诊断干眼的非侵入性新检测技术及应用价值

本文对诊断干眼的非侵入性新检测技术及其在干眼诊断中的作用进行综述,其中包括泪液量、泪膜稳定性、睑板腺形态及功能、角膜形态、生物标志物、眼表温度的成像技术,以及泪液渗透压、光学质量、眨眼测试等。新的检测技术可提供客观参数以评价眼表、泪液情况及视觉质量等。泪液量、睑板腺成像和泪液渗透压等检测技术已被广泛认可并应用于临床,与传统测试相比表现出了更高的特异性和敏感性。其它检测技术,如SM技术,干涉术、光散射技术、双通道系统,眨眼测试等目前处于临床研究阶段,未来或将转化为临床常规检测技术。新的检测技术,可无创评估眼表及泪液情况,并测量与病情相关的成分变化,在干眼的诊断、分类、临床管理和疗效评估中发挥重要作用。     

An overview on dry eye disease diagnosis: options for new non-invasive testing technologies

This literature review intends to provide an overview of the new non-invasive testing technologies and their role in the diagnosis of dry eye disease (DED). Including imaging technologies of tear volume, tear film stability, meibomian glands morphology and function, corneal morphology, biomarkers and ocular surface temperature, as well as tear osmolarity, optical quality, blinking test and so on. New testing technologies can provide an indirect and objective assessment of the ocular surface, tear condition and visual quality. Testing technologies, such as tear volume, meibography and tear osmolarity have been widely recognized and applied in clinical practice, showing higher specificity and sensitivity than traditional tests. Others, such as strip meniscometry, interferometer, light scattering technology, double-pass system, blinking test and so on, are currently in the stage of clinical research and improvement, and may translate to routine clinical detection techniques in the future. The new non-invasive testing technologies can non-invasively evaluate the ocular surface and tears, and measure the changes of components related to the disease, which play an important role in the diagnosis, classification, clinical management and curative effect evaluation of DED.     

TFOS DEWS II Tear Film Report

The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular surface. The tear film is composed of many substances including lipids, proteins, mucins and electrolytes. All of these contribute to the integrity of the tear film but exactly how they interact is still an area of active research. Tear film osmolarity increases in DED. Changes to other components such as proteins and mucins can be used as biomarkers for DED. The Subcommittee recommended areas for future research to advance our understanding of the tear film and how this changes with DED. The final report was written after review by all Subcommittee members and the entire TFOS DEWS II membership.     

Role of lymphotoxin alpha as a new molecular biomarker in revolutionizing tear diagnostic testing for dry eye disease

Dry eye disease (DED), primarily classified as multifactorial ocular surface disorder, afflicts tens of millions of individuals worldwide, adversely impacting their quality of life. Extensive research has been conducted on tear film analysis over the past decades, offering a range of tests to evaluate its volume, health, and integrity. Yet, early diagnosis and effective treatment for DED continue to pose significant challenges in clinical settings. Nevertheless, by recognizing key phenomena in DED such as ocular surface inflammation, hyperosmolarity, and tear film instability, this article provides a comprehensive overview of both traditional and recently developed methods for diagnosing and monitoring DED. The information serves as a valuable resource not only for clinical diagnosis but also for further research into DED.     

干眼症检查的进展

干眼症是导致眼部不适,甚至引起视力障碍的常见病,其病因及病理生理十分复杂。在干眼症的诊断中,传统的泪液分泌试验、泪膜破裂时间、眼表面荧光素染色、虎红染色等检查均存在其不足。近年来干眼症的检查手段得到很大发展,检查方法达数十种之多,不仅提高了此病诊断的准确性,而且可进行病因诊断和病情严重程度的分析。复习了近年来关于传统的和新发展的干眼症检查方面的文献,对各检查方法的原理,优缺点及适应证进行综述。     

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。     

干眼检查方法的研究进展

干眼是以泪膜稳态失衡为主要特征并伴有眼部不适症状的多因素眼表疾病。近年来,干眼的发病率逐年增多,有关干眼的诊断与治疗也在不断地发展、创新,但由于传统检查方法存在相应的弊端而新型检查方法尚缺乏大量的临床试验研究,目前干眼的诊疗仍缺乏一套统一的“金标准”。本文对国内外有关干眼的不同检查方法的文献进行了广泛搜索,包括有前景的检查工具和技术的最新进展及其存在的争议,从而通过泪液量、泪膜的性质、眼睑及睑板腺和眼表上皮细胞损害程度的检查等方面做一综述,为干眼的诊断和治疗提供参考。     

Advances in understanding and managing dry eye disease

PURPOSE: To present evidence from the literature and scientific meetings to support fundamental changes in concepts regarding the prevalence, pathogenesis, definition, diagnosis, management of dry eye disease (DED) and the prospects for the development of new therapies. DESIGN: Analysis and clinical perspective of the literature and recent presentations. METHODS: Review and interpretation of literature. RESULTS: The tear film and ocular surface form an integrated physiologic unit linking the surface epithelia and secretory glands via a neural network. This sensory-driven network regulates secretory activity in quantity and composition, supporting the homeostasis of the system. The tear film forms a metastable covering between blinks, subserving clear vision, and maintains the health and turnover of the ocular surface cells. Disturbance of intrinsic factors such as increasing age; hormonal balance; systemic or local autoimmune disease, or both; systemic drugs or extrinsic factors including topical medications; environmental stress; contact lens wear; or refractive surgery result in a final common pathway of events at the tear film and ocular surface, resulting in DED. Diagnosis of DED and the design of clinical trials for new drugs have been hampered by a lack of correlation between signs and symptoms and flawed endpoints; successful new drug applications likely will require new approaches, such as the use of objective biomarkers for disease severity. CONCLUSIONS: Recent advances in our knowledge of the causation of DED open opportunities for improving diagnosis and disease management and for developing new, more effective therapies to manage this widely prevalent and debilitating disease state.     

TFOS DEWS II Diagnostic Methodology report

The role of the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) II Diagnostic Methodology Subcommittee was 1) to identify tests used to diagnose and monitor dry eye disease (DED), 2) to identify those most appropriate to fulfil the definition of DED and its sub-classifications, 3) to propose the most appropriate order and technique to conduct these tests in a clinical setting, and 4) to provide a differential diagnosis for DED and distinguish conditions where DED is a comorbidity. Prior to diagnosis, it is important to exclude conditions that can mimic DED with the aid of triaging questions. Symptom screening with the DEQ-5 or OSDI confirms that a patient might have DED and triggers the conduct of diagnostic tests of (ideally non-invasive) breakup time, osmolarity and ocular surface staining with fluorescein and lissamine green (observing the cornea, conjunctiva and eyelid margin). Meibomian gland dysfunction, lipid thickness/dynamics and tear volume assessment and their severity allow sub-classification of DED (as predominantly evaporative or aqueous deficient) which informs the management of DED. Videos of these diagnostic and sub-classification techniques are available on the TFOS website. It is envisaged that the identification of the key tests to diagnose and monitor DED and its sub-classifications will inform future epidemiological studies and management clinical trials, improving comparability, and enabling identification of the sub-classification of DED in which different management strategies are most efficacious.     

Dry Eye Disease

Dry eye (DED) is a multifactorial disease that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface, accompanied by increased osmolarity of the tear film and inflammation. DED is a common clinical problem and is among the most frequent diagnoses in ophthalmology. It substantially affects quality of life because of the constant ocular discomfort and decrease in visual function. This review discusses the etiology, classification, diagnosis procedures, clinical, and surgical treatments of dry eye.     

蛋白质组学技术在干眼研究及针刺治疗干眼中的应用

干眼是指由泪液的质、量和动力学异常等原因导致的泪膜稳定性下降或眼表微环境失衡，造成多种眼部不适甚至视功能障碍。其发病机制复杂，目前治疗尚局限于缓解症状，保护视功能。针刺治疗干眼有效，但作用机制尚未完全明确。蛋白质组学技术能系统全面反映蛋白质的功能、结构以及相互作用关系，将蛋白质组学技术应用于针刺治疗干眼的研究，不仅可从不同病因病程揭示干眼蛋白质水平的动态变化，寻找潜在生物标志物，还能系统挖掘针刺治疗干眼的调控机制，为针刺治疗的理论研究和针刺作用的基础研究提供依据。本文旨在探讨蛋白质组学在干眼临床和基础研究中的潜在应用价值，为干眼的诊疗及针刺机制研究提供科学有效的思路。     

Visual Performance and the Ocular Surface in Traumatic Brain Injury

The pathophysiology of neurotrauma is reviewed and an original study investigating the prevalence of dry eye disease in a sample of veterans with traumatic brain injury (TBI) is presented. Fifty-three veterans with TBI were evaluated by history of injury, past ocular history, and medication use. Ocular Disease Surface Index (OSDI), ocular examination, cranial nerve evaluation, tear osmolarity, tear film break-up time (TFBUT), ocular surface staining and tear production testing were performed. A matched comparison group underwent similar testing. TBI causes were blast (44) or non-blast (9). TBI subjects scored significantly worse on the OSDI (P<.001), and ocular surface staining by Oxford scale (P<.001) than non-TBI subjects. Scores for tear film breakup (P=.6), basal tear production less than 3 mm (P=.13), and tear osmolarity greater than 314 mOsm/L (P=.15) were all higher in TBI subjects; significantly more TBI subjects had at least one abnormal dry eye measure than comparisons (P<.001). The OSDI related to presence of dry eye symptoms (P<.01). These effects were present in both blast and non-blast TBI. Seventy percent of TBI subjects were taking at least one medication in the following classes: antidepressant, atypical antipsychotic, anticonvulsant, or h1-antihistamine. There was no association between any medication class and the OSDI or dry eye measures. Reduced corneal sensation in 21 TBI subjects was not associated with OSDI, tear production, or TFBUT, but did correlate with reduced tear osmolarity (P=.05). History of refractive surgery, previous contact lens wear, facial nerve weakness, or meibomian gland dysfunction was not associated with DED. In summary, we found a higher prevalence of DED in subjects with TBI, both subjectively and objectively. This effect is unrelated to medication use, and it may persist for months to years. We recommend that patients with TBI from any cause be evaluated for DED using a battery of standard testing methods described in a protocol presented in this article. Further research into the pathophysiology and outcomes of DED in neurotrauma is needed.     

泪液的相关研究与进展

泪液是主要由泪腺分泌的一种水样液体,通过瞬目运动覆盖在眼表面形成泪膜。当前就泪膜的特殊结构和功能等方面,已开展了大量研究,将收集到的泪液,睑板腺分泌物,印迹细胞学、刷检细胞学、结膜活组织检查收集到的眼表细胞,应用电泳、色谱分析联合质谱分析及聚合酶链式反应（PCR）等分子生物学技术,分析泪膜脂质、蛋白、黏蛋白分子及其mRNA是较常用的方法。泪液成分分析技术的进步为I临床医师了解泪膜,诊断及治疗干眼症提供了有力的依据。就泪液成分分析的基本方法和研究现状进行综述。     

糖尿病患者泪液及泪膜变化的研究进展

随着糖尿病在全球发病率的持续增加,由其引发的眼部并发症也日益受到关注.除了引起视网膜病变、白内障等常见的并发症外,糖尿病患者的眼表在结构及微环境方面也可能发生改变,进而影响泪液的成分、质量及泪膜的稳定性.本文就糖尿病患者眼表,泪液和泪膜的变化、相关检查方法以及影响因素的研究进展作一综述.     

Evaluation of dry eye

Dry eye is a common yet complex condition. Intrinsic and extrinsic factors can cause dysfunction of the lids, lacrimal glands, meibomian glands, ocular surface cells, or neural network. These problems would ultimately be expressed at the tear film-ocular surface interface. The manifestations of these problems are experienced as symptoms such as grittiness, discomfort, burning sensation, hyperemia, and secondary epiphora in some cases. Accurate investigation of dry eye is crucial to correct management of the condition. Techniques can be classed according to their investigation of tear production, tear stability, and surface damage (including histological tests). The application, validity, reliability, compatibility, protocols, and indications for these are important. The use of a diagnostic algorithm may lead to more accurate diagnosis and management. The lack of correlation between signs and symptoms seems to favor tear film osmolarity, an objective biomarker, as the best current clue to correct diagnosis.     

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.     

Tear film,contact lenses and tear biomarkers

This article summarises research undertaken since 1993 in the Willcox laboratory at the University of New South Wales, Sydney on the tear film, its interactions with contact lenses, and the use of tears as a source of biomarkers for ocular and non‐ocular diseases. The proteome, lipidome and glycome of tears all contribute to important aspects of the tear film, including its structure, its ability to defend the ocular surface against microbes and to help heal ocular surface injuries. The tear film interacts with contact lenses in vivo and interactions between tears and lenses can affect the biocompatibility of lenses, and may be important in mediating discomfort responses during lens wear. Suggestions are made for follow‐up research.     

Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre,double-masked randomised controlled trial

PurposeTo assess the six-month therapeutic profiles of lipid and non-lipid-based artificial tear supplements in managing dry eye disease (DED).MethodsNinety-nine participants fulfilling the TFOS DEWS II diagnostic criteria for DED (64% females; mean ± SD age, 44 ± 16 years) were enrolled in a prospective, multicentre, double-masked, parallel group, randomised controlled trial. Participants instilled lipid-based nanoemulsion drops or non-lipid-based aqueous drops for six months, at least four times daily. Symptomology, tear film and ocular surface characteristics were assessed at Days 0, 30, 60, 90, 120, 150 and 180.ResultsSustained reductions in OSDI, DEQ-5, and SANDE symptom scores from baseline were observed from Day 30 onwards in both groups (all p < 0.05) and decreased superior lid wiper epitheliopathy grades from Day 60 onwards (all p ≤ 0.01). Improvements in non-invasive tear film breakup time, and sodium fluorescein and lissamine green staining scores followed from Day 120 onwards in both groups (all p < 0.05). Tear lipid layer grades increased from Day 90 onwards only with the lipid-based drops, and with significantly greater improvement in those with suboptimal lipid layer thickness at baseline (grade ≤3; p = 0.02). By Day 180, 19% of participants no longer fulfilled the diagnostic criteria for DED.ConclusionsOver a six-month treatment period, improvements in dry eye symptomology preceded tear film and ocular surface changes with regular use of both lipid and non-lipid-based artificial tear supplements. Both formulations addressed most mild-to-moderate forms of aqueous deficient and evaporative DED, while evaporative cases benefitted preferentially from lipid-based supplementation. This represents a first step towards mapping DED therapeutic strategies according to disease subtype and severity.     

Ocular surface investigations in dry eye

Dry eye is a complex clinicopathological entity involving tear film, lacrimal glands, eyelids, and a wide spectrum of ocular surface cells, including epithelial, inflammatory, immune, and goblet cells. From the tightly regulated lacrimal film functions and structure, a large variety of investigations have been developed, including tear meniscus measurements, fluorophotometry, meibometry, interference pattern analysis, evaporation rate, tear osmolarity, and thermography. Dry eye conditions also interfere with the ocular surface, causing corneal irregularities that may be explored using the techniques of videokeratography and in vivo confocal microscopy, or optical impairment, as confirmed by aberrometry. At the level of ocular surface cells, impression cytology remains a standard for assessing cell alterations. It has greatly benefited from new confocal microscopy, molecular biology, and flow cytometry techniques. Biological assessment of tear proteins or other mediators is also useful. Major limits should be acknowledged, however, such as technical issues in tear film collection, especially in dry eyes, and the lack of standardization of most measurements. Tear osmolarity, electrophoresis, and dosage of normal tear proteins, such as lysozyme or lactoferrin, remain the most useful tests. Finally, some extraocular explorations such as accessory gland biopsy or serum antinuclear antibody dosage may be useful for assessing the diagnosis of Sj?gren's syndrome.     

TFOS DEWS II Definition and Classification Report

The goals of the TFOS DEWS II Definition and Classification Subcommittee were to create an evidence-based definition and a contemporary classification system for dry eye disease (DED). The new definition recognizes the multifactorial nature of dry eye as a disease where loss of homeostasis of the tear film is the central pathophysiological concept. Ocular symptoms, as a broader term that encompasses reports of discomfort or visual disturbance, feature in the definition and the key etiologies of tear film instability, hyperosmolarity, and ocular surface inflammation and damage were determined to be important for inclusion in the definition. In the light of new data, neurosensory abnormalities were also included in the definition for the first time. In the classification of DED, recent evidence supports a scheme based on the pathophysiology where aqueous deficient and evaporative dry eye exist as a continuum, such that elements of each are considered in diagnosis and management. Central to the scheme is a positive diagnosis of DED with signs and symptoms, and this is directed towards management to restore homeostasis. The scheme also allows consideration of various related manifestations, such as non-obvious disease involving ocular surface signs without related symptoms, including neurotrophic conditions where dysfunctional sensation exists, and cases where symptoms exist without demonstrable ocular surface signs, including neuropathic pain. This approach is not intended to override clinical assessment and judgment but should prove helpful in guiding clinical management and research.