泪液渗透压在干眼发病机制中的作用及诊疗进展

干眼是一种以眼表稳态丧失,泪膜不稳定性增加为特征的多因素疾病,伴有眼干涩、异物感、灼烧感、眼红、疼痛、畏光、流泪、眼疲劳、视力下降、分泌物增多、对外界刺激敏感等眼部症状,其病理生理机制主要是泪膜不稳定、泪液渗透压(tear osmolarity, Tosm)升高、眼表炎症和损伤及神经感觉异常。Tosm是维持泪膜稳定性和眼表舒适度的重要因素。Tosm升高可造成干眼患者眼部不适、角膜上皮损伤、杯状细胞丢失及眼部炎症反应,炎症反应可进一步降低泪膜稳定性和增加Tosm,使干眼陷入恶性循环。为了更全面地了解泪液高渗(tear hyperosmolarity, THO)与干眼的关系,本文将从病理生理学方面,重点讨论THO在干眼发病机制、干眼诊断、干眼严重程度分级中的作用,及其针对性治疗。     

干眼病理损害中的炎症机制

干眼是一种泪液和眼表的多因素性疾病,可引起眼部不适、视觉障碍、泪膜不稳定和眼表损害,并伴有泪膜渗透性升高和眼表炎症。目前研究表明,炎症在干眼的发病和病理损害中起着重要作用。本文从炎症与泪液渗透压、眼表黏蛋白表达、角结膜上皮结构及功能、泪腺及睑板腺结构和功能等方面对炎症造成干眼眼表和泪液功能损害的可能机制进行综述。     

生活方式相关性干眼的研究进展

干眼是常见的眼表慢性疾病,是多种因素导致的泪膜不稳定和眼表微环境失衡,从而引起各种症状和/或视力障碍,并可能同时伴有眼表损伤的疾病.近年来,随着生活方式和环境等多种因素的改变,干眼的发病率逐年增加.既往关于干眼致病因素的研究多集中于器质性因素,然而近年研究发现,非器质性因素对干眼的发生也有不可忽视的作用.本文介绍了近年...     

Dry eye: an update on clinical diagnosis,management and promising new treatments

Dry eye conditions are prevalent with one in four to five patients presenting to eye care practitioners having dry eye signs and/or symptoms. An intimate relationship exists between the ocular surface and the tear film. The cycle of tear film instability and ocular surface damage characteristic of dry eye conditions suggests that dry eye represents a dysfunction of an integrated ocular surface‐lacrimal gland unit. Therefore, dry eye is a multifactorial condition and an approach based on clinical subtypes is required for diagnosis and management. There is increasing evidence that inflammation is a contributing and exacerbating factor in dry eye conditions and anti‐inflammatory or immunomodulatory therapy for chronic dry eye conditions may facilitate ocular surface healing. Other promising new treatments for dry eye include new generation artificial tear polymers and preservative systems, secretagogues, topical androgen supplements and surgical techniques for ocular surface reconstruction.     

TFOS DEWS II pathophysiology report

The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease. Its central mechanism is evaporative water loss leading to hyperosmolar tissue damage. Research in human disease and in animal models has shown that this, either directly or by inducing inflammation, causes a loss of both epithelial and goblet cells. The consequent decrease in surface wettability leads to early tear film breakup and amplifies hyperosmolarity via a Vicious Circle. Pain in dry eye is caused by tear hyperosmolarity, loss of lubrication, inflammatory mediators and neurosensory factors, while visual symptoms arise from tear and ocular surface irregularity. Increased friction targets damage to the lids and ocular surface, resulting in characteristic punctate epithelial keratitis, superior limbic keratoconjunctivitis, filamentary keratitis, lid parallel conjunctival folds, and lid wiper epitheliopathy. Hybrid dry eye disease, with features of both aqueous deficiency and increased evaporation, is common and efforts should be made to determine the relative contribution of each form to the total picture. To this end, practical methods are needed to measure tear evaporation in the clinic, and similarly, methods are needed to measure osmolarity at the tissue level across the ocular surface, to better determine the severity of dry eye. Areas for future research include the role of genetic mechanisms in non-Sjögren syndrome dry eye, the targeting of the terminal duct in meibomian gland disease and the influence of gaze dynamics and the closed eye state on tear stability and ocular surface inflammation.     

眼表成像技术在干眼患者泪膜分析评价中的应用

干眼是一种复杂的眼表疾病,主要由于泪膜不稳定或眼表微环境失衡所导致。临床上常用泪膜破裂时间、角膜荧光染色评分和泪液分泌试验等指标来评估干眼,这些指标具有较强的主观性,且侵入性的操作也会干扰患者眼表。近年来出现各种客观无创的眼表成像技术用于泪膜分析,如角膜地形图、泪膜干涉测量、泪膜蒸发速率测量、眼前节光学相干断层成像和像差测量等。这些检测手段有助于对干眼进行诊断和疗效评估。本文就眼表成像技术在干眼患者泪膜分析评价中的应用作一综述。     

Diagnosis of dry eye

Dry eve disease is characterized by symptoms, ocular surface damage, reduced tear film stability, and tear hyperosmolarity. There are also inflammatory components. These features can be identified by various kinds of diagnostic tests (symptom questionnaires, ocular surface staining, tear break-up time, and osmometry), although there may not be a direct correlation between the number or severity of symptoms and the degree of ocular surface damage or tear deficiency. Once the diagnosis of dry eye disease has been established, further tests can be used to classify the condition into tear-deficient or evaporative dry eve. The two forms of dry eye are not mutually exclusive and often co-exist. The optimal diagnosis of dry eye disease, therefore, depends on the results of several tests, and this article suggests an appropriate order for performing these tests at a single clinic visit.     

A mass and solute balance model for tear volume and osmolarity in the normal and the dry eye

Tear hyperosmolarity is thought to play a key role in the mechanism of dry eye, a common symptomatic condition accompanied by visual disturbance, tear film instability, inflammation and damage to the ocular surface. We have constructed a model for the mass and solute balance of the tears, with parameter estimation based on extensive data from the literature which permits the influence of tear evaporation, lacrimal flux and blink rate on tear osmolarity to be explored. In particular the nature of compensatory events has been estimated in aqueous-deficient (ADDE) and evaporative (EDE) dry eye.The model reproduces observed osmolarities of the tear meniscus for the healthy eye and predicts a higher concentration in the tear film than meniscus in normal and dry eye states. The differential is small in the normal eye, but is significantly increased in dry eye, especially for the simultaneous presence of high meniscus concentration and low meniscus radius. This may influence the interpretation of osmolarity values obtained from meniscus samples since they need not fully reflect potential damage to the ocular surface caused by tear film hyperosmolarity.Interrogation of the model suggests that increases in blink rate may play a limited role in compensating for a rise in tear osmolarity in ADDE but that an increase in lacrimal flux, together with an increase in blink rate, may delay the development of hyperosmolarity in EDE. Nonetheless, it is predicted that tear osmolarity may rise to much higher levels in EDE than ADDE before the onset of tear film breakup, in the absence of events at the ocular surface which would independently compromise tear film stability. Differences in the predicted responses of the pre-ocular tears in ADDE compared to EDE or hybrid disease to defined conditions suggest that no single, empirically-accessible variable can act as a surrogate for tear film concentration and the potential for ocular surface damage. This emphasises the need to measure and integrate multiple diagnostic indicators to determine outcomes and prognosis. Modelling predictions in addition show that further studies concerning the possibility of a high lacrimal flux phenotype in EDE are likely to be profitable.     

干眼症眼表损害炎症机制

干眼症为一种多因素造成泪膜稳定性和眼表功能损害的疾病,易引起眼部不适、视力障碍、泪膜不稳定与眼表的潜在危害,可伴有泪液渗透压升高及眼表炎症反应。炎症是干眼发病中最关键因素,多种免疫细胞和炎症因子参与了干眼症的发生与发展过程。细胞凋亡、神经调节异常、性激素失调等也共同参与了干眼的发病过程。最近尽管在阐述干眼的病理生理和发病机制取得了一定进展,但目前还未形成统一标准。本文将对炎症造成干眼症眼表和泪液功能损害的可能机制进行综述。     

Keratitis in Dry Eye Disease and Topical Ciclosporin A

Tear film alterations in dry eye disease (DED) include reduced tear volume and an increase in inflammatory cytokines. Instability and reduced tear production initiate a vicious cycle where hyperosmolarity, ocular inflammation, and apoptosis may induce damage of the ocular surface including keratitis. Topical cyclosporine (CsA) has been used for the treatment of moderate-to-severe DED; however, previous studies failed to demonstrate its benefits by the European Agency standards. A new formulation of CsA 0.1% has been recently approved in the EU to treat severe keratitis in DED patients. Patients with severe keratitis showed a better improvement after 6 months of treatment with CsA compared with vehicle. HLA-DR expression was significantly reduced by CsA treatment. The clinically significant improvement in keratitis associated with the inflammatory biomarker HLA-DR confirms the efficacy of CsA to improve inflammation and its damaging effect on the ocular surface in DED patients.     

眼表病理生理改变在干眼中的研究进展

干眼的发病率逐年升高,目前已成为最常见的眼部疾病之一。干眼的症状主要为眼部的干涩感、异物感、烧灼感、痒、分泌物等,这些不适很大程度上影响了干眼患者的日常生活、工作学习、心理健康和身体功能。干眼是一种多因素眼病,其特征是泪膜稳态的丧失,泪液的高渗透压、眼表炎性反应和损伤以及神经感觉异常等参与了干眼的发生发展,同时,干眼患者眼部会出现组织结构及眼表微环境的改变。由于干眼是一种日益严重的公共卫生问题,严重影响人们的视觉质量和生活质量,因此,研究干眼的病理生理对开展高效的诊断、更具针对性的治疗及减少不良事件的发生具有重要意义。本文对近年来干眼的病理生理学的研究进展进行综述。     

Role of Hyperosmolarity in the Pathogenesis and Management of Dry Eye Disease: Proceedings of the OCEAN Group Meeting

Dry eye disease (DED), a multifactorial disease of the tears and ocular surface, is common and has a significant impact on quality of life. Reduced aqueous tear flow and/or increased evaporation of the aqueous tear phase leads to tear hyperosmolarity, a key step in the vicious circle of DED pathology. Tear hyperosmolarity gives rise to morphological changes such as apoptosis of cells of the conjunctiva and cornea, and triggers inflammatory cascades that contribute to further cell death, including loss of mucin-producing goblet cells. This exacerbates tear film instability and drives the cycle of events that perpetuate the condition. Traditional approaches to counteracting tear hyperosmolarity in DED include use of hypotonic tear substitutes, which have relatively short persistence in the eye. More recent attempts to counteract tear hyperosmolarity in DED have included osmoprotectants, small organic molecules that are used in many cell types throughout the natural world to restore cell volume and stabilize protein function, allowing adaptation to hyperosmolarity. There is now an expanding pool of clinical data on the efficacy of DED therapies that include osmoprotectants such as erythritol, taurine, trehalose and L-carnitine. Osmoprotectants in DED may directly protect cells against hyperosmolarity and thereby promote exit from the vicious circle of DED physiopathology.     

Das trockene Auge

The etiology of dysfunctional tear syndrome ("dry eye") is multifactorial and complex. Recent evidence suggests an important role of androgens in regulating tear film secretion onto the ocular surface. In addition, inflammatory processes of the ocular surface seem to be the common final pathway of all chronic forms of dry eye. Novel concepts of pathogenesis and state-of-the-art diagnostic tools are discussed. In vivo confocal microscopy allows quantification of ocular surface inflammatory cells. This is of increasing importance for evaluation of anti-inflammatory treatments in dry eye patients.     

糖尿病性干眼发病机制及治疗进展

糖尿病是一种主要以损害微血管为主的病变。随着生活水平的提高,糖尿病患者的数量也逐渐增加,据最新数据显示,全球的糖尿病患病率高达9.3%(4.63亿人)。糖尿病相关的视网膜病变是导致工作人群视力障碍最主要的原因,近年来人们逐渐认识到高糖也可以引起眼表泪膜的不稳定、角膜神经功能障碍、角膜感知功能下降、泪液渗透压升高。糖尿病引起的眼表功能障碍原因复杂,机制多样,包括高糖导致泪膜各层结构破坏、树突状细胞-神经沟通障碍、炎性因子破坏泪腺分泌泪液等。本文就糖尿病性相关干眼的发生机制、研究进展进行综述,以期眼科医师在诊疗糖尿病干眼患者时更多考虑全身情况。     

New Perspectives on Dry Eye Definition and Diagnosis: A Consensus Report by the Asia Dry Eye Society

For the last 20 years, a great amount of evidence has accumulated through epidemiological studies that most of the dry eye disease encountered in daily life, especially in video display terminal (VDT) workers, involves short tear film breakup time (TFBUT) type dry eye, a category characterized by severe symptoms but minimal clinical signs other than short TFBUT. An unstable tear film also affects the visual function, possibly due to the increase of higher order aberrations. Based on the change in the understanding of the types, symptoms, and signs of dry eye disease, the Asia Dry Eye Society agreed to the following definition of dry eye: “Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage.” The definition stresses instability of the tear film as well as the importance of visual impairment, highlighting an essential role for TFBUT assessment. This paper discusses the concept of Tear Film Oriented Therapy (TFOT), which evolved from the definition of dry eye, emphasizing the importance of a stable tear film.     

The correlation between the tear film lipid layer and dry eye disease

Dry eye, also known as keratoconjunctivitis sicca, can be due either to insufficient tear production or excessive tear evaporation, both resulting in tear hyperosmolarity that leads to symptoms of discomfort and ocular damage. Additionally, the severity of dry eye symptoms appears to be correlated to lipid layer thickness. It is now generally recognized that increased evaporation due to a compromised lipid layer is one of the most common etiologies for hyperosmolarity of the tear film. Thus, therapies targeted at replenishing or stabilizing the lipid layer are key to the treatment of dry eye, either as monotherapy or in conjunction with therapies designed to enhance aqueous production.     

Conjunctival mucin deficiency in complete androgen insensitivity syndrome (CAIS)

Sex steroid hormones are essential for a healthy ocular surface and the androgen receptor impairment found in patients with complete androgen insensitivity syndrome (CAIS) has been described to cause meibomian gland dysfunction and functional dry eye for lipid tear film layer instability. However, it has not been reported if the mucous layer is also affected. A 37-year-old CAIS patient with persistent symptoms of dry eye underwent ophthalmological examination and was evaluated for qualitative and quantitative tear function tests and conjunctival cytology. Samples obtained from the conjunctival epithelium were stained for histology and immunohistochemistry and compared with three age-matched female controls. Western blot and relative real-time RT-PCR for MUC1 and MUC5AC were also performed on these samples. Immunohistochemistry, Western blot and relative real-time RT-PCR showed a decrease in the expression of MUC1 and MUC5AC in CAIS. Changes in the tear film mucous layer were accompanied by a reduction in the tear film break up time test. This is the first report describing mucous layer alteration associated with androgen receptor impairment. Decreased mucin levels contribute in explaining the tear film instability in CAIS and should be considered an additional cause of dry eye in sex steroid hormone pathology.     

Osmolality and tear film dynamics

The tear film is a nourishing, lubricating and protecting layer that bathes the ocular surface. It is continuously replenished through cycles of production and elimination via evaporation, absorption and drainage. These processes are often referred to as tear film dynamics. Osmolality is an objective clinical measurement that provides insight into the balance of these complex tear film dynamics. Balanced tear production and elimination is vital for tear film integrity, stability and normal osmolality. Imbalances cause alterations of the tear film structure and composition, ultimately leading to tear film instability and measurable tear film hyperosmolality. Elevated tear film osmolality is considered a core mechanism in dry eye, forming the basis of dry eye symptoms and leading to ocular surface damage. Despite its immense potential in the diagnosis of dry eye, tear film osmolality is not commonly assessed. This review will focus on the current knowledge of tear film dynamics and tear film osmolality.     

眼表微环境与泪膜稳态对视觉质量影响的新认识

2020年发布的中国干眼专家共识第一次将眼表微环境的概念新增到了干眼的定义中。强调了泪膜不稳定和眼表微环境失衡在干眼发病机制中的重要地位,并将视功能障碍作为干眼病情发展的重要结局之一。为了加强对新共识的认识,推动相关的基础与临床研究的开展及转化,为广大干眼患者提供更为细致的诊疗建议,专家组于2021年3年26日在江西吉安召开讨论会,对眼表微环境和泪膜稳态这两方面的研究现状及存在的问题进行分析,主要围绕干眼的这两个核心机制的新认识、与视觉质量的关系、临床的评估和治疗手段的建议和未来发展新方向等提出建议和推荐意见。     

干眼症的研究进展

干眼症是一种由各种不同的功能和眼表保护机制紊乱所致的眼表疾病,它是眼科中发病率最高的眼表疾病之一。干眼症的发病是多方面因素导致的,眼表组织和泪膜的缺失等都会引起干眼症,目前研究显示神经机能、性激素和炎症因子等在调节泪液分泌的过程中起重要作用。我们回顾了国内外相关文献,主要就目前干眼症的发病机制、动物模型和治疗作一综述。