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      Associations between signs and symptoms of dry eye disease: a systematic review

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          Abstract

          Purpose

          The accurate diagnosis and classification of dry eye disease (DED) is challenging owing to wide variations in symptoms and lack of a single reliable clinical assessment. In addition, changes and severity of clinical signs often do not correspond to patient-reported symptoms. To better understand the inconsistencies observed between signs and symptoms, we conducted a systematic literature review to evaluate published studies reporting associations between patient-reported symptoms and clinical signs of DED.

          Methods

          PubMed and Embase were searched for English-language articles on the association between clinical signs and symptoms of DED up to February 2014 (no lower limit was set).

          Results

          Thirty-four articles were identified that assessed associations between signs and symptoms, among which 33 unique studies were reported. These included 175 individual sign–symptom association analyses. Statistical significance was reported for associations between sign and symptom measures in 21 of 33 (64%) studies, but for only 42 of 175 (24%) individual analyses. Of 175 individual analyses, 148 reported correlation coefficients, of which the majority (129/148; 87%) were between −0.4 and 0.4, indicating low-to-moderate correlation. Of all individual analyses that demonstrated a statistically significant association, one-half (56%) of reported correlation coefficients were in this range. No clear trends were observed in relation to the strength of associations relative to study size, statistical methods, or study region, although results from three studies did suggest that disease severity may be a factor.

          Conclusion

          Associations between DED signs and symptoms are low and inconsistent, which may have implications for monitoring the response to treatment, both in the clinic and in clinical trials. Further studies to increase understanding of the etiopathogenesis of DED and to identify the most reliable and relevant measures of disease are needed to enhance clinical assessment of DED and the measurement of response to therapeutic interventions.

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          Most cited references55

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          Development of the 25-item National Eye Institute Visual Function Questionnaire.

          To develop and test the psychometric properties of a 25-item version of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Prospective observational cohort study of persons with 1 of 5 chronic eye diseases or low vision who were scheduled for nonurgent visits in ophthalmology practices and a reference sample of persons without eye disease. Eleven university-based ophthalmology practices and the NEI Clinical Center. Eligible participants had to have 1 of the following eye conditions: age-related cataracts, age-related macular degeneration, diabetic retinopathy, primary open-angle glaucoma, cytomegalovirus retinitis, or low vision from any cause. Seven of the 12 sites also enrolled persons in a reference sample. Reference sample participants had no evidence of underlying eye disease but were scheduled for either screening eye examinations or correction of refractive error. All eligible persons had to be 21 years or older, English speaking, and cognitively able to give informed consent and participate in a health status interview. To provide the data needed to create the NEI VFQ-25, all subjects completed an interview that included the 51-item NEI VFQ. Estimates of internal consistency indicate that the subscales of the NEI VFQ-25 are reliable. The validity of the NEI VFQ-25 is supported by high correlations between the short- and long-form versions of the measure, observed between-group differences in scores for persons with different eye diseases of varying severity, and the moderate-to-high correlations between the NEI VFQ-25 subscales that have the most to do with central vision and measured visual acuity. The reliability and validity of the NEI VFQ-25 are comparable to those of the 51-item NEI VFQ field test version of the survey. This shorter version will be more feasible in settings such as clinical trials where interview length is a critical consideration. In addition, preliminary analyses indicate that the psychometric properties of the NEI VFQ-25 are robust for the eye conditions studied; this suggests that the measure will provide reproducible and valid data when used across multiple conditions of varying severity.
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            The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007).

            (2007)
            The report of the Epidemiology Subcommittee of the 2007 Dry Eye WorkShop summarizes current knowledge on the epidemiology of dry eye disease, providing prevalence and incidence data from various populations. It stresses the need to expand epidemiological studies to additional geographic regions, to incorporate multiple races and ethnicities in future studies, and to build a consensus on dry eye diagnostic criteria for epidemiological studies. Recommendations are made regarding several characteristics of dry eye questionnaires that might be suitable for use in epidemiological studies and randomized controlled clinical trials. Risk factors for dry eye and morbidity of the disease are identified, and the impact of dry eye disease on quality of life and visual function are outlined. Suggestions are made for further prospective research that would lead to improvement of both eye and general public health.
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              The lack of association between signs and symptoms in patients with dry eye disease.

              The purpose of this report was to examine the relation between clinical tests and dry eye symptoms in patients with dry eye disease. Seventy-five patients with dry eye disease (ICD-9 code 375.15) were included in these analyses. There was no specific entry criterion for enrollment in addition to a previous dry eye diagnosis in this clinic-based sample. Patients represented varying types and severity of dry eye disease and were previously diagnosed by clinic attending doctors in this university clinic setting. The study examination included a symptom interview that assessed dryness, grittiness, soreness, redness, and ocular fatigue. The interview was followed by a clinical dry eye examination conducted in the following sequence: meibomian gland assessment, tear meniscus height, tear breakup time test, fluorescein staining, the phenol red thread test, Schirmer test, and rose bengal staining. Partial Spearman correlation coefficients, the Wilcoxon rank sum test, chi 2 test, and multivariate logistic regression were used to evaluate the relationship between dry eye tests and symptoms. Symptoms were generally not associated with clinical signs in patients with dry eye disease. There were no significant correlations between signs and symptoms after adjustment for age and artificial tear use. The rank of each clinical test result did not statistically differ when stratified by the presence of patient symptoms in Wilcoxon rank sum analyses. Likewise, the frequency of patient symptoms did not differ statistically when stratified by a positive clinical test result in chi 2 analyses. In multivariate logistic regression analyses, no clinical test significantly predicted frequently reported symptoms after adjustment for age and artificial tear use. These results suggest a poor relation between dry eye tests and symptoms, which represents a quandary in dry eye clinical research and practice.
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                Author and article information

                Journal
                Clin Ophthalmol
                Clin Ophthalmol
                Clinical Ophthalmology
                Clinical Ophthalmology (Auckland, N.Z.)
                Dove Medical Press
                1177-5467
                1177-5483
                2015
                16 September 2015
                : 9
                : 1719-1730
                Affiliations
                [1 ]Department of Optometry, School of Optometry, The University of Alabama at Birmingham, Birmingham, AL, USA
                [2 ]Global Health Economics, Outcomes Research, and Epidemiology Department, Research and Development Division, Shire, Wayne, PA, USA
                [3 ]Pharmerit International, Bethesda, MD, USA
                Author notes
                Correspondence: Jimmy D Bartlett, School of Optometry, University of Alabama at Birmingham, 1716 University Blvd., Birmingham, AL 35294, USA, Tel +1 205 907 6764, Fax +1 205 969 2551, Email jbartlett049@ 123456gmail.com
                Article
                opth-9-1719
                10.2147/OPTH.S89700
                4577273
                26396495
                6ece3a56-64c2-4258-8959-a0f19e4b6c65
                © 2015 Bartlett et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Review

                Ophthalmology & Optometry
                associations,correlations,dry eye disease,signs,symptoms,systematic literature review

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