Tear osmolarity in the diagnosis and management of dry eye disease
TL;DR: Tear osmolarity is the best single metric both to diagnose and classify dry eye disease and intereye variability is a characteristic of dry eye not seen in normal subjects.
About: This article is published in American Journal of Ophthalmology.The article was published on 2011-05-01. It has received 537 citations till now. The article focuses on the topics: Meibomian gland.
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TL;DR: The role of the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) II Diagnostic Methodology Subcommittee was to identify tests used to diagnose and monitor dry eye disease (DED) to identify those most appropriate to fulfil the definition of DED and its sub-classifications.
Abstract: 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.
1,152 citations
University of Oxford1, Anglia Ruskin University2, Baylor College of Medicine3, Massachusetts Eye and Ear Infirmary4, University of Illinois at Chicago5, Charité6, University of New South Wales7, Keio University8, Bascom Palmer Eye Institute9, Kyoto Prefectural University of Medicine10, Tufts University11
TL;DR: The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease, finding 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 to be important.
Abstract: 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-Sjogren 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.
994 citations
Cites background from "Tear osmolarity in the diagnosis an..."
...Tear osmolarity threshold values that discriminate a healthy eye from an eye with DED varies in the literature from 308 mOsm/L to 316 mOsm/L [269,270]....
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...limits and is remarkably stable in healthy eyes [269]....
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TL;DR: The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED), biophysical and biochemical aspects of tears and how these change in DED and recommended areas for future research.
Abstract: 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.
582 citations
Cites background from "Tear osmolarity in the diagnosis an..."
...Differences between readings can be considered a marker for tear film instability [128,133,146]....
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...Such interpretation may be supported by studies showing higher variability between measurements or eyes with higher osmolarity values or more severe dry eye [128,133,137,139,165]....
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TL;DR: The proportion of subjects exhibiting signs of evaporative dry eye resulting from MGD far outweighs that of subjects with pure ADDE in a general clinic-based patient cohort.
Abstract: Purpose:To evaluate in a general clinic-based cohort of patients with dry eye disease (DED) the distribution of patients with aqueous-deficient or evaporative subtype of DED.Methods:Schirmer tests and meibomian gland dysfunction (MGD) (Foulks–Bron scoring) were evaluated in both eyes of 299 normal s
396 citations
Cites background or methods from "Tear osmolarity in the diagnosis an..."
...The remaining 299 subjects were categorized according to an objective scale that classifies normal controls and mild/moderate and severe DED based on quartiles of a composite continuous severity index previously described for this patient cohort.(25,26) Specifically, a continuous dry eye severity scale was generated from 7 frequently used tests to measure signs and symptoms of DED: tear osmolarity, Schirmer tests, tear breakup times (TBUT) using fluorescein, corneal staining, meibomian grading, conjunctival staining, and Ocular Surface Disease Index (OSDI) score....
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...Because the raw scores for these tests have widely different ranges, each test was assigned scores ranging between 0 (representing the least evidence of disease) and 1 (representing the most evidence of dry eye).(25,26) This composite severity index has been described in more detail in a previous publication....
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...In this context, the principal purpose of this study was to determine the distribution of ADDE, EDE, and mixed forms of DED in a clinic-based cohort of dry eye patients, for which an objective measurement of disease severity has been described.(25,26)...
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...5 has been previously established to be a useful cutoff for the diagnosis of impaired meibomian gland function.(25,32)...
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...This composite severity index has been described in more detail in a previous publication.(25) Based on the composite severity index, a total of 224 subjects were identified as having DED and were included for analysis in this study (174 women and 50 men, average age of 49....
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TL;DR: The treatment of dry eye has evolved from tear substitution alone to a rationally based therapeutic algorithm and currently focuses on pathophysiology, new diagnostic techniques, and novel therapies including secretagogues, topical androgens, and new anti- inflammatory drugs.
Abstract: Background
Dry eye disease (DED) is common; its prevalence around the world varies from 5% to 34%. Its putative pathogenetic mechanisms include hyperosmolarity of the tear film and inflammation of the ocular surface and lacrimal gland. Dry eye is clinically subdivided into two subtypes: one with decreased tear secretion (aqueous-deficient DED), and one with increased tear evaporation (hyperevaporative DED).
346 citations
References
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TL;DR: It is suggested that information maximization provides a unifying framework for problems in "blind" signal processing and dependencies of information transfer on time delays are derived.
Abstract: We derive a new self-organizing learning algorithm that maximizes the information transferred in a network of nonlinear units. The algorithm does not assume any knowledge of the input distributions, and is defined here for the zero-noise limit. Under these conditions, information maximization has extra properties not found in the linear case (Linsker 1989). The nonlinearities in the transfer function are able to pick up higher-order moments of the input distributions and perform something akin to true redundancy reduction between units in the output representation. This enables the network to separate statistically independent components in the inputs: a higher-order generalization of principal components analysis. We apply the network to the source separation (or cocktail party) problem, successfully separating unknown mixtures of up to 10 speakers. We also show that a variant on the network architecture is able to perform blind deconvolution (cancellation of unknown echoes and reverberation in a speech signal). Finally, we derive dependencies of information transfer on time delays. We suggest that information maximization provides a unifying framework for problems in "blind" signal processing.
9,157 citations
TL;DR: Tear hyperosmolarity, defined by a referent of 316 mOsmol/L, was superior in overall accuracy to any other single test for dry eye diagnosis, even when the other test measures were applied to a diagnosis within the sample groups from which they were derived.
Abstract: PURPOSE. To determine new referents, or cutoff levels for tear film hyperosmolarity in the diagnosis of keratoconjunctivitis sicca (KCS) and to assess their effectiveness in independent patient groups. METHOD. A meta-analysis was performed on published data for tear osmolarity in samples of normal eyes and various subtypes of dry eye, and pooled estimates of the mean and standard deviations for normal and (all) dry eye subjects were determined. Diagnostic referents were derived from the intercept between the distributions of osmolarity in the two samples and from receiver operator characteristic (ROC) curves. This referent was tested for effectiveness of diagnosis in independent groups with normal and dry eyes. RESULTS. An osmolarity referent of 315.6 mOsmol/L was derived from the intercept of the distribution curves, and 316 mOsmol/L from the ROC curve. When applied to independent groups of normal and dry eye subjects a value of 316 mOsmol/L was found to yield sensitivity of 59%, specificity of 94%, and an overall predictive accuracy of 89% for the diagnosis of dry eye syndrome. CONCLUSIONS. Tear hyperosmolarity, defined by a referent of 316 mOsmol/L, was superior in overall accuracy to any other single test for dry eye diagnosis (Lactoplate, Schirmer test, and Rose Bengal staining), even when the other test measures were applied to a diagnosis within the sample groups from which they were derived. For overall accuracy in the diagnosis of dry eye, the osmolarity test was found to be comparable with the results of combined (in parallel or series) tests.
538 citations
TL;DR: The purpose of this review is to synthesize a clinical description of meibomian gland disease and to provide a scheme for diagnosis, classification, and quantification that will be of value in the clinical setting and in the conduct of clinical trials.
Abstract: Although meibomian gland disease (MGD) is one of the most common disorders encountered in ophthalmic practice, there has been no descriptive system consistently accepted to clinically characterize the anatomical and correlative biochemical alterations that occur in this condition. The purpose of this review is to synthesize a clinical description of meibomian gland disease and to provide a scheme for diagnosis, classification, and quantification that will be of value in the clinical setting and in the conduct of clinical trials.
472 citations
TL;DR: Tear film osmolarity was found to be the single best marker of disease severity across normal, mild/moderate, and severe categories and supports the rationale for redefining severity on the basis of a continuum of clinical signs.
Abstract: Purpose A prospective, multisite clinical study (10 sites in the European Union and the United States) evaluated the clinical utility of commonly used tests and tear osmolarity for assessing dry eye disease severity. Methods Three hundred fourteen consecutive subjects between the ages of 18 and 82 years were recruited from the general patient population, 299 of which qualified with complete datasets. Osmolarity testing, Schirmer test without anesthesia, tear film breakup time (TBUT), corneal staining, meibomian dysfunction assessment, and conjunctival staining were performed bilaterally. A symptom questionnaire, the Ocular Surface Disease Index (OSDI), was also administered to each patient. Distributions of clinical signs and symptoms against a continuous composite severity index were evaluated. Results Osmolarity was found to have the highest correlation coefficient to disease severity (r(2) = 0.55), followed by conjunctival staining (r(2) = 0.47), corneal staining (r(2) = 0.43), OSDI (r(2) = 0.41), meibomian score (r(2) = 0.37), TBUT (r(2) = 0.30), and Schirmer result (r(2) = 0.17). A comparison of standard threshold-based classification with the composite severity index revealed significant overlap between the disease severities of prospectively defined normal and dry eye groups. Fully 63% of the subjects were found to be poorly classified by combinations of clinical thresholds. Conclusions Tear film osmolarity was found to be the single best marker of disease severity across normal, mild/moderate, and severe categories. Other tests were found to be informative in the more severe forms of disease; thus, clinical judgment remains an important element in the clinical assessment of dry eye severity. The results also indicate that the initiation and progression of dry eye is multifactorial and supports the rationale for redefining severity on the basis of a continuum of clinical signs. (ClinicalTrials.gov number, NCT00848198.).
466 citations
TL;DR: Patients with DTS have higher levels of inflammatory mediators in their tears that show correlation with clinical disease parameters and significant correlations were observed between IL-6 and irritation symptoms and between a number of cytokines and chemokines and clinical parameters.
451 citations