眼睛由屈光系统和视觉神经系统两大部分构成,是人体最重要的感觉器官之一。眼部各组织的发育或功能异常都可能造成不同程度的视力损害。目前主要通过动物实验或体外细胞培养的方法探究眼病的病理生理机制和治疗手段,但上述两种方法都存在一定的局限性。体外细胞培养不能完全反映器官的形态、结构和生化特征,而动物模型的物种和遗传背景具有异质性。近年来,随着原代组织、胚胎干细胞、诱导多能干细胞衍生的体外三维结构类器官和器官微流控芯片技术的不断发展,构建出了与在体器官的结构、功能更为相似的器官克隆模型,能够提供更敏感、定量、规模化的表型分析,更好地应用于眼的发育、生理结构、疾病机制、个性化医学诊断和治疗方法等方面的研究。目前,眼科的微流控器官芯片与类器官技术在角膜、晶状体、泪腺、视网膜结构发育和疾病模型均展现出巨大的应用潜力。
The eye is composed of refractive system and visual nervous system. It is one of the most important sensory organs of the human body. The abnormal development or function of eye tissues may cause various degrees of visual impairment. At present, the pathophysiological mechanism and treatment of eye diseases are mainly explored through animal experiments and in-vitro cell culture. However, they are of certain limitations. The in-vitro cell culture cannot fully reflect the morphological, structural and biochemical characteristics of organs, whereas the animal models are heterogeneous of species and genetic background. In recent years, with the continuous development of in-vitro three-dimensional structure organoids and organ microfluidic organ-on-a-chip technology derived from primary tissues, embryonic stem cells and induced pluripotent stem cells, organ cloning models more similar to in vivo organs in terms of the structure and function have been constructed. These models can provide more sensitive, quantitative and large-scale phenotypic analysis, and can be better applied to the research of eye development, physiological structure, disease mechanism, personalized medical diagnosis and treatment. At present, microfluidic organ-on-a-chip and organoids technologies have shown great application potential in the structural development and disease models’ construction of cornea, lens, lacrimal gland and retina.
神经退行性疾病会损害大脑和神经系统的结构和功能,导致认知和行为能力逐渐下降,因此,早期诊断神经系统疾病可以促进预防、监测和治疗,从而改善患者的预后。眼与脑在结构和胚胎学上的相似之处为评估中枢神经系统的神经和微血管变化提供了潜在可能。眼组学是眼科学、遗传学和生物信息学的交叉学科,目标是开发快速、无创、具有成本效益的生物标志物,用于全身性疾病的筛查、诊断和风险分层。随着诊断和眼科成像技术的进步,用于检测眼的结构、功能和视觉变化的各项技术得到了快速发展。眼部生物标志物成为评估神经退行性疾病进展有前景的工具。文章采用眼部影像学(例如 OCT、OCTA)和电生理学(例如 VEP、ERG)等筛查方法检测眼部异常神经退行性疾病,总结了眼组学在神经退行性疾病的应用,包括阿尔茨海默病、帕金森病、额颞叶痴呆、肌萎缩侧索硬化症和亨廷顿病,旨在为神经退行性疾病的诊断和治疗提供新的思路。尽管并非所有生物标志物都是疾病特异性的,但未来大数据、人工智能和眼组学的融合,有可能进一步深入了解这些神经退行性疾病。
Neurodegenerative diseases can damage the structure and function of the brain and nervous system, leading to a gradual decline in cognitive and behavioral abilities. Therefore, early diagnosis of neurological diseases can promote prevention, monitoring, and treatment, thereby improving the prognosis of patients. The structural and embryological similarities between the eyes and the brain provide potential for evaluating neurological and microvascular changes in the central nervous system. oculomics is an interdisciplinary field that combines ophthalmology, genetics, and bioinformatics, with the goal of developing rapid, non-invasive, and cost-effective biomarkers for screening, diagnosis, and risk stratification of systemic diseases. With the advancement of diagnostic and ophthalmic imaging technologies, various techniques for detecting the structure, function, and visual changes of the eye have been rapidly developed. Eye biomarkers have become promising tools for assessing the progression of neurodegenerative diseases. The article uses screening methods such as eye imaging (such as OCT, OCTA) and electrophysiology (such as VEP, ERG) to detect abnormal neurodegenerative diseases in the eyes. It summarizes the application of oculomics in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, frontotemporal dementia, amyotrophic lateral sclerosis, and Huntington's disease, aiming to provide new ideas for the diagnosis and treatment of neurodegenerative diseases. Although not all biomarkers are disease-specific, the integration of big data, artificial intelligence, and oculomics in the future may further deepen our understanding of these neurodegenerative diseases.
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.
暴露性角膜炎是角膜失去眼睑保护而暴露在空气中,引起角膜干燥、上皮细胞脱落进而继发感染的角膜炎症,多见于眼睑缺损、眼球突出、睑外翻、面神经麻痹、手术麻醉等。泪液的缺失、眼睑闭合不全、眼表暴露等因素皆会影响角膜健康,使其处于炎症、溃疡及穿孔的危险中。暴露性角膜炎治疗目的是去除暴露因素、保护角膜上皮和维持眼表湿润,目前常用的治疗手段有手术治疗与药物治疗,有些是暂时性的,有些是永久性的。
Exposure keratitis is an inflammation of the cornea that occurs when the cornea loses the protection of the eyelid and is exposed to air, resulting in dryness, epithelial exfoliation, and secondary infection. Most of them are found in eyelid defect, protopsis, eyelid ectropion, facial palsy, and anesthesia. Loss of tears, lagophthalmos and exposed ocular surface all affect the health of the cornea, putting it at risk of inflammation, ulceration, and perforation. The purpose of treatment is to remove exposure factors, protect the corneal epithelium and keep ocular surface moist.Currently, the commonly used treatments are surgical treatment and medical treatment, and some of them are temporary while others are permanent.
血源性滴眼液是治疗干眼的一种有效的治疗方法。来源可分为自体、供体,其中供体来源又可分为成人外周血及脐带血,并以血清、富血小板血浆、血小板来源生长因子以及血小板裂解产物的形式制成。由于各种血液制品的原理及适应症不同,本文将对不同血源性滴眼液制品的制备及面临的挑战的共识问题进行解读。
Blood-based eye drops can be used effectively in the treatment of dry eyes. The sources of blood-based eye drops can be divided into autologous and donor, and donor sources can be divided into adult peripheral blood and umbilical cord blood, which are prepared in the form of serum, platelet-rich plasma, platelet-derived growth facters and platelet lysate. Due to the different principles and indications of various blood products, the consensus issues on the preparation and challenges of different blood-based eye drop products are reviewed.
在热带和亚热带国家,真菌性角膜炎是角膜盲的一个重要原因。随着现代医学的进展,早期真菌性角膜炎通过药物或者手术治疗后治愈率有了显著改善,但是很多真菌性角膜炎患者由于缺乏及时合理的治疗,病情变得迁延难治,预后较差。随着无数学者的努力,近年来在难治性真菌性角膜炎领域在抗真菌药物、给药方式及其他治疗方式上有了一些新的进展,目前可选的难治性真菌性角膜炎治疗方式各有特点及优劣之处。了解目前可用的抗真菌治疗方式、其适应证及不良反应等,是处理难治性真菌性角膜炎病例的必要条件。
Fungal keratitis is a significant cause of corneal blindness in tropical and subtropical countries. With the development of modern medicine, the cure rate of early fungal keratitis has been significantly improved after medical or surgical treatment. However, due to the lack of timely and reasonable treatment for many patients with fungal keratitis, the disease has become difficult to treat and the prognosis is poor. With the efforts of numerous scholars, some new advances have been made in the treatment of recalcitrant fungal keratitis in recent years, such as antifungal drugs and administration methods. At present, the treatment methods of recalcitrant fungal keratitis have their own characteristics, advantages and disadvantages. It is necessary to understand the available antifungal therapies, their indications and side effects for the treatment of recalcitrant fungal keratitis.
目的:探讨大气污染物NO<sub>2</sub>水平与干眼患病的相关性。方法:选取2014年1月至2018年1月共计75 279例干眼患者的临床资料,进行资料汇总。空气质量和天气数据来自西安市气象局2014—2018年的每日环境空气质量数据。分析中包括的环境空气污染物NO<sub>2</sub>。所有数据均按小时收集。计算每个变量的每日平均值,并计算本研究中使用的每周平均值。本研究中患者均自愿参加,并经南昌大学第一附属医院医学研究伦理委员会批准。结果:干眼的门诊就诊次数与NO<sub>2</sub>水平显著相关。本研究发现不同年龄段的人受到不同的参数变化影响,环境中NO<sub>2</sub>的浓度对于全年龄段的人患干眼有显著相关性,对性别无选择性,男女均会因为NO2在环境中的不同水平而患干眼。较高水平的环境NO<sub>2</sub>会增加门诊患者干眼的概率。我们通过对患者人数的累计与环境中NO<sub>2</sub>浓度进行相关性分析,发现其有显著相关性,因此环境空气污染和天气变化可能导致干眼的恶化。结论:大气污染物NO2与干眼患病有显著相关性。
Objective: To investigate the correlation between NO2 levels in air pollutants and dry eye. Methods: The clinical data of 75 279 patients with dry eye from January 2014 to January 2018 were selected and summarized. The air quality and weather data were from the daily ambient air quality data of Xi’an Meteorological Bureau from 2014 to 2018. Environmental air pollutants NO2 was included in the analysis. All data were collected on an hourly basis. We calculated the daily average for each variable and then calculated the weekly average used in this study.All patients in this study volunteered to participate. , and this study was approved by the Medical Research Ethics Committee of the First Affiliated Hospital of Nanchang University. Results: We found that the number of outpatient visits for dry eye was significantly correlated with NO2 levels. Our study found that people of different ages were affected by different parameter changes. The concentration of NO2 in the environment was significantly correlated with dry eyes in all age groups, and is not selective for gender. Both men and women could develop dry eyes due to different levels of NO2 in the environment. Our results showed that higher levels of environmental NO2 increased the chances of dry eyes in outpatients. By analyzing the correlation between the cumulative number of patients and the NO2 concentration in the environment, we found that the correlation was significant.Therefore, ambient air pollution and weather changes may lead to the deterioration of dry eye. Conclusion: There is a significant correlation between atmospheric pollutant NO2 and dry eye disease.
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.
泪膜的不同组成成分通过相互作用共同维持眼球表面的湿润,从而维持眼部健康。当这些组成成分出现病理性改变,将会不同程度的影响泪膜稳态,从而导致干眼的发生。而瞬目运动一定程度上影响着泪膜组成成分的分布,随着对干眼相关机制研究的逐步深入,以泪膜为导向的诊断(tear-film-oriented diagnosis,TFOD)的新概念被提出,并被逐渐被接受。我们可以通过泪膜破裂方式来确定眼球表面所缺乏的组成成分,并在此基础上对干眼进行诊断,从而定向补充泪膜缺失成分,重新恢复泪膜稳态。本文将着重分析瞬目、泪膜形成及泪膜破裂机制之间的关系,从而进一步明确泪膜定向诊断的新概念及发展方向。
Different components of the tear film work together to maintain the wettability of the ocular surface, thus maintaining eye health. When the pathological changes of these components occur, the tear film homeostasis will be affected to varying degrees, leading to dry eye. Blinking movement affects the distribution of tear film components to some extent. With the continuous development of research and understanding of the concept and mechanism of dry eye, new concepts of tear-film-oriented diagnosis (TFOD) have been gradually proposed and widely accepted. We can determine the components lacking on the surface of the eye through the tear film breakup patterns (BUPs). On this basis, dry eye is diagnosed, so as to replenish the lacking components of tear film directionally and restore the stability of tear film. This paper will focus on analyzing the relationship between blinking, tear film formation and tear film break-up mechanism, so as to further clarify the new concept and development direction of tear-film oriented diagnosis.