目的：评价欧堡Daytona 200度超广角激光扫描检眼镜检查近视患者眼底周边部视网膜病变的应用价值。方法：本研究为前瞻性病例研究，收集爱尔眼科医院要求行屈光手术的近视患者1 000例(2 000只眼)，分别进行小瞳下欧堡Daytona 200度超广角激光扫描检眼镜眼底检查和散瞳后三面镜检查，记录检查结果并进行比较分析。结果：通过欧堡Daytona 200度超广角激光扫描检眼镜检查发现有周边视网膜病变共230例(310只眼)，检出阳性率为15.50%；三面镜检查发现周边部视网膜病变共242例(322只眼)，检出阳性率为16.10%。两种检查方法对近视患者周边部视网膜病变检出阳性率具有很好的一致性(Kappa值0.8~1.0)。结论：欧堡Daytona 200度超广角成像系统为检查周边部视网膜病变提供了更省时高效的方法，在屈光手术前筛查视网膜周边部病变，具有广阔的临床应用前景。
Objectives: To evaluate the clinical value of peripheral retinal diseases in myopic patients examined by 200-degree ultra-wide field laser ophthalmoscope (Daytona). Methods: This was a prospective case-control study. We collected 1 000 myopic patients (2 000 eyes) who were scheduled to undergo refractive surgery in Aier Eye Hospital. They were examined by 200-degree ultra-wide field laser ophthalmoscope (Daytona) with non-mydriasis and three-mirror contact lens with mydriasis. The examination results were recorded and statistically analyzed. Results: A total of 230 cases (310 eyes) with peripheral retinopathy were found by 200-degree ultra-wide field laser ophthalmoscope (Daytona). The positive rate was 15.50%; 242 cases (322 eyes) with peripheral retinopathy were found by three- mirror contact lens, and the positive rate was 16.10%. The two methods were consistent in the detection of peripheral Retinopathy in myopic patients (the Kappa value is between 0.8 and 1.0). Conclusion: 200-degree ultra-wide field laser ophthalmoscope (Daytona) is an effective and rapid method for detecting peripheral retinopathy. It provides a broad clinical application prospects for peripheral retinopathy screening before refractive surgery.
视网膜微循环与脑小血管具有相似的特征。视网膜被认为是可检测到的“窗口”，以检测在神经退行性疾病中发生的微血管损伤。光学相干断层扫描血管造影(optical coherence tomography angiography，OCTA)是一种非侵入性成像方式，可提供视网膜、脉络膜和视神经中血流的深度分辨图像。现总结有关OCTA在与眼科相关的阿尔茨海默病、帕金森病、多发性硬化症及视神经退行性疾病等神经系统疾病中的应用，并讨论其可否作为早期诊断和监测神经退行性疾病的重要工具。
Retinal microcirculation shares similar features with cerebral small blood vessels. Thus, the retina may be considered as an accessible ‘window’ to detect the microvascular damage occurred during the development and progression of neurodegenerative disorders. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality providing in-depth and high-resolved images of blood flow in the retina, choroid,and optic nerve. In this review, we summarize the current advances in the application of OCT-A in neurological diseases associated with ophthalmology such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and optic nerve degenerative diseases. Future directions for evaluating whether OCTA can be used as an important tool to early diagnose and monitor the neurodegenerative disorders are also discussed.
目的：制备抗水通道蛋白4(aquaporin 4，AQP4)单克隆抗体，鉴定其免疫学性能为后期临床应用奠定基础。方法：合成AQP4优势抗原表位多肽，经过免疫小鼠、细胞融合及亚克隆筛选，制备可分泌高效价高亲和力的单克隆抗体细胞株，后期获取大量单克隆抗体通过酶联免疫吸附和免疫组织化学实验进行初步实验应用。结果：获得4株杂交瘤细胞株，均能稳定分泌高亲和力抗体，经酶联免疫吸附测定实验和免疫组织化学实验证实均能特异性识别人的AQP4蛋白。结论：成功制备了亲和力高、特异性强的抗人AQP4优势抗原表位的单克隆抗体，为小分子抗体以及抗体人源化制备奠定了基础，进而为治疗视神经脊髓炎相关疾病提供理论依据和技术支持。
Objective: To lay the foundation for clinical applications in the future, we prepare and identify the immunological properties of aquaporin 4 (AQP4) monoclonal antibodies. Methods: The dominant epitope polypeptides of AQP4 were synthesized and used to obtain the cell lines which secrete high tiler and high affinity monoclonal antibodies by immunizing BALB/c mouse cell fusion and screening of subclone. The large amount of monoclonal antibodies were obtained and used for practice via immunohistochemical staining and Enzyme-linked immunosorbent assay (ELISA). Results: Four hybridomas that can stably secret anti-AQP4 antibodies were obtained. ELISA, Western blot and Immunohistochemistry results suggested that the monoclonal antibodies specifically recognized human AQP4 protein.Conclusion: The anti-human AQP4 monoclonal antibody with high affinity and specificity was successfully generated, which thereby provides the foundation for the preparation of small molecule antibodies or humanized antibodies, and then lays a theoretical and technical basis for the treatment of neuromyelitis optica (NMO).
CRISPR(clustered regularly interspaced short palindromic repeats)基因编辑技术通过精准改变细胞DNA序列，控制细胞命运及表型，是有望从根本上改变疾病治疗的新技术。由于眼球独特的生理构造，基因编辑疗法在治疗眼科疾病方面的应用具有明显的优势。目前，CRISPR基因编辑疗法治疗10型Leber先天性黑矇(Leber congenital amaurosis 10，LCA10)的临床试验已经展开，治疗其他多种眼科疾病的临床试验也即将开始。随着新一代CRISPR基因编辑技术的发展，基因编辑疗法有望为眼科疾病的治疗提供新的手段。
Clustered regularly interspaced short palindromic repeats (CRISPR) genome editing is a newly developed technology to precisely modify cellular DNA sequence, which could control cell fate and phenotype and fundamentally reform disease treatment. The structure of the eye offers unique advantages as a genome editing target. Recently, a CRISPR genome editing therapy has begun to be tested in Leber congenital amaurosis 10 (LCA10) patients, and the clinical trials for more ocular diseases are about to start. The development of CRISPR/Cas genome editing tools will drive major advances in the application of gene therapies in the treatment of ophthalmic disease.
干眼是以泪膜稳态丢失及伴随眼部不适症状为特征的最常见眼表疾病，泪膜不稳定、泪液高渗透性、眼表炎症及感觉神经异常为其主要病因。地夸磷索钠是一种P2Y2受体激动剂，能刺激黏蛋白及泪液分泌，其独特的作用机制为干眼的治疗开辟了新的方向，本文就地夸磷索钠近年的临床及基础研究进展作一综述。
Dry eye is one of the most common ocular surface diseases. It is characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and tear hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities play major etiological roles. Diquafosol tetrasodium is a purinergic P2Y2 receptor agonist that promotes mucin and aqueous tear secretion. The unique pharmacological mechanism of diquafosol tetrasodium opens up a new direction for the medical therapies of dry eye. This article reviews the clinical therapeutic effect and research progress of diquafosol tetrasodium for the past few years.
局部点药是眼部用药最常见的方式，但一般药物通过角膜困难，药物生物利用度低。纳米载体药物于8 0年代开始用于眼部，脂质体和类脂质囊泡(niosomes)与眼表的黏蛋白相互作用，延长药物在眼表的停留时间。纳米乳剂(nanoemulsion)的表面活性剂可以松解角膜上皮细胞紧密连接，形成转运开口，抑制细胞表面糖蛋白酶P(glycoprotein P，Pgp)降解药物活性蛋白。纳米粒子(nanoparticles)通过角膜上皮和结膜上皮而不会引起毒性。纳米胶囊(nanocapsules)更深地内化到角膜上皮(50 μm处)。聚合物胶束(polymeric micelles)自组装成核-壳纳米载体增强药物渗透角膜的能力。阴离子高代聚酰氨基胺(poly-amidoamine，PAMAM)树枝状大分子增强药物通透性，中性和阳离子低代树枝状大分子通过网格蛋白途径介导药物更高的通透性。纳米晶体(nanocrystal)，除增强药物溶解度和溶解速率之外，它的高黏附能力帮助药物保留和渗透到眼组织中。纳米结构材料与干眼关联密切，为干眼的治疗、诊断提供手段。
Topical administration is the most common method of ocular medication, but it is generally difficult for the drug to pass through the cornea, and the bioavailability of the drug is low. Nanocarrier drugs were used in eyes in the 1980s, and liposomes and lipoids vesicles (Niosomes) interacted with ocular surface mucins to prolong the residence time of the drug on the ocular surface. Nanoemulsion surfactants can release the tight junctions of corneal epithelial cells, form transport openings, and inhibit the degradation of pharmaceutically active proteins by cell surface glycoprotein P (Pgp). Nanoparticles pass through the corneal and conjunctival epithelium without causing toxicity. Nanocapsules internalize deeper into the corneal epithelium (at 50 μm). Polymeric micelles self-assemble into core-shell nanocarriers to enhance the ability of drugs to penetrate the cornea. Anionic high-generation poly-amidoamine (PAMAM) dendrimers enhance drug permeability. Neutral and cationic low-generation dendrimers mediate higher drug permeability through clathrin pathway. Nanocrystal, in addition to enhancing drug solubility and dissolution rate, its high adhesion ability helps drug retention and penetration into ocular tissues. Nanostructured materials are closely related to dry eye and provide a choice for the treatment and diagnosis of dry eye.
近视是危害儿童青少年视力最常见的眼部疾病，高度近视对视功能造成极大的威胁。近年来，我国近视发病率逐年升高，对近视筛查与防控的需求也不断增加，随着人工智能理论与技术的不断发展与成熟，可以辅助眼科医生进行近视筛查、诊断与治疗。本文将简要介绍人工智能在近视的筛查、预测、检测、病理性近视以及角膜屈光手术中的应用，浅谈了目前人工智能在研究中存在的可比度较低、影像要求较高、可解释性较低及隐私保护等问题，并展望人工智能在近视相关领域的应用前景。
Myopia is the most common ocular disease that harms the vision of children and adolescents. High myopia poses a great threat to visual function. The incidence of myopia in China has been increasing in recent years, and the demand for myopia screening, prevention and control has also expanded. With the continuous development of artificial intelligence theory and technology, Artificial intelligence can assist ophthalmologists in myopia screening, diagnosis and treatment. This review will briefly introduce artificial intelligence in the screening, prediction, and detection of myopia; also, the application in pathological myopia and corneal refractive surgery. This review will discuss some problems of current artificial intelligence research, such as low comparability, high image requirements, low interpretability, privacy protection, and the application prospects of artificial intelligence in myopia.
目的：运用Lea Symbols视力表、HOTV视力表对2.5~5.0岁正常儿童视力发育情况进行探究，并评价2种视力表的应用效果。方法：以随机顺序先后应用Lea Symbols视力表与HOTV视力表对广州地区2所早教中心及3所幼儿园共461例儿童(922只眼)进行单眼视力检查，所有儿童提前1 d行小瞳下检影验光、眼前节裂隙灯检查、眼底情况、眼球活动、眼位检查，筛选无器质性眼病、屈光度在正常范围的儿童作为研究对象。视力值采用5分记录方法表示。结果：1 )可测率(视力表使用配合程度)。407名儿童完成Lea Symbols视力检查，总体可测率92.08%；402名儿童完成HOTV视力检查，总体可测率90.95%；前者可测率高于后者，差异无统计学意义(χ2 =0.417，P=0.580)。进一步研究发现2种视力的可测率随年龄增长不断提高，儿童3岁之后基本都能完成2种视力的检查。2)2种视力结果及比较(5分记录法表示)。Lea视力值：右眼为4.89±0.05，左眼为4.90±0.05；HOTV视力值：右眼为4.84±0.05，左眼为4.85±0.04；前者视力好于后者，差异有统计学意义(右眼：t=3.171，P=0.003；左眼：t=3.230，P=0.003)。3)视力发育与年龄的相关性。2种视力发育与年龄存在显著正相关(P<0.001)，即随着年龄的增长，视力水平逐渐提高。4)视力发育与眼别、性别的关系。左右眼之间的视力发育差异无统计学意义(P>0.05)；男性儿童的视力发育好于女性，且差异有统计学意义(P<0.05)。结论：Lea Symbols及HOTV视力表建议用于年龄大于3岁儿童的视力检查，且儿童更容易接受Lea Symbols视力表的检查。伴随年龄的增长，儿童的视力发育呈现提高的趋势；Lea视力优于HOTV视力。视力的发育与眼别无关，男性儿童的视力发育快于女性儿童。
Objective: To conduct a preliminary study of the Lea Symbols and HOTV charts to explore the visual development of children aged 2.5 to 5.0 years, and evaluate the application values of the two charts. Methods: A total of 461 children (922 eyes) in 2 early education centers and 3 kindergartens in Guangzhou were examined by using the Lea Symbols visual acuity chart and HOTV visual acuity chart in random order. All the children underwent low-pupil photometry, anterior section slit-lamp examination, retinal condition, eye movement, and eye position examination 1 day in advance. Children with no organic eye disease and normal diopter were selected as subjects. Visual acuity was recorded with 5 points. Results: 1) Measurable rate (visual acuity chart use degree of cooperation). 407 children completed visual examination of Lea Symbols, with an overall detectable rate of 92.08%; 402 children completed HOTV vision examination, with an overall detectable rate of 90.95%. The detectable rate of the former was higher than that of the latter, but the difference was not statistically significant (χ2 =0.417, P=0.580). Further study found that the detectable rate of both visual acuities increased with age, and children were able to complete both visual acuity tests after the age of 3. 2) Results and comparison of two visual acuity (5-point recording method). The visual acuity of Lea was 4.89±0.05 in the right eye and 4.90±0.05 in the left eye. HOTV visual acuity was 4.84±0.05 in the right eye and 4.85±0.04 in the left eye. The visual acuity of the former was better than that of the latter, the difference was statistically significant (right eye: t=3.171, P=0.003; left eye: t=3.230, P=0.003). 3) Correlation between visual development and age. There was a significant positive correlation between the two types of visual development and age (P<0.001), that is, visual acuity gradually improves with age. 4) The relationship between visual development and eye and sex. There was no difference in visual development between the left and right eyes, but male children had better visual development than female, and the difference was statistically significant (P<0.05). Conclusion: Lea Symbols and HOTV visual acuity charts are recommended for visual acuity examination of children over 3 years old, and children are more likely to receive examination of Lea Symbols visual acuity chart. With the growth of age, the visual development of children shows a trend of improvement. Lea vision is superior to HOTV vision. Vision development has nothing to do with the eye, male children’s vision development is faster than female children.
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.
