目的:获取眼表图像的综合信息,建立眼表疾病综合诊断和评估。方法:将超高分辨率光学相干断层成像仪(ultra-high resolution optical coherence tomography,UHR-OCT)与基于裂隙灯生物显微镜的微血管成像系统相结合,开发了一种多模态、非接触式的眼科光学成像平台。结果:UHR-OCT模块在组织中实现轴向分辨率约为2 μm 。眼表微血管成像模块在最大放大倍率下横向分辨率约为3.5 μm。通过集成在裂隙灯显微镜成像光学路径的不同模块,多模态成像平台能够执行实时前段OCT结构成像、结膜微血管成像和传统裂隙灯成像功能。利用自主开发的软件,进一步分析结膜血管网络图像和血流图像,获取血管分形维数、血流速度、血管直径等定量形态学和血流动力学参数。结论:通过在健康受试者和角膜炎患者的在体成像测试,表明多模态眼前段成像设备可为眼科临床应用及人工智能提供结构和功能信息数据。
Objective: To obtain the comprehensive information of the anterior eye image, establish complementary information for the diagnosis and evaluation of ocular diseases. Methods: We developed a multi-modal, non-invasive optical imaging platform by combining ultra-high resolution optical coherence tomography (UHR-OCT) with a microvascular imaging system based on slit-lamp biomicroscopy. Results: The uHR-OCT module achieved an axial resolution of approximately 2 μm in tissues. The lateral resolution of the ocular surface microvascular imaging module under maximum magnification was approximately 3.5 μm. By combining the imaging optical paths of different modules, the customized multi-modal eye imaging platform was capable of performing real-time cross-sectional UHR-OCT imaging of the anterior eye, conjunctival vessel network imaging, high-resolution conjunctival blood flow videography, and traditional slit-lamp imaging on a single device. With self-developed software, a conjunctival vessel network image and blood flow videography were further analyzed to acquire quantitative morphological and hemodynamics parameters, including vessel fractal dimensions, blood flow velocity and vessel diameters. Conclusion: The ability of the multi-modal anterior eye imager to provide both structural and functional information for ophthalmic clinical applications can be demonstrated in a healthy human subject and a keratitis patient.
视网膜退行性疾病的种类繁多、患病人口基数大,该病特征为终末期严重的视网膜细胞丢失。视网膜类器官(retinal organoid,RO)可通过3D干细胞体外分化培养技术大量获取,并拥有完整的各亚型视网膜细胞和经典的视网膜分层结构。因此,RO可作为最佳的视网膜退行性疾病建模方法之一,以便于发现潜在致病机制。目前,RO衍生物已被广泛用于视网膜细胞替代治疗的动物实验和临床研究,具体的成效参差不齐,可能的影响因素包括移植细胞数量、移植时间窗、移植工具等。随着RO相关研究的快速发展,视网膜退行性疾病在分子和个体上的诊断和治疗将进一步完善。
Retinal degenerative diseases, characterized by severe retinal cell loss at the end stage, are of various kinds and haunt vast amounts of patients. Retinal organoid (RO) with complete retinal cell subtypes and classic retinal stratification structures can be obtained in large quantities through stem cells in vitro 3D differentiation and culture method. Therefore, RO can serve as one of the best ways for retinal degenerative disease modeling to facilitate the decipherment of underlying pathogenic mechanisms. At present, RO derivatives have been widely used in animal experiments and clinical studies of retinal cell replacement therapy with varying results possibly affected by cell quantity, time window, or tools in terms of transplantation. With the booming progress of RO-related research, the diagnosis and treatment on molecular and individual level for retinal degenerative diseases will be further improved.
目的:建立能驱动GFP在视网膜神经节细胞(retinal ganglion cell,RGC)中特异性表达的小鼠胚胎干细胞系。方法:通过同源重组的方式建立Brn3b-GFP敲入的小鼠胚胎干细胞系(Brn3b-GFP ESC),利用3D培养将其诱导成视网膜类器官检测GFP表达的细胞特异性,再用流式细胞分选富集GFP阳性RGC,采用玻璃体腔注射的方式将GFP阳性RGC移植到健康小鼠和NMDA损伤模型小鼠眼中探索该细胞的应用价值。结果:Brn3b-GFP ESC经3D视网膜诱导培养后在RGC中特异性表达GFP,将这些GFP阳性RGC移植到两种小鼠中2周后能在所有视网膜内观察到GFP阳性细胞存活,且均能观察到有供体RGC整合到宿主视网膜RGC层。结论:本研究建立了RGC特异的报告基因干细胞系Brn3b-GFP ESC,通过将该细胞系诱导成视网膜类器官进而获得的GFP阳性RGC移植后能够整合进宿主视网膜。该细胞系的建立将为青光眼及相关疾病提供重要的研究手段和工具。
Objective: This study was designed to establish a mouse embryonic stem cell line that can drive GFP expression specifically in retinal ganglion cells (RGCs). Methods: In this study, we established a Brn3b-GFP knock-in embryonic stem cell line (Brn3b-GFP ESC) by homologous recombination. By 3D culture, we induced these cells into retinal organoids to investigate the cell-specificity of GFP expression. GFP-positive RGCs were then enriched by flow cytometry and transplanted by intravitreal injection into the eyes of healthy mice and NMDA injury model mice to explore the feasibility of a potential clinical application. Results: GFP was specifically expressed in RGCs following induction of Brn3b-GFP ESCs into 3D retinal organoids. Two weeks after these GFP-positive RGCs were transplanted into the control and injured mice, GFP-positive cells were observed in all transplanted retinas, and donor RGCs were seen to integrate into the RGC layer of the host retina. Conclusion: This study has established a retinal ganglion cell-specific reporter stem cell line Brn3b-GFP ESC. The GFP-positive RGCs obtained by inducing the cell line into retinal organoids can be integrated into the host retina after transplantation. The establishment of such a cell line will provide an important research tool for glaucoma and related diseases.
视网膜疾病大多以周边视网膜病变为首要表现,后者的早期诊断、监测对于视网膜疾病的治疗及预防起着至关重要的作用。以往传统眼底成像技术仅能提供20°视网膜的可视范围,即便使用蒙太奇拍摄技术,也只能采集部分眼底范围。目前眼底成像技术已步入最新的超广角时代,其所提供的眼底视野至少可达200°,并且基于该技术的超广角眼底彩色照相、荧光素血管造影、光学相干断层扫描及其血管造影等已广泛应用于临床实践中,对于诊断及评估视网膜疾病发挥重要作用,如糖尿病性视网膜病变、视网膜静脉阻塞、早产儿视网膜病变、视网膜色素变性及视网膜脱离等。本文将从超广角成像技术的产生、发展及其国内外的临床应用现状作一综述,旨在为临床工作及研究提供指导意义。
Retinal diseases primarily feature with peripheral retinopathy, and its early diagnosis as well as the later following up both play a vital role in the treatment and prevention of retinal diseases. In the past, traditional fundus imaging technology can only provide the visual range of 20 degrees. Even if montage photography technology is used, it can only partially reveal the fundus field. At present, fundus imaging technology has entered the latest era of ultra-wide-field, which provides at least 200-degree fundus field of vision. Ultra-wide-field fundus photochromy, fluorescein angiography, optical coherence tomography and angiography based on this technology have been widely used in clinical practice, and play an important role in the diagnosis and evaluation of retinal diseases, such as diabetes retinopathy, retinal vein occlusion, retinopathy of prematurity, retinitis pigmentosa and retinal detachment. This article aims to review the occurrence and development of ultra-wide-field fundus imaging technology and its clinical applications up to now to provide a relative guideline for clinic and research.
白内障作为一种常见的眼科疾病,是全球第一位致盲眼病,目前尚无药物能够治疗,手术是唯一有效的办法。随着现代眼科手术技术的发展以及人工晶状体(intraocular lens,IOL)设计和功能的更新升级,人们对视觉质量的要求越来越高,白内障超声乳化联合IOL植入术已经从单纯的复明手术转变为个性化的屈光手术。为满足不同需求的患者术后获得较好的视觉质量,IOL经历了从单焦点到多焦点、球面到非球面的发展,还有散光型IOL和各类功能性IOL的临床应用,也为患者提供了更多的选择。充分了解不同类型IOL的优势和特点,根据患者自身眼部情况、日常用眼习惯以及需求,个性化地选择IOL植入对视觉质量的恢复和满意度起着至关重要的作用。因此本文将针对不同类型的IOL,从设计与分类、术后临床效果及适应人群进行综述,为IOL的选择提供指导建议。
As a common eye disease, cataract is the first-leading cause of blindness in the world. Currently, there is no drug to treat it, and surgery is the only effective way. With the development of modern ophthalmic surgical technology and the updating and upgrading of the design and function of intraocular lens (IOL), people have higher and higher requirements for visual quality. Cataract phacoemulsification combined with IOL implantation has transformed from a simple vision restoration to personalized refractive surgery. In order to meet the needs of patients with different needs to obtain better visual quality after surgery, IOL has experienced the development from monofocal to multifocal, spherical to aspherical, as well as the clinical application of astigmatic IOL and various functional IOLs, which also provides more choices for patients. Fully understanding the advantages and characteristics of different types of IOLs, according to the patient’s own eye conditions, daily eye habits and needs, individualized selection of IOL implantation plays a crucial role in the recovery and satisfaction of visual quality. Therefore, this article will review different types of IOLs from the aspects of design and classification, postoperative clinical effects and adaptation to the population, and provide guidance for the selection of IOLs.
本文根据上海鹰瞳医疗科技有限公司的创新产品《糖尿病视网膜病变眼底图像辅助诊断软件》在国家药品监督管理局(NMPA,原CFDA)历时两年半的上市前创新申报与注册申报经历,介绍了人工智能类医疗器械产品的产品研发、注册申报流程及相关重点难点,并且列明了在整个过程中需要遵循和参考的法律法规,为此类产品的上市前注册工作提供参考。
Based on the NMPA premarket application through two and a half years for the computer aided diagnosis software using fundus images of diabetic retinopathy, which is an innovative medical device of Shanghai EagleVision Medical Technology Co., Ltd. (Airdoc), this article introduced the development process, the premarket application, and the key points in the application of this artificial intelligence device, also lists the related regulations and guidelines as references to provide some ideas for the follow-up premarketing application of such kind of products.
眼睛是人体最重要的感觉器官之一,主要由角膜和晶状体构成的屈光系统和视网膜构成的视觉神经系统2个部分构成。眼睛各组织的发育和功能异常都可影响视功能,甚至致盲。现有的致盲眼病的治疗方式均存在各自瓶颈问题,新的诊治方法亟待开发。近年来,得益于干细胞和组织工程学的发展,结合现有眼各组织的发育理论知识,研究者们利用多种来源的干细胞在体外成功诱导出具有组织特异结构和功能的眼类器官。眼类器官研究为利用干细胞研究眼组织发育和眼病发病机制、药物筛选以及替代治疗创造了新机遇,将干细胞治疗眼病的转化研究推向了一个更高平台。本文将对现有眼类器官的技术发展及应用进行综述。
Being one of the most important sensory organs, the eye is composed of the cornea, the lens, which are responsible for refraction, and the retina, which is the neural sensory part of the eye. Various kinds of developmental abnormalities and functional defects could lead to visual dysfunctions, and even blindness. Current treatments for blindness-causing eye diseases all have their own limitations, awaiting new efficient diagnostic and treating methods. Thanks to the development in stem cell biology and bioengineering, taking advantage of the rich knowledge accumulated on the mechanisms governing eye development, researchers have successfully generated various ocular organoids using multiple sources of stem cells in vitro, which resemble their counterparts in vivo on both the structural level and functional level. Ocular organoids provide valuable material and models for studying eye development, pathology, drug screening, and cell replacement therapy, pushing translational studies of ocular stem cell to a new era. Here, the paper reviews the development and application of ocular organoid technologies.
目的:观察盐酸艾司氯胺酮联合丙泊酚在小儿眼睑肿物刮除术中的临床应用效果,评价盐酸艾司氯胺酮联合丙泊酚在小儿眼睑肿物刮除术麻醉中的有效性和安全性。方法:选择2020年11月至2021年7月在佛山市第二人民医院择期行眼睑肿物刮除术的70例患儿,随机分为A组和B组,每组35例。A组采用七氟烷联合丙泊酚复合麻醉,B组采用盐酸艾司氯胺酮联合丙泊酚复合麻醉。记录两组患儿诱导时间、手术时间、苏醒时间、复苏总时间;监测麻醉前、麻醉后5 min、手术开始前、手术结束后患儿血流动力学及呼吸频率变化;记录两组患儿苏醒后即刻、返回病房即刻的东安大略儿童医院疼痛评分量表(Children’s Hospital of Eastern Ontario Pain Scale,CHEOPS)疼痛评分、躁动评分、恶心呕吐评分。结果:两组患儿麻醉诱导时间比较差异无统计学意义(P>0.05);两组患儿麻醉过程中血流动力学水平、呼吸频率差异无统计学意义(P>0.05);B组患儿苏醒时间、复苏总时间均明显低于A组(P<0.05);B组患儿苏醒后即刻及返回病房即刻CHEOPS疼痛评分、躁动评分、恶心呕吐评分均明显低于A组(P<0.05)。另外,B组患儿术后出现恶心呕吐概率低于A组(P<0.05)。结论:盐酸艾司氯胺酮联合丙泊酚应用于小儿眼睑肿物刮除术麻醉,能提供良好麻醉镇痛效果,降低躁动反应和恶心呕吐的发生
Objective: To investigate the anesthetic effect and to evaluate the efficacy and safety of combination application of esketamine and propofol in curettage of eyelid tumors of children. Methods: This study selected 70 children who underwent elective eyelid tumor curettage in Foshan Second People’s Hospital from November 2020 to July 2021. They were randomly divided into group A and group B, with 35 cases in each group. Patients in Group A were anesthetized with sevoflurane combined with propofol. Patients in Group B were anesthetized with esketamine combined with propofol. The anesthetic induction time, operation time, recovery time and total recovery time of the two groups were recorded. The haemodynamics and respiratory frequency changes of patients were being monitored before anesthesia, 5 minutes after anesthesia, before the operation and after the operation. The scores of Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) pain, agitation and nausea and vomiting were recorded immediately after the patients awakened and were sent back to the ward. Results: There was no significant difference in anesthesia induction time between the two groups (P>0.05). There was also no significant difference in the haemodynamics and respiratory frequency changes during the anaesthetic process between the two groups (P>0.05). The recovery time and total recovery time in group B were significantly lower than those in group A (P<0.05). The scores of CHEOPS pain, agitation and nausea and vomiting in group B were significantly lower than those in group A immediately after the patients awakened and were sent back to the ward (P<0.05). Besides, the probability of nausea and vomiting after curettage of eyelid tumors was lower in group B than in group A (P<0.05). Conclusion: Combination application of esketamine and propofol in curettage of eyelid tumors of children can provide good anesthetic and analgesic effect and reduce the occurrence of restlessness, nausea and vomiting.
近年来人工智能(artificial intelligence,AI)技术在医学领域的应用发展迅猛,尤其在眼科领域,成果显著,极大地提高了相关影像数据的诊断效率,推动了该领域研究的进展。然而,大多数AI的应用都集中于成人眼病,在婴幼儿眼病方向的研究较少。究其原因,可能是婴幼儿眼部影像数据采集配合度低,部分影像设备应用受限,且相关领域专业眼科医生数量匮乏。然而,婴幼儿期是视觉发育最重要的阶段,也是出生缺陷早期筛防诊治的重灾区,对患儿的视觉发展具有长远且重要的影响,亟需AI相关产品提高婴幼儿眼病筛查效率,缓解医疗资源不足的现状。本文将对近年AI在婴幼儿眼病领域的研究应用现状、进展及存在的相关问题进行综述。
In recent years, the application of artificial intelligence (AI) in medicine, especially in ophthalmology, has developed rapidly with remarkable results. This has greatly improved the diagnostic efficiency of relevant imaging data and promoted further research in this field. However, most applications of AI are focused on adult eye diseases, and few studies have addressed infantile eye diseases. This may be because of the non-cooperative nature of infants, the limited availability of imaging equipment in infants, and the lack of pediatric ophthalmologists. Infancy is the most important stage of vision development. Disturbance during this period have a profound and lasting influence on vision development. Hence, early screening, diagnosis, and treatment of birth defects is important. AI-related products, which improves the efficacy of infant eye disease screening, are urgently needed. This paper reviews the current status, progress, and existing problems of recent research related to application of AI in infantile eye diseases.