Definition Of Dry Eye Disease Research Articles

Artificial Tears: A Systematic Review.

Artificial tears are the mainstay of dry eye disease management, but also have a role in corneal abrasion and wound healing, pain and inflammation management, conjunctivitis, keratitis, contact lens rewetting and removal, and foreign body removal. A systematic review of randomized controlled trials (PROSPERO registration CRD42022369619) comparing the efficacy of artificial tears in patients with dry eye to inform prescribing choices using Web of Science, PubMed and Medline databases identified 64 relevant articles. There is good evidence that artificial tears improve symptoms of dry eye disease within a month of regular use, applied about four times a day, but signs generally take several months to improve. Not all patients with dry eye disease benefit from artificial tears, so if there is no benefit over a month, alternative management should be considered. Combination formulations are more effective than single active ingredient artificial tears. Artificial tears containing polyethylene glycol are more effective than those containing carboxymethylcellulose/carmellose sodium and hydroxypropyl methylcellulose. Those classified as having evaporative dry eye disease, benefit from artificial tears with liposomes, especially of higher concentration. The data available is limited by the definition of dry eye disease applied in published studies being variable, as well as the disease severity examined and compliance with artificial tears being rarely quantified.

What is Important in Diagnosing Dry Eye Disease - Recommendations According to current Guidelines (DEWS II, DOG/BVA)

Dry Eye is one of the most common ocular diseases worldwide with an increasing number of patients. The pathogenesis of this disease is multifactorial and complex and the basis for diagnostic strategies and therapies. The current definition of dry eye disease as described in DEWS II includes inflammatory mechanisms at the ocular surface, a loss of homeostasis, hyperosmolarity of the tear film and neurosensory abnormalities. Subject symptom scores, a detailed patient history, certain diagnostic tools, and interdisciplinary interactions are necessary to enable an efficient, individualized and successful therapy. Important diagnostics include risk factor analysis, slit lamp examination, tear secretion tests, tearfilm stability tests, and tests for measuring the ocular surface inflammation.

Defining Dry Eye from a Clinical Perspective.

Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: “Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities.” The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.

Updated definition and classification of dry eye disease: Renewed proposals using the nominal group and Delphi techniques.

The aim of our research was to obtain expert consensus for updated definition and classification of dry eye disease using formal methodology. The nominal group technique (NGT) involved a steering committee of four ophthalmologists began with collection of ideas followed by group discussion. The ideas were collated, refined, and voted upon. The main characteristics considered, each with different degrees of severity in types I, II, and III, were the ability or not of the ocular surface to re-equilibrate itself, frequency of symptoms, presence of inflammation, epithelial alterations, and possible alterations in the quality of vision. This was followed by three rounds of a "mini-Delphi" involving an expert panel of 13 ophthalmologists, with the last round including all 17 ophthalmologists. Consensus in the final round of voting (⩾75% of votes) was reached on the definition of dry eye disease and on criteria for its classification in three forms. Type I is a transient and reversible form with subclinical inflammation, possible epithelial alterations, and occasional alterations in vision. Type II is a recurrent form characterized by a reduced ability to re-equilibrate the ocular surface, frequent symptoms and alterations in vision with clinically-evident inflammation, and clear evidence of epithelial alterations. Type III is a chronic form with inability to re-equilibrate the ocular surface and accompanied by clinically-evident and chronic inflammation, persistent epithelial alterations, and frequent alterations in quality of vision. The vast majority of patients with dry eye disease can be easily classified into one of these three forms. Dry eye disease definition was updated accordingly.

Dry eye disease treatment: the role of tear substitutes, their future, and an updated classification.

The aim of this review is to summarize the results of a consensus meeting held by a group of experts in dry eye disease (DED) to discuss the importance of tear substitutes in the treatment of DED. The meeting focused especially on the main characteristics of lacrimal substitutes, the development of in vitro models to investigate DED pathophysiology and treatment, the importance of conducting rigorous clinical trials, the requirements of the upcoming European Legislation on medical devices, the advances in the formulation of safer preservatives, the peculiarities of treatment in younger subjects, and the importance of an updated terminology for lacrimal substitutes. A literature search was conducted using MEDLINE, with different combinations of pertinent keywords, depending on the subject under discussion, such as "dry eye disease"; "tear substitutes"; "in vitro models"; "ocular surface"; "clinical trials"; "European Regulation"; "preservatives" "younger patients". Also, each author included in the discussion selected articles from their personal library. Using a consensus-based method called nominal group technique to reach a conclusion and proposal for a new classification of eye drops used to improve the tear film and ocular surface epithelia, the experts also conducted a round table meeting. The new terms proposed by the authors are "wetting agents", "multiple-action tear substitutes" or "ocular surface modulators". The new classification is needed to distinguish eye drops used to improve the tear film and ocular surface epithelia, in line with the new definition of DED, which recognizes the loss of ocular homeostasis, and the creation of a vicious circle of chronic inflammation and ocular damage as fundamental aspects of DED pathophysiology. Although tear substitutes have been historically used to provide eye lubrication to the ocular surface, recent advances in the pathophysiology of dry eye disease (DED) clarified that treatment should not just focus on tear film quality or quantity, but address the loss of homeostasis of the ocular surface, blocking the vicious circle of chronic inflammation and ocular damage. Given the scant comparative evidence on tear substitutes currently on the market, further studies should focus on developing new agents, considering the advantages provided by in vitro models, importance of conducting rigorous clinical trials, availability of less harmful preservatives and obligations related to the new European legislation on medical devices. Based on the discussion of these topics, a group of experts held a consensus meeting to identify new and more appropriate terms for different tear substitutes. The proposed terms are wetting agents, multiple-action tear substitutes and ocular surface modulators. Regardless of the agent used, it is important to note that tear substitutes represent one of many options for DED treatment, which should not overlook the psychological aspects of the disease and the peculiarities of younger subjects, who seem to have a higher risk for DED, possibly related to digital devices excessive use.

Pain and sensation in dry eye disease

AbstractThe recent definition of dry eye disease (DED) proposed by DEWS II includes, for the first time, neurosensory abnormalities in etiology of the disease. In DED, reduced tear secretion leads to inflammation and corneal nerve damage, which induce sensitization of corneal polymodal and mechano‐nociceptors, and an abnormal activity of cold thermoreceptors thus evoking pain and eye dryness sensations. Moreover, long‐term nerve damage and inflammation, modify the expression of ion channels involved in the stimulus detection (transduction) and excitability of ocular sensory neurons, changing their impulse firing and their connectivity at the CNS, which is the basis of neuropathic pain and dysesthesia referred to the eye surface in DED patients. These altered transducing and encoding ion channels are potential molecular targets to modulate neuropathic nerve activity in DED, currently under study. Although many subjective (surveys and questionnaires, corneal sensitivity measurement) and objective metrics (morphology and density of subbasal corneal nerves and immune cells, blink parameters, biomarkers in tears) are currently used to evaluate pain in DED patients, new instruments and procedures designed to obtain more reliable information on eye sensations and pain in DED need to be developed (SAF‐2017‐83674‐C2‐1‐R and 2‐R, Agencia Estatal de Investigación‐ERDF, Spain‐EU, and PROMETEO/2018/114, Generalitat Valenciana, Spain).

Meibomian Gland Dysfunction

Dry eyes is a common, chronic condition that has a prevalence of about 5- 50%.1 According to the Dry Eye Workshop II report (DEWS II report), published in 2017, the updated definition of Dry Eye Disease is, “a multifactorial disease of the ocular surface characterised by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyper-osmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.” The Tear Film & Ocular Surface Society (TFOS) released their report on the international work on Meibomian Gland Dysfunction (MGD)2 in 2011, which defined MGD, classified it and considered it as the primary cause of dry eye disease worldwide. Previously dry eye disease was considered as an aqueous deficiency problem, but after this report by TFOS, there is a paradigm shift towards “not producing enough lipids to retain the tears that are being produced”. This has led to a huge impact on the treatment protocols which were previously focused on managing the sequelae and symptoms of dry eyes rather than targeting directly on the underlying cause, the MGD. It has now been accepted worldwide that dry eye occurs when the ocular surface system cannot adequately protect itself from the desiccating stress due to the lack of a healthy meibomian gland secretion. This article is mainly focussed on the Meibomian Gland Dysfunction, discussing the normal anatomy of the glands, how they are affected by disease, its implications on the ocular surface and finally, the various treatment strategies.
 Key words: Blepharitis, Dry eyes, Meibomian gland dysfunction, blepharospasm.

Correlation between conjunctival scraping cytology and other clinical dry eye metrics in determination of dry eye related inflammation

Background/Aim. New and improved definition of dry eye disease (DED) emphasized that hiperosmolarity and inflammation with initial tear film instability play etiological role. The aim of this study was to explore relation of some commonly used clinical tests to dry eye disease (DED) related inflammation measured by conjunctival scraping cytology. Methods. We examined 100 subjects, 80 of them having DED. We performed Schirmer without anesthesia (Schirmer I), Fluorescein Tear Break Up Time (FTBUT), Rose Bengal (RB), Lid Parallel Conjunctival Folds (LIPCOF), Tear Meniscus Height (TMH) and Tear Ferning (TF) and compared the values to scraping scores of tarsal conjunctiva. Results. FTBUT had the best sensitivity (93.6%). The highest specificity was found with RB (93.2%), but it was also high with Schirmer I, TF and FTBUT (respectively 89.8%, 84.5%, 78.0%). RB and FTBUT had the highest correlation with conjunctival scraping score (r = 0.707, p < 0.001; r = -0.507, p < 0.001). Conclusion. In our study, FTBUT, though often used in many combinations of the DED tests, showed a remarkably high sensitivity and specificity on its own, as well as good correlation with DED related inflammation detected with conjunctival scraping cytology.

Assessment of Dry Eye Symptoms: Current Trends and Issues of Dry Eye Questionnaires in Japan.

Dry eye disease (DED) is one of the most common disease in the ophthalmic clinic, and the reasons DED patients visit ophthalmic clinics are symptoms such as stinging, burning, or scratchy sensations. The symptoms and visual disturbances of DED have a negative impact on the daily routines and social lives of the patients (i.e., their quality of life [QOL]). The presence of symptoms was required in the definition of DED by the National Eye Institute/Industry Workshop in 1995; therefore, disease-specific questionnaires were essential for monitoring and managing patients with DED. Thereafter, many questionnaires have been developed to evaluate the specific symptoms of dry eyes. Although many questionnaires are available to assess the dry eye symptoms, it is essential that they provide valid answers and are easy to use to assess the effects of DED on the QOL. The Asia Dry Eye Society and Japan Dry Eye Society have proposed a new definition of DED that is a combination of symptoms and an unstable tear film, and information on these two factors is sufficient to make a definitive diagnosis of DED. Therefore, the assessments of the symptoms are fundamental in the diagnosis of DED.

Irregular Astigmatism and Higher-Order Aberrations in Eyes With Dry Eye Disease.

Visual disturbances were included in the definition of dry eye disease in the 2007 Dry Eye Workshop report. As a result, quality of vision (QoV) in dry eye patients has received increased attention. Corneal topography and wavefront sensors have been used to objectively and quantitatively evaluate optical quality, with data showing increases in irregular astigmatism and higher-order aberrations (HOAs) in dry eye patients. Furthermore, ocular optical characteristics are influenced by the tear film, which constantly fluctuates over time. Therefore, dynamic quantitative assessments of optical quality with continuous measurements are essential to understanding QoV in dry eye patients. This review summarizes what is known and what advances have been made in evaluating and understanding QoV in dry eye patients. In particular, corneal topographic and wavefront analyses, conducted both overseas and in Japan, are described.

Effects of tear film dynamics on quality of vision

The precorneal tear film is maintained by blinking and exhibits different phases in the tear cycle. The tear film serves as the most anterior surface of the eye and plays...

Variability of Tear Osmolarity Measurements With a Point-of-Care System in Healthy Subjects-Systematic Review.

To assess the variability of osmolarity measured by the point-of-care TearLab system in healthy eyes. A systematic review was performed by searching MEDLINE, Scopus, and the Web of Science Databases until November 2016 and checking reference lists of included articles and reviews. The requirements for inclusion were the availability of TearLab results in healthy subjects and a minimum study sample of 20 eyes. Two reviewers assessed articles against the inclusion criteria, extracted relevant data, and examined the methodological quality. We computed the weighted mean osmolarity using the study size as the weighting factor and calculated the rate of subjects with osmolarity values >308 mOsm/L, the Dry Eye Workshop Report 2017 (DEWS) cut-off value for dry eye disease (DED). We repeated the analysis after excluding reports with a possible conflict of interest or missing description of subject selection. Searches retrieved 105 nonduplicate articles, and we included 33 studies investigating 1362 eyes of healthy participants who were asymptomatic and showed no clinical signs of DED. Sixty-three percent were female, and mean age was 37.3 years (range: 21.5-69.0 yr). Weighted mean osmolarity was 298 mOsm/L (95% confidence interval, 282-321 mOsm/L). The result of the subgroup analysis was similar. Overall, 386 of 1362 eyes (28.3%) fulfilled the DEWS's definition of DED (>308 mOsm/L). There is a high variability of osmolarity measurements with the TearLab system. A substantial number of healthy subjects fulfill the DEWS's definition of DED. We propose interpreting the TearLab osmolarity results cautiously and in the context of other established methods.