. Chromoblastomycosis, a neglected tropical disease, is one of the most frequently encountered subcutaneous mycoses. The disease is usually caused by traumatic inoculation of a specific group of dematiaceous fungi. Chromoblastomycosisis characterized by slowly expanding skin lesions and is associated with low cure and high relapse rates. In recent years, effective methods, such as photodynamic therapy (PDT), have been employed for inhibiting the pathogen's activity. The authors treated 5 refractory and complex cases of chromoblastomycosis with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with oral antifungal drugs. The lesions improved after 4 to 9 sessions of ALA-PDT treatment at an interval of one or two weeks, and in some cases, mycological testing results became negative. The authors also found that ALA-PDT alter the fungi cell wall and increase reactive oxygen species production. This research provides the basis for the development of a new therapeutic approach, and ALA-PDT combined with oral antifungal drugs constitutes a promising alternative method for the treatment of refractory and complex cases of chromoblastomycosis. [ABSTRACT FROM AUTHOR]

• We construct a fine-grained classification dataset of wet Age-related macular degeneration (AMD). • A knowledge-driven deep learning model, KFWC, is proposed to improve accuracy in fine-grained disease classification with insufficient data. • KFWC can detect 10 signs of lesions on medical images and can diagnose two subtypes of wet-AMD. • Multiple experiments demonstrate the effectiveness and interpretability of the proposed KFWC. Automated diagnosis using deep neural networks can help ophthalmologists detect the blinding eye disease wet Age-related Macular Degeneration (AMD). Wet-AMD has two similar subtypes, Neovascular AMD and Polypoidal Choroidal Vasculopathy (PCV). However, due to the difficulty in data collection and the similarity between images, most studies have only achieved the coarse-grained classification of wet-AMD rather than a fine-grained one of wet-AMD subtypes. Therefore, designing and building a deep learning model to diagnose neovascular AMD and PCV is a great challenge. To solve this issue, in this paper, we propose a Knowledge-driven Fine-grained Wet-AMD Classification Model (KFWC) to enhance the model's accuracy in the fine-grained disease classification with insufficient data. We innovatively introduced a two-stage method. In the first stage, we present prior knowledge of 10 lesion signs through pre-training; in the second stage, the model implements the classification task with the help of human knowledge. With the pre-training of priori knowledge of 10 lesion signs from input images, KFWC locates the powerful image features in the fine-grained disease classification task and therefore achieves better classification. To demonstrate the effectiveness of KFWC, we conduct a series of experiments on a clinical dataset collected in cooperation with a Grade III Level A ophthalmology hospital in China. The AUC score of KFWC reaches 99.71%, with 6.69% over the best baseline and 4.14% over ophthalmologists. KFWC can also provide good interpretability and effectively alleviate the pressure of data collection and annotation in the field of fine-grained disease classification for wet-AMD. The model proposed in this paper effectively solves the difficulties of small data volume and high image similarity in the wet-AMD fine-grained classification task through a knowledge-driven approach. Besides, this method effectively relieves the pressure of data collection and annotation in the field of fine-grained classification. In the diagnosis of wet-AMD, KFWC is superior to previous work and human ophthalmologists. [ABSTRACT FROM AUTHOR]

Background Growth differentiation factor 6 (GDF6) has been reported to be a novel disease gene for agerelated macular degeneration (AMD) in Caucasians. This study aimed to investigate whether rs6982567 was associated with neovascular AMD (nAMD) or polypoidal choroidal vasculopathy (PCV) in a Han Chinese cohort. Methods A total of 612 participants (251 PCV patients, 157 nAMD patients and 204 controls) were included in this study. The SNaPshot system was used to genotype the rs6982567. PLINK software was used to evaluate the genotypes and allele frequencies of patients and controls. Results The allele frequencies of rs6982567 were not significantly associated with nAMD, PCV or PCV and nAMD combined. Subjects with the TT genotype had a 2.42-fold greater risk of PCV (95% confidence interval, 1.07-5.43, p = 0.0290) than subjects with CC genotype. A recessive model of rs6982567 was statistically significantly associated with PCV (odds ratio, 2.29; 95% confidence interval, 1.04-5.05; p = 0.0351). However, the association did not withstand stringent Bonferroni correction. There were no significant differences in genotype distributions or models in nAMD. Conclusions There was a possible weak association between the rs6982567 near GDF6 and PCV in this replication study with an independent Han Chinese cohort. A complete survey of the GDF6 locus with a larger sample size is needed in future studies. [ABSTRACT FROM AUTHOR]

PurposeTo determine the frequency of haemorrhagic pigment epithelial detachment (PED) among patients presenting with either polypoidal choroidal vasculopathy (PCV) or choroidal neovascularization (CNV) and calculate the degree to which the presence of a haemorrhagic PED can be used to predict the diagnosis of PCV.MethodsA retrospective review of 290 eyes of 253 patients presenting to the Singapore National Eye Centre with serosanguineous maculopathy. Patients underwent ophthalmologic examination including digital colour fundus photography and stereoscopic fluorescein angiography and indocyanine green angiography (ICGA). Classification into PCV or CNV was based on ICGA findings, and presence or absence of haemorrhagic PED was documented.ResultsIn total, 138 eyes of 123 patients were diagnosed with PCV and 152 eyes of 130 patients with CNV. A haemorrhagic PED was a significantly more common (P<0.001) presenting feature in PCV eyes (63, 45.7%) than CNV eyes (6, 3.9%) (odds ratio (OR) 20.4, 95% confidence interval (CI) 8.5–49.4). Age-related maculopathy was found significantly more frequently (P<0.001) in the unaffected fellow eye of CNV patients (57, 52.8%) than PCV patients (28, 22.8%) (OR 3.2, 95% CI 1.8–5.7).ConclusionsIn patients of Chinese ethnicity, a haemorrhagic PED is significantly more likely to be the presenting feature of PCV than CNV. Patients presenting with this clinical feature should make the clinician suspicious of an underlying diagnosis of PCV. [ABSTRACT FROM AUTHOR]

Background: To investigate the association of systemic, serum lipids and genetic variants in the high-density lipoprotein (HDL) metabolic pathway with polypoidal choroidal vasculopathy (PCV) in China. Methods: The case-control study was included 150 controls and 66 cases with PCV. Serum levels of total cholesterol (TC), low-density lipoprotein (LDL), HDL, triglycerides (TG), apolipoprotein A1 (APOA1), apolipoprotein B (APOB) together with systemic risk factors including gender, hyperlipidemia, diabetes mellitus (DM), hypertension, coronary artery disease (CAD) and asthma were identified. All subjects were genotyped for four single nucleotide polymorphisms (SNPs) from three genes in the HDL metabolic pathway: rs10468017 of hepatic lipase (LIPC), rs12678919 of lipoprotein lipase (LPL), rs3764261 and rs173539 of cholesterol ester transfer protein (CETP) with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Student's t-tests, chi-square tests, anova and logistic regression were used to evaluate associations. Results: Hyperlipidemia was a risk factor (odds ratio (OR) = 1.19, P = 0.001) for PCV. HDL, LDL and APOB levels were associated with PCV (OR = 0.001, P = 0.004; OR = 0.099, P = 0.010; OR = 0.839, P = 0.018). Higher level of TC was potently associated with increased risk of PCV (OR = 109.8, P = 0.000). LIPC rs10468017 was a risk factor for PCV (OR = 11.68, P = 0.000). CETP rs3764261 conferred a decreased risk for PCV (OR = 0.08, P = 0.000). No associations of LPL rs12678919 or CETP rs173539 with PCV were found. Mean level of HDL increased with T allele of the CETP gene (p = 0.026): 1.24 mmol/L (±0.31) for the GG genotype and 1.66 mmol/L (±0.54) for the TT genotype. Additionally, T allele was associated with the following increase in APOA1: 136.78 mg/dl (±20.53) for the CC genotype and 149.57 mg/dl (±22.67) for the TT genotype of LIPC and 137.91 mg/dl (±20.36) for the GG genotype and 162.67 mg/dl (±22.50) for the TT genotype of CETP gene. Conclusion: Our study suggested that the significant association was found between hyperlipidemia, the serum levels of TC, HDL, LDL and APOB and PCV. The result of present study also showed that the association of LIPC rs10468017 and CETP rs3764261 with PCV. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of monthly and pro re nata (PRN, guided by visual acuity stabilization and disease activity criteria) ranibizumab regimens in Chinese patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV)., Methods: This double-masked study randomized nAMD patients (1:1) to ranibizumab monthly from baseline to Month (M) 11 to a PRN regimen from M12 to M23 (monthly group, n = 167) versus ranibizumab three monthly doses followed by a PRN regimen up to M23 (PRN group, n = 166). Subgroups were assessed based on the presence/absence of PCV (indicated by indocyanine green angiography)., Results: Of 334 randomized patients, 41.7% had PCV at baseline. Mean average best-corrected visual acuity (BCVA) change from M3 to M4 through M12 was 3.3 letters with monthly and 1.7 letters with PRN (mean difference: 1.6; 95% CI: -2.95, -0.20, primary end-point). Mean change in BCVA from baseline (monthly/PRN, 53.8/53.7) to M12 and M24 was 12.3 and 11.3 letters in monthly and 9.6 and 9.3 letters in PRN group. Corresponding values for patients with PCV/without PCV were 12.7/12.1 letters (M12) and 12.3/10.6 letters (M24) in monthly and 9.4/9.4 letters (M12) and 9.7/8.7 letters (M24) in PRN groups. The mean number of injections was 11.4 (monthly) and 8.2 (PRN) from Day 1 to M11 and 4.8 (monthly) and 5.0 (PRN) from M12 to M23. No new safety findings were reported., Conclusions: The study results support the use of either ranibizumab monthly or PRN regimens in Chinese patients with nAMD, regardless of presence of PCV., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To record the coexistence of polypoidal choroidal vasculopathy (PCV) with other rare fundus diseases in a Chinese population., Method: In this retrospective hospital-based study, a chart review of 861 patients with newly diagnosed PCV was performed. The clinical features of rare fundus comorbidities of PCV were recorded., Results: Five eyes of 5 patients aged 63.4 ± 11.22 years (0.58%) had PCV coexisting with other fundus diseases in the same eye. Of the 5 PCV patients, 2 (0.23%) had myelinated nerve fiber, 2 (0.23%) had branch retinal vein occlusion, and 1 (0.12%) had retinal angiomatous proliferation., Conclusion: We reported rare fundus comorbidities of PCV in a large Chinese cohort. These comorbidities included myelinated nerve fiber, branch retinal vein occlusion and retinal angiomatous proliferation. The combination might constitute an accidental occurrence.

Purpose: To investigate whether common genetic variants in the endothelial nitric oxide synthase gene (eNOS) are associated with neovascular age-related macular degeneration (nAMD) and polypoidal choroidalvasculopathy (PCV) in a Chinese Han population., Methods: DNA samples were obtained from 157 nAMD patients, 250 PCV patients and 204 healthy control subjects. Tag single nucleotide polymorphisms (SNPs) across the extended eNOS region were selected using data derived from the HapMap project. Genotyping of each tag SNP was performed by Multiplex SNaPshot system and direct DNA sequencing techniques. Genotypes and allele frequencies were evaluated with PLINK software for each group., Results: Seven SNPs for eNOS, rs1799983, rs1800783, rs3918186, rs3800787, rs3918188, rs7830, and rs3918227, were chosen as tag SNPs. Among these tag SNPs, rs1800783, rs3918186, rs3918188, and rs3918227 were not associated with nAMD or PCV. Rs1799983, rs3800787, and rs7830 was significantly associated with nAMD (p = 0.0192, 0.0170, and 0.0164, respectively), but not associated with PCV (p = 0.4852, 0.4568, and 0.4014, respectively). The discovered associations were no longer significant after Bonferroni correction., Conclusions: We found no sufficient evidence to support the role of any common eNOS variants in the susceptibility to nAMD or PCV in a Chinese Han population.

Purpose: To investigate whether three previously identified variants for age-related macular degeneration (AMD), the single nucleotide polymorphism (SNP) variants of or near the vascular endothelial growth factor A gene (VEGFA), were associated with neovascular AMD or polypoidal choroidal vasculopathy (PCV) in a Han Chinese cohort., Methods: This was a case-control study comprising 251 PCV patients, 157 neovascular AMD patients, and 204 control participants in a Han Chinese population. The rs833069, rs943080 and rs4711751 SNP were genotyped using the Multiplex SNaPshot system. Genotypes and allele frequencies of patients and controls were evaluated for the SNPs using PLINK software., Results: None of the allelic or genotypic effects of these three variants was significantly associated with PCV, neovascular AMD or combined both patient categories., Conclusions: No association was found to support the role for the rs833069, rs943080 and rs4711751 variants of or near VEGFA gene in susceptibility to either PCV or neovascular AMD in Han Chinese population. Further replication is necessary to validate these results.

Background: Recently, one of our studies has revealed that the serum matrix metalloproteinase 9 (MMP9) level is elevated in polypoidal choroidal vasculopathy (PCV) but not in age-related macular degeneration (AMD). Previous studies have demonstrated that abnormal extracellular matrix (ECM) metabolism plays an important role in the pathogenesis of AMD and PCV. MMP9 is an important regulating enzyme in ECM metabolism, and the MMP9 gene may be a candidate gene for the susceptibility of PCV and AMD. In this study, we aimed to investigate whether the MMP9 gene polymorphism is associated with PCV and neovascular AMD (nAMD) in a Chinese Han population., Methods: We performed a case-control study in a Chinese Han population. Three tag single nucleotide polymorphisms (SNPs) (rs17576, rs3787268 and rs2274755) of the MMP9 gene were genotyped in 251 patients with PCV, 157 patients with nAMD, and 204 control individuals using the Multiplex SNaPshot system and the direct DNA sequencing technique. The three SNPs genotypes and allele frequencies in the PCV, nAMD and control groups were evaluated using PLINK software and binary logistic regression analysis., Results: In the PCV, nAMD, and control groups, the minor allele frequencies were 0.2099, 0.2070 and 0.2108 for the rs17576 variant; 0.4442, 0.4522 and 0.4461 for the rs3787268 variant; and 0.1036, 0.1338 and 0.1225 for the rs2274755 variant, respectively. The three tag SNPs were not significantly associated with susceptibility to PCV (p = 0.9524, 0.9553, and 0.3672, respectively) or nAMD (p = 0.9015, 0.8692, and 0.6543, respectively). None of the p values for the additive, dominant, or recessive models were statistically significant in the PCV or nAMD group., Conclusions: No evidence was found to support an association between the MMP9 gene variants and susceptibility to either nAMD or PCV in a Chinese Han population.

Purpose: To investigate whether 11 variants in complement factor H gene contributed differently in patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) of Chinese descent., Methods: We performed a case-control study in a group of Chinese patients with nAMD (n = 344) or PCV (n = 368) and contrasted the results against an independent control group comprising 511 mild cataract patients without any evidence of age-related maculopathy. Association analysis of allele and genotype frequencies was performed for 11 haplotype-tagging single-nucleotide polymorphisms (SNPs) at the CFH locus (rs1061170, rs1329428, rs1410996, rs2284664, rs375396, rs529825, rs551397, rs7540032, rs800292, rs2274700, and rs1065489). Multinomial logistic regression analyses were performed to estimate and compare the effect of these 11 CFH polymorphisms on AMD and PCV, using the wild-type genotype as reference. Differences in the observed genotypic distributions between cases and controls were tested by using χ(2) tests, with age and sex adjusted for using logistic regression., Results: CFH rs1065489 was not significantly associated with the nAMD phenotype in Chinese collections either on univariate or multivariate analysis (P > 0.05 for all comparisons). The other 10 SNPs of CFH were significantly associated with the nAMD phenotype. As for PCV, all 11 SNP markers were significantly associated with risk of PCV before or after correction for age and sex differences. Eight of the 11 SNP markers showed significant evidence of heterogeneity between AMD and PCV (P < 0.05 for all comparisons)., Conclusions: Our data suggest that the genetic architecture at the CFH locus is complex with some markers showing significant skewing of the genotypes toward nAMD or PCV in Asians. This further supports the clinical observation that nAMD and PCV could have distinct pathogenesis mechanisms, which will require larger studies to accurately dissect.