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.     

The effects of LASIK on the ocular surface

Laser in situ keratomileusis (LASIK) can affect corneal sensation, aqueous tear production, wound healing, and the incidence of corneal erosions. Virtually all patients experience dry eye at least transiently after LASIK. Because intact corneal sensation drives tear production, denervation associated with the LASIK procedure is the most significant cause of post-LASIK dry eye. To prevent symptomatic postoperative dry eye, it is crucial to identify and treat pre-existing dry eye before surgery. This review addresses the pathophysiology and management of dry eye, as well as the relationship between LASIK and corneal erosions, and suggests intra- and post-operative management techniques to minimize complications and maximize the stability of the ocular surface. Contraindications to LASIK and alternative refractive surgical procedures are discussed.     

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.     

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。     

Impact of corneal refractive surgery on the precorneal tear film

Corneal refractive surgeries are one of the commonly performed procedures for correction of refractive errors. Tear film abnormality is the most common postoperative complication of corneal refractive surgeries. Consequently, these procedures represent a clinically significant cause of dry eye disease. The mechanisms which lead to dry eye disease include corneal sensory nerve dysfunction, ocular surface desiccation, glandular apoptosis and ocular surface inflammation. Although transient tear film abnormalities occur in almost all patients following surgery, patients with pre-existing dry eye symptoms or dry eye disease are at significant risk of developing more severe or long-term ocular surface disease. As such, careful patient selection and preoperative evaluation is essential to ensuring successful surgical outcomes. This is particularly important with LASIK which has the strongest association with dry eye disease. Appropriate surface lubrication and anti-inflammatory therapy remains the cornerstone treatment. Timely and effective management is important to facilitate visual rehabilitation and reduce the risk of secondary complications. In this review we describe the causes, pathophysiology, risk factors, manifestations, and management of tear film dysfunction and dry eye disease following corneal refractive surgery.     

干眼与眼部神经病理性疼痛相关性进展

干眼（dry eye，DE）是一种常见的多因子眼表疾病，具有较高的发病率。DE的症状包括视力模糊、刺激和眼部疼痛。研究表明，DE和神经病理性疼痛在流行病学、发病机制和临床表现上有许多相似之处。本文综述了DE与眼部神经病理性疼痛的相似处，重点介绍临床特征、眼部神经性疼痛评估及治疗方法。     

LASIK and dry eye

Dry eye is one of the most common complications after laser-assisted in situ keratomileusis (LASIK). The clinical signs of post-LASIK dry eye include positive vital staining of ocular surface, decreased tear film breakup time and Schirmer test, reduced corneal sensitivity, and decreased functional visual acuity. The symptoms and signs last at least 1 month after LASIK. Although the mechanisms for developing post-LASIK dry eye are not completely understood, loss of corneal innervation by flap-making may affect the reflex loops of the corneal-lacrimal gland, corneal-blinking, and blinking-meibomian gland, and blinking-meibomian gland, resulting in decreased aqueous and lipid tear secretion and mucin expression. As LASIK enhancement by flap-lifting induces less dry eye symptoms and signs than first surgery, it is suggested that other factors rather than loss of neurotrophic effect may be involved in the mechanisms of post-LASIK dry eye. The treatments of dry eye include artificial tears, topical cyclosporine, hot compress, punctal plugs, and autologous serum eye drops. For patients with severe preoperative dry eye, a combination of punctal plugs and serum eye drops is required to be used before surgery.     

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。     

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.     

Neurotrophic keratopathy--a post-LASIK case report

BACKGROUND: Neurotrophic keratopathy is a degenerative affection of the cornea caused by impairment of corneal sensitivity and represents a therapeutic challenge for ophthalmologists. The present article concentrates on the etiology, pathogenesis, diagnosis, therapeutic aspects and future therapeutic models for treating neurotrophic keratopathy and will present a case report: Also we evaluate the effects of autologous serum eye drops in bilateral LASIK-induced neurotrophic keratopathy with epithelial breakdown revealed by positive fluorescence and rose bengal staining and reduced tear film break-up time. METHODS: We treated a 42-year-old patient with post-LASIK neurotrophic keratopathy and tear film instability with autologous serum eye drops (5 x daily) and emulsion eye drops (Refresh Endura, Allergan, Irvine, CA, USA) after insertion of punctal plugs. RESULTS: Stabilization of vision, healing of the epithelium and reduction of the previously experienced symptoms like redness, itching and burning were achieved within 6 weeks. 10 months after changing therapy, the patient only complained about slight pain during lid movement. CONCLUSIONS: Severe denervation after bilateral LASIK disrupts ocular tear film dynamics and causes irritation symptoms of the ocular surface. Autologous serum eye drops may be an effective treatment of severe epithelial breakdown and be helpful to reestablish the disturbed ocular surface integrity, as shown by negative vital staining. Therefore, autologous serum eye drops represent a significant approach in the therapy of LASIK-induced severe dry eye and associated pain.     

干眼的流行病学研究进展

干眼是一种临床常见的慢性眼表疾病,是指由于泪液质和量的异常或泪液流体动力学异常引起的泪膜不稳定和眼表损害,从而导致眼部不适症状的一类疾病。不适感觉包括眼干涩、眼红、眼痒、异物感等。近年来,随着干眼发病率的增加,干眼越来越受到人们的重视。我们就干眼的诊断、分类和病因流行病学研究等方面进行综述。     

Inflammation in dry eye

Dry eye is a condition of altered tear composition that results from a diseased or dysfunctional lacrimal functional unit. Evidence suggests that inflammation causes structural alterations and/or functional paralysis of the tear-secreting glands. Changes in tear composition resulting from lacrimal dysfunction, increased evaporation and/or poor clearance have pro-inflammatory effects on the ocular surface. This inflammation is responsible in part for the irritation symptoms, ocular surface epithelial disease, and altered corneal epithelial barrier function in dry eye. Anti-inflammatory therapies for dry eye target one or more of the inflammatory mediators/pathways that have been identified in dry eye.     

Management of the ocular surface and tear film before, during, and after laser in situ keratomileusis

PURPOSE: To identify evidence-based, best practice strategies for managing the ocular surface and tear film before, during, and after laser in situ keratomileusis (LASIK). METHODS: After a comprehensive review of relevant published literature, evidence-based recommendations for best practice management strategies are presented. RESULTS: Symptoms of ocular irritation and signs of dysfunction of the integrated lacrimal gland/ocular surface functional gland unit are common before and after LASIK. The status of the ocular surface and tear film before LASIK can impact surgical outcomes in terms of potential complications during and after surgery, refractive outcome, optical quality, patient satisfaction, and the severity and duration of dry eye after LASIK. Before LASIK, the health of the ocular surface should be optimized and patients selected appropriately. Dry eye before surgery and female gender are risk factors for developing chronic dry eye after LASIK. Management of the ocular surface during LASIK can minimize ocular surface damage and the risk of adverse outcomes. Long-term management of the tear film and ocular surface after LASIK can reduce the severity and duration of dry eye symptoms and signs. CONCLUSIONS: Strategies to manage the integrated ocular surface/lacrimal gland functional unit before, during, and after LASIK can optimize outcomes. As problems with the ocular surface and tear film are relatively common, attention should focus on the use and improvement of evidence-based management strategies.     

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.     

干眼的研究现状

干眼是一种临床常见的慢性眼表疾病,是指由于泪液质和量的异常或泪液流体动力学异常引起的泪膜不稳定和眼表损害,从而导致眼部不适症状的一类疾病。不适感觉包括眼干涩、眼红、眼痒、异物感等。近年来,随着干眼发病率的增加,干眼越来越受到人们的重视。就干眼的临床症状、流行病学研究、病因、发病机制、分类和诊断等方面进行综述。     

我国干眼流行病学的研究进展

干眼是一种临床常见的慢性眼表疾病.它是由泪膜的质或量以及泪液动力学异常所致的泪膜不稳定和(或)眼表的损害,进而出现眼部不适及视功能障碍的一类疾病.近年来,我国开展了大量较高水平的干眼流行病学调查研究项目,在干眼的流行病学研究上取得了显著成果.本文中笔者就干眼在我国不同地域和人群中流行病学分布的特征和危险因素进行综述.     

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.     

P2Y2受体激动剂用于干眼治疗的研究进展

干眼属常见的眼表疾病,是指由于泪液的量和（或）质的异常引起的泪膜不稳定和眼表面的损害,从而导致眼部不适症状的一类疾病。目前我国干眼的治疗包括病因治疗、人工泪液替代治疗、抗炎治疗、免疫抑制剂治疗、手术治疗以及中医治疗等。Ｐ２Ｙ２受体激动剂是一种治疗干眼的新型药物,它能够通过激动位于眼表的Ｐ２Ｙ２受体,促使结膜上皮细胞泪液的分泌以及结膜杯状细胞对黏蛋白的分泌,从而增强泪膜稳定性,改善干眼症状。３０ｇ·Ｌ－１地夸磷索四钠滴眼液是目前唯一上市的Ｐ２Ｙ２受体激动剂。本文就近年来地夸磷索四钠用于干眼治疗的临床疗效、安全性以及相关研究进展作一综述。     

Lid scrubbing with a gel combining natural extracts for dry eye treatment

AIM: To evaluate the effect of lid scrubbing using a gel combining different natural extracts on ocular signs and symptoms of dry eye patients. METHODS: A retrospective study was performed on 19 dry eye patients (51.1±16.0y). Non-invasive tear break-up time, tear meniscus height, meibomian gland loss, lipid layer thickness, conjunctival redness, corneal staining, ocular surface disease index (OSDI), and ocular pain intensity were measured before (baseline), 1wk, and 2mo after lid scrubbing with a gel containing different natural extracts (okra extract, aloe vera leaf juice, hydrolysed soy protein, caffeine, citrus unshiu peel extract, and raspberry seed oil). RESULTS: Compared with the baseline, there was a statistically significant improvement in both first (P=0.048) and average (P=0.026) non-invasive tear break-up time 2mo after treatment, as well as in corneal staining (P=0.043, 0.012), OSDI (P<0.001), and ocular pain intensity (P<0.001) after 1wk and 2mo. In addition, there was no correlation between ocular signs and symptoms. CONCLUSION: The lid scrubbing with a gel combining different natural extracts show beneficial effects on tear film stability, corneal damage, and ocular symptoms, which is the reason why this therapeutic procedure is proposed as an alternative for dry eye management. However, it is not possible to attribute this beneficial effect solely to the presence of the natural extracts in the gel, primarily due to the absence of a negative control group.     

The Role of Corneal Innervation in LASIK-Induced Neuropathic Dry Eye

Almost half the patients who undergo laser in situ keratomileusis (LASIK) experience dry eye following the procedure. However, the etiology of LASIK-induced dry eye is unclear. The purpose of this review is to examine and summarize the current evidence for the etiology of LASIK-induced dry eye, with a focus on ocular surface sensitivity and corneal innervation. Evidence suggests that the alteration of corneal nerves after LASIK is the most likely cause of the subjective symptoms of LASIK-induced dry eye, even though corneal sensitivity and the clinical indicators of dry eye return to apparently normal values within a year due to the partial recovery of the corneal nerve plexus. The hypothesis is explored that dry eye symptoms following LASIK may result from abnormal sensation due to LASIK-induced corneal neuropathy. Other factors, such as alterations in conjunctival goblet cell density, might also contribute to the symptoms and signs of LASIK-induced dry eye. Inter-relationships between nerve morphology, tear neuropeptide levels and dry eye require further investigation. A better understanding of this phenomenon may result in improved management of post-LASIK dry eye.