近些年来，眼科疾病的临床诊断治疗及其病理发展的研究对医学影像学技术的要求日益增高，磁共振技术已广泛应用于研究眼科疾病的发病机制、治疗和分析预后。基于体素的形态学分析(voxel-based morphometry，VBM)作为一种新型的磁共振图像的分析方式，VBM可以对活体脑进行无创的形态学研究，定量分析磁共振图像中每一个单独体素内的白质、灰质的密度和体积的变化，从而反映对应区域的解剖学结构差异，能发现常规MRI不能检测到的灰质和白质结构的细微改变。不同于那些只作用于预设的感兴趣区域的分析方法，VBM完全没有偏向性，它探测全脑的异常变化，无需对感兴趣区的先验性假设，不会被研究人员的主观思维影响。这提供了一种全新的方法来探索眼科疾病中的神经病理变化，尤其在青光眼和弱视的研究中应用最多。
With the increasing requirements for medical imaging technologies in clinical diagnosis, treatment and pathological basis research of ophthalmic diseases, magnetic resonance imaging (MRI) has been broadly used in the diagnosis and prognostic evaluation of ophthalmic diseases. As a novel analytic method of MR images, voxel-based morphometry (VBM) quantitatively analyzes the changes in brain gray, white matter density and volume in each individual voxel in MR images to reflect the differences of anatomical structures in the corresponding areas, and it provides a novel way to reveal the neuronal pathological changes in ophthalmic diseases.
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).
目的：探索用细胞块制备试剂盒对眼内玻璃体液微量细胞制备细胞块的成功率，苏木素-伊红(hematoxylin-eosin，HE)染色效果及技术要点。方法：收集中山大学中山眼科中心临床病理科2020年9月至2021年1月由临床送检的25例玻璃体液(含玻璃体切割液)，应用细胞块制备试剂盒制备细胞块后，常规固定、脱水、包埋、切片，随后进行HE染色，观察染色效果。结果：25例玻璃体细胞蜡块制作成功率达到100%，制片后HE染色效果好，背景干净，细胞形态清晰，核质对比分明。结论：应用细胞块制备试剂盒能将眼内玻璃体液微量细胞制成蜡块，极大提高了标本的利用率，为后续的病理研究提供丰富的材料。
Objective: To explore the effect and technical key points of the cell block preparation kit for collecting a few cells in ocular vitreous humor. Methods: A total of 25 cases of vitreous humor (including vitrectomy fluid) were collected from Zhongshan Ophthalmic Center, Sun Yat-sen University from September 2020 to January 2021.Cell block preparation kit was used to prepare cell blocks, which were routinely fixed, dehydrated, embedded,sectioned, and then hematoxylin-eosin (HE) stained. Results: The success rate of 25 cases of vitreous cell paraffinblocks reached 100%, and the morphology of the cells was clear with clean background and shape contrast of nucleus and plasma in HE staining. Conclusion: The cell block preparation kit can make the cells of intraocular vitreous humor into paraffin blocks, which greatly improves the utilization rate of specimens and is conducive to providing abundant materials for pathological studies.
光学相干断层扫描血管成像(optical coherence tomography angiography，OCTA)是一种非接触、无创的、快速的血管造影技术，它通过检测红细胞在血管内的光学相干断层扫描(optical coherence tomography，OCT)信号的变化来提供血管影像。由于这项技术不需要注射血管造影剂，使得它比传统的眼科血管造影技术更安全。在前节疾病的检查中，OCTA不仅能够量化前节血管的范围和密度，还显示出良好的成像质量，为临床监测疾病的病程和对治疗的反应提供客观的评价。
Optical coherence tomography angiography (OCTA) is a noncontact, noninvasive, and rapid angiography technique. It provides vascular images by detecting changes in the optical coherence tomography (OCT) signal of red blood cells in the blood vessel. Since this technique does not require injection of angiography, it is safer than traditional ophthalmic angiography. In the examination of anterior segment diseases, OCTA can not only quantify the range and density of anterior segment blood vessels, but also shows good imaging quality, providing an objective evaluation for clinical monitoring of the disease course and response to treatment.
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.
目的：探讨赋能教育模式在干眼患者健康教育中的应用价值。方法：选取2017年6月至12月期间首诊于南方医科大学珠江医院眼科的干眼患者，按照完全随机分配法分为试验组(n=73)及对照组(n=73)，试验组采用赋能教育模式，对照组采用传统健康教育方式。经治疗1周、1个月、2个月及6个月后，分别随访并记录每组患者的眼表疾病指数(ocular surface disease index，OSDI)、泪膜破裂时间值(tear film break up time，BUT)，同时记录患者家庭护理(清洁睑缘、热敷、睑板腺按摩)频率以及复诊频率。结果：赋能教育组家庭护理频率及复诊频率均优于传统教育组(P<0.05)。治疗前两组OSDI和BUT差异均无统计学意义(P>0.05)，但试验组OSDI随时间的推移呈下降趋势，BUT值呈上升趋势；而对照组OSDI以及BUT值的变化均不明显。结论：运用赋能教育模式有助于提高干眼患者治疗的依从性，提高患者的家庭护理频率和复诊频率，显著改善患者的眼表情况，进而提高长期治疗效果。
Objective: To evaluate the application value of empowerment education mode in health education for patients with dry eye syndrome. Methods: Patients with dry eye syndrome were recruited from Department of Ophthalmology, Zhujiang Hospital, Southern Medical University from June 2017 to December 2017. All patients were randomly divided into the experimental group (n=73), educated with empowerment education mode, and control group (n=73), treated with traditional health education. Patients were followed up after 1 week, 1 month,2 months and 6 months, respectively. Data were collected in each follow-up visit including ocular surface disease index (OSDI), tear film break up time (BUT), the frequency of home care (cleaning eyelid margin, hot compress,palpebral gland massage) and re-visit frequency. Results: The OSDI and BUT were similar between two groups before corresponding treatment (P>0.05). After the treatment, patients in the experimental group showed a downtrend in the OSDI and uptrend in the BUT. No significant changes were found in the control group during the follow-up. The frequency of family nursing and re-visit in the experimental group was statistically higher than that in the control group. Conclusion: The application of empowering education mode can improve the compliance of dry eye patients, improve the frequency of home care and follow-up visit, and mitigate the ocular surface of patients, thereby enhancing the long-term efficacy.
光学相干断层扫描血管成像术(optical coherence tomography angiography，OCTA)作为一项新兴的检查手段，现已被广泛应用于眼科临床及科研工作中。鉴于OCTA在血管成像方面的独特优势，近年来关于其在眼前段的临床应用和研究也愈发得到关注。关于OCTA对结膜、巩膜、角膜以及虹膜的血管和相关眼表疾病的研究日益增多，其在眼前段应用潜力巨大。
As a new examination method, optical coherence tomography angiography (OCTA) has been increasingly used in ophthalmology clinical work and scientific research. In view of the unique advantages of OCTA in angiography,the clinical application and research of OCTA in the anterior segment have attracted more and more attention in recent years. Studies of OCTA in vessels of conjunctiva, sclera, cornea, iris, and related ocular surface diseases have shown great potential for its application in the anterior segment.
目的：应用彩色多普勒超声造影检查测定不同类型原发性青光眼患者的视神经血液供应情况，探讨血流变化与青光眼的关系。方法：选取2012年1 2月至2014年3月在哈尔滨医科大学附属第二医院眼科经临床确诊的原发性闭角型青光眼(primary angle closure glaucoma，PACG)患者16例(20只眼)和原发性开角型青光眼(primary open angle glaucoma，POAG)患者8例(10只眼)，分别设为PACG组和POAG组；同时，选取1 0例1 0只正常眼设为对照组。所有受试者分别行彩色多普勒及超声造影检查，观察眼动脉(ophthalmic artery，OA)、视网膜中央动脉(central retinal artery，CRA)、睫后短动脉(short posterior ciliary artery，SPCA)的血流动力学指标，包括收缩期最大血流速度(peak systolic velocity，PSV)、舒张末期血流峰值速度(diastolic peak velocity,EDV)、血流阻力指数(resistance index，RI)、造影剂到达时间(arrival time，AT)及消退时间(departure time，DT)等指标，并对结果进行统计学分析。结果：超声造影测定POAG组的眼动脉造影剂AT较正常对照组延长(P=0.035)，PACG组及POAG组的眼动脉造影剂DT均较正常对照组延长(P=0.010)；彩色多普勒测定PACG组及POAG组的OA和SPCA，以及POAG组的CRA的PSV、EDV均较正常对照组减低(P=0.003)；同时，PACG组及POAG组的OA以及POAG组的CRA的RI较正常对照组增高(P<0.001)。结论：彩色多普勒及超声造影可以检测青光眼患者的眼部血供明显低于正常人群，为临床诊治青光眼及评价眼部疾病患者的眼部血供状态提供了一种新的技术手段。
Objective: This study used Doppler imaging and contrast-enhanced ultrasound to measure ocular haemodynamic of patients with primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG), to investigate the association between the blood flow changes and glaucoma. Methods: Doppler imaging and contrast-enhanced ultrasound were performed on 16 PACG patients (20 eyes, PACG group), 8 POAG patients(10 eyes, POAG group) who were diagnosed in the Department of Ophthalmology, the Second Affiliated Hospital of Harbin Medical University from Dec. 2012 to Mar. 2014. The normal eyes from 10 persons were selected as control group. The flow velocity of ophthalmic artery, central retinal artery, and posterior ciliary artery were observed, including the peak systolic velocity, diastolic peak velocity, resistance index, and the arrival time and departure time of the ultrasound microbubbles (SonoVue). Results: Compared to control group, the arrival timeof the ultrasound microbubbles (SonoVue) of ophthalmic artery of patients with POAG increased (P=0.035),and the departure time of ophthalmic artery of patients with PACG and POAG increased (P=0.010). Both peak systolic velocity and diastolic peak velocity of the ophthalmic artery and short posterior ciliary artery of patients with PACG and POAG and the central retinal artery of patients with POAG decreased (P=0.003). Meanwhile, the resistance index of ophthalmic artery of patients with PACG and POAG and the central retinal artery of patients with POAG were higher than those in the control group (P<0.001). Conclusion: The flow velocity of ocular vascular was worse than that of normal group respectively. This study provides a new technology for the diagnosis of glaucoma and the evaluation of the flow velocity of ocular vascular.
目的：借助于人工智能(artificial intelligence,AI)眼底筛查远程接转诊系统，探索“患者-社区-医院”远程筛查模式，推进眼科分级诊疗和双向转诊实施，为地市级医疗机构开展眼底疾病人工智能筛查工作提供一定的经验借鉴。方法：通过AI辅助远程筛查基层医疗机构的4886例患者，完成眼科检查并经AI初判、人工复核形成眼底诊断结论。通过医联体和专科联盟模式，对基层医疗机构的4886例患者的AI诊断系统结果和上级医师审核结果进行对照分析，分析AI诊断系统在眼科常见病种筛查中的推广应用的可信度和可行性。结果：AI检出DR的灵敏度为94.70%，特异度96.06%；DME的灵敏度96.43%，特异度96.55%；AMD的灵敏度77.55%，特异度95.74%；同时，其在病理性近视、白内障、青光眼等常见病种眼底筛查中也有一定作用。结论：AI辅助远程筛查系统对于绝大多数眼底疾病有较高的敏感性和特异性，适用于眼底疾病的筛查工作，利于基层医院或社区医院对于眼底疾病的初步诊断，落实眼科分级诊疗，有借鉴推广意义。
Objective: With the help of artificial intelligence (AI) based fundus screening remote referral telemedicine system,it enables us to explore the remote screening mode of patient-community-hospital, and promote the two-way referral and ophthalmic graded diagnosis. This investigation provides certain practice experiences for prefecture-level medical institutions to carry out AI screening for fundus diseases. Methods: Ophthalmologic examination was performed on 4,886 patients in primary medical institutions through AI-aided remote screening, and the final fundus diagnosis conclusion was formed after AI preliminary judgment and manual review. Through the Medical Consortium and specialty alliance model, the results of the AI diagnosis system and the audit results of superior physicians for 4 886 patients in primary care institutions were compared and analyzed, and the credibility and feasibility of the AI diagnosis system application in the screening of common ophthalmic diseases were discussed. Results: The sensitivity and specificity of AI detection of diabetic retinopathy were 94.70% and 96.06%, respectively. In the diabetic macular edema classification, the sensitivity and specificity were 96.43% and 96.55%, respectively. In the age-related macular degeneration classification, the sensitivity and specificity were 77.55% and 95.74%, respectively. Meanwhile, it also plays a role in screening common fundus diseases such as pathological myopia, cataract and glaucoma. Conclusion: The AI-aided remote screening system has high sensitivity and specificity for most of fundus diseases, indicating it is promising for fundus diseases screening in primary medical institutions. It is conducive for primary hospitals or community hospitals to carry out the initial diagnosis of fundus diseases, as well as the implementation of graded diagnosis and treatment of ophthalmology, which has reference and promotion significance.
