目的:探讨原发性慢性闭角型青光眼(chronic primary angle-closure glaucoma,CPACG)患者的视网膜血流密度(vessel density,VD)与视野缺损程度的相关性。方法:光学相干断层血管成像技术(optical coherence tomography angiography,OCTA)测量89例(112眼)视野缺损的CPACG患者的黄斑区VD、视盘旁VD,分析VD与视野缺损程度的相关性。结果:视盘旁VD与视野缺损程度成负相关(r>–0.728,P<0.05)。黄斑浅层总VD的受试者工作曲线(receiver operating characteristic,ROC)及曲线下面积(area under the curve,AUC)为0.874。在控制年龄、眼压及视力的情况下,黄斑总浅层VD每降低1%,视野平均缺损(mean deviation,MD)值增加–0.639 dB。结论:CPACG患者VD与视野缺损呈线性负相关,OCTA可以方便无创地观察青光眼患者眼底血流情况,在视野缺损前发现视网膜VD降低,从而可以作为CPACG早期诊断的参考指标。
Objective: To investigate the correlation between the retinal vessel density (VD) and the degree of visual field loss in chronic primary angle-closure glaucoma (CPACG). Methods: Eighty-nine CPACG patients (112 eyes)with different degrees of visual field loss were measured with optical coherence tomography angiography (OCTA) for macular VD and para-optic microcirculation VD, and the correlation between them and the degree of visual field defect were analyzed. Results: There was a negative correlation between the VD of the microcirculation in each zone next to the optic disc and the degree of visual field loss (r>–0.728, P<0.05). The receiver operating characteristic (ROC) and area under the curve (AUC) of the total VD of the superficial macula is 0.874. Under the condition of controlling age, intraocular pressure and vision, for every 1% decrease in the total superficial macular VD, the average visual field defect mean deviation (MD) value increases –0.639 dB. Conclusion: The VD of CPACG patients is linearly negatively correlated with visual field defects. OCTA can conveniently and non-invasively observe the blood flow of the fundus in patients with glaucoma. It is found that the retinal VD is reduced before visual field defects, which can be used as a reference index for early diagnosis of CPACG.
抗血管内皮生长因子(vascular endothelial growth factor,VEGF)治疗视网膜静脉阻塞(retinal vein occlusion,RVO)继发黄斑水肿(macular edema,ME)的有效性及安全性已得到广泛证实。但抗VEGF治疗方案尚无统一标准。现行的治疗方案主要包括固定治疗方案、按需(pro re nata,PRN)治疗方案、稳定性标准驱使的按需(stabilization criteria-driven PRN)治疗方案、治疗与延长(treat and extend,T&E)方案。近年来不少研究综合比较了各个治疗方案在改善视功能、量化评估疾病活动性、调整随访频率等多个维度的表现,为临床医生提供选择抗VEGF治疗方案的参考依据。本文旨在回顾并总结近年来对抗VEGF药物治疗RVO继发ME的研究,阐述抗VEGF治疗方案的研究进展。
The efficacy and safety of anti-vascular endothelial growth factor (VEGF) in the treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) have been widely confirmed. However, there is no unified standard for anti-VEGF treatment regimens. Current treatment regimens mainly include fixed treatment regimen, pro re nata (PRN) treatment regimen, stabilization criteria-driven PRN treatment regimen, and treat and extend (T&E) regimen. In recent years, many studies have compared different treatment regimens in composite dimensions,including improving visual function, assessing disease activity quantitatively and adjusting the follow-up frequency,to provide clinicians with a reference of choosing anti-VEGF treatment regimens. The purpose of this article is to review and summarize recent researches on anti-VEGF drugs in the treatment of ME secondary to RVO, and to clarify the research progress in the anti-VEGF treatment regimens.
目的:应用生物信息学方法分析视网膜母细胞瘤(retinoblastoma,RB)基因表达谱芯片,从转录水平探讨RB与正常视网膜组织的差异表达基因(differentially expressed genes,DEGs)的功能及相互作用。方法:通过公共基因表达数据库(gene expression omnibus,GEO)数据库中选取GSE97508和GSE110811两个芯片数据,共有34个RB组织和6个正常视网膜组织。利用GEO2R工具对和Draw Venn Diagrams软件,筛选出正常视网膜组织与RB组织间的DEGs。通过在线STRING检索工具(search tool for the retrieval of interacting genes,STRING),对DEGs进行基因本体注释(gene ontology,GO)、KEGG富集通路分析、蛋白互作(protein-protein interaction,PPI)K分析。结果:在2个芯片中发现视网膜母细胞瘤共有20个DEGs,包括3个上调DEGs和17个下调DEGs,GO本体注释结果显示表达上调DEGs所富集的功能主要在细胞分裂、染色体浓缩、核分裂和DNA构象改变。下调DEGs主要富集在光传导、视觉感知、光感受器细胞修复、感光细胞内外节和调节视紫红质介导的信号通路等。KEGG通路显示上调DEGs没有显著的信号通路,下调DEGs参与光传导信号通路,其中包括CNGA1,CNGB1,RHO,SAG四个基因,通过PPI网络提示这4个基因相互联系,并发现与其他节点连接最紧密核心基因RHO。结论:利用生物信息学方法能有效对RB基因芯片数据进行挖掘,为进一步研究RB发生发展机制及寻找潜在的药物治疗靶点提供参考。
Objective: To find differentially expressed genes between retinoblastoma and normal retinal tissues by bioinformatics analysis, and to investigate their molecular function and interactions in the transcriptional level.Methods: The gene expression profile datasets GSE97508 and GSE110811, including 34 retinoblastoma (RB) tissues and 6 normal retinal tissues, were downloaded from gene expression omnibus (GEO). Differentially expressed genes (DEGs) between normal retinal tissues and RB tissues were identified by GEO2R tool and the Draw Venn Diagrams software. The gene ontology (GO) analysis, KEGG pathway and protein-protein interaction (PPI) were analyzed by STRING. Results: In two microarrays of retinoblastoma we found total 20 DEGs were identified, including 3 up-regulated and 17 down-regulated genes. The GO ontology annotation results showed that the enrichment functions of up-regulated genes were mainly in cell division, chromosome enrichment, nuclear division, and DNA conformation change. Down-regulated genes were mainly concentrated in light conduction,visual perception, photoreceptor cell repair, photoreceptor cell inner and outer segment, and regulation of rhodopsin mediated signaling pathway. The KEGG pathway showed that there was no significant signal pathway in which up-regulated genes up-regulated DEGs, and down-regulated genes were involved in the phototransduction signaling pathway, including four genes of CNGA1, CNGB1, RHO and SAG. PPI network suggested that these four genes were interlinked, and RHO was found to be the most closely connected core gene with other nodes.Conclusion: Bioinformatics can be used effectively to analyze RB microarray data to provide theoretical reference for further exploration of tumorigenesis mechanism and help search for potential drug therapeutic targets.
目的:分析不同程度2型糖尿病视网膜病变的血清生化全套指标,探讨各生化指标与糖尿病性视网膜病变(diabetic retinopathy,DR)程度的相关性。方法:回顾性收集2018年5月至2020年10月在福建医科大学附属第二医院就诊的2型糖尿病患者。根据眼底情况分为3组:糖尿病不伴视网膜病变(non-diabetic retinopathy,NDR)组(17例)、糖尿病伴非增殖性视网膜病变(non-proliferative diabetic retinopathy,NPDR)组(29例)、糖尿病伴增殖期视网膜病变(proliferative diabetic retinopathy,PDR)组(34例)。采用SPSS 24.0分析比较3组血清生化全套各指标水平,对差异指标与DR相关性采用Pearson相关分析与多重线性回归分析。结果:3组年龄差异无统计学意义(P>0.05);3组的总蛋白、白蛋白、白球比、钙浓度差异均有统计学意义(均P<0.05)。组间比较发现NPDR和PDR组总蛋白、白蛋白、白球比、钙浓度低于NDR组,差异有统计学意义(P<0.05)。Pearson相关分析显示总蛋白(r=?0.290)、白蛋白(r=?0.304),钙浓度(r=?0.252)与DR呈负相关(均P<0.05),多重线性回归提示总蛋白、白蛋白及血钙浓度是DR保护因素(P<0.05)。结论:血清指标总蛋白、白蛋白及血钙浓度与DR成负相关,在生理范围内将这些指标维持相对较高的水平,或许可以为糖尿病视网膜病变的防治提供新思路。
Objective: To analyze the serum biochemical indexes of different degrees of type 2 diabetic retinopathy, and the correlation between biochemical indexes and the degree of diabetic retinopathy (DR). Methods: Patients with type 2 diabetes admitted to the Fujian Medical University 2nd Affiliate Hospital from May 2018 to October 2020 were retrospectively collected. The patients were divided into 3 groups according to fundus conditions: non-diabetic retinopathy (NDR) group (n=17), diabetes with non-proliferative diabetic retinopathy (NPDR) group (n=29),diabetes with proliferative diabetic retinopathy (PDR) group (n=34). SPSS 24.0 was used to compare the levels of a complete set of serum biochemical indexes in the three groups. Pearson correlation analysis and multiple linear regression analysis were used for the correlation between the different indexes and DR. Results: There was no statistically significant difference in age between the three groups. The differences in total protein, albumin, white sphere ratio, and calcium concentration of the three groups were statistically significant (P<0.05). The comparison between the groups showed that the total protein, albumin, white sphere ratio, and calcium concentration in the NPDR and PDR groups were lower than those in the NDR group. The difference was statistically significant (P<0.05). Pearson correlation analysis showed that total protein (r=?0.290), albumin (r=?0.304), andcalcium concentration (r=?0.252) were negatively correlated with DR (all P<0.05). Multiple linear regression indicated total protein, albumin and blood calcium concentration were the protective factors of DR (P<0.05).Conclusion: This study found that serum levels of total protein, albumin, and blood calcium levels are negatively correlated with DR. Maintaining a relatively high level of these indexes within the physiological range may provide new ideas for the prevention and treatment of diabetic retinopathy.
目的:研究玻璃膜疣主要成分胆固醇对人视网膜色素上皮细胞ARPE-19中金属硫蛋白表达的影响。方法:体外培养ARPE-19细胞,将细胞分为对照组和胆固醇处理组(2.5 mg/mL),取样时间为0,6,12,24,48,72h。通过实时定量PCR检测hMT1a,hMT2a和hMT3在转录水平的表达,用蛋白质印迹法检测总金属硫蛋白的表达。结果:在转录水平上hMT1a,hMT2a和hMT3受到胆固醇影响mRNA表达上调,且hMT3上调倍数最大;总金属硫蛋白的蛋白表达随着胆固醇处理时间延长明显增多。结论:玻璃膜疣主要成分胆固醇可以上调人视网膜色素上皮细胞中金属硫蛋白的表达,提示金属硫蛋白表达可受到玻璃膜疣形成起始阶段的刺激,其检测是否能用于年龄相关性黄斑变性的早期发现及早期诊断还需深入探讨。
Objective: To study the effects of cholesterol, the main component of drusen, on the expression of metallothionein of ARPE-19 cells. Methods: The ARPE-19 cell line was cultured in vitro, and the cells were divided into a control group and a cholesterol treatment group (2.5 mg/mL). The treatment time was 0, 6, 12, 24, 48, 72 hours. Real- time quantitative PCR was used to detect the expression of hMT1a, hMT2a and hMT3 at the mRNA level, and Western blot was used to detect the expression at the protein level. Results: The mRNA expression of hMT1a, hMT2a and hMT3 were up-regulated by cholesterol and the protein expression of total MTs was increased with cholesterol treatment. Conclusion: Cholesterol, the main component of drusen, can up-regulate the expression of metallothionein in human retinal pigment epithelial cells, suggesting that the expression of metallothionine can be stimulated by the initial stage of drusen formation. However, whether its detection can be used for the early detection and early diagnosis of age-related macular degeneration or not still needs to be further explored.
眼结核的表现形式多样,有时会被误诊漏诊。本病例为一年轻男性,以右眼视力突发下降为主诉就诊,眼部表现可见黄斑区脉络膜占位病灶及视网膜内小病灶,经γ-干扰素释放试验、胸部CT等检查,确诊为血型播散性肺结核,眼部诊断为结核性脉络膜结节联合视网膜结节,全身接受抗结核治疗后,眼部病灶消退。
Ocular tuberculosis encompasses a variety of clinical manifestations, which is easily misdiagnosed sometimes. In this article, a young male was admitted to our hospital with a chief complaint of sudden blurred vision in his right eye. His ocular examination detected a tiny mass in the choroid and a small lesion in the retina. After interferon-gamma release assay (IGRA) and chest CT scan, the patient was diagnosed with military tuberculosis. The ocular examination confirmed the diagnosis of choroidal tubercle complicated with intrarentinal tubercle, which were healed after systemic anti-tuberculosis therapy.
目的:观察急性中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)的自然病程中渗漏点的形态及变化。方法:本研究为前瞻性研究,使用光学相干断层扫描(optical coherence tomography,OCT)观察从发病到发病后5~13个月的CSC患者的渗漏点的OCT形态,测量并计算Hall层、脉络膜全层各自厚度及比值,并进行比较。结果:共20例患者[男14例,女6例,年龄33~59(中位数41)岁]纳入研究。随访时间为5~13个月。在19例患者中观察到微小视网膜色素上皮脱离(pigment epithelium detachment,PED)。1例患者可见视网膜色素上皮(retinal pigment epithelium, RPE)小凸起。在随访期间,仅1例患者的PED完全恢复,其他19例患者在视网膜下液被完全吸收时,RPE和Bruch膜之间仍存在微小分离。渗漏点处的Haller层/脉络膜厚度显著高于中央凹处(初诊时0.806±0.08 vs 0.863±0.06,P=0.003;最后1次随访时为0.801±0.07 vs 0.851±0.06,P=0.004)。结论:本研究观察到在急性CSC患者自然病程中,即使视网膜下液吸收,OCT显示渗漏点处仍存在持续的PED,更厚的Haller层及更薄的内层脉络膜,这些发现为CSC的发病机制提供了更多线索。
Objective: To observe the morphology and changes of leakage points in the natural course of acute central serous chorioretinopathy (CSC). Methods: This study was a prospective study, using optical coherence tomography to observe the OCT morphology of leakage points in CSC patients from onset to 5 to 13 months after onset, measuring the thickness and ratio of Hall layer and the whole choroid, and then compare them. Results: A total of 20 patients were included in the study, including 14 males and 6 females, aged from 33 to 59, with the median being 41 years old. The follow-up time ranged from 5 months to 13 months. Minute retinal pigment epithelial detachments (PED) were observed in 19 patients. A small bulge of retinal pigment epithelium (RPE) was observed in 1 patient. During the follow-up, only one patient totally recovered. Small separation between RPE and Bruch membrane still exit even subretinal fluid were absorbed completely in the other 19 patients. The thickness of Haller layer or choroid at the leakage point was significantly higher than that of the fovea (0.806±0.08 vs 0.863±0.06, P=0.003, at the first visit; 0.801±0.07 vs 0.851±0.06, P=0.004, at the last follow-up). Conclusion: This study observed that in the natural course of acute CSC patients, even if the subretinal fluid was absorbed, OCT still showed that there was persistent PED at the leakage point, thicker Haller layer and thinner inner choroid layer. These findings provided more clues to the pathogenesis of CSC.
目的:对视网膜光学相干断层扫描图像中不同层和积液区域的分割。方法:提出一种基于深度学习的轻量级的神经网络,参考DRUNet体系、膨胀卷积和残差网络的架构,通过连接不同深度网络处得到的上采样输出,进行多尺度特征融合,使网络能够更好地识别出图像中的边界信息。结果:改进型DRUNet显著提升了视网膜分层的效果,准确率较U-Net提高了1.25%,同时能提前1~2次迭代达到传统U-Net的准确度。结论:本文采用的网络结构提高了对视网膜光学相干断层扫描图像的分割性能,同时降低了网络参数,具有强大的应用潜力。
Objective: To achieve the segmentation of different layers and fluid areas on the optical coherence tomography (OCT) image of the retina. Methods: A lightweight neural network based on deep learning was proposed. The network structure adopted in this study was designed based on the architecture of dilated-residual U-Net. By connecting the upsampling output obtained at different depth networks, multi-scale feature fusion was performed to enable the system to accurately identify the boundaries on the OCT image. Results: Compared with U-Net, this algorithm could achieve the same accuracy with 1–2 epochs less, and the accuracy was also improved by 1.25%. Conclusion: The proposed network improves the segmentation performance of retinal OCT images, and reduces the number of parameters, which demonstrates the network has great application potential.
目的:评价不同操作者使用视网膜自动图像分析(automated retinal image analyzer,ARIA)软件测量糖尿病患者视网膜血管管径和迂曲度的重复性和再现性。方法:采用前瞻性诊断性试验研究设计,由2名熟练操作者应用ARIA软件对49名糖尿病患者以视盘为中心的45°数码眼底彩照进行视网膜血管半自动分析。通过测量距离视盘0.5~1.0个视盘直径内的视网膜动静脉血管参数,各选取6条最粗的动静脉综合计算得到中央动脉管径当量(central retinal artery equivalent,CRAE)、视网膜中央静脉管径当量(central retinal vein equivalent,CRVE)、视网膜动静脉比值(arteriole-to-venule ratio,AVR)、平均视网膜动脉迂曲度(mean retinal arteriolar tortuosity,MRAT)、平均视网膜静脉迂曲度(mean retinal venular tortuosity,MRVT)。在此基础上,评价同一操作者与不同操作者间测量结果的重复性和再现性,并绘制Bland-Altman图进行一致性分析。结果:操作者A两次测量的CRAE、CRVE、AVR差异无统计学意义(t= -0.089、-1.425、1.214,均P>0.05),重复性良好(ICC≥0.725)且高度正相关(r≥0.721)。操作者A与操作者B对同一受试者2次测量的CRAE、CRVE、AVR差异无统计学意义(t= -1.169、-0.050、0.941,均P>0.05),再现性良好(ICC≥0.750)且高度正相关( r≥0.697)。同一操作者和不同操作者间的MR AT、MRVT差异无统计学意义(P≥0.05),Spearman非参数相关性分析重复性和再现性较好(r≥0.571,r≥0.588,均P<0.01)。结论:利用ARIA软件测量糖尿病患者视网膜血管管径及迂曲度具有良好的重复性和再现性。
Objective: To assess the repeatability and reproducibility in measurements of retinal vessel diameter and tortuosity in diabetic patients using the Automated Retinal Image Analyzer (ARIA). Methods: A prospective diagnostic trial was performed; 2 skilled researchers performed a semi-automatic analysis of retinal vessels in digital color fundus photography (45° field of view centered on the optic disc) from 49 diabetic patients using ARIA software. Six largest arterioles and venules coursing through an area of 0.5–1.0 disc diameter surrounding the optic disc were selected. Then the retinal vessel parameters were calculated into the central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), arteriole-to-venule ratio (AVR), mean retinal arteriolar tortuosity (MRAT) and mean retinal venular tortuosity (MRVT). To evaluate the repeatability of those values in 2 measurements by the same researcher and the reproducibility between different researchers. Bland-Altman analysis was employed to assess the agreement of the outcomes. Results: There was no significant difference in the CRAE, CRVE, and AVR values in the two-time measurements of researcher A (t= -0.089, -1.425 and 1.214, all P>0.05). It also showed a good repeatability and a highly positive correlation (ICC≥0.725, r≥0.721). There was no significant difference in those measurements between researcher A and B (t= -1.169, -0.050, 0.941, all P>0.05). It also showed a good reproducibility and a highly positive correlation (ICC≥0.750, r≥0.697). Results showed that there was no significant difference in the MRAT and MRVT values both in intraobserver and interobserver measurements (P≥0.05). Besides, Spearman’s nonparametric correlation analysis showed good repeatability and reproducibility (r≥0.571, r≥0.588, all P<0.01). Conclusion: ARIA software yields good repeatability and reproducibility in the measurements of retinal vessel diameter and tortuosity in diabetic patients.