Role of corneal cold thermoreceptors in the occurrence and development of dry eye北大核心CSCD

Dry eye is a multifactorial disease caused by changes in tear quality, volume and dynamics.Disturbance of tear film as the main character is accompanied by discomfort, visual disorder, and damage to the ocular surface and nerves.Cold thermoreceptors existing on the ocular surface are sensitive to alterations in corneal temperature and tear osmolality.They can give rise to the sensations of cold and pain, and regulate tear secretion, and are considered to be associated with the clinical manifestations of dry eye in some ways.This article reviewed the progress of corneal cold thermoreceptors in the regulation of corneal sensation and tear secretion, the related factors of corneal sensory regulation, and the clinical applications of TRPM8-related drugs, so as to provide ideas for the treatment of dry eye. © 2023 Henan Institute of Ophthalmology. All rights reserved.     

Dry Eye Disease and Microbial Keratitis: Is There a Connection?

Dry eye is a common ocular surface disease of multifactorial etiology characterized by elevated tear osmolality and inflammation leading to a disrupted ocular surface. The latter is a risk factor for ocular surface infection, yet overt infection is not commonly seen clinically in the typical dry eye patient. This suggests that important innate mechanisms operate to protect the dry eye from invading pathogens. This article reviews the current literature on epidemiology of ocular surface infection in dry eye patients and laboratory-based studies on innate immune mechanisms operating at the ocular surface and their alterations in human dry eye and animal models. The review highlights current understanding of innate immunity in dry eye and identifies gaps in our knowledge to help direct future studies to further unravel the complexities of dry eye disease and its sequelae.     

泪膜动态改变对视觉质量的影响

泪膜的动态变化包括泪膜厚度、脂质层和泪膜破裂区域的动态变化.干眼患者常伴有视力波动,泪膜对视觉质量的作用主要取决于泪膜的同质性及均匀性.近年来使用Hartmann-Shack波前像差仪、视觉质量分析系统等仪器定量连续测量健康眼及干眼瞬目后持续睁眼状态时及其应用人工泪液后泪膜动态改变对视觉质量影响.正常人瞬目后持续睁眼视觉质量下降,高阶像差和客观散射指数呈现出与干眼相似的上升趋势.干眼患者泪膜动态改变较正常人出现更早,高阶像差和客观散射指数均较正常眼增大.长期使用人工泪液可以改善干眼患者泪膜稳定性及瞬目后的视觉质量.视觉质量的动态检测可反映泪膜动态变化,有助于敏感地发现泪膜不稳定,及早进行临床诊治.     

干眼症临床检查的新进展

完整的泪膜是维持眼表健康和功能的基础,而泪液的产生、保留、稳定排泄是维持这种健康状态的必备条件。任何原因引起眼表面泪膜的异常均将引起干眼。当前干眼症的临床检查方法很多,主要针对泪液或泪膜的不同方面,如:检测泪液的量、物理特性、化学成分,泪膜的厚度、稳定性等,力求为干眼症的诊断和治疗提供有力的依据。但由于至今尚未有一种检查方法在干眼症的诊断上能称之为"金标准",因而必须联合至少3种检查法综合判定干眼情况。     

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.     

儿童干眼症病因学分析

干眼症是指任何原因引起的泪液质或量及动力学的异常,导致泪膜不稳定和(或)眼表面的异常,并伴有眼部不适症状的一类疾病。传统观念认为干眼症多见于40岁以上的人群,与泪液分泌功能随年龄增长而逐渐减弱有关,所以对成年人干眼症的研究较多,而忽视了儿童干眼症。临床上越来越多的儿童出现了类似于成年人干眼症的临床表现,而且通过常规的抗感染治疗病情反而加重。因此,儿童干眼症应该受到重视。重度维生素A缺乏(VitaminAdeficiency,VAD)导致的儿童眼干燥症曾是儿童致盲的重要原因。随着生活水平的提高,城镇儿童重度VAD十分少见。但亚临床维生素A缺乏(sub-clinical Vitamin Adeficiency,SVAD)、视频终端(video display terminal,VDT)的普及、不良的瞬目习惯、宠物和玩具等密切接触、系统免疫性疾病以及变态反应性疾病均可引起泪膜不稳定而导致干眼症。     

Effect of inflammation on lacrimal gland function

The lacrimal gland is the main contributor to the aqueous layer of the tear film. It secretes proteins, electrolytes and water, which helps to nourish and protect the ocular surface. Lacrimal gland secretion is primarily under neural control, which is achieved through a neural reflex arc. Stimuli to the ocular surface activate afferent sensory nerves in the cornea and conjunctiva. This in turn activates efferent parasympathetic and sympathetic nerves in the lacrimal gland to stimulate secretion. Sex steroid hormones are also important regulators of lacrimal gland functions. A decrease or lack of lacrimal gland secretion is the leading cause of aqueous tear deficient dry eye syndrome (DES). It has been suggested that DES is an inflammatory disorder that affects the ocular surface and the lacrimal gland. In several pathological instances, the lacrimal gland can become a target of the immune system and show signs of inflammation. This can result from autoimmune diseases (Sj?gren's syndrome), organ transplantation (graft versus host disease), or simply as a result of aging. The hallmarks of lacrimal gland inflammation are the presence of focal lymphocytic infiltrates and increased production of proinflammatory cytokines. The mechanisms leading to lacrimal gland dysfunction are still poorly understood. Apoptosis, production of autoantibodies, hormonal imbalance, alterations in signaling molecules, neural dysfunction, and increased levels of proinflammatory cytokines have been proposed as possible mediators of lacrimal gland insufficiency in disease states.     

Modulation of tear film protein secretion with phosphodiesterase inhibitors

A double-blind randomized clinical study was conducted to determine whether nicardipine hydrochloride was a useful treatment for dry eye.We examined its effect on the tear film, ocular surface and ocular comfort. Nicardipine hydrochloride, 3-isobutyl-1-methylxanthine and pilocarpine hydrochloride were dissolved in an artificial tear vehicle and applied topically to one eye of 12 subjects on separate days. Ocular physiology, ocular comfort and tear volume were assessed. The trial was repeated with nicardipine in an aqueous gel vehicle. Tears were collected and assessed for protein concentration and protein profile, using electrophoresis and mass spectrometry. Nicardipine induced conjunctival redness and symptoms of dryness and irritation. There was no change in total tear protein concentration or volume. An increase in a 68 kDa protein was observed, this was probably due to conjunctival vessel dilation and leakage of albumin. The adverse symptomatology and increased conjunctival redness experienced with nicardipine make it an undesirable treatment for dry eye.     

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.     

New Instruments for Dry Eye Diagnosis

Several non-invasive techniques for dry eye diagnosis have been developed in the past decade. These include quantitative assessment of tear volume, tear film stability, tear dynamics, and integrity of ocular surface epithelium. A combination of meniscometry and interferometry is useful for proving focal dry eye, by confirming whether or not tears at the meniscus have an effect on the ocular surface. Interferometer is also useful to evaluate tear dynamics on soft contact lenses. Fluorophotometry is useful for assessing the severity of dry eye from the view point of corneal epithelial barrier function and measuring the tear turnover rate. Both video-meibography and meibometry are useful for screening meibomian gland dysfunction. The advances in these techniques accumulate knowledge regarding pathophysiology of dry eye and allow precise diagnosis of dry eye. More targeted treatment will become feasible based on the clearer pathophysiology.     

Das „feuchte“ trockene Auge

Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability, with potential damage to the ocular surface. The two main causes are reduced production of aqueous tears and increased evaporation of tears. The evaporative form of dry eye results in ocular surface irritation with a secondary increase in tear production; this presents to the examiner and patient as a wet eye or epiphora. Knowledge and understanding of the basic pathologies and differential diagnoses of dry eye disease are essential to differentiate this very common form of dry eye from disorders of the lacrimal drainage system and to initiate adequate management.     

New instruments for dry eye diagnosis

Several non-invasive techniques for dry eye diagnosis have been developed in the past decade. These include quantitative assessment of tear volume, tear film stability, tear dynamics, and integrity of ocular surface epithelium. A combination of meniscometry and interferometry is useful for proving focal dry eye, by confirming whether or not tears at the meniscus have an effect on the ocular surface. Interferometer is also useful to evaluate tear dynamics on soft contact lenses. Fluorophotometry is useful for assessing the severity of dry eye from the view point of corneal epithelial barrier function and measuring the tear turnover rate. Both video-meibography and meibometry are useful for screening meibomian gland dysfunction. The advances in these techniques accumulate knowledge regarding pathophysiology of dry eye and allow precise diagnosis of dry eye. More targeted treatment will become feasible based on the clearer pathophysiology.     

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。     

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。     

Dry eye after LASIK: Comparison of outcomes for Asian and Caucasian eyes

Background : Dry eye is a common complication of LASIK surgery. Our clinical impression was that post‐LASIK dry eye was more problematic for our Asian patients. The aim of this study was to determine if dry eye after LASIK is more prevalent, more sustained and more severe in Asian eyes compared with Caucasian eyes. Methods : This study was based on a retrospective analysis of a clinical database. Data (n = 932 eyes, 932 patients) was collected before and after (week 2 and months 1, 3 and 6) LASIK surgery. Patients were defined as Asian if both parents were of East Asian ethic origin. Assessments included dry eye symptoms, ocular surface staining, tear volume, tear secretion, tear film stability and corneal sensation. Results : Asian eyes had greater ocular surface staining, poorer tear film stability and lower tear volume before LASIK and at all times after LASIK. Dry eye symptoms occurring ‘often or constantly’ were more prevalent at all time points after LASIK in Asian eyes. Chronic dry eye persisting six months or more after LASIK was diagnosed in 28 per cent of Asian eyes and 5 per cent of Caucasian eyes (p < 0.001). Asian patients with chronic dry eye were predominantly female, reported dry eye symptoms, had greater ocular surface staining and lower tear secretion, stability and volume before surgery. After LASIK, Asian eyes had a slower return to pre‐operative values for ocular surface staining, tear volume and corneal sensation. Discussion : The risk of chronic dry eye after LASIK was significantly higher in Asian eyes. Contributing factors could include racial differences in eyelid and orbital anatomy, tear film parameters and blinking dynamics and higher attempted refractive corrections in Asian eyes.     

A practical treatment algorithm for managing ocular surface and tear disorders

Management of ocular surface irritation and morbidity associated with dry eye has been plagued by the complex interplay of different pathogenic elements and substantial variability of ocular surface deficits in patients. A practical algorithm is proposed to achieve effective management of dry eye. When the eye is open, ocular surface health is governed by a stable tear film that is maintained by neuroanatomic integration via 2 reflexes. Any dysfunctional element in this neuroanatomic integration is potentially pathogenic and creates ocular surface deficits leading to dry eye. In general practice, 5 major dysfunctional elements have been identified: decreased ocular surface sensitivity, aqueous tear deficiency, lipid tear deficiency, delayed tear clearance, and ineffective tear spread. Clinical workup should be individualized to identify all such dysfunctional elements in each patient through history taking, external and slit-lamp examination, and special tests. However, practical management lies in the detection of delayed tear clearance. The following strategies are advised: (1) eliminate all intrinsic inflammatory, infectious, allergic, and toxic insults, especially those associated with delayed tear clearance; (2) correct diseases that impede and interfere with tear spread and capacity; (3) create delayed tear clearance for aqueous tear-deficient dry eye by punctual occlusion; and (4) treat lipid-deficient dry eye after sufficient aqueous tears have been conserved. The aforementioned algorithm ameliorates ocular surface irritation and curtails morbidity in most patients. This algorithm can also be adopted for complex cicatricial ocular surface diseases before managing the remaining deficits resulting from hydrodynamic deficiency.     

Recent developments on dry eye disease treatment compounds

Dry eye syndrome is a common tears and ocular surface multifactorial disease, described by changes in the ocular surface epithelia related to reduced tears quantity and ocular surface sensitivity, leading to inflammatory reaction. Managing the eye inflammation proved helpful to patients with dry eye disease and current treatment is based on the use of topically applied artificial tear products/lubricants, tear retention management, stimulation of tear secretion and using anti-inflammatory drugs. In this article we revise the corresponding literature and patents assembling the new treatment approaches of novel and future pharmaceutical compounds destined for the dry eye disease treatment. The most frequent categories of compounds presented are secretagogues and anti-inflammatory drugs. These compounds are the research outcome of novel therapeutic strategies designed to reduce key inflammatory pathways and restore healthy tear film.     

基于泪膜破裂方式的干眼诊断新思路

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(tearfilm-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。     

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。     

The ocular surface and tear film and their dysfunction in dry eye disease

The ocular surface, tear film, lacrimal glands, and eyelids act as a functional unit to preserve the quality of the refractive surface of the eye and to resist injury and protect the eye against changing bodily and environmental conditions. Events that disturb the homeostasis of this functional unit can result in a vicious cycle of ocular surface disease. The tear film is the most dynamic structure of the functional unit, and its production and turnover is essential to maintaining the health of the ocular surface. Classically, the tear film is reported to be composed of three layers: the mucin, aqueous, and lipid layers. The boundaries and real thickness of such layers is still under discussion. A dysfunction of any of these layers can result in dry eye disease.