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Background Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. Hyaluronidase 1 (HYAL1) was found to be upregulated in fibroblasts from IPF patients, and overexpression of HYAL1 could prevent human fetal lung fibroblast proliferation. However, the genetic correlation between the HYAL1 and IPF or connective tissue diseases related interstitial lung disease (CTD‐ILD) has not been determined. Methods A two‐stage study was conducted in Southern Han Chinese population. We sequenced the coding regions and flanking regulatory regions of HYAL1 in stage one (253 IPF cases and 125 controls). A statistically significant variant was further genotyped in stage two (162 IPF cases, 182 CTD‐ILD cases, and 225 controls). Results We identified a nonsynonymous polymorphism (rs117179004, T392M) significantly associated with increased IPF risk (dominant model: OR = 2.239, 95% CI = 1.212–4.137, p = 0.010 in stage one; OR = 2.383, 95% CI = 1.376–4.128, p = 0.002 in stage two). However, we did not observe this association in CTD‐ILD (OR = 1.401, 95% CI = 0.790–2.485, p = 0.248). Conclusion Our findings suggest that the nonsynonymous polymorphism (rs117179004, T392M) may confer susceptibility to IPF in Southern Han Chinese, but is not associated with susceptibility to CTD‐ILD., A nonsynonymous polymorphism (rs117179004, T392M) of hyaluronidase 1 (HYAL1) is associated with increased risk of idiopathic pulmonary fibrosis (IPF) (p = 0.002 in allele‐model) but not connective tissue diseases related interstitial lung disease (CTD‐ILD) (p = 0.181 in allele‐model) in Southern Han Chinese.

BACKGROUND: Although studies have identified hundreds of genetic variants associated with asthma risk, a large fraction of heritability remains unexplained, especially in Chinese individuals. METHODS: To identify genetic risk factors for asthma in a Han Chinese population, 211 asthma‐related genes were first selected based on database searches. The genes were then sequenced for subjects in a Discovery Cohort (284 asthma patients and 205 older healthy controls) using targeted next‐generation sequencing. Bioinformatics analysis and statistical association analyses were performed to reveal the associations between rare/common variants and asthma, respectively. The identified common risk variants underwent a validation analysis using a Replication Cohort (664 patients and 650 controls). RESULTS: First, we identified 18 potentially functional rare loss‐of‐function (LOF) variants in 21/284 (7.4%) of the asthma cases. Second, using burden tests, we found that the asthma group had nominally significant (p

Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and cytokine storm. Exploring the immune-inflammatory characteristics of COVID-19 patients is essential to reveal pathogenesis and predict progression. In this study, COVID-19 patients showed decreased CD3+, CD4+, and CD8+ T cells but increased neutrophils in circulation, exhibiting upregulated neutrophil-to-lymphocyte and neutrophil-to-CD8+ T cell ratio. IL-6, TNF-α, IL-1β, IL-18, IL-12/IL-23p40, IL-10, Tim-3, IL-8, neutrophil extracellular trap–related proteinase 3, and S100A8/A9 were elevated, whereas IFN-γ and C-type lectin domain family 9 member A (clec9A) were decreased in COVID-19 patients compared with healthy controls. When compared with influenza patients, the expressions of TNF-α, IL-18, IL-12/IL-23p40, IL-8, S100A8/A9 and Tim-3 were significantly increased in critical COVID-19 patients, and carcinoembryonic Ag, IL-8, and S100A8/A9 could serve as clinically available hematologic indexes for identifying COVID-19 from influenza. Moreover, IL-6, IL-8, IL-1β, TNF-α, proteinase 3, and S100A8/A9 were increased in bronchoalveolar lavage fluid of severe/critical patients compared with moderate patients, despite decreased CD4+ T cells, CD8+ T cells, B cells, and NK cells. Interestingly, bronchoalveolar IL-6, carcinoembryonic Ag, IL-8, S100A8/A9, and proteinase 3 were found to be predictive of COVID-19 severity and may serve as potential biomarkers for predicting COVID-19 progression and potential targets in therapeutic intervention of COVID-19.

Background:No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods:We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered withClinicalTrials.gov,NCT04257656. Findings:Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation:In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies.

Background Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. Methods The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. Discussion This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. Trial registration ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.

Purpose The aim of this study was to describe the genetic and clinical characteristics of Chinese patients with autosomal recessive bestrophinopathy (ARB). Methods This study presents a retrospective observational case series. Twenty-one ARB patients and 25 clinically healthy family members were recruited. The coding regions and adjacent intronic regions of BEST1 were analysed via Sanger sequencing. Clinical examinations, including ultrasound biomicroscopy, A-scan, optical coherence tomography, fundus autofluorescence, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and visual electrophysiology, were reviewed. Results Six novel mutations (c.380C>T, p.T127M; c.397A>G, p.N133D; c.500A>G, p.E167G; c.817G>A, p.V273M; c.174_176del, p.Q58del; and c.950_955del, p.S318_L319) and 8 previously reported mutations were identified. The p.R255W mutation had the highest frequency in our cohort. Twenty patients had serous retinal detachment with multifocal subretinal vitelliform deposits in the posterior poles. One patient exhibited chorioretinal atrophy. FFA revealed peripheral vascular leakage in 10 patients, and ICGA revealed hyperfluorescent spots in 8 patients. Visual electrophysiology was abnormal in all patients. Fifteen patients with angle closure (AC) or angle-closure glaucoma (ACG) had shallower anterior chambers and shorter axial lengths than the patients with open angle, contributing to their risk of developing AC/ACG. One patient developed AC during the 7-year follow-up period. The misdiagnosis and missed rates were 35.3% and 58.8%, respectively. Conclusion The six novel mutations and high frequency of p.R255W suggest ethnical differences in the BEST1 mutation spectrum among Chinese patients. BEST1 gene screening and detailed clinical examinations help establishing a diagnosis of ARB. Clinical evaluations of the risk of developing AC/ACG are recommended for ARB patients.

Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. However, a large fraction of genetic cause remains unexplained, especially in sporadic IPF (∼80% IPF). By systemically reviewing related literature and potential pathogenic pathways, 92 potentially IPF-related genes were selected and sequenced in genomic DNAs from 253 sporadic IPF patients and 125 matched health controls using targeted massively parallel next-generation sequencing. The identified risk variants were confirmed by Sanger sequencing. We identified two pathogenic and 10 loss-of-function (LOF) candidate variants, accounting for 4.74% (12 out of 253) of all the IPF cases. In burden tests, rare missense variants in three genes (CSF3R, DSP, and LAMA3) were identified that have a statistically significant relationship with IPF. Four common SNPs (rs3737002, rs2296160, rs1800470, and rs35705950) were observed to be statistically associated with increased risk of IPF. In the cumulative risk model, high risk subjects had 3.47-fold (95%CI: 2.07-5.81, P = 2.34 × 10-6 ) risk of developing IPF compared with low risk subjects. We drafted a comprehensive map of genetic risks (including both rare and common candidate variants) in patients with IPF, which could provide insights to help in understanding mechanisms, providing genetic diagnosis, and predicting risk for IPF.

Background To develop a deep neural network able to differentiate glaucoma from non-glaucoma visual fields based on visual filed (VF) test results, we collected VF tests from 3 different ophthalmic centers in mainland China. Methods Visual fields obtained by both Humphrey 30–2 and 24–2 tests were collected. Reliability criteria were established as fixation losses less than 2/13, false positive and false negative rates of less than 15%. Results We split a total of 4012 PD images from 1352 patients into two sets, 3712 for training and another 300 for validation. There is no significant difference between left to right ratio (P = 0.6211), while age (P = 0.0022), VFI (P = 0.0001), MD (P = 0.0039) and PSD (P = 0.0001) exhibited obvious statistical differences. On the validation set of 300 VFs, CNN achieves the accuracy of 0.876, while the specificity and sensitivity are 0.826 and 0.932, respectively. For ophthalmologists, the average accuracies are 0.607, 0.585 and 0.626 for resident ophthalmologists, attending ophthalmologists and glaucoma experts, respectively. AGIS and GSS2 achieved accuracy of 0.459 and 0.523 respectively. Three traditional machine learning algorithms, namely support vector machine (SVM), random forest (RF), and k-nearest neighbor (k-NN) were also implemented and evaluated in the experiments, which achieved accuracy of 0.670, 0.644, and 0.591 respectively. Conclusions Our algorithm based on CNN has achieved higher accuracy compared to human ophthalmologists and traditional rules (AGIS and GSS2) in differentiation of glaucoma and non-glaucoma VFs. Electronic supplementary material The online version of this article (10.1186/s12880-018-0273-5) contains supplementary material, which is available to authorized users.

Milk fat globule epidermal growth factor 8 (MFG-E8) is an opsonin involved in the phagocytosis of apoptotic cells. In patients with chronic obstructive pulmonary disease (COPD), apoptotic cell clearance is defective. However, whether aberrant MFG-E8 expression is involved in this defect is unknown. In this study, we examined the expression of MFG-E8 in COPD patients. MFG-E8, interleukin (IL)-1β and transforming growth factor (TGF)-β levels were measured in the plasma of 96 COPD patients (93 males, 3 females; age range: 62.12±10.39) and 87 age-matched healthy controls (85 males, 2 females; age range: 64.81±10.11 years) using an enzyme-linked immunosorbent assay. Compared with controls, COPD patients had a significantly lower plasma MFG-E8 levels (P

Background and Aims Autoimmune processes are involved in the progression of chronic obstructive pulmonary disease (COPD). Autoantibodies against cytokeratin 18 (CK18) and cytokeratin 19 (CK19) could be associated with lung injury. We undertook this study to investigate the role of these autoantibodies against CK18 and CK19 in the development of COPD. Methods and Results We used blood samples from 228 COPD patients or 136 healthy controls and male C57BL/6j mice as experimental subjects to analyze the serum autoantibody levels against CK18 or CK19 autoantigen by enzyme-linked immunosorbent assay (ELISA). We found that the circulating autoantibody levels of IgG, IgA, IgM against CK18 and CK19 were elevated in patients with COPD compared with healthy controls, which were increased gradually as the severity of the disease increases, especially in GOLD III and GOLD IV with the exception of anti-CK19 IgG and anti-CK18 IgA autoantibodies. Moreover, we observed that the serum levels of anti-CK18 and anti-CK19 IgG autoantibodies were higher in mice exposed to cigarette smoke compared with mice exposed to room air for 6 months and 9 months. Additionally, we identified the distribution of antibodies and the presence of autoantibodies (IgG) against CK18 and CK19 in the damaged lung tissues of mice. Conclusions Increased circulating autoantibodies against CK18 and CK19 are closely related to the progression of COPD, which play an important role in the process of lung injury in COPD, suggesting that it is promising for anti-CK18 and anti-CK19 autoantibodies to serve as a tool to monitor lung damage and guide treatment.

Amblyopia is a neurodevelopmental disorder of vision that occurs when the visual cortex receives decorrelated inputs from the two eyes during an early critical period of development. Amblyopic eyes are subject to suppression from the fellow eye, generate weaker visual evoked potentials (VEPs) than fellow eyes and have multiple visual deficits including impairments in visual acuity and contrast sensitivity. Primate models and human psychophysics indicate that stronger suppression is associated with greater deficits in amblyopic eye contrast sensitivity and visual acuity. We tested whether transcranial direct current stimulation (tDCS) of the visual cortex would modulate VEP amplitude and contrast sensitivity in adults with amblyopia. tDCS can transiently alter cortical excitability and may influence suppressive neural interactions. Twenty-one patients with amblyopia and twenty-seven controls completed separate sessions of anodal (a-), cathodal (c-) and sham (s-) visual cortex tDCS. A-tDCS transiently and significantly increased VEP amplitudes for amblyopic, fellow and control eyes and contrast sensitivity for amblyopic and control eyes. C-tDCS decreased VEP amplitude and contrast sensitivity and s-tDCS had no effect. These results suggest that tDCS can modulate visual cortex responses to information from adult amblyopic eyes and provide a foundation for future clinical studies of tDCS in adults with amblyopia.

To identify the subtype frequency and clinical features of neovascular age-related macular degeneration (AMD) in Chinese patients. From January 2003 to August 2006, we investigated prospectively 155 newly diagnosed patients with presumed neovascular AMD. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed in both eyes of all patients. Subtype frequency and clinical features were recorded according to their angiograms. Three subtypes of lesion were noted, which were polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP) and mixed lesions. Of the 155 patients, 105 (67.7%) had choroidal neovascularization (CNV) of the typical type seen in AMD, 38 (24.5%) had PCV and seven (4.5%) had RAP. In five (3.2%) additional cases, mixed lesions were noted. In 38 cases (47 eyes) with PCV, the rates of subfoveal, juxtafoveal and extrafoveal lesion were respectively 29.8% (14 eyes), 8.5% (four eyes), and 61.7% (29 eyes), compared with 75.6%, 14.6% and 9.8% for CNV lesion (P

To evaluate the changes of the photoreceptor layer (PRL) thickness with spectral domain optical coherence tomography (SD-OCT) and the retinal function by mfERG, as well as the correlation of morphology and function parameters in subjects with early and intermediate age-related macular degeneration (AMD). Subjects with clinical diagnosis of early or intermediate AMD and age-matched healthy subjects were recruited prospectively in this study. Color fundus photography, SD-OCT, and mfERG were conducted. Retinal photoreceptor thickness was measured, and first-order kernel responses were recorded. The differences between AMD group and control group were compared, and the correlations between macular photoreceptor thickness and the mfERG were analyzed. PRL thickness (μm) in four areas including foveola and 0.5, 1.5, and 3 mm away from foveola was 192.48 ± 17.37, 163.73 ± 12.95, 130.93 ± 9.20, and 108.78 ± 7.81, respectively, in normal eyes, whereas in AMD group, they were 158.61 ± 45.25, 138.91 ± 20.92, 118.91 ± 12.85, and 95.00 ± 9.64, respectively (P

The purpose of this study was to analyze indocyanine green (ICG) angiographic findings of Dalen-Fuchs nodules in Vogt-Koyanagi-Harada (VKH) disease. ICG angiograms of 15 patients (30 eyes) with Dalen-Fuchs nodules in VKH disease of between 2 months and 5 years after the initial diagnosis were retrospectively studied. Findings of ICG angiography were compared with features of fundus fluorescein angiography (FFA). Dalen-Fuchs nodules were easily found in the inferior (30 eyes, 100%) and temporal periphery (22 eyes, 73%) and showed two kinds of fluorescence in ICG angiography. In ten patients (20 eyes), the nodules showed small round hypofluorescent dark dots in the whole process of angiography, and the dark dots were larger in size than the nodules in FFA. Disease course in these patients was relatively long—between 1 year and 5 years. On clinical examination, the nodules were atrophic, and hyperpigmentation was found around them. In another five patients (ten eyes), parts of the nodules showed small hyperfluorescent dots in the early phase, but they were faint in the intermediate phase and became large, hypofluorescent dark dots in the late phase. Disease course in these patients was between 2 and 8 months. The nodules were bright yellow, fresh, and much larger than those in the first kind of ICG fluorescence. Dalen-Fuchs nodules in VKH are mostly present in the inferior and temporal periphery. The two kinds of fluorescence of Dalen-Fuchs in ICG angiography may reflect obliteration of choriocapillaris under the nodules and different quantities of lipofuscin in the nodules at different time points of the disease.

Purpose: To compare multifocal electroretinograms (ERGs) in control subjects and patients with central serous chorioretinopathy (CSC). Method: Eighteen eyes of control subjects and 15 eyes affected by CSC were tested with a VERIS Sciences 4.0 system. The average response densities and latencies of six annular retinal regions in control subjects were compared with those with CSC. Results: The N1, P1 average response densities of the first and second annuli were decreased and the N1, P1 latencies of first to third rings were delayed in CSC. Conclusion: The multifocal ERG can be used to evaluate retinal dysfunction in CSC.

To describe the severity and morphological features of high myopic maculopathy in Chinese patients and to evaluate their association with age, refractive error and visual acuity.Six hundred and four eyes of 337 patients (ages 8-88 years) with high myopia (refractive error ≤ -6.0 D) presenting to the Zhongshan Ophthalmic Center were studied retrospectively. All patients underwent an ophthalmological examination including digital colour fundus photography. Fundus fluorescein angiography was performed in 251 patients (443 eyes) and indocyanine green angiography was performed in 35 patients (63 eyes). The type and severity of myopic degeneration were categorized in each eye. Risk factors associated with high myopic maculopathy were evaluated using General Estimating Equation models.Two hundred and fifty-one patients (443 eyes) presented with maculopathy in this study. The most common subtype of high myopic maculopathy was lacquer cracks (prevalence 29.1%). The most commonly observed degree was M(3) (choroidal pallor and tessellation, with posterior staphyloma and lacquer cracks). Older age was significantly associated with diffuse chorioretinal atrophy (p = 0.024), patchy chorioretinal atrophy (p0.001), choroidal neovascularisation (CNV, p0.001) and macular atrophy (p = 0.002). Younger age was associated with lacquer cracks (p0.001). A higher degree of myopia was a risk factor for almost all kinds of maculopathy: tessellated fundus (p = 0.001), lacquer cracks (p0.001), diffuse chorioretinal atrophy (p0.001), patchy chorioretinal atrophy (p = 0.025) and macular atrophy p0.001), whereas a lower degree of myopia was associated with CNV (p = 0.001). A worse visual acuity was associated with lacquer cracks (p = 0.001), macular atrophy (p0.001) and CNV p0.001), while better visual acuity was associated with tessellated fundus (p0.001) and diffuse atrophy (p = 0.002). Older age (p0.001), more myopic refractive error (p0.001) and worse visual acuity (p0.001) were significantly associated with a greater severity of maculopathy. There was no gender difference in the type and severity of myopic maculopathy.Age and refractive error are important risk factors playing different roles in the development of distinct subtypes and varying severities of high myopic maculopathy. Visual acuity is significantly associated with various subtypes and the severity of high myopic maculopathy.

To characterize the clinical features of punctate inner choroidopathy (PIC) in Chinese patients.A retrospective chart review of all patients admitted with PIC from June 1999 to October 2009.Of the 75 patients (112 eyes) diagnosed with PIC, 72% were women, 80% were myopic, and 49% exhibited bilateral involvement. The mean age at presentation was 32 years. Blurred central vision (64%) and scotoma (40%) were the most common symptoms. Multifocal PIC lesions were mostly restricted to the posterior pole (95%). The acute lesions were yellow and demonstrated hyperfluorescence (61%) or mild hyperfluorescence (36%) on fluorescein angiography, mostly (75%)200 μm in diameter and10 in number. Indocyanine angiography showed subclinical hypofluorescent spots in 32% of the affected eyes. Choroidal neovascularization developed in 63% of affected eyes. Papilledema (3%) and segmental retinal phlebitis (2%) were rare. Intact follow-up data of 27 patients (43 eyes) were available. Acute lesions turned into punched-out atrophic lesions within 3 months. New visible lesions developed in 5 eyes within 1 year after symptom onset. New choroidal neovascularization developed in five eyes. The mean best-corrected visual acuity significantly improved at last follow-up (P = 0.039).Punctate inner choroidopathy in Chinese is not rare and primarily affects young myopic women. It features multifocal, small, yellow lesions that develop within a short period, principally in the posterior pole, with subsequent atrophy. Complicated choroidal neovascularization is frequent. General visual prognosis is moderately good.

This study compared the efficacy and safety of tiotropium bromide inhalation powder (spiriva) and doxofylline oral tablet (doxofylline) in the treatment of chronic obstructive pulmonary disease (COPD). A multi-center, randomized, double-blind, double-dummy, parallel-controlled study involved 127 eligible stable moderate to severe COPD patients treated with inhaled tiotropium dry powder (18 μg/day) or oral doxofylline tablets (0.2 g/time, 2 times a day) for 12 and 24 weeks. Before and after treatment for 12 weeks and 24 weeks, respectively, pulmonary function, 6-min walking distance and dyspnea index were recorded. The results showed that in both tiotropium group and doxofylline groups, after 12-week treatment, FEV(1), FEV(1)/FVC% and 6-min walk distance were significantly higher than those before the medication, while dyspnea index decreased as compared with that before treatment. After 24-week treatment, a slight improvement in the measures was observed as compared with that of 12-weeks treatment, but the difference was not statistically significant. With both 12-week and 24-week treatment, the effect of tiotropium was slightly better than that of doxofylline tablets, with the difference being statistically insignificant. The major adverse events in the tiotropium group and doxofylline group were observed in 9 cases (9.9%) and 12 cases (12.9%), respectively, and no statistically significant difference was found between them. We are led to conclude that both tiotropium at 18 μg a day and doxofylline tablets at 0.2 g/day (two times a day) are effective and safe for the treatment of COPD.

Purpose To investigate whether common genetic variants in the complement component 1 inhibitor gene (serpin peptidase inhibitor, clade G, member 1, SERPING1) are associated with polypoidal choroidal vasculopathy (PCV) in a Chinese Han population. Methods DNA samples were obtained from 118 PCV patients and 115 healthy subjects. Data derived from the HapMap project were used to select tag single nucleotide polymorphisms (SNPs) across the extended SERPING1 region. A previously reported age-related macular degeneration-related risk factor (rs2511989) was forcibly included. Genotyping of each tag SNP was performed by PCR restriction fragment length polymorphism and direct DNA sequencing techniques. Results Four SNPs for SERPING1, rs2509897, rs1005510, rs11603020, and rs2511989, were chosen as tag SNPs. None of these tag SNPs were associated with PCV, according to the single-SNP association test (p=0.41–0.83). Evaluation of common haplotypes across SERPING1 did not reveal any association with PCV (p=0.49–0.82). Conclusions We found no evidence to support the role of any common SERPING1 variants, including the rs2511989 variant, in the susceptibility to PCV in a Chinese Han population.

To investigate the autofluorescence of stale fundus haemorrhage in age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) with indocyanine green angiography (ICGA).The color photographs and ICGA were performed in 36 eyes of 36 cases of exudative AMD or PCV with stale fundus haemorrhage. All of the cases were examined by funduscopy and fundus fluorescein angiography (FFA).Autofluorescence could be observed in all of the stale haemorrhage cases. Stale haemorrhage showed grayish color and the shapes and sizes of autofluorescence in ICGA were in accordance with those of the stale haemorrhage in the color photographs. The boundaries of autofluorescence were clear and the intensities were strong. The percentage of choroidal neovascularization (CNV) or PCV in or beside stale haemorrhage was significantly higher than that outside the stale haemorrhage (27 eyes, 75%).Autofluorescence of stale haemorrhage in ICGA can be mixed up with the high fluorescence of CNV and grapes-like polypoidal dilatation. It is helpful to compare the color photographs with ICGA and recognize the different ICGA characteristics in the assessment of ICGA results in these circumstances.

To compare the features of waveform and retinal distribution between first order kernel (FOK) and second order kernel (SOK) of multifocal electro retinogram (mfERG) in normal subjects.The mfERG were recorded in 17 normal eyes. The recordings were finished by the VERIS Science 4.0 system, with the condition of 96% contrast and 103 hexagons stimulating pattern.Compared with the FOK, the waveform of SOK was complex with more wavelets. Generally, there were 3 positive and 3 negative waves in the first slice of SOK, and 4 positive and 4 negative in the second slice of SOK. Except the latencies, the retinal distributions of amplitude responses of FOK and SOK were almost the same as the following. The amplitude densities from central hexagon were the highest, and gradually decreased as the acentric degree increased. The amplitudes were larger in upper and temporal retina than those of lower and nasal retina. But the total energy of it was much smaller than that of FOK.The features of retinal distribution of SOK were almost the same as FOK in normal people. It needs further research on whether it has the specificity for some kinds of fundus diseases or not.

To measure and compare the difference between normal control and patients with idiopathic epiretinal membrane with multifocal Electroretinography (mfERG).Seventeen normal control (20 eyes) and 15 cases (19 eyes) of idiopathic epiretinal membrane were measured with VERIS Science 4.0.The abnormal mfERG was found in all of the patients with idiopathic epiretinal membrane. There existed statistically significant difference of P1 average response density and N1 latencies in all 6 ring retinal regions between the normal control and patients with idiopathic epiretinal membrane. The visual acuity of the patients were not related to average response densities of the first ring retinal region but correspondent to the latencies of the first ring retinal region.The mfERG can be used to evaluate the visual function of patients with idiopathic epiretinal membrane.

To compare cone and rod system function in patients with early age- related macular degeneration (ARMD) and control group using multifocal electroretinogram (MERG) and perimetry, to investigate whether there is rod system dysfunction in the central retina in ARMD. Cone-mediated MERG, photopic sensitivity, rod-mediated MERG, and scotopic sensitivity in 16 eyes of control subjects and 24 eyes of early dry-form ARMD were measured with VERIS Science 4.0 and Octopus 101 perimetry. The latencies and average response densities of the summed responses and five ring retinal regions, average sensitivity of all locus and eight ring retinal regions in control eyes were compared with those in ARMD. Mean scotopic and photopic sensitivity of ARMD patients were significantly lower than that of normal controls. Sotopic sensitivity reduced more than photopic sensitivity and the greatest deficit was 2.5-5.0 degrees. The amplitudes of N1 and P1 wave in one ring (5.0 degrees) of rod MERG were significantly lower of ARMD patients than that of normal subjects. Our results suggest that rod function decreased and the parafoveal rod cells were predominantly damaged in ARMD. The rod function testing in macula may be a useful tool to diagnose and measure the fundus dysfunction of ARMD.

To observe the summation effect of binocular visual field in persons with normal or abnormal visual field and study the validity of four kinds of theory (best eye, average eye, best location, binocular summation) on binocular visual field formation.The monocular and binocular visual field were tested in 15 cases with normal visual field and 58 cases of different kinds of ocular diseases with abnormal visual field.The mean rates of summation in normal visual field group and abnormal group were 93.00% and 93.10% respectively with no significant difference (P0.05). The mean degree of binocular visual field summation of normal visual field group was 7.05. The abnormal group had a greater variation of summation degree than that of normal group. The comparison of four theoretic simulating mathematical methods with the tested mean retinal sensitivity (MS) of binocular visual field in both groups showed minimum difference between the MS calculated by the model of best location and the actual MS value.Binocular summation is a common vision phenomena. In the four kinds of theory on binocular visual field formation, the model of best location can best reveal the phenomena of binocular visual field summation.

To show the abnormal choroidal vessels in aged patients with indocyanine-green angiography (ICGA).ICGA was performed in 350 patients with TOPCON TRC-50IA fundus camera. The images were recorded and retrospectively reviewed.Five aged patients out of 350 cases were found to have abnormal choroidal vessels. The incidence was 1.43%. The abnormal choroidal vessels showed round- shapet, focal enlargement, abnormal shape and entrance, satellite appearance, and vascular loops. These might be due to congenital abnormality of choroid.ICGA could be used to observe the abnormal choroidal vessels.

To analysis and evaluate the fundus characteristics and visual prognosis of macular hemorrhage in pathological myopia without choroidal neovasculopathy.Thirty-seven patients (38 eyes) of pathological myopia with macular hemorrhage and without choroidal neovascularization (CNV) underwent color photograph and fundus fluorescein angiography (FFA) examinations. Indocyanine green angiography (ICGA) was also performed on 11 patients (11 eyes). Follow-up ranged from 3 to 21 months.The macular hemorrhage in pathological myopia without CNV demonstrated oval, less than 1PD, without edema and exudation. Lacquer cracks appeared at the site of previous subretinal bleeding in 84.2% of the eyes. The visual acuities were improved in 81.6% of eyes during the follow-up period. ICGA revealed linear hypofluorescence in 7 of 11 eyes (63.6%), indicating a ruptured Bruch's membrance at the onset of subretinal bleeding.A rupture of choriocapillaris complex and Bruch's membrane causes macular hemorrhage of pathological myopia without CNV, leading to the formation of a new lacquer crack. Its prognosis is favorable.

To evaluate the visual function in different area at retinal posterior pole for the patients with cystoid macular edema (CME).Multifocal ERG was tested using visual evoked response imaging system (VERIS) 4.0 for 24 patients (27 eyes) with CME and 25 normal control subjects whose ages matched patient's ages, the traces and 3D function maps of first order kernel response were recorded on 103 retinal locations of 26.6 degrees X22.1 degrees visual field.The latencies of N1 and P1 waves were remarkably prolonged at whole area and the 6 rings in the CME, there were statistically significant differences between the normal control group and CME (P0.01). Compared with normal control group, the average response densities of N1 wave at 1, 2, and 3 rings in the CME were seriously reduced (P0.01), but they in 4, 5 and 6 rings were not significantly changed (P0.05), the average response densities of P1 at whole area and the 6 rings were reduced (P0.05).The mfERG is a promising tool to evaluate the visual function in different area at retinal posterior pole for the patients with CME. The response densities of N1 wave are better analysis index for CME.

To compare the differences of multifocal electroretinogram (mERG) in six kinds of macular diseases.The mERGS of 6 kinds of macular diseases were recorded and compared with normal corresponding age groups.The differences of mERG between maculopathies and control were significant. The amplitude densities of N1 and P1 of all 6 rings were remarkably decreased, the latencies were also significantly prolonged in all kinds of macular diseases(P0.01). The amplitudes in central 1 ring were lowered most seriously comparing with other rings. There was a tendency that the differences of amplitudes of mERG between the maculopathies and normal groups were decreased as the acentric degree increased. In the 6 kinds of macular diseases, the 1 ring amplitudes of mERGs of exudative age-related macular degeneration (ARMD), central exudative chorioretinitis, idiopathic macular hole and Stargardt's disease were more seriously decreased than those of atrophic ARMD, idiopathic epiretinal macular membrane and idiopathic central serious chorioretinpathy.mERG is an effective method to test macular function. There are group differences of macular function between different kinds of macular diseases.

To measure and compare the multifocal electroretinography in normal control and X-linked juvenile retinoschisis, 13 cases (13 right eyes) of normal control and nine cases (17 eyes) of X-linked juvenile retinoschisis were measured with VERIS Science 4.0. Four cases (eight eyes) out of the nine retinoschisis cases were tested with Ganzfeld ERG at the same day. The results showed statistically significant difference of average response densities and latencies in six ring retinal regions between the normal control and retinoschisis. The trace array and 3-D topography of multifocal ERG showed multi-area amplitude decrease with absence or reduction of central peak amplitude in patients with retinoschisis. The P1/N1 ratio of multifocal ERG average response densities in six ring retinal regions was different from the b/a ratio of Ganzfeld ERG. The multifocal ERG and Ganzfeld ERG each had its advantage in the diagnosis of retinoschisis.

Purpose To analyze choroidal folds in Vogt-Koyanagi-Harada (VKH) disease by fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). Design Retrospective, consecutive case series. Methods Records of 95 patients diagnosed with VKH disease from October 2001 to July 2006 were reviewed. All patients underwent FA, 17 patients underwent ICGA, and 20 underwent OCT. Results Of the 95 patients, 11 (12.0%) had choroidal folds and showed 10 to 15 hypofluorescent bands radiating from the optic disk that were similar to the large retinal vessels in shape and number on FA. On ICGA, the choroidal folds showed hyperfluorescence at the late stage. OCT showed clear folds but the number of folds was larger than on FA and ICGA. Conclusions Choroidal folds are not uncommon in VKH disease. FA, ICGA, and OCT can help to identify their pathogenesis.